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The objective of this study is to investigate the effect of nano-plastics (NPs) on the growth, photosynthesis, oxidative stress and antioxidant enzymes in Grateloupia turuturu and Chondrus ocellatus. Difference of surface characteristics between G. turuturu and C. ocellatus may affect adherence of plastics to their surface. The seaweed samples were cultivated at 5 different NP concentrations (0, 20, 200, 2000, 20000 ng/L) for 21 days. The accumulation of nano-plastics on surface of C. ocellatus was higher than that of G. turuturu. The highest concentration of NPs (20000 ng/L) inhibited the growth and photosynthesis activity of C. ocellatus. At the same concentrations, oxidative stress was caused with increase of antioxidant enzyme activities. G. turuturu was not affected by NPs at all tested concentrations. Based on these results, toxic effects of nano-plastics may be species specific. Toxicity is dependent on the capacity of macroalgae to accumulate nano-plastics on their surface., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Jang Kyun Kim reports financial support was provided by National Research Foundation of Korea. Jang Kyun Kim reports financial support was provided by Ministry of Oceans and Fisheries of Korea. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background: This study was conducted to evaluate the feasibility and surgical outcomes of minimally invasive video-assisted thyroidectomy (MIVAT) and three remote-access approaches, namely the robotic bilateral axillo-breast approach (BABA-R), endoscopic breast-chest approach (BCA-E), and robotic gasless transaxillary approach (GTAA-R) in lateral neck dissection for papillary thyroid carcinoma, compared with conventional transcervical approach (CTA)., Methods: The literature search was conducted in the PubMed, EMBASE, and Cochrane Library databases, covering the period January 2000 to February 2024. A systematic review and network meta-analysis were performed to compare surgical feasibility, safety, and oncologic outcomes between approaches., Results: Fourteen articles on lateral neck dissection in patients with papillary thyroid carcinoma were included after systematic screening. The number of removed and metastatic lateral lymph nodes, the extent of lateral neck dissection, the rate of transient recurrent laryngeal nerve palsy and hypoparathyroidism, serum-stimulated thyroglobulin levels, and recurrence were not significantly different between the MIVAT and three remote-access approaches. Additionally, these were comparable to those of the CTA. However, the MIVAT and remote-access approaches took a longer operative time but provided superior cosmetic outcomes compared to the CTA., Conclusion: Lateral neck dissection using the MIVAT and three remote-access approaches was feasible and comparable to CTA in the number of lymph nodes removed, complications, stimulated thyroglobulin level, and recurrence. The MIVAT and remote-access approaches lasted longer but provided significantly superior cosmetic outcomes compared to the CTA., (Copyright © 2024 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.)

Background: Idiopathic pulmonary fibrosis (IPF) is a progressive interstitial lung disease of unknown etiology. The aim of this study was to evaluate the environmental and occupational risk factors of IPF., Methods: This hospital-based, case-control study included 206 patients with IPF selected from the Seoul National University Bundang Hospital Interstitial Lung Disease registry and 167 controls without lung disease. Data on occupation, lifestyle, transportation, and types of environmental and occupational dust exposure were obtained using a questionnaire. IPF diagnosis was confirmed based on the recent guidelines, and the possibility of hypersensitivity pneumonitis was excluded. Multiple logistic regression was performed to determine the risk factors for IPF., Results: After adjusting for age and sex, ever-smokers (odds ratio [OR], 2.35; 95 % confidence interval [CI]: 1.51-3.68) and individuals who smoked more than 30 pack-years (OR, 2.79; 95%CI: 1.70-4.68) showed an increased risk for IPF. Any occupational dust exposure (adjusted OR, 2.08; 95%CI: 1.19-3.72), especially exposure to chemicals (adjusted OR, 3.52; 99%CI: 1.56-9.05), was associated with IPF after adjusting for age, sex, and smoking., Conclusions: Smoking and occupational dust exposure are associated with an increased risk for IPF. Both factors have dose and duration-dependent relationships with the risk for IPF., Competing Interests: Declaration of competing interest None., (Copyright © 2024. Published by Elsevier Ltd.)

As microplastics (MPs) are particulate pollutants, their size and shape, and the presence of prey in the media can affect their toxicity. However, the size- and shape-dependent toxicities of MPs and their prey-dependent ingestion patterns in marine zooplankton are not well understood. Thus, we investigated the ingestion and egestion patterns, and toxicity of different shapes and sizes of MPs on two marine zooplankton, Brachionus koreanus and Diaphanosoma celebensis, under different prey conditions. The ingestion assay showed that smaller MPs were ingested more frequently, regardless of their shape. However, fragmented MPs showed higher toxicity than spherical MPs of comparable size. Prey in the media reduced the uptake and toxicity of MPs in both species depending on the taxa's feeding strategy. Our findings demonstrate that the size and shape of MPs are important factors in determining toxicity and that the presence of prey should also be considered when assessing MP toxicity., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background: Hypoxic-ischemic brain injury (HIBI) is a common complication of out-of-hospital cardiac arrest (OHCA)., Objectives: We investigated whether grey-to-white matter ratio (GWR) values, measured using early head computed tomography (HCT), were associated with neurologic outcomes based on the severity of HIBI in survivors of OHCA., Methods: This retrospective multicenter study included adult comatose OHCA survivors who underwent an HCT scan within 2 h after the return of spontaneous circulation. HIBI severity was assessed using the revised post-Cardiac Arrest Syndrome for Therapeutic hypothermia (rCAST) scale (low, moderate, and severe). Poor neurologic outcomes were defined as Cerebral Performance Categories 3 to 5 at 6 months after OHCA., Results: Among 354 patients, 27% were women and 224 (63.3%) had poor neurologic outcomes. The distribution of severity was 19.5% low, 47.5% moderate, and 33.1% severe. The area under the receiver operating curves of the GWR values for predicting rCAST severity (low, moderate, and severe) were 0.52, 0.62, and 0.79, respectively. The severe group had significantly higher predictive performance than the moderate group (p = 0.02). Multivariate logistic regression analysis revealed a significant association between GWR values and poor neurologic outcomes in the moderate group (adjusted odds ratio = 0.012, 95% CI 0.0-0.54, p = 0.02)., Conclusions: In this cohort study, GWR values measured using early HCT demonstrated variations in predicting neurologic outcomes based on HIBI severity. Furthermore, GWR in the moderate group was associated with poor neurologic outcomes., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Microplastics (MPs) are a major concern in marine ecosystem because MPs are persistent and ubiquitous in oceans and are easily consumed by marine biota. Although many studies have reported the toxicity of MPs to marine biota, the toxicity of environmentally relevant types of MPs is little understood. We investigated the toxic effects of fragmented polyethylene terephthalate (PET) MP, one of the most abundant MPs in the ocean, on the marine rotifer Brachionus koreanus at the individual and molecular level. No significant rotifer mortality was observed after exposure to PET MPs for 24 and 48 h. The ingestion and egestion assays showed that rotifers readily ingested PET MPs in the absence of food but not when food was supplied; thus, there were also no chronic effects of PET MPs. In contrast, intracellular reactive oxygen species levels and glutathione S-transferase activity in rotifers were significantly increased by PET MPs. Transcriptomic and metabolomic analyses revealed that genes and metabolites related to energy metabolism and immune processes were significantly affected by PET MPs in a concentration-dependent manner. Although acute toxicity of PET MPs was not observed, PET MPs are potentially toxic to the antioxidant system, immune system, and energy metabolism in rotifers., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Marine plastic debris (MPD) is a potential threat to marine ecosystems, but its function as a vector for the transportation of harmful microalgae and its impact on the habitats of other marine organisms are uncertain. To address this gap in knowledge, we performed month-long experiments in 30 L microcosms that contained plates made of six different plastic polymers (polypropylene [PP], low-density polyethylene [LDPE], high-density polyethylene [HDPE], polyvinyl chloride [PVC], polyethylene terephthalate [PET], and polystyrene [PS]), and examined the time course of changes in planktonic and periphytic microalgae. There were no significant differences in the composition of periphytic microalgae or biomass among the different plastic polymers (p > 0.05). Nutrient depletion decreased the abundance of planktonic microalgae, but increased the biomass of attached periphytic microalgae (p < 0.05). In particular, analysis of the plastic plates showed that the abundance of benthic species that are responsible for harmful algal blooms (HABs), such as Amphidinium operculatum and Coolia monotis, significantly increased over time (days 21-28; p < 0.05). Our findings demonstrated that periphyton species, including benthic microalgae that cause HABs, can easily attach to different types of plastic and potentially spread to different regions and negatively impact these ecosystems. These observations have important implications for understanding the potential role of MPD in the spread of microalgae, including HABs, which pose a significant threat to marine ecosystems., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

Background: Teledentistry is the usage of information-based technologies to deliver healthcare services remotely. It is used to deliver care in regional, rural and remote regions and was particularly useful to deliver care during the COVID-19 pandemic., Objective: This systematic review and meta-analysis aimed to determine teledentistry utilisation in Australia., Methods: The databases PubMed, Google Scholar, EMBASE and Web of Science were searched from inception to June-2024. The phrases "Dental" AND "Telehealth" AND "Australia" and "Teledentistry" AND "Australia" were used. Two authors completed the study selection and data extraction. The Joanna Briggs Institute Critical Appraisal Tools were used to assess quality and bias., Results: Eighteen articles met the inclusion criteria. There were six diagnostic tests, six cross-sectional studies, 4 economic evaluations, one qualitative study and one expert opinion. Teledentistry was accurate for screening caries (average sensitivity=69.7 %, average specificity=97.4 %). There also appeared to be a non-significant negative correlation between specificity and sensitivity (r = 0.432). Opinions regarding teledentistry were mixed from clinicians but positive from patients. Teledentistry may also lead to savings for patients and healthcare providers., Conclusion: Teledentistry increases healthcare access especially for people in regional, rural and remote areas. It is an effective screening tool for caries. Whilst the opinions of clinicians were mixed, potential implementation barriers were identified which could improve opinions of clinicians and increase implementation., Clinical Importance: This study demonstrates teledentistry as a satisfactory tool for screening caries. This could be beneficial to those with difficulties visiting dentists in-person, particularly if they live in regional, rural or remote areas., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

This severe monkeypox case described a 23-year-old male with advanced HIV-1 disease presenting perirectal abscess, extensive anal ulcerative lesions requiring colostomy, and tecovirimat resistance. Radiologically non-liquefied perirectal abscess presented diagnostic challenges highlighting the complexity of aggressive monkeypox manifestations in immunocompromised individuals., (Copyright © 2024 Japanese Society of Chemotherapy, Japanese Association for Infectious Diseases, and Japanese Society for Infection Prevention and Control. Published by Elsevier Ltd. All rights reserved.)

Background: Per- and polyfluoroalkyl substances (PFAS) can disrupt metabolism. Early-to-mid pregnancy is characterized by amplified metabolic processes and inflammation to support maternal adaptations and fetal growth. Thus, we cross-sectionally evaluated whether PFAS are individually and jointly associated with these processes in early-to-mid pregnancy., Methods: Pregnant Illinois women (n = 452) provided fasted blood samples at median 17 weeks gestation. We quantified serum perfluorononanoic (PFNA), perfluorooctane sulfonic (PFOS), perfluorooctanoic (PFOA), methyl-perfluorooctane sulfonamide acetic acid (Me-PFOSA-AcOH), perfluorohexanesulfonic (PFHxS), perfluorodecanoic (PFDeA), and perfluoroundecanoic (PFUdA) acid. Key outcomes were plasma glucose, insulin, C-peptide, insulin-like growth factor 1 (IGF-1), adiponectin, leptin, triglycerides, free fatty acids, total cholesterol, high-density lipoprotein (HDL) cholesterol, C-reactive protein, tumor necrosis factor alpha (TNF-α), monocyte chemoattractant protein-1 (MCP-1), and interleukin 6. We calculated homeostatic model assessment for insulin resistance (HOMA-IR), low-density lipoprotein (LDL) cholesterol, and very low-density lipoprotein (VLDL). We evaluated associations of PFAS with each metabolic/inflammatory biomarker individually using covariate-adjusted linear regression and jointly using quantile-based g-computation., Results: In linear regression, all PFAS (except Me-PFOSA-AcOH) were negatively associated with insulin, HOMA-IR, and leptin, whereas all PFAS were positively associated with HDL cholesterol. We also observed negative associations of some PFAS with TNF-α and MCP-1; positive associations with adiponectin and total cholesterol also emerged. Additionally, PFOS was positively, whereas Me-PFOSA-AcOH was negatively, associated with triglycerides and VLDL. Each 25% increase in the PFAS mixture was associated with -31.3% lower insulin (95%CI: -45.8, -12.9), -31.9% lower HOMA-IR (95%CI: -46.4, -13.4), and -9.4% lower leptin (95%CI: -17.3, -0.8), but 7.4% higher HDL cholesterol (95%CI: 4.6, 10.3). For most outcomes, the major contributors to the PFAS mixture often differed compared to single-PFAS analyses., Implications: Individual and joint PFAS exposures were associated with markers of maternal metabolism and inflammation in pregnancy. Further investigation is needed to elucidate possible mechanisms and consequences of these findings., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Heat shock factor 1 (HSF1) primarily regulates various cellular stress responses. Previous studies have shown that low pH within the physiological range directly activates HSF1 function in vitro. However, the detailed molecular mechanisms remain unclear. This study proposes a molecular mechanism based on the trimerization behavior of HSF1 at different pH values. Extensive mutagenesis of human and goldfish HSF1 revealed that the optimal pH for trimerization depended on the identity of residue 103. In particular, when residue 103 was occupied by tyrosine, a significant increase in the optimal pH was observed, regardless of the rest of the sequence. This behavior can be explained by the protonation state of the neighboring histidine residues, His101 and His110. Residue 103 plays a key role in trimerization by forming disulfide or non-covalent bonds with Cys36. If tyrosine resides at residue 103 in an acidic environment, its electrostatic interactions with positively charged histidine residues prevent effective trimerization. His101 and His110 are neutralized at a higher pH, which releases Tyr103 to interact with Cys36 and drives the effective trimerization of HSF1. This study showed that the protonation state of a histidine residue can regulate the intramolecular interactions, which consequently leads to a drastic change in the oligomerization behavior of the entire protein., Competing Interests: Declaration of competing interest The authors declare that they have no known completion financial interests or personal relationships that could have appeared to influence the reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Though gelatin emulsifying properties have been intensively studied, how low-molecular-weight (LMW) fish gelatin affects astaxanthin (AST)-loaded fish oil emulsion stability remains elusive. In this study, subcritical water hydrolysis (SWH)-modified LMW fish gelatin (SWHG) was produced from 110 °C to 180 °C and used to enhance the AST steadiness in oil/water emulsions in the presence of an emulsifier, lecithin. In the prepared emulsions, the surface charge increased while droplet size decreased with the decrease in gelatin MW due to the reduced thickness of the adsorbed gelatin membrane. LMW gelatin and lecithin could form a firm-absorbed layer on the droplet surface by electrostatic interaction between amide groups of gelatin molecules and phosphate groups of lecithin, thus stabilizing the emulsions. SWHG improved the creaming stability of the emulsions and hindered the oxygen- and light-induced AST degradation for 11 months compared to high MW gelatin. Whereas, the control emulsion showed noticeable phase separation after two weeks of storage. These findings prove the advantage of the SWH approach and propose the use of SWHG in oil-in-water emulsions for AST stabilization., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Competing Interests: Disclosures The authors have no conflicts of interest to disclose.

Objective: We sought to evaluate the clinical impact of lordosis orientation (LO) on proximal junctional kyphosis (PJK) development in adult spinal deformity surgery., Methods: This study included 152 patients who underwent low thoracic (T9-T12) to pelvis fusion and were followed up for ≥2 years. In the literature, 6 radiographic parameters representing LO were introduced, such as uppermost instrumented vertebra (UIV) slope, UIV inclination, UIV-femoral angle (UIVFA), thoracolumbar tilt, thoracolumbar slope, and lordosis tilt. Various clinical and radiographic factors including 6 LO parameters were investigated using logistic regression analysis to identify risk factors for PJK., Results: The mean age was 69.4 years, and 136 patients were females (89.5%). PJK developed in 65 patients (42.8%). Multivariate logistic regression analysis revealed that only small postoperative pelvic incidence (PI)-lumbar lordosis (LL) (odds ratio [OR] = 0.962, 95% confidence interval: 0.929-0.996, P = 0.030) and large UIVFA (OR = 1.089, 95% confidence interval: 1.028-1.154, P = 0.004) were significant for PJK development. UIVFA showed significantly positive correlation with pelvic tilt (CC = 0.509), thoracic kyphosis (CC = 0.384), and lordosis distribution index (CC = 0.223). UIVFA was also negatively correlated with sagittal vertical axis (CC = -0.371). However, UIVFA did not correlate with LL, PI-LL, or T1 pelvic angle., Conclusions: LO significantly increases the risk of PJK development in ASD surgery. Multivariate analysis revealed that smaller postoperative PI-LL and greater UIVFA were significant risk factors for PJK. Surgeons should avoid undercorrection and overcorrection to prevent PJK development., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Capturing the breadth of chemical exposures in utero is critical in understanding their long-term health effects for mother and child. We explored methodological adaptations in a Non-Targeted Analysis (NTA) pipeline and evaluated the effects on chemical annotation and discovery for maternal and infant exposure. We focus on lesser-known/underreported chemicals in maternal and umbilical cord serum analyzed with liquid chromatography-quadrupole time-of-flight mass spectrometry (LC-QTOF/MS). The samples were collected from a demographically diverse cohort of 296 maternal-cord pairs (n = 592) recruited in San Francisco Bay area. We developed and evaluated two data processing pipelines, primarily differing by detection frequency cut-off, to extract chemical features from non-targeted analysis (NTA). We annotated the detected chemical features by matching with EPA CompTox Chemicals Dashboard (n = 860,000 chemicals) and Human Metabolome Database (n = 3140 chemicals) and applied a Kendrick Mass Defect filter to detect homologous series. We collected fragmentation spectra (MS/MS) on a subset of serum samples and matched to an experimental MS/MS database within the MS-Dial website and other experimental MS/MS spectra collected from standards in our lab. We annotated ~72 % of the features (total features = 32,197, levels 1-4). We confirmed 22 compounds with analytical standards, tentatively identified 88 compounds with MS/MS spectra, and annotated 4862 exogenous chemicals with an in-house developed annotation algorithm. We detected 36 chemicals that appear to not have been previously reported in human blood and 9 chemicals that were reported in less than five studies. Our findings underline the importance of NTA in the discovery of lesser-known/unreported chemicals important to characterize human exposures., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Chronic obstructive pulmonary disease (COPD) is a group of illnesses associated with unresolved inflammation in response to toxic environmental stimuli. Persistent exposure to PM is a major risk factor for COPD, but the underlying mechanism remains unclear. Using our established mouse model of PM-induced COPD, we find that repeated PM exposure provokes macrophage-centered chronic inflammation and COPD development. Mechanistically, chronic PM exposure induces transcriptional downregulation of HAAO, KMO, KYNU, and QPRT in macrophages, which are the enzymes of de novo NAD + synthesis pathway (kynurenine pathway; KP), via elevated chromatin binding of the CCCTC-binding factor (CTCF) near the transcriptional regulatory regions of the enzymes. Subsequent reduction of NAD + and SIRT1 function increases histone acetylation, resulting in elevated expression of pro-inflammatory genes in PM-exposed macrophages. Activation of SIRT1 by nutraceutical resveratrol mitigated PM-induced chronic inflammation and COPD development. In agreement, increased levels of histone acetylation and decreased expression of KP enzymes were observed in pulmonary macrophages of COPD patients. We newly provide an evidence that dysregulated NAD + metabolism and consecutive SIRT1 deficiency significantly contribute to the pathological activation of macrophages during PM-mediated COPD pathogenesis. Additionally, targeting PM-induced intertwined metabolic and epigenetic reprogramming in macrophages is an effective strategy for COPD treatment., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Background: Distal radial access (DRA) as an alternative access route lacks evidence, despite its recent reputation., Objectives: The aim of this study was to evaluate the safety and feasibility of DRA on the basis of daily practice., Methods: The KODRA (Korean Prospective Registry for Evaluating the Safety and Efficacy of Distal Radial Approach) trial was a prospective multicenter registry conducted at 14 hospitals between September 2019 and September 2021. The primary endpoints were the success rates of coronary angiography (CAG) and percutaneous coronary intervention (PCI). The secondary endpoints included successful distal radial artery puncture, access-site crossover, access site-related complications, bleeding events, and predictors of puncture failure., Results: A total of 4,977 among 5,712 screened patients were recruited after the exclusion of 735 patients. The primary endpoints, the success rates of CAG and PCI via DRA, were 100% and 98.8%, respectively, among successful punctures of the distal radial artery (94.4%). Access-site crossover occurred in 333 patients (6.7%). The rates of distal radial artery occlusion and radial artery occlusion by palpation were 0.8% (36 of 4,340) and 0.8% (33 of 4,340) at 1-month follow-up. DRA-related bleeding events were observed in 3.3% of patients, without serious hematoma. Multilevel logistic regression analysis identified weak pulse (OR: 9.994; 95% CI: 7.252-13.774) and DRA experience <100 cases (OR: 2.187; 95% CI: 1.383-3.456) as predictors of puncture failure., Conclusions: In this large-scale prospective multicenter registry, DRA demonstrated high success rates of CAG and PCI, with a high rate of puncture success but low rates of distal radial artery occlusion, radial artery occlusion, bleeding events, and procedure-related complications. Weak pulse and DRA experience <100 cases were predictors of puncture failure. (Korean Prospective Registry for Evaluating the Safety and Efficacy of Distal Radial Approach [KODRA]; NCT04080700)., Competing Interests: Funding Support and Author Disclosures Samjin Pharmaceutical and the Gangwon Chapter of the Korean Society of Cardiology sponsored the KODRA trial. The authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2024 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

In this study, the recovery of Atrina pectinata posterior adductor polysaccharides (APP-PS) using subcritical water extraction (SWE) was optimized by response surface methodology (RSM) and the physicochemical and biological properties of the recovered APP-PS were evaluated. The optimal extraction conditions, which resulted in a maximum yield of 55.58 ± 1.12 %, were temperature, 152.08 °C; extraction time, 10 min; solid-liquid ratio, 30 g/600 mL. The obtained APP-PS was found to be 88.05 ± 0.17 % total sugar. Fourier transform infrared (FT-IR) and Nuclear magnetic resonance (NMR) analyses confirmed the presence of the α-coordination of D-glucan in the polymer sample. The analysis of monosaccharide composition, along with thermogravimetric analysis, revealed the typical structure of the sample, composed of glucose alone. Total phenolic contents of APP-PS were measured as 5.47 ± 0.01 mg Gallic acid/g of dry sample and total flavonoids contents were determined to be 0.78 ± 0.06 mg Quercetin/g of dry sample. For biological activities, ABTS + , DPPH and FRAP antioxidant activities were measured to be 20.00 ± 0.71, 2.35 ± 0.05 and 4.02 ± 0.07 μg Trolox equivalent/100 g of dry sample, respectively. Additionally ACE inhibitory was confirmed to be 87.02 ± 0.47 %. These results showed that SWE is an effective method to recover biofunctional materials from marine organisms., Competing Interests: Declaration of competing interest The authors declare that there is no conflict of interests regarding the publication of this article., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Objective: To analyze preoperative predictors of ambulatory recovery after surgical treatment in metastatic spinal cord compression (MSCC) patients with delayed surgical timing and progressive paraplegia., Methods: We reviewed patients with a preoperative lower-extremity motor grade of ≤3 and surgical timing ≥48 hours after the nonambulatory status. The recovery group (group R) and nonrecovery group (group NR) were classified according to ambulation assessment during follow-up. The data on patient demographics, origin of the primary tumor, pre and postoperative chemotherapy and radiation therapy, surgical procedures, Tokuhashi score, Karnofsky score, preoperative lower-extremity motor grade, and surgical timing were collected for analyzing predictors of postoperative ambulatory recovery., Results: Of the 55 patients, 24 (43.6%) were group R and 31 patients were group NR. The preoperative motor grade of the lower extremities was the only predictive factor (P < 0.05). The mean hip flexor and knee extensor motor grades in group R were 2.0 ± 1.0 and 2.4 ± 1.1 respectively, while in group NR, they were 1.2 ± 1.0 and 1.3 ± 1.0. The odds ratios for failing to regain ambulatory ability were 12.6 in the knee extensor and 4.8 in the hip flexor when the motor grades 0-2 and 3 groups were compared. The rescue ratio of the preoperative hip flexor and knee extensor motor grade 0-2 group were 34.1% and 21.2%, grades 3 group were 71.4% and 77.3%, respectively., Conclusions: The significant predictive factor for ambulatory recovery was the preoperative lower-extremity motor grade. The preoperative knee extensor motor grade was identified as a more important factor than hip flexor motor grade in predicting ambulatory recovery., (Copyright © 2023. Published by Elsevier Inc.)

Given their worldwide distribution and toxicity to aquatic organisms, methylmercury (MeHg) and microplastics (MP) are major pollutants in marine ecosystems. Although they commonly co-exist in the ocean, information on their toxicological interactions is limited. Therefore, to understand the toxicological interactions between MeHg and MP (6-μm polystyrene), we investigated the bioaccumulation of MeHg, its cytotoxicity, and transcriptomic modulation in the brackish water flea Diaphanosoma celebensis following single and combined exposure to MeHg and MP. After single exposure to MeHg for 48-h, D. celebensis showed high Hg accumulation (34.83 ± 0.40 μg/g dw biota ) and cytotoxicity, which was reduced upon co-exposure to MP. After transcriptomic analysis, 2, 253, and 159 differentially expressed genes were detected in the groups exposed to MP, MeHg, and MeHg+MP, respectively. Genes related to metabolic pathways and the immune system were significantly affected after MeHg exposure, but the effect of MeHg on these pathways was alleviated by MP co-exposure. However, MeHg and MP exhibited synergistic effects on the expression of gene related to DNA replication. These findings suggest that MP can reduce the toxicity of MeHg but that their toxicological interactions differ depending on the molecular pathway., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Objectives: Dentists in Australia are the second largest prescriber group, and are generally not formally taught how to prescribe. The objective of this review is to describe the Prescribing Competencies Framework and its relevance to dentistry., Data: The four-model stage of prescribing by Coombes and colleagues, and the seven competencies within the Prescribing Competencies Framework devised by the Australian National Prescribing Service MedicineWise, are discussed and applied to dentistry., Sources and Study Selection: Each of the seven competencies are analysed and detailed in the context of clinical dental practice. Competencies 1-5 describe the skillset and tasks required by dentists to safely prescribe, whereas Competencies 6 and 7 describe the clinical environment and recommended resources to support dentists to prescribe safely and effectively., Conclusions: The Prescribing Competencies Framework provides an overview of safe and effective prescribing. Prescribing is a process, and a separate skillset to clinical dentistry. The process involves information gathering, clinical assessment, effective communication and review of the patient. Access to timely and appropriate resources and relevant electronic sources of health information for clinicians are important to provide the support required for better informed prescribing decisions. The framework describes a patient-centered prescribing process, and ultimately prescribing should be a shared decision between the dentist and the patient., Clinical Significance: Safe and effective prescribing is an integral part of dentistry and dentists are the second largest prescriber group. However, dentists display high rates of inappropriate and unnecessary prescribing, and to minimise errors, the Prescribing Competencies Framework has been established. This article details how the Framework applies to clinical practice dentistry., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier Ltd.)

Objectives: Given the increasing incidence of oral cancer, it is essential to provide high-risk communities, especially in remote regions, with an affordable, user-friendly tool for visual lesion diagnosis. This proof-of-concept study explored the utility and feasibility of a smartphone application that can photograph and diagnose oral lesions., Methods: The images of oral lesions with confirmed diagnoses were sourced from oral and maxillofacial textbooks. In total, 342 images were extracted, encompassing lesions from various regions of the oral cavity such as the gingiva, palate, and labial mucosa. The lesions were segregated into three categories: Class 1 represented non-neoplastic lesions, Class 2 included benign neoplasms, and Class 3 contained premalignant/malignant lesions. The images were analysed using MobileNetV3 and EfficientNetV2 models, with the process producing an accuracy curve, confusion matrix, and receiver operating characteristic (ROC) curve., Results: The EfficientNetV2 model showed a steep increase in validation accuracy early in the iterations, plateauing at a score of 0.71. According to the confusion matrix, this model's testing accuracy for diagnosing non-neoplastic and premalignant/malignant lesions was 64% and 80% respectively. Conversely, the MobileNetV3 model exhibited a more gradual increase, reaching a plateau at a validation accuracy of 0.70. The MobileNetV3 model's testing accuracy for diagnosing non-neoplastic and premalignant/malignant lesions, according to the confusion matrix, was 64% and 82% respectively., Conclusions: Our proof-of-concept study effectively demonstrated the potential accuracy of AI software in distinguishing malignant lesions. This could play a vital role in remote screenings for populations with limited access to dental practitioners. However, the discrepancies between the classification of images and the results of "non-malignant lesions" calls for further refinement of the models and the classification system used., Clinical Significance: The findings of this study indicate that AI software has the potential to aid in the identification or screening of malignant oral lesions. Further improvements are required to enhance accuracy in classifying non-malignant lesions., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Diffuse large B-cell lymphoma (DLBCL) is a prevalent and aggressive non-Hodgkin's lymphoma, and 40% of patients succumb to death. Despite numerous clinical trials aimed at developing treatment strategies beyond the conventional R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) regimen, there have been no positive results thus far. Although the selective BCL2 inhibitor venetoclax has shown remarkable efficacy in chronic lymphocytic leukemia, its therapeutic effect in DLBCL was limited. We hypothesized that the limited therapeutic effect of venetoclax in DLBCL may be attributed to the complex expression and interactions of BCL2 family members, including BCL2. Therefore, we aimed to comprehensively analyze the expression patterns of BCL2 family members in DLBCL. We analyzed 157 patients with de novo DLBCL diagnosed at Asan Medical Center and Ajou University Hospital. The mRNA expression levels of BCL2 family members were quantified using the NanoString technology. BCL2 family members showed distinct heterogeneous expression patterns both intra- and inter-patient. Using unsupervised hierarchical cluster analysis, we were able to classify patients with similar BCL2 family expression pattern and select groups with clear prognostic features, C1 and C6. In the group with the best prognosis, C1, the expression of pro-apoptotic and pro-apoptotic BH3-only group gene expressions were increased, while anti-apoptotic group expression was significantly increased in both C1 and C6. Based on this, we generated the BCL2 signature score using the expression of pro-apoptotic genes BOK and BCL2L15, and anti-apoptotic gene BCL2. The BCL2 signature score 0 had the best prognosis, score 1/2 had intermediate prognosis, and score 3 had the worst prognosis (EFS, p = 0.0054; OS, p = 0.0011). Multivariate analysis, including COO and IPI, showed that increase in the BCL2 signature score was significantly associated with poor prognosis for EFS, independent of COO and IPI. The BCL2 signature score we proposed in this study provides information on BCL2 family deregulation based on the equilibrium of pro-versus anti-apoptotic BCL2 family, which can aid in the development of new treatment strategies for DLBCL in the future., Competing Interests: Declaration of competing interest The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: Hypertensive disorders during pregnancy are associated with the risk of long-term cardiovascular disease after pregnancy, but it has not yet been determined whether genetic predisposition for hypertensive disorders during pregnancy can predict the risk for long-term cardiovascular disease., Objective: This study aimed to evaluate the risk for long-term atherosclerotic cardiovascular disease according to polygenic risk scores for hypertensive disorders during pregnancy., Study Design: Among UK Biobank participants, we included European-descent women (n=164,575) with at least 1 live birth. Participants were divided according to genetic risk categorized by polygenic risk scores for hypertensive disorders during pregnancy (low risk, score ≤25th percentile; medium risk, score 25th∼75th percentile; high risk, score >75th percentile), and were evaluated for incident atherosclerotic cardiovascular disease, defined as the new occurrence of one of the following: coronary artery disease, myocardial infarction, ischemic stroke, or peripheral artery disease., Results: Among the study population, 2427 (1.5%) had a history of hypertensive disorders during pregnancy, and 8942 (5.6%) developed incident atherosclerotic cardiovascular disease after enrollment. Women with high genetic risk for hypertensive disorders during pregnancy had a higher prevalence of hypertension at enrollment. After enrollment, women with high genetic risk for hypertensive disorders during pregnancy had an increased risk for incident atherosclerotic cardiovascular disease, including coronary artery disease, myocardial infarction, and peripheral artery disease, compared with those with low genetic risk, even after adjustment for history of hypertensive disorders during pregnancy., Conclusion: High genetic risk for hypertensive disorders during pregnancy was associated with increased risk for atherosclerotic cardiovascular disease. This study provides evidence on the informative value of polygenic risk scores for hypertensive disorders during pregnancy in prediction of long-term cardiovascular outcomes later in life., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: The present study assumed that the effects of deformity correction amounts on proximal junctional kyphosis (PJK) development after long deformity surgery would vary according to uppermost instrumented vertebrae (UIV) levels. Our study was to reveal the association between the amount of correction and PJK according to UIV levels., Methods: Adult spinal deformity patients aged >50 years who underwent thoracolumbar fusion (≥4 levels) were included. PJK was defined by proximal junctional angles ≥15°. Presumed demographic and radiographic risk factors for PJK were evaluated including parameters regarding the correction amount such as postoperative change in lumbar lordosis and postoperative offset grouping, the value associated with age-adjusted pelvic incidence-lumbar lordosis mismatch. The patients were divided according to UIV levels of T10 or above (group A) and T11 or below (group B). Multivariate analyses were performed separately for both groups., Results: The present study included 241 patients (74 for group A and 167 for group B). PJK developed in approximately half of all patients within an average of 5 years of follow-up. For group A, only body mass index (P = 0.002) was associated with PJK. No radiographic parameters were correlated. For group B, postoperative change in lumbar lordosis (P = 0.009) and offset value (P = 0.030) were significant risk factors for PJK development., Conclusions: The correction amount of sagittal deformity increased the risk of PJK only in patients with UIV at or below T11. However, it was not associated with PJK development in patients with UIV at or above T10., (Copyright © 2023. Published by Elsevier Inc.)

Phytoremediation of metals from water (WM) and nutrient (NM) media exposed to waste metal cutting fluid (WMCF) along with temperature (T) and humidity (H) stress was tested using Azolla imbricata (Roxb.) Nakai. In the absence of WMCF, biomass was higher in NM than in WM during all tests. Surprisingly, opposite results were noted in the presence of WMCF, with growth failing at exposure to > 0.1% and > 0.5% in NM and WM, respectively. Further, correlation analysis of the growth data following WM exposure revealed that biomass was affected positively by T and negatively by H and metal accumulation. Simultaneously, metal accumulation was affected negatively by T and positively by H. The average accumulations of Al, Cd, Cr, Fe, Pb, and Zn across all T/H tests were 540, 282, 71, 1645, 2494 and 1110 mg·kg -1 , respectively. The observed bioconcentration factor indicated that A. imbricata acts as a hyperaccumulator or accumulator of Zn (>10) and as either accumulator (>1) or excluder (<1) of the other metals. Overall, the phytoremediation performance of A. imbricata in multi-metal-contaminated WMCF was high in WM under all environmental conditions. Therefore, the use of WM is an economically feasible approach for the removal of metals from WMCF., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Gelatin/carrageenan (Ge/Car) active packaging films incorporated with turmeric essential oil (TEO) encapsulated in zein nanoparticles (ZNP) were developed. The efficacy of these active packaging films and their antimicrobial properties were also investigated to ensure their practical application. Three different types of nanocomposite films (Ge/Car, Ge/Car/TEO, and Ge/Car/ZNP) were prepared. The characterization of the films was elucidated using Fourier transform infrared (FTIR), X-ray diffraction analyses (XRD), and scanning electron microscope (SEM). Physicochemical and mechanical properties of the films were enhanced, owing to the application of TEO-containing nanocomposites. Supercritical-CO 2 extracted TEO showed excellent biological activities, alongside GC-MS analysis identified that TEO contained 33 bioactive compounds where the major constituent was Zingiberene. ZNP proved an excellent carrier of TEO. The nanocomposite film sustainably released TEO, improving the shelf life of the chicken meat by reducing bacterial colonies from 3.08 log CFU/g to 2.81 log CFU/g after 14 days incubation against Salmonella enterica compared with 6.66 log CFU/g observed in the control film. The overall results of this study suggest that the nanocomposite active film is an excellent candidate for food packaging to ensure a better world., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Background: The prognostic significance of the presence of cystic features in patients with newly diagnosed glioblastoma (GB) is highly controversial. The purpose of this study was to determine whether cystic GB patients have a more favorable prognosis compared to non-cystic GB patients., Methods: The records of all GB patients diagnosed between August 2008 and December 2020 at Seoul St. Mary's Hospital were reviewed retrospectively. Out of 254 GB patients, we excluded patients with a confirmed isocitrate dehydrogenase (IDH) mutation or an unknown IDH mutation status. A total of 145 patients met our eligibility criteria., Results: Of the 145 patients we analyzed, 16 patients were classified as the cystic group, and 129 patients were classified into the non-cystic group. As there was a significant difference in the extent of resection between the two groups, 32 patients were matched according to propensity score matching. A Kaplan-Meier survival curve of the two groups indicated that the cystic group had better survival than the non-cystic group (28.6 months versus 18.8 months, respectively; p = 0.055). On multivariate analysis, the presence of cystic features (hazard ratio [HR]: 0.40, 95% confidence interval [CI]: 0.17-0.91, p = 0.029) was significantly related with a longer OS. Longer OS was also related with well-known prognostic factors, such as grossly total resection (HR: 0.05, CI: 0.01-0.31, respectively; p = 0.001) and lower European Cooperative Oncology Group (ECOG) score (HR: 3.67, CI: 1.56-9.02, respectively; p = 0.003)., Conclusion: Our results suggest that the presence of cystic features could be an independent prognostic factor suggesting better survival in GB patients. Further larger and prospective studies to validate our findings are needed., Competing Interests: Conflicts of Interest Nothing to declare., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Vitamin D is important because it has roles in maintaining musculoskeletal health, redox homeostasis, and the immune system; however, it is commonly dysregulated by endocrine disrupting chemicals, particularly phthalates and bisphenol A (BPA). Continuous exposure to phthalates and BPA may alter the endogenous metabolite profiles associated with vitamin D activity, although the specific metabolites are yet to be identified. In this study, we identified the endogenous metabolites altered by phthalates and BPA exposure through untargeted metabolic profiling and investigated the role of these metabolites in vitamin D activity. Plasma metabolic profiling using liquid chromatography-mass spectrometry was performed in two groups: severe 25-hydroxyvitamin D (25(OH)D) deficiency and high exposure to phthalates and BPA (Group A) and 25(OH)D deficiency and low exposure to phthalates and BPA (Group B). Multivariate analysis revealed a distinct separation between the two groups. A total of six metabolites were annotated, of which levels of two were significantly different between the two groups: platelet-activating factor (PAF) C16 or lysophosphatidylcholine (lysoPC) 18:0, and 11Z-eicosenamide. Plasma levels of PAF C16 or lysoPC 18:0 were increased in Group A and exhibited an area under the curve of 0.769 with an accuracy of 74.4% in a receiver operating characteristic curve analysis. These metabolites are generated as byproducts of lipid peroxidation, which supports the fact that phthalates and BPA induce oxidative stress in cells. Furthermore, PAF C16 and lysoPC 18:0 may be involved in the network that interferes with the antioxidant activity of vitamin D upon exposure to phthalates and BPA. This study results provide useful information on how the activity of vitamin D on the antioxidant system is inhibited when exposure to phthalates and BPA., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Recent lithium consumption is doubled in a decade due to the Li-ion battery (LIB) demand for electric vehicles, the energy storage system, etc. The LIBs market capacity is expected to be in strong demand due to the political drive by many nations. Wasted black powders (WBP) are generated from the manufacturing of the cathode active material and spent LIBs. The recycling market capacity is also expected to expand rapidly. This study is to propose a thermal reduction technique for recovering Li selectively. The WBP, containing 7.4 % Li, 62.1 % Ni, 4.5 % Co, and 0.3 % Al, was reduced in a vertical tube furnace using a 10 % H 2 gas as a reducing agent at 750 ºC for 1 h, and 94.3 % of Li was recovered from a water leaching, while other metal values, including Ni and Co remained in the residue. A leach solution was treated in a series of crystallisations, filtering, and washing. An intermediate product was produced and re-dissolved in hot water at 80 ºC for 0.5 h to minimise Li 2 CO 3 content into a solution. A final solution was crystallised repeatedly to produce the final product. A 99.5 % of LiOH·H 2 O was characterised and passed the impurity specification by the manufacturer as a marketable product. The proposed process is relatively simple to utilise to scale up for bulk production, and it can also be contributed to the battery recycling industry as the spent LIBs are expected to overabundance within the near future. A brief cost evaluation confirms the process feasibility, particularly, for the company that produces cathode active material (CAM) and generates WBP in their own supply chain., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

The response of seaweeds to environmental stressors can be population-specific, and be related to the regime of their habitats. To explore the growth and physiological responses of Ulva prolifera, two strains of this alga (Korean and Chinese strains) were studied under an interaction of temperature (20 and 25 °C), nutrients (low nutrients: 50 μM of nitrate and 5 μM of phosphate; high nutrients: 500 μM of nitrate and 50 μM of phosphate) and salinity (20, 30 and 40 psu). The lowest growth rates of both strains were observed at 40 psu of salinity, independent of temperature and nutrient levels. At 20 °C and low nutrients condition, the carbon: nitrogen (C: N) ratio and growth rate in the Chinese strain were increased by 31.1% and 21.1% at a salinity of 20 psu in comparison to the salinity of 30 psu, respectively. High nutrients decreased the ratio of C:N in both strains with increasing tissue N content. At the same time, high nutrients also increased soluble protein and pigments contents, as well as photosynthetic and growth rates in both strains at the same salinity levels at 20 °C. Under 20 °C and high nutrients conditions, the growth rates and C:N ratio of both strains were significantly decreased with increasing salinity. The pigment, soluble protein and tissue N showed an inverse trend with the growth rate at all conditions. Moreover, the higher temperature of 25 °C inhibited the growth in both strains regardless of nutrients levels. The temperature of 25 °C enhanced the contents of tissue N and pigments in the Chinese strain only at the low nutrients level. The interaction of high nutrients and 25 °C led to the accumulation of tissue N and pigment contents in both strains under all salinity conditions compared to the 20 °C and high nutrients level. The temperature of 25 °C and high nutrients decreased the growth rate in the Chinese strain at both salinities of 30 and 40 psu more than the 20 °C, and low nutrients level at the same salinity. These results suggest that the Ulva blooms caused by the Chinese strain were more impacted at hypo-salinity levels compared to the Korean strain. Eutrophic or high nutrients level enhanced the salinity tolerance in both strains of U. prolifera. There will be a decline of U. prolifera blooms of the Chinese strain at hyper-salinity levels., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Despite the curtailment of atmospheric condensing precursor gases during the Coronavirus disease 2019 (COVID-19) lockdown (LD) period, unexpected haze events via the formation of new particles and their subsequent growth have been identified. This study investigated the impact of emission reduction during the Chinese LD period on the new particle formation (NPF) frequency and corresponding particle number size distribution (PNSD) at three regional background atmospheric monitoring sites in the western coastal areas of the Korean Peninsula. During this duration, the number concentrations of the nucleation- (<25 nm) and accumulation-mode (>90 nm) particles significantly decreased in Baengryeong (BRY), showing decreases of 34% and 29%, respectively. Unlike BRY, the PNSD in Anmyeon (AMY), which is influenced by nearby industrial emissions, remained nearly unchanged during the LD period, possibly because the reduction in industrial emissions was not significant during the social distancing period enforced by Korea. Bongseong (BOS) showed a similar variation to that of BRY; however, the magnitude of the reduction was weaker because of its higher altitude compared to other sites. The cyclostationary empirical orthogonal function technique was applied to the measured PNSDs at the three sites to objectively classify NPF events. Because mode 1 of cyclostationary loading vectors commonly represented the typical diurnal variation of PNSD during regional NPF events at three sites, mode 1 of the corresponding principal component time series was used for NPF classification. The NPF frequency decreased by 7%, 1%, and 7% in BRY, AMY, and BOS, respectively, despite favorable meteorological conditions, such as increased temperature and insolation during the LD period. The diurnal variation in the sulfuric acid (H 2 SO 4 ) proxy implied that the H 2 SO 4 proxy acted as a determining factor for NPF events during the NPF occurrence time (8-12 local hours) in AMY and BOS; however, NPF occurrence in BRY was not connected to the H 2 SO 4 proxy level. This suggests that BRY was more likely to be influenced by the reduction in organic species in the continental upwind regions, while the occurrence of NPF events in AMY and BOS can be suppressed in association with the distinct reduction in inorganic compounds represented by the H 2 SO 4 proxy during the LD period., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier B.V. All rights reserved.)

To understand the co-variance between common free-living bacteria and Cochlodinium polykrikoides harmful algal blooms (HABs) and their metabolic functions, we investigated 110 sampling sites in the Southern Sea of South Korea. These sampling sites were divided into three groups based on environmental factors and phytoplankton data with a similarity of 85% using non-metric multidimensional scaling. One group represented high-severity C. polykrikoides blooms, while the other two represented low-severity or no blooms. In high-severity HABs, inorganic phosphorous and dissolved organic carbon concentrations were strongly correlated with C. polykrikoides density (p < 0.01). This may reflect the changes in biochemical cycling due to inorganic and organic substrates released by HAB cells (or by cell destruction). Furthermore, 88 common bacterial operational taxonomic units (OTUs, with mean relative abundance > 1%) were identified. These included Gammaproteobacteria (36 OTUs), Flavobacteriia (24), Alphaproteobacteria (18), and other taxa (11). When C. polykrikoides blooms intensified, the relative abundances of Gammaproteobacteria also increased. OTU #030 (Flavicella sp., Flavobacteria, 96%) was positively correlated with C. polykrikoides abundance (r = 0.77, p < 0.001). Functional analysis based on the dominant bacterial OTUs revealed that chemoheterotrophy-related functions were more common in high-severity sites of HABs than in other groups. Therefore, the occurrence of HABs highlighted their interactions with bacteria and affected the bacterial community structure and metabolic functions., Competing Interests: Declaration of Competing Interest There are no conflicts of interests to declare., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Background: Laparoscopic sleeve gastrectomy (LSG) has established popularity as a bariatric and metabolic surgery. However, the incidence of gastroesophageal reflux disease (GERD) following LSG is controversial. This study aims to describe the prevalence of de novo GERD after LSG., Methods: A retrospective chart review was performed for 130 patients who underwent a routine endoscopic surveillance before and after LSG between January 2013 and October 2018. The diagnosis of GERD was determined by presence of symptoms, history of PPI treatment, and endoscopic findings. The esophagogastroduodenoscopy (EGD) was performed annually after LSG and/or when the patients complained of severe reflux symptoms., Results: The prevalence of GERD before surgery was 18.5%. At 1 year after LSG, GERD was present in 70 (53.8%) of the 130 patients. GERD consisted of 55 patients with newly developed GERD, and 15 with preexisting GERD. 9 (37.5%) out of pre-existing GERD patients were free of symptoms and abnormal finding at EGD following LSG. During the LSG, 66 (50.8%) patients with hiatal hernia underwent re-approximation of the diaphragmatic crura. There was no significant relationship between hiatal hernia repair and postoperative GERD (p = 0.39). Number of patients taking PPI medication before and after LSG were 34 (26.2%) and 49 (37.7%). Out of 56 (43.1%) patients with endoscopic lesions, LA grade A was 31 (23.9%), B = 15 (11.5%), C = 4 (3.1%), and D = 6 (4.6%)., Conclusion: In this study, 42.3% (n = 55) of total patients developed newly developed GERD, and 7.7% (n = 10) had LA grade C or D esophagitis., Competing Interests: Declaration of competing interest The authors declare that they have no conflict of interest., (Copyright © 2022 Asian Surgical Association and Taiwan Robotic Surgery Association. Published by Elsevier B.V. All rights reserved.)

Multiple Myeloma (MM) is an emerging ailment of global concern. Its diagnosis at the early stages is critical for recovery. Therefore, efforts are underway to produce digital pathology tools with human-level intelligence that are efficient, scalable, accessible, and cost-effective. Following the trend, a medical imaging challenge on "Segmentation of Multiple Myeloma Plasma Cells in Microscopic Images (SegPC-2021)" was organized at the IEEE International Symposium on Biomedical Imaging (ISBI), 2021, France. The challenge addressed the problem of cell segmentation in microscopic images captured from the slides prepared from the bone marrow aspirate of patients diagnosed with Multiple Myeloma. The challenge released a total of 775 images with 690 and 85 images of sizes 2040×1536 and 1920×2560 pixels, respectively, captured from two different (microscope and camera) setups. The participants had to segment the plasma cells with a separate label on each cell's nucleus and cytoplasm. This problem comprises many challenges, including a reduced color contrast between the cytoplasm and the background, and the clustering of cells with a feeble boundary separation of individual cells. To our knowledge, the SegPC-2021 challenge dataset is the largest publicly available annotated data on plasma cell segmentation in MM so far. The challenge targets a semi-automated tool to ensure the supervision of medical experts. It was conducted for a span of five months, from November 2020 to April 2021. Initially, the data was shared with 696 people from 52 teams, of which 41 teams submitted the results of their models on the evaluation portal in the validation phase. Similarly, 20 teams qualified for the last round, of which 16 teams submitted the results in the final test phase. All the top-5 teams employed DL-based approaches, and the best mIoU obtained on the final test set of 277 microscopic images was 0.9389. All these five models have been analyzed and discussed in detail. This challenge task is a step towards the target of creating an automated MM diagnostic tool., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier B.V. All rights reserved.)

The chicken has potential as an efficient bioreactor system because of its outstanding protein production capacity and low cost. The CRISPR/Cas9-mediated gene-editing system enables production of highly marketable exogenous proteins in transgenic chicken bioreactors. However, because it takes approximately 18 mo to evaluate the recombinant protein productivity of the bioreactor due to the generation interval from G0 founders to G1 egg-laying hens, to verification of the exogenous protein at the early stage is difficult. Here we propose a system for sequential validation of exogenous protein production in chicken bioreactors as in hatching female chicks as well as in egg-laying hens. We generated chicken OVALBUMIN (OVA) EGFP knock-in (KI) chicken (OVA EGFP KI) by CRISPR/Cas9-mediated nonhomologous end joining at the chicken OVA gene locus. Subsequently, the estrogen analog, diethylstilbestrol (DES), was subcutaneously implanted in the abdominal region of 1-wk-old OVA EGFP KI female chicks to artificially increase OVALBUMIN expression. The oviducts of DES-treated OVA EGFP KI female chicks expressed OVA and EGFP at the 3-wk-old stage (10 d after DES treatment). We evaluated the expression of EGFP protein in the oviduct, along with the physical properties of eggs and egg white from OVA EGFP KI hens. The rapid identification and isolation of exogenous protein can be confirmed at a very early stage and high-yield production is possible by targeting the chicken oviduct., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

The microRNA (miRNA) gene cluster on chromosome 19, C19MC, is the largest primate-specific miRNA gene cluster. The 46 homologous miRNA genes in C19MC are highly expressed in the placenta, but repressed in other tissues by DNA methylation. Here, we found that the SET domain bifurcated 1(SETDB1), a histone H3-lysine 9 (H3K9)-specific methyltransferase 1, transcriptionally controls C19MC miRNA genes in a coordinated manner in human HAP1 cells. SETDB1 knockout (KO) resulted in the overexpression of C19MC miRNA genes, which was accompanied by a reduction of H3K9 trimethylation (H3K9me3) in the cluster. We found that SETDB1 specifically binds to and modifies the upstream promoter locus of C19MC with H3K9me3, suggesting its role as a C19MC repressor. Overexpression of C19MC miRNA genes was not related to DNA methylation because cytosine methylation levels were not altered in the C19MC of SETDB1 KO cells, indicating that SETDB1 KO does not cause DNA demethylation in the C19MC promoter and body regions. In conclusion, our results suggest that SETDB1 binding and H3K9 methylation at the C19MC promoter and body regions are responsible for the coordinated regulation of miRNA genes in the cluster., Competing Interests: Declaration of competing interest The authors have no conflict of interest to declare., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Exposure to environmental chemicals during pregnancy adversely affects maternal and infant health, and identifying socio-demographic differences in exposures can inform contributions to health inequities., Methods: We recruited 294 demographically diverse pregnant participants in San Francisco from the Mission Bay/Moffit Long (MB/ML) hospitals, which serve a primarily higher income population, and Zuckerberg San Francisco General Hospital (ZSFGH), which serves a lower income population. We collected maternal and cord sera, which we screened for 2420 unique formulas and their isomers using high-resolution mass spectrometry using LC-QTOF/MS. We assessed differences in chemical abundances across socioeconomic and demographic groups using linear regression adjusting for false discovery rate., Results: Our participants were racially diverse (31% Latinx, 16% Asian/Pacific Islander, 5% Black, 5% other or multi-race, and 43% white). A substantial portion experienced financial strain (28%) and food insecurity (20%) during pregnancy. We observed significant abundance differences in maternal (9 chemicals) and cord sera (39 chemicals) between participants who delivered at the MB/ML hospitals versus ZSFGH. Of the 39 chemical features differentially detected in cord blood, 18 were present in pesticides, one per- or poly-fluoroalkyl substance (PFAS), 21 in plasticizers, 24 in cosmetics, and 17 in pharmaceuticals; 4 chemical features had unknown sources. A chemical feature annotated as 2,4-dichlorophenol had higher abundances among Latinx compared to white participants, those delivering at ZSFGH compared to MB/ML, those with food insecurity, and those with financial strain. Post-hoc QTOF analyses indicated the chemical feature was either 2,4-dichlorophenol or 2,5-dichlorophenol, both of which have potential endocrine-disrupting effects., Conclusions: Chemical exposures differed between delivery hospitals, likely due to underlying social conditions faced by populations served. Differential exposures to 2,4-dichlorophenol or 2,5-dichlorophenol may contribute to disparities in adverse outcomes., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022. Published by Elsevier Inc.)

The centra of shark vertebrae consist of cartilage mineralized by a bioapatite similar to bone's carbonated hydroxyapatite, and, without a repair mechanism analogous to remodeling in bone, these structures still survive millions of cycles of high-strain loading. The main structures of the centrum are an hourglass-shaped double cone and the intermedialia which supports the cones. Little is known about the nanostructure of shark centra, specifically the relationship between bioapatite and cartilage fibers, and this study uses energy dispersive diffraction (EDD) with polychromatic synchrotron x-radiation to study the spatial organization of the mineral phase and its crystallographic texture. The unique energy-sensitive detector array at beamline 6-BM-B, the Advanced Photon Source, enables EDD to quantify the texture within each sampling volume with one exposure while constructing 3D maps via specimen translation across the sampling volume. This study maps a centrum from two shark orders, a carcharhiniform and a lamniform, with different intermedialia structures. In the blue shark (Prionace glauca, Carcharhiniformes), the bioapatite's c-axes are oriented laterally within the centrum's cone walls but axially within the wide wedges of the intermedialia; the former is interpreted to resist lateral deformation, the latter to support axial loads. In the shortfin mako (Isurus oxyrinchus, Lamniformes), there is some tendency for c-axis variation with position, but the situation is unclear because one dimension of the sampling volume is considerably larger than the thickness and spacing of the intermedialia's radially-oriented lamellae. Because elastic modulus in collagen plus bioapatite mineralized tissues varies significantly with both volume fraction of bioapatite and crystallographic texture, the present 3D EDD-derived maps should inform future 3D numerical models of shark centra under applied load., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Background & Aims: Nucleos(t)ide reverse transcriptase inhibitors do not completely suppress HBV DNA in chronic HBV infection (cHBV). Vebicorvir (VBR) is an investigational core inhibitor that interferes with multiple aspects of HBV replication. This phase II trial evaluated the safety and efficacy of VBR in combination with entecavir (ETV) in treatment-naïve patients with cHBV., Methods: HBeAg-positive, treatment-naïve patients without cirrhosis were randomised 1:1 in a double-blind manner to once-daily VBR 300 mg+ETV 0.5 mg or placebo (PBO)+ETV 0.5 mg for 24 weeks. The primary endpoint was change in mean log 10 HBV DNA from Baseline to Week 12 and 24., Results: All patients in both treatment groups (PBO+ETV: 12/12; VBR+ETV: 13/13) completed the study. At Week 12, VBR+ETV led to a greater mean (SD) reduction from Baseline in log 10 IU/ml HBV DNA (-4.45 [1.03]) vs. PBO+ETV (-3.30 [1.18]; p = 0.0077). At Week 24, VBR+ETV led to a greater reduction from Baseline in log 10 IU/ml HBV DNA (-5.33 [1.59]) vs. PBO+ETV (-4.20 [0.98]; p = 0.0084). Greater mean reductions in pregenomic RNA were observed at Week 12 and 24 in patients receiving VBR+ETV vs. PBO+ETV (p <0.0001 and p <0.0001). Changes in viral antigens were similar in both groups. No drug interaction between VBR and ETV was observed. Two patients experienced HBV DNA rebound during treatment, with no resistance breakthrough detected. The safety of VBR+ETV was similar to PBO+ETV. All treatment-emergent adverse events and laboratory abnormalities were Grade 1/2. There were no deaths, serious adverse events, or evidence of drug-induced liver injury., Conclusions: In this 24-week study, VBR+ETV provided additive antiviral activity over PBO+ETV in treatment-naïve patients with cHBV, with a favourable safety and tolerability profile., Clinical Trial Number: NCT03577171 LAY SUMMARY: Hepatitis B is a long-lasting viral infection of the liver. Current treatments can suppress hepatitis B virus but do not offer the opportunity of cure, hence, new treatment approaches are required. Herein, we show that the combination of the novel core inhibitor vebicorvir with an existing antiviral (entecavir) in treatment-naïve patients chronically infected with hepatitis B virus demonstrated greater antiviral activity than entecavir alone. Additionally, vebicorvir was safe and well tolerated. Thus, further studies evaluating its potential role in the treatment of chronic hepatitis B are warranted., Competing Interests: Conflict of interest Mark S. Sulkowski reports receiving grants from AbbVie, Assembly Biosciences, Gilead Sciences, Janssen, and the National Institutes of Health; and receiving personal fees from AbbVie, Antios Therapeutics, Arbutus Biopharma, Atea Pharmaceuticals, Gilead Sciences, FH360, and Immunocore. Kosh Agarwal reports being on the advisory board, a consultant, and a speaker for AbbVie, Assembly Biosciences, Aligos, Arbutus, Bristol-Myers Squibb, Gilead Sciences, Immunocore, Janssen, Merck, Novartis, Roche, Sobi, Shinoigi, and Vir; and receiving grants from Bristol-Myers Squibb, Gilead Sciences, and Roche. Xiaoli Ma reports being a consultant and being on the speakers bureau for Gilead Sciences. Tuan T. Nguyen reports receiving research grant support from Gilead Sciences and Assembly Biosciences. Eugene R. Schiff reports receiving research and grant support from Assembly Biosciences, Celgene, and the University of Florida (TARGET) and receives royalties from the Schiff Diseases of the Liver, 12th edition. Hie-Won L. Hann reports serving on the National Advisory Board and receives research grant support from Gilead Sciences. Douglas T. Dieterich reports being a consultant for Gilead Sciences and Intercept Pharmaceuticals. Ronald G. Nahass reports having served on advisory boards and as a speaker for Gilead Sciences, Merck, and Janssen; and having conducted research for Gilead Sciences, Merck, Janssen, and AbbVie. James S. Park reports receiving research grants from Assembly Biosciences and GlaxoSmithKline and consulting fees from Gilead Sciences. Sing Chan reports receiving clinical trial–related payments from Assembly Biosciences. Steven-Huy Han reports being a consultant and being on the speakers bureau for Gilead Sciences. Edward J. Gane reports serving on advisory boards for AbbVie, Aligos Therapeutics, Arbutus Biopharma, Arrowhead Pharmaceuticals, Assembly Biosciences, Avilia Therapeutics, Clear B Therapeutics, Dicerna, Enanta Pharmaceuticals, Finch Therapeutics, Gilead Sciences, GlaxoSmithKline, Immunocore, Janssen, Roche, Silverback, and Vir Bio; and having served as a speaker for Gilead Sciences, AbbVie, and Roche. Michael Bennett reports having no conflicts of interest. Katia Alves reports being a former employee of and holding stock interest in Assembly Biosciences. Marc Evanchik reports having been an employee of and holding stock interest in Assembly Biosciences and is currently an employee of Edgewise Therapeutics. Ran Yan reports being an employee of and holding stock interest in Assembly Biosciences. Qi Huang reports being an employee of and holding stock interest in Assembly Biosciences. Uri Lopatin reports being a former employee and holding stock interest in Assembly Biosciences. Richard Colonno reports being an employee of and holding stock interest in Assembly Biosciences. Julie Ma reports being an employee of and holding stock interest in Assembly Biosciences. Steven J. Knox reports being an employee of and holding stock interest in Assembly Biosciences. Luisa M. Stamm reports being an employee of and holding stock interest in Assembly Biosciences. Maurizio Bonacini reports being a member of the speaking bureau for Intercept Pharmaceuticals, Gilead Sciences, and AbbVie and has received research support from Assembly Biosciences, Intercept Pharmaceuticals, Viking Therapeutics, and Boehringer Ingelheim. Ira M. Jacobson reports being a consultant or on advisory boards for AbbVie, Aligos Therapeutics, Arbutus Biopharma, Gilead Sciences, Janssen, Madrigal and Virion; having conducted research (all payments to institution) for Assembly Biosciences, Bristol-Myers Squib, Eli Lilly, Enanta Pharmaceuticals, Gilead Sciences, Janssen, Merck, and Novo Nordisk; receiving payment from the Chronic Liver Disease Foundation for manuscript preparation; and reports participation on a Data Safety Monitoring Board for GSK, Redhill, Galmed, NeuroBo, and Arrowhead Pharmaceuticals. Walid S. Ayoub reports being a member of the speaking bureau for both Gilead Sciences and Intercept Pharmaceuticals and has conducted research for Assembly Biosciences, Intercept Pharmaceuticals, Enanta Pharmaceuticals, and Gilead Sciences. Frank Weilert reports being a study investigator for AbbVie. Natarajan Ravendhran reports advising, being on the speakers’ bureau for, and receiving grants from Gilead Sciences and AbbVie; being on the speakers' bureau for Salix and Onyx; and having received grants from Bristol-Myers Squibb and Merck. Alnoor Ramji reports receiving grant support, lecture fees, and advisory board fees from AbbVie, Celgene, Gilead Sciences, Intercept Pharmaceuticals, Novartis, and Merck. Paul Yien Kwo reports being an advisor/consultant for AbbVie, Aligos Therapeutics, Antios Therapeutics, Enanta Pharmaceuticals, Gilead Sciences, Janssen, and receives grant/research supports from Assembly Biosciences, Arrowhead Pharmaceuticals, Eiger Biopharmaceuticals, Bristol-Myers Squibb, Altimmune, and Target Registries. Magdy Elkhashab reports receiving grants from AbbVie, Bristol-Myers Squibb, Eisai, Gilead Sciences, and Roche; and serving on advisory boards for AbbVie, Bristol-Myers Squibb, Gilead Sciences, and Merck. Tarek Hassanein reports being on the advisory committee, review panel, or consulting for AbbVie, Bristol-Myers Squibb, Gilead Sciences, Mallinckrodt Pharmaceuticals, Merck, and Organovo and receiving research support from AbbVie, Allergan, Cytodyn, Assembly Biosciences, Astra Zeneca, Boehringer Ingelheim, Bristol-Myers Squibb, CARA, DURECT Corporation, Enanta Pharmaceuticals, Galectin Therapeutics, Gilead Sciences, Grifols, Intercept Pharmaceuticals, Janssen, Merck, Mirum, Novartis, Novo Nordisk, Nucorion Pharmaceuticals, Pfizer, Salix Pharmaceuticals, Sonic Incytes, Terns Pharmaceuticals, and Valeant. Ho S. Bae reports having consultancy agreements with and receiving research support from Bristol-Myers Squibb and Gilead Sciences. Jacob P. Lalezari reports having no conflicts of interest. Scott K. Fung reports receiving fees for speaking and teaching and/or serving on advisory committees for AbbVie, Assembly Biosciences, Gilead Sciences, Janssen, and Springbank Pharma. Man-Fung Yuen reports being an advisor/consultant for and/or having received grant/research support from AbbVie, Aligos Therapeutics, Antios Therapeutics, Arbutus Biopharma, Arrowhead Pharmaceuticals, Assembly Biosciences, Bristol-Myers Squibb, Clear B Therapeutics, Dicerna Pharmaceuticals, Finch Therapeutics, Fujirebio Incorporation, GlaxoSmithKline, Gilead Sciences, Immunocore, Janssen, Merck Sharp and Dohme, Roche, Springbank Pharmaceuticals, Silverback Therapeutics, Sysmex Corporation and Vir Biotechnology. Please refer to the accompanying ICMJE disclosure forms for further details., (Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Tumor spread through airspaces (STAS) is a recently determined pathologic phenomenon of lung cancer with significant prognostic impact. This study aimed to analyze the unexplored correlation between preoperative biopsy procedure and a higher risk of STAS and its impact on STAS-related outcomes in resected stage I non-small cell lung cancer (NSCLC)., Research Question: Does preoperative biopsy procedure affect the risk of STAS and STAS-related outcomes in surgically treated stage I NSCLC?, Study Design and Methods: We examined 2,169 patients who underwent surgery for pathologic stage I NSCLC from January 2011 through December 2019 at the Seoul National University Bundang Hospital, a tertiary center in South Korea. Factors including percutaneous needle biopsy (PCNB) and bronchoscopic biopsy were assessed for determining the association between preoperative biopsy procedure and an elevated risk of STAS. In addition, the impact of preoperative biopsy on STAS-related prognosis (recurrence and lung cancer-specific mortality) was evaluated with multivariate Cox regression analyses., Results: STAS findings were positive in 638 of 2,169 patients (29.4%). An insignificant association was found between preoperative biopsy (both PCNB and bronchoscopic biopsy) and STAS. After adjustments for preoperative tumor biopsy, STAS was a significant risk factor for cancer recurrence (hazard ratio [HR], 1.72; 95% CI, 1.20-2.48). Additionally, sublobar resection remained a significant risk factor for recurrence (HR, 3.20; 95% CI, 1.65-6.21) and lung cancer-specific mortality (HR, 12.71; 95% CI, 3.68-43.92) in patients with positive STAS findings. However, this association was insignificant for patients without STAS. Preoperative biopsy was not a significant risk factor for either recurrence and mortality, regardless of STAS positivity., Interpretation: Preoperative biopsy in stage I NSCLC neither was associated with an elevated risk of STAS nor influenced the prognosis related to STAS. Physicians can be less apprehensive about performing preoperative biopsy in relationship to STAS., (Copyright © 2022 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.)

Background: With the introduction of new anti-tuberculosis drugs, all-oral regimens with shorter treatment durations for multidrug-resistant tuberculosis have been anticipated. We aimed to investigate whether a new all-oral regimen was non-inferior to the conventional regimen including second-line anti-tuberculosis drugs for 20-24 months in the treatment of fluoroquinolone-sensitive multidrug-resistant tuberculosis., Methods: In this multicentre, randomised, open-label phase 2/3 non-inferiority trial, we enrolled men and women aged 19-85 years with multidrug-resistant tuberculosis confirmed by phenotypic or genotypic drug susceptibility tests or rifampicin-resistant tuberculosis by genotypic tests at 12 participating hospitals throughout South Korea. Participants with fluoroquinolone-resistant multidrug-resistant tuberculosis were excluded. Participants were randomly assigned (1:1) to two groups using a block randomisation, stratified by the presence of diabetes and cavitation on baseline chest radiographs. The investigational group received delamanid, linezolid, levofloxacin, and pyrazinamide for 9 months, and the control group received a conventional 20-24-month regimen, according to the 2014 WHO guidelines. The primary outcome was the treatment success rate at 24 months after treatment initiation in the modified intention-to-treat population and the per-protocol population. Participants who were "cured" and "treatment completed" were defined as treatment success following the 2014 WHO guidelines. Non-inferiority was confirmed if the lower limit of a 97·5% one-sided CI of the difference between the groups was greater than -10%. Safety data were collected for 24 months in participants who received a predefined regimen at least once. This study is registered with ClinicalTrials.gov, NCT02619994., Findings: Between March 4, 2016, and Sept 14, 2019, 214 participants were enrolled, 168 (78·5%) of whom were included in the modified intention-to-treat population. At 24 months after treatment initiation, 60 (70·6%) of 85 participants in the control group had treatment success, as did 54 (75·0%) of 72 participants in the shorter-regimen group (between-group difference 4·4% [97·5% one-sided CI -9·5% to ∞]), satisfying the predefined non-inferiority margin. No difference in safety outcomes was identified between the control group and the shorter-regimen group., Interpretation: 9-month treatment with oral delamanid, linezolid, levofloxacin, and pyrazinamide could represent a new treatment option for participants with fluoroquinolone-sensitive multidrug-resistant tuberculosis., Funding: Korea Disease Control and Prevention Agency, South Korea., Competing Interests: Declaration of interests We declare no competing interests., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Background: Despite the lack of high-level evidence, laparoscopic distal pancreatectomy (LDP) is frequently performed in patients with pancreatic ductal adenocarcinoma (PDAC) owing to advancements in surgical techniques. The aim of this study was to investigate the long-term oncologic outcomes of LDP in patients with PDAC via propensity score matching (PSM) analysis using data from a large-scale national database., Methods: A total of 1202 patients who were treated for PDAC via distal pancreatectomy across 16 hospitals were included in the Korean Tumor Registry System-Biliary Pancreas. The 5-year overall (5YOSR) and disease-free (5YDFSR) survival rates were compared between LDP and open DP (ODP)., Results: ODP and LDP were performed in 846 and 356 patients, respectively. The ODP group included more aggressive surgeries with higher pathologic stage, R0 resection rate, and number of retrieved lymph nodes. After PSM, the 5YOSRs for ODP and LDP were 37.3% and 41.4% (p = 0.150), while the 5YDFSRs were 23.4% and 27.2% (p = 0.332), respectively. Prognostic factors for 5YOSR included R status, T stage, N stage, differentiation, and lymphovascular invasion., Conclusion: LDP was performed in a selected group of patients with PDAC. Within this group, long-term oncologic outcomes were comparable to those observed following ODP., (Copyright © 2022. Published by Elsevier Ltd.)

Background & Aims: HBV nucleos(t)ide reverse transcriptase inhibitors (NrtIs) do not completely suppress HBV replication. Previous reports indicate persistent viremia during NrtI treatment despite HBV DNA being undetectable. HBV core inhibitors may enhance viral suppression when combined with NrtIs. This phase II trial (NCT03576066) evaluated the efficacy and safety of the investigational core inhibitor, vebicorvir (VBR), in virologically- suppressed patients on NrtIs., Methods: Non-cirrhotic, NrtI-suppressed patients with chronic HBV were randomised to VBR 300 mg once daily or matching placebo (PBO) for 24 weeks. Treatment was stratified by hepatitis B e antigen (HBeAg) status. The primary endpoint was change from Baseline in serum HBeAg or hepatitis B surface antigen (HBsAg) after 24 weeks., Results: Of 73 patients enrolled, 47 were HBeAg positive and 26 were HBeAg negative. In HBeAg-positive and -negative patients, there were no differences in the change from Baseline at Week 24 for HBsAg or HBeAg. Using a novel, high-sensitivity assay to detect HBV DNA, a greater proportion of patients with detectable HBV DNA at Baseline achieved undetectable HBV DNA at Week 24 in the VBR+NrtI vs. PBO+NrtI group. In HBeAg-positive patients, a greater change from Baseline in HBV pregenomic (pg)RNA was observed at Week 24 with VBR+NrtI vs. PBO+NrtI. Treatment-emergent adverse events (TEAEs) in VBR+NrtI patients included upper respiratory tract infection, nausea, and pruritus. No serious adverse events, Grade 4 TEAEs, or deaths were reported., Conclusions: In this 24-week study, VBR+NrtI demonstrated a favourable safety and tolerability profile. While there were no significant changes in viral antigen levels, enhanced viral suppression was demonstrated by greater changes in DNA and pgRNA with the addition of VBR compared to NrtI alone., Clinical Trials Number: NCT03576066., Lay Summary: Core inhibitors represent a novel approach for the treatment of chronic hepatitis B virus (HBV) infection, with mechanisms of action distinct from existing treatments. In this study, vebicorvir added to existing therapy reduced HBV replication to a greater extent than existing treatment and was generally safe and well tolerated., Competing Interests: Conflict of interest Man-Fung Yuen reports being an advisor/consultant for and/or having received grant/research support from AbbVie, Aligos Therapeutics, Antios Therapeutics, Arbutus Biopharma, Arrowhead Pharmaceuticals, Assembly Biosciences, Bristol-Myers Squibb, Clear B Therapeutics, Dicerna Pharmaceuticals, Finch Therapeutics, Fujirebio Incorporation, GlaxoSmithKline, Gilead Sciences, Immunocore, Janssen, Merck Sharp and Dohme, Roche, Springbank Pharmaceuticals, Silverback Therapeutics, Sysmex Corporation, and Vir Biotechnology. Kosh Agarwal reports being on the advisory board, a consultant, and a speaker for AbbVie, Assembly Biosciences, Aligos, Arbutus, Bristol-Myers Squibb, Gilead Sciences, Immunocore, Janssen, Merck, Novartis, Roche, Sobi, Shinoigi, and Vir; and receiving grants from Bristol-Myers Squibb, Gilead Sciences, and Roche. Xiaoli Ma reports being a consultant and being on the speakers bureau for Gilead Sciences. Tuan T. Nguyen reports receiving research grant support from Gilead Sciences and Assembly Biosciences. Eugene R. Schiff reports receiving research and grant support from Assembly Biosciences, Celgene, and the University of Florida (TARGET) and receives royalties from the Schiff Diseases of the Liver, 12th edition. Hie-Won L. Hann reports serving on the National Advisory Board and receives research grant support from Gilead Sciences. Douglas T. Dieterich reports being a consultant for Gilead Sciences and Intercept Pharmaceuticals. Ronald G. Nahass reports having served on advisory boards and as a speaker for Gilead Sciences, Merck, and Janssen; and having conducted research for Gilead Sciences, Merck, Janssen, and AbbVie. James S. Park reports receiving research grants from Assembly Biosciences and GlaxoSmithKline and consulting fees from Gilead Sciences. Sing Chan reports receiving clinical trial-related payments from Assembly Biosciences. Steven-Huy Han reports being a consultant and being on the speakers bureau for Gilead Sciences. Edward J. Gane reports serving on advisory boards for AbbVie, Aligos Therapeutics, Arbutus Biopharma, Arrowhead Pharmaceuticals, Assembly Biosciences, Avilia Therapeutics, Clear B Therapeutics, Dicerna, Enanta Pharmaceuticals, Finch Therapeutics, Gilead Sciences, GlaxoSmithKline, Immunocore, Janssen, Roche, Silverback, and Vir Bio. and having served as a speaker for Gilead Sciences, AbbVie, and Roche. Michael Bennett reports having no conflicts of interest. Katia Alves reports being a former employee of and holding stock interest in Assembly Biosciences. Marc Evanchik reports having been an employee of and holding stock interest in Assembly Biosciences and is currently an employee of Edgewise Therapeutics. Ran Yan reports being an employee of and holding stock interest in Assembly Biosciences. Qi Huang reports being an employee of and holding stock interest in Assembly Biosciences. Uri Lopatin reports being a former employee and holding stock interest in Assembly Biosciences. Richard Colonno reports being an employee of and holding stock interest in Assembly Biosciences. Julie Ma reports being an employee of and holding stock interest in Assembly Biosciences. Steven J. Knox reports being an employee of and holding stock interest in Assembly Biosciences. Luisa M. Stamm reports being an employee of and holding stock interest in Assembly Biosciences. Maurizio Bonacini reports being a member of the speaking bureau for Intercept Pharmaceuticals, Gilead Sciences, and AbbVie and has received research support from Assembly Biosciences, Intercept Pharmaceuticals, Viking Therapeutics, and Boehringer Ingelheim. Ira M. Jacobson reports being a consultant or on advisory boards for AbbVie, Aligos Therapeutics, Arbutus Biopharma, Gilead Sciences, Janssen, Madrigal and Virion; having conducted research (all payments to institution) for Assembly Biosciences, Bristol-Myers Squib, Eli Lilly, Enanta Pharmaceuticals, Gilead Sciences, Janssen, Merck, and Novo Nordisk; receiving payment from the Chronic Liver Disease Foundation for manuscript preparation; and reports participation on a Data Safety Monitoring Board for GSK, Redhill, Galmed, NeuroBo, and Arrowhead Pharmaceuticals. Walid S. Ayoub reports being a member of the speaking bureau for both Gilead Sciences and Intercept Pharmaceuticals and has conducted research for Assembly Biosciences, Intercept Pharmaceuticals, Enanta Pharmaceuticals, and Gilead Sciences. Frank Weilert reports being a study investigator for AbbVie. Natarajan Ravendhran reports advising, being on the speakers’ bureau for, and receiving grants from Gilead Sciences and AbbVie; being on the speakers' bureau for Salix and Onyx; and having received grants from Bristol-Myers Squibb and Merck. Alnoor Ramji reports receiving grant support, lecture fees, and advisory board fees from AbbVie, Celgene, Gilead Sciences, Intercept Pharmaceuticals, Novartis, and Merck. Paul Yien Kwo reports being an advisor/consultant for AbbVie, Aligos Therapeutics, Antios Therapeutics, Enanta Pharmaceuticals, Gilead Sciences, Janssen, and receives grant/research support from Assembly Biosciences, Arrowhead Pharmaceuticals, Eiger Biopharmaceuticals, Bristol Myer Squibb, Altimmune, and Target Registries. Magdy Elkhashab reports receiving grants from AbbVie, Bristol-Myers Squibb, Eisai, Gilead Sciences, and Roche; and serving on advisory boards for AbbVie, Bristol-Myers Squibb, Gilead Sciences, and Merck. Tarek Hassanein reports being on the advisory committee, review panel, or consulting for AbbVie, Bristol-Myers Squibb, Gilead Sciences, Mallinckrodt Pharmaceuticals, Merck, and Organovo and receiving research support from AbbVie, Allergan, Cytodyn, Assembly Biosciences, Astra Zeneca, Boehringer Ingelheim, Bristol-Myers Squibb, CARA, DURECT Corporation, Enanta Pharmaceuticals, Galectin Therapeutics, Gilead Sciences, Grifols, Intercept Pharmaceuticals, Janssen, Merck, Mirum, Novartis, Novo Nordisk, Nucorion Pharmaceuticals, Pfizer, Salix Pharmaceuticals, Sonic Incytes, Terns Pharmaceuticals, and Valeant. Ho S. Bae reports having consultancy agreements with and receiving research support from Bristol-Myers-Squibb and Gilead Sciences. Jacob P. Lalezari reports having no conflicts of interest. Scott K. Fung reports receiving fees for speaking & teaching and/or serving on advisory committees for AbbVie, Assembly Biosciences, Gilead Sciences, Janssen, and Springbank Pharma. Mark S. Sulkowski reports receiving grants from AbbVie, Assembly Biosciences, Gilead Sciences, Janssen, and the National Institutes of Health; and receiving personal fees from AbbVie, Antios Therapeutics, Arbutus Biopharma, Atea Pharmaceuticals, Gilead Sciences, FH360, and Immunocore. Please refer to the accompanying ICMJE disclosure forms for further details., (Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)

Guyon canal (GC) syndrome is a rare peripheral neuropathy involving the distal part of the ulnar nerve. Several causes are associated with GC syndrome, including anatomic variations, space-occupying tumors, and trauma. Because of disease rarity, the only reported studies of GC syndrome are case series with small sample size. We conducted a multicenter study to identify the basic characteristics of patients with surgically treated GC syndrome and the risk factors for the disease. This retrospective multicenter study was conducted between January 2001 and December 2020. We screened 70 patients who underwent GC release surgery by seven hand surgeons at six institutes. A total of 56 patients were included in this study, including 38 patients (67.9%) who underwent isolated GC decompression and 18 (32.1%) who underwent combined peripheral nerve decompression. The mean patient age was 48.4 years (range: 20-89 years), and 40 patients (71.4%) were male. The average preoperative symptom duration was 18.5 months, and most patients were office workers. Ultrasound was positive for GC syndrome in 7/10 patients evaluated, CT in 2/5, MRI in 17/23, and electrodiagnostic studies in 35/44. The most common cause of GC syndrome was tumor (n = 23), followed by idiopathic (n = 17), trauma (n = 12), anatomic variants (n = 3), and inflammation (n = 3). In conclusion, most patients with GC syndrome in this study were male and had symptoms in one wrist. The most common cause of GC syndrome in this study was a tumor, including a ganglion cyst. Level of Evidence: Level IV case series., Competing Interests: Declaration of Conflicting Interests All named authors hereby declare that they have no conflict of interest to disclose., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Purpose: Exacerbation of asthma is affected by genetic and environmental factors, but little is known about genetic differences according to smoking status. We evaluated genetic factors associated with asthma exacerbations in smokers and non-smokers, and identified the underlying mechanisms via a genome-wide association study (GWAS) and gene-level analyses according to smoking status., Methods: A GWAS on the annual frequency of asthma exacerbations was performed in 420 non-smoking and 188 smoking patients with asthma. Gene-wise associations were analyzed by Multi-marker Analysis of GenoMic Annotation (MAGMA); Gene Ontology analysis was also performed., Results: In the non-smoker group, 189 genes showed significant associations with the annual frequency of exacerbations (permutated P < 0.001). The top 10 genes were F5, KLRC1, TAFA2, AIRE, IER3IP1, CHMP2A, IL31RA, ZNF497, DNMT3L, and MYT1L (permutated P = 1.0 × 10 -4 - 1.7 × 10 -4 ). In smoking asthmatics, 140 genes-including KANK1, ZMYND12, ZNF34, ANXA11, VAV2, CCDC150, CCDC30, CATSPER3, ARMH2, and MPRIP (permutated P = 9.23 × 10 -5 - 5.50 × 10 -4 )-were associated with asthma exacerbations. Genes participating in the innate immune response in non-smokers and the regulation of cell fate (including apoptosis) in smokers were the major causal genes of asthma exacerbation (FDR q < 0.05)., Conclusions: Our findings not only suggest novel genetic candidates for predicting asthma exacerbations, but also that asthma treatment strategies should take into account smoking behavior., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Colorectal cancer (CRC) is the third most common cancer and the second leading cause of cancer-related deaths worldwide. The standard methods for diagnosing CRC, endoscopy and tissue biopsy, are invasive and time-consuming. Herein, we propose a novel method for the accurate and non-invasive diagnosis of CRC based on the analysis of exosomes that are circulating in biological fluids using a DNA barcode-based nucleic acid lateral flow assay (NALFA). Our technology combines reverse transcription using a stem-loop primer with DNA barcode-based NALFA. A colorimetric signal is generated only in the presence of the target exosomal miRNA, which can be determined even with the naked eye. The proposed system successfully detected miR-92a and miR-141, which are overexpressed in CRC exosomes. Moreover, when applied to plasma samples from CRC patients, our system simultaneously detected multiple markers in one strip. By combining these markers, we achieved high analytical performance with a sensitivity and a specificity of 95.24% and 100.0%, respectively, demonstrating that the proposed assay can be a simple diagnostic platform for the detection of exosomal miRNA., (Copyright © 2022 Elsevier B.V. All rights reserved.)