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Objective: To introduce a new method using calcium phosphate cement/Danshen drug delivery system for treating ischemic necrosis of the femoral head and evaluate its curative effect.Methods: From May 2000 to June 2005, 48 adult patients (54 hips) with ischemic necrosis of the femoral head at Stages I, II and III of antigen reactive cell opsonization (ARCO) were treated with implantation of calcium phosphate cement/Danshen drug delivery system in the involved femoral head. The operation consisted of removal of the necrotic bone under weight-loading cartilage and the implantation of phosphate cement/Danshen drug delivery system, and all manipulations were made percutaneously through a bone tunnel in the trochanter. The functions of the hip joint were evaluated and X-ray films were taken preoperatively and postoperatively.Results: Postoperative follow-up was 45.5 months on average, ranging from 27 to 78 months. According to the evaluation criterion of "Dandong 1995" for therapeutic effect of adult ischemic necrosis of the femoral head, the therapeutic effects were excellent in 33 hips, good in 17, fair in 3 and poor in 1, with the excellent and good rate of 92.6%.Conclusions: This method is relatively simple with little invasion. It not only improves the microcirculation of the femoral head by local application of traditional Chinese medicine, but also provides mechanic buttress in the weight-loading area to prevent collapse during repairing, which is beneficial to repair and reconstruction of femoral head. It may be a choice of minimal invasion surgery for ischemic necrosis of the femoral head at Stages I, II and III of ARCO. [ABSTRACT FROM AUTHOR]

Electron donor tetrathiafulvalene (TTF) and electron acceptor naphthalene diimide (NDI) derivatives were used to synthesize a 3D Zn-TTF/NDI-MOF. Multiple redox active sites and charge transfer endow the pristine MOF anode with excellent rate behavior and long term cycling performance (with an average specific capacity of 956 mA h g -1 at 1 A g -1 over 600 cycles). This study highlights the great potential of elaborately-designed MOFs for developing efficient anode materials.

This paper provides an in-depth review of the advancements and challenges associated with Titanium Matrix Composites (TMCs) in Selective Laser Melting (SLM). Material selection, SLM processing parameters, and their influence on the microstructure and properties of TMCs are discussed. The relationship between processing parameters, material characteristics, and the development of defects such as balling, porosity, and cracking is examined. Critical factors influencing the evolution of microstructure and defect formation in TMCs processed by SLM are highlighted. Strengthening mechanisms such as dislocation movements, grain refinement, the Orowan process, and load-bearing capacity are analyzed, and their roles in enhancing hardness, tensile strength, corrosion resistance, and wear resistance are explored. It is indicated by key findings that less than 5 % reinforcement content by volume can significantly enhance mechanical properties, achieving maximum hardness values of approximately 1000 HV and tensile strength close to 1500 MPa. However, this improvement is accompanied by a notable decrease in elongation. The importance of optimizing SLM parameters such as laser power, scan speed, hatch distance, layer thickness, and particle contents to minimize defects and enhance material performance is underscored. Existing research gaps in defect management and material distribution are identified. Future research directions on improving TMCs performance through advanced SLM techniques are suggested., Competing Interests: The authors declare that they have no competing financial interests that could have influenced the work reported in this paper., (© 2024 Published by Elsevier Ltd.)

Importance: Most patients use a traditional socket prosthesis (TSP) to ambulate independently following transtibial amputation. However, these patients generally require prosthesis repairs more than twice annually and an entirely new prosthesis every two years. Furthermore, transtibial amputation patients have four times the skin ulceration rate of transfemoral patients, prompting more frequent prosthesis refitting and diminished use. Trans-Tibial osseointegration (TTOI) is a promising technique to address the limitations of TSP, but remains understudied with only four cohorts totaling 41 total procedures reported previously. Continued concerns regarding the risk of infection and questions as to functional capacity postoperatively have slowed adoption of TTOI worldwide., Objective: This study reports the changes in mobility, quality of life (QOL), and the safety profile of the largest described cohort of patients with unilateral TTOI following traumatic amputation., Design: Retrospective observational cohort study. The cohort consisted of patients with data outcomes collected before and after osseointegration intervention., Setting: A large, tertiary referral, major metropolitan center., Participants: Twenty-one skeletally mature adults who had failed socket prosthesis rehabilitation, with at least two years of post-osseointegration follow-up., Main Outcomes and Measures: Mobility was evaluated by K-level, Timed Up and Go (TUG), and Six Minute Walk Test (6MWT). QOL was assessed by survey: daily prosthesis wear hours, prosthesis problem experience, general contentment with prosthesis, and Short Form 36 (SF36). Adverse events included any relevant unplanned surgery such as for infection, fracture, implant loosening, or implant failure., Results: All patients demonstrated statistically significant improvement post osseointegration surgery with respect to K-level, TUG, 6MWT, prosthesis wear hours, prosthesis problem experience, general prosthesis contentment score, and SF36 Physical Component Score (p < 0.01 for all). Three patients had four unplanned surgeries: two soft tissue refashionings, and one soft tissue debridement followed eventually by implant removal. No deaths, postoperative systemic complications, more proximal amputations, or periprosthetic fractures occurred., Conclusions and Relevance: TTOI is likely to confer mobility and QOL improvements to patients dissatisfied with TSP rehabilitation following unilateral traumatic transtibial amputation. Adverse events are relatively infrequent and not further disabling. Judicious use of TTOI seems reasonable for properly selected patients., Level of Evidence: 2 (Therapeutic investigation, Observational study with dramatic effect)., Competing Interests: Declaration of competing interest 1) Munjed Al Muderis: Receives royalties, stock or stock options, and is a paid consultant for Osseointegration International Ltd, which makes implants discussed in this manuscript. 2) Yao Chang Tan: was formerly an employee of Osseointegration International Ltd, which makes implants discussed in this manuscript. 3) William Lu: is an employee of Osseointegration International Ltd, which makes implants discussed in this manuscript., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Cancer harbours extensive proteomic heterogeneity. Inspired by the prior success of single-cell RNA sequencing (scRNA-seq) in characterizing minute transcriptomics heterogeneity in cancer, researchers are now actively searching for information regarding the proteomics counterpart. Therefore recently, single-cell proteomics by mass spectrometry (SCP) has rapidly developed into state-of-the-art technology to cater the need. This review aims to summarize application of SCP in cancer research, while revealing current development progress of SCP technology. The review also aims to contribute ideas into research gaps and future directions, ultimately promoting the application of SCP in cancer research., (© 2024 Wiley‐VCH GmbH.)

Minimally invasive abdominal surgery (MAS) can exert a physical cost. Surgical trainees spend years assisting minimally-invasive surgeries, increasing the risk of workplace injury. This prospective questionnaire-based cohort study was conducted amongst general surgery residents in Singapore. Residents assisting major MAS surgery were invited to complete anonymous online survey forms after surgery. The Phase 1 survey assessed physical discomfort scores and risk factors. Intraoperative measures to improve ergonomics were administered and evaluated in Phase 2. During Phase 1 (October 2021 to April 2022), physical discomfort was reported in at least one body part in 82.6% (n = 38) of respondents. Over a third of respondents reported severe discomfort in at least one body part (n = 17, 37.0%). Extremes of height, training seniority, longer surgical duration and operative complexity were significant risk factors for greater physical discomfort. In Phase 2 (October 2022 to February 2023), the overall rate of physical symptoms and severe discomfort improved to 81.3% (n = 52) and 34.4% (n = 22) respectively. The ergonomic measure most found useful was having separate television monitors for the primary surgeon and assistants, followed by intraoperative feedback on television monitor angle or position. Close to 20% of survey respondents felt that surgeon education was likely to improve physical discomfort., (© 2024. The Author(s).)

Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by the accumulation of amyloid-β (Aβ) protein aggregates, leading to synaptic dysfunction and neuronal cell death. In this study, we used a comprehensive approach encompassing in vitro assays, computational analyses, and an in vivo Caenorhabditis elegans model to evaluate the inhibitory effects of various xanthones, focusing on Garcinone D (GD), on Aβ42 oligomer formation. Dot blot analysis revealed concentration-dependent responses among xanthones, with GD consistently inhibiting Aβ42 oligomer formation at low concentrations (0.1 and 0.5 μM, inhibitions of 84.66 ± 2.25% and 85.06 ± 6.57%, respectively). Molecular docking and dynamics simulations provided insights into the molecular interactions between xanthones and Aβ42, highlighting the disruption of key residues involved in Aβ42 aggregation. The neuroprotective potential of GD was established using transgenic C. elegans GMC101, with substantial delays in paralysis reported at higher concentrations. Our findings show that GD is a potent suppressor of Aβ42 oligomer formation, suggesting its potential as a therapeutic candidate for AD. The concentration-dependent effects observed in both in vitro and in vivo models underscore the need for nuanced dose-response assessments. These findings contribute novel insights into the therapeutic landscape of xanthones against AD, emphasizing the multifaceted potential of GD for further translational endeavors in neurodegenerative disorder research., 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.)

Atypical hemolytic uremic syndrome (aHUS) is a rare disease caused by uncontrolled complement activation due to complement dysregulation. It is often triggered by precipitating events such as infections, inflammation, pregnancy, or medications. Dengue, an endemic viral infection in Southeast Asia, can activate the complement pathway, thereby triggering aHUS in genetically susceptible individuals. Here, we present the case of a 33-year-old male who presented with Dengue fever and subsequently developed aHUS. Plasma exchange (PLEX) successfully normalized his neurological status and hematological parameters. Although his renal function improved, it failed to normalize. Eculizumab, a monoclonal antibody that inhibits C5, was administered for a total of six months. The treatment was successfully discontinued without evidence of relapse after six months of follow-up. This case report demonstrates the safety of discontinuing eculizumab in patients who do not possess pathogenic mutations or variants in complement factors., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2024, Tan et al.)

Titanium-oxo cluster (TOC)-based metal-organic frameworks (MOFs) have received considerable attention in recent years due to their ability to expand the application of TOCs to fields that require highly stable frameworks. Herein, a new cyclic TOC formulated as [Ti 6 O 6 (O i Pr) 8 (TTFTC)(phen) 2 ] 2 ( 1 , where TTFTC = tetrathiafulvalene tetracarboxylate and phen = phenanthroline) was crystallographically characterized. TOC 1 takes a rectangular ring structure with two phen-modified Ti 6 clusters as the width and two TTFTC ligands as the length. An intracluster ligand-to-ligand (TTF-to-phen) charge transfer in 1 was found for TOCs for the first time. Compound 1 undergoes topotactic conversion to generate stable TOC-MOF P1 , in which the rectangular framework in 1 formed by a TOC core and ligands is retained, as verified by comprehensive characterization. P1 shows an efficient and rapid selective adsorption capacity for cationic dyes. The experimental adsorption capacity ( q ex ) of P1 reaches a value of up to 789.2 mg/g at 298 K for the crystal violet dye, which is the highest among those of various adsorbents. The calculated models are first used to reveal the structure-property relationship of the cyclic host to different guest dyes. The results further confirmed the host MOF structure of P1 .

Coolant-assisted liquid nitrogen (LN) flash freezing of frozen tissues has been widely adopted to preserve tissue morphology for histopathological annotations in mass spectrometry-based spatial proteomics techniques. However, existing coolants pose health risks upon inhalation and are expensive. To overcome this challenge, we present our pilot study by introducing the EtOH-LN workflow, which demonstrates the feasibility of using 95 % ethanol as a safer and easily accessible alternative to existing coolants for LN-based cryoembedding of frozen tissues. Our study reveals that both the EtOH-LN and LN-only cryoembedding workflows exhibit significantly reduced freezing artifacts compared to cryoembedding in cryostat (p < 0.005), while EtOH-LN (SD = 0.56) generates more consistent results compared to LN-only (SD = 1.29). We have modified a previously reported morphology restoration method to incorporate the EtOH-LN workflow, which successfully restored the tissue architecture from freezing artifacts (p < 0.05). Additional studies are required to validate the impact of the EtOH-LN workflow on the molecular profiles of tissues., Competing Interests: Declaration of competing interest All authors declare no conflicts of interest to report., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Presently, the rapid depletion of resources and drastic climate change highlight the importance of sustainable development. In this case, nanochitin derived from chitin, the second most abundant renewable polymer in the world, possesses numerous advantages, including toughness, easy processability and biodegradability. Furthermore, it exhibits better dispersibility in various solvents and higher reactivity than chitin owing to its increased surface area to volume ratio. Additionally, it is the only natural polysaccharide that contains nitrogen. Therefore, it is valuable to further develop this innovative technology. This review summarizes the recent developments in nanochitin and specifically identifies sustainable strategies for its preparation. Additionally, the different biomass sources that can be exploited for the extraction of nanochitin are highlighted. More importantly, the life cycle assessment of nanochitin preparation is discussed, followed by its applications in advanced manufacturing and perspectives on the valorization of chitin waste.

Objectives: To update a systematic review of the efficacy and safety of transcranial direct current stimulation (tDCS) for analgesia, for antidepressant effects, and to reduce the impact of fibromyalgia (FM), looking for optimal areas of stimulation., Methods: We searched five databases to identify randomized controlled trials comparing active and sham tDCS for FM. The primary outcome was pain intensity, and secondary outcome measures included FM Impact Questionnaire (FIQ) and depression score. Meta-analysis was conducted using standardized mean difference (SMD). Subgroup analysis was performed to determine the effects of different regional stimulation, over the primary motor cortex (M1), dorsolateral prefrontal cortex (DLPFC), opercular-insular cortex (OIC), and occipital nerve (ON) regions. We analyzed the minimal clinically important difference (MCID) by the value of the mean difference (MD) for an 11-point scale for pain, the Beck Depressive Inventory-II (BDI-II), and the Fibromyalgia Impact Questionnaire (FIQ) score. We described the certainty of the evidence (COE) using the tool GRADE profile., Results: Twenty studies were included in the analysis. Active tDCS had a positive effect on pain (SMD= -1.04; 95 % CI -1.38 to -0.69), depression (SMD= -0.46; 95 % CI -0.64 to -0.29), FIQ (SMD= -0.73; 95 % CI -1.09 to -0.36), COE is moderate. Only group M1 (SD=-1.57) and DLPFC (SD=-1.44) could achieve MCID for analgesia; For BDI-II, only group DLPFC (SD=-5.36) could achieve an MCID change. Adverse events were mild., Conclusion: tDCS is a safe intervention that relieves pain intensity, reduces depression, and reduces the impact of FM on life. Achieving an MCID is related to the stimulation site and the target symptom., Competing Interests: Declaration of competing interest None reported., (Copyright © 2024 The Author(s). Published by Elsevier Masson SAS.. All rights reserved.)

Nanocellulose has been widely used as a reinforcing agent for hydrogel systems, but its functions on thermal responsive hydrogels are rarely investigated. In this study, we extracted cellulose nanofibers (CNFs) from coconut biomass (coir fibers and piths, respectively) and aimed to study their effects on the material properties on a new class of thermogel (poly(PCL/PEG/PPG urethane). The CNFs extracted from fiber (FF) and piths (FP) showed different morphology and fiber lengths. FF are uniformed individual fibrous networks with a fiber length of 664 ± 416 nm, while FP display a hybrid structure consisting of individual fiber and large bundles with a relative shorter fiber length of 443 ± 184 nm. Integrating both CNFs into thermogels remained the thermal-responsive characteristics with an enhanced rheological property. The results showed that gels with FF resulted in a higher storage modulus and lower Tan δ value compared to those with FP, indicating that the CNFs with a longer length could form a more intertwined network interacting with the thermogel matrix. Furthermore, we demonstrated the improved capabilities of the nanocomposite thermogels for sustained drug delivery in vitro. This study not only value-adds lignocellulose valorization but also elevates the versatility of thermogels., 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.)

Over 75% of malaria-attributable deaths occur in children under the age of 5 years. However, the first malaria vaccine recommended by the World Health Organization (WHO) for pediatric use, RTS,S/AS01 (Mosquirix), has modest efficacy. Complementary strategies, including monoclonal antibodies, will be important in efforts to eradicate malaria. Here we characterize the circulating B cell repertoires of 45 RTS,S/AS01 vaccinees and discover monoclonal antibodies for development as potential therapeutics. We generated >28,000 antibody sequences and tested 481 antibodies for binding activity and 125 antibodies for antimalaria activity in vivo. Through these analyses we identified correlations suggesting that sequences in Plasmodium falciparum circumsporozoite protein, the target antigen in RTS,S/AS01, may induce immunodominant antibody responses that limit more protective, but subdominant, responses. Using binding studies, mouse malaria models, biomanufacturing assessments and protein stability assays, we selected AB-000224 and AB-007088 for advancement as a clinical lead and backup. We engineered the variable domains (Fv) of both antibodies to enable low-cost manufacturing at scale for distribution to pediatric populations, in alignment with WHO's preferred product guidelines. The engineered clone with the optimal manufacturing and drug property profile, MAM01, was advanced into clinical development., (© 2024. The Author(s).)

Objective: Complications of parotidectomy can have a massive impact on patients' quality of life. This study aimed to evaluate the readability and quality of online health information on parotidectomy., Method: The search terms 'parotidectomy', 'parotid surgery', 'parotidectomy patient information' and 'parotid surgery patient information' were parsed through three popular search engines., Results: The websites were analysed using readability scores of the Flesch Reading Ease test and the Gunning Fog Index. The DISCERN instrument was used to assess quality and reliability. The average Flesch Reading Ease score was 50.2 ± 9.0, indicating that the materials were fairly difficult to read, the Gunning Fog Index score showed that the patient health information was suitable for an individual above 12th grade level, and the DISCERN score indicated that the online patient health information had fair quality. The Kruskal-Wallis test showed a significant difference in Flesch Reading Ease and DISCERN tool scores according to website category ( p < 0.05)., Conclusion: Current online patient health information on parotidectomy is too difficult for the public to understand, and it exceeds the reading levels recommended by Health Education England and the American Medical Association.

Papillary thyroid cancer (PTC) is a histological type of thyroid cancer, and CD8T is important for the immune response. The single-cell RNA data were acquired from Gene Expression Omnibus. SingleR package was used for cluster identification, and CellChat was exploited to evaluate the interaction among several cell types. Bulk RNA data obtained from the cancer genome atlas were used for determination of prognosis using Kaplan-Meier and Receiver Operating Characteristic curve. The Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analysis were applied for assessment of function enrichment. The drug sensitivity was calculated in Gene Set Cancer Analysis. The regulatory network was constructed by STRING and Cytoscape. We identified 23 cell clusters and 10 cell types. Cell communication results showed CD8T cell was vital among all immune cell types. Enrichment analysis found the marker genes of CD8T cell was enriched in some signal pathways related to tumor development. Overall, FAM107B and TUBA4A were considered as hub genes and used to construct a risk model. Most immune checkpoint expressions were upregulated in tumor group. Tumor mutation burden results indicated that prognosis of PTC was not related to the mutation of hub genes. Drug sensitivity analysis showed some drugs could be effectively used for the treatment of PTC, and regulatory network identified some targets for the immunotherapy. A 2-gene model of PTC was developed based on the single-cell RNA and bulk RNA data. Besides, we found CD8T was essential for the immune response in PTC., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2023 the Author(s). Published by Wolters Kluwer Health, Inc.)

Background: Botulinum toxin (BoNT) injection is an important adjunctive method to treat sialorrhea. The purpose of this systematic review was to analyze the effect and safety of BoNT injections in the intervention of sialorrhea with Parkinson's disease (PD)., Methods: We searched PubMed, Web Of Science (WOS), Scopus, Cochrane CENTRAL, and Embase from inception until April 2022. Randomized controlled trials or randomized crossover trials comparing BoNT with placebo in sialorrhea with PD were eligible. PRISMA guidelines were used to carry out the meta-analysis. The Drooling Severity Frequency Scale (DSFS) score and the number of adverse events (AEs) were the primary and secondary outcomes, respectively. Standardized mean differences (SMDs) and risk differences (RDs) are used to express continuous and categorical outcomes, respectively. Heterogeneity among these studies was evaluated using I 2 tests. We used the GRADE tool to assess the certainty of evidence (COE)., Results: Eight articles involving 259 patients compared BoNT injections with a placebo for PD with sialorrhea. This meta-analysis showed a significant reduction in DSFS scores between BoNT injections and placebo (SMD=-0.98; 95% CI, -1.27 to 0.70, p<0.001; COE: high). This meta-analysis showed a significant difference in AEs between BoNT injections and placebo (RD=0.15; 95% CI, 0.05 to 0.24, p=0.002; COE: low)., Conclusions: The pooled results suggest that BoNT injections have some effect on DSFS scores with sialorrhea caused by PD. There are also mild adverse events, which generally recover within a week or so. The results indicate that BoNT injection is one of the treatments for sialorrhea caused by PD, but we need to pay attention to adverse events. In addition, the follow-up time was extended to observe oral hygiene, ulceration or dental caries, and digestive function., Trial Registration: Our review protocol was registered on PROSPERO (42021288334)., (© 2023. BioMed Central Ltd., part of Springer Nature.)

This research aimed to optimize the camera calibration process by identifying the optimal distance and angle for capturing checkered board images, with a specific focus on understanding the factors that influence the reprojection error (ϵRP). The objective was to improve calibration efficiency by exploring the impacts of distance and orientation factors and the feasibility of independently manipulating these factors. The study employed Zhang's camera calibration method, along with the 2 k full-factorial analysis method and the Latin Hypercube Sampling (LHS) method, to identify the optimal calibration parameters. Three calibration methods were devised: calibration with distance factors (D, H, V), orientation factors (R, P, Y), and the combined two influential factors from both sets of factors. The calibration study was carried out with three different stereo cameras. The results indicate that D is the most influential factor, while H and V are nearly equally influential for method A; P and R are the two most influential orientation factors for method B. Compared to Zhang's method alone, on average, methods A, B, and C reduce ϵRP by 25%, 24%, and 34%, respectively. However, method C requires about 10% more calibration images than methods A and B combined. For applications where lower value of ϵRP is required, method C is recommended. This study provides valuable insights into the factors affecting ϵRP in calibration processes. The proposed methods can be used to improve the calibration accuracy for stereo cameras for the applications in object detection and ranging. The findings expand our understanding of camera calibration, particularly the influence of distance and orientation factors, making significant contributions to camera calibration procedures.

Neoscytalidium dimidiatum and Bipolaris species are fungal plant pathogens that have been reported to cause human diseases. Recently, we have isolated numerous N. dimidiatum and Bipolaris species from the skin scrapings and nails of different patients. In this work, we have sequenced the genome of one strain of N. dimidiatum. The sequenced genome was compared to that of a previously reported Bipolaris papendorfii genome for a better understanding of their complex lifestyle and broad host-range pathogenicity. Both N. dimidiatum UM 880 (~ 43 Mb) and B. papendorfii UM 226 (~ 33 Mb) genomes include 11,015-12,320 putative coding DNA sequences, of which 0.51-2.49% are predicted transposable elements. Analysis of secondary metabolism gene clusters revealed several genes involved in melanin biosynthesis and iron uptake. The arsenal of CAZymes related to plants pathogenicity is comparable between the species, including genes involved in hemicellulose and pectin decomposition. Several important gene encoding keratinolytic peptidases were identified in N. dimidiatum and B. papendorfii, reflecting their potential pathogenic role in causing skin and nail infections. In this study, additional information on the metabolic features of these two species, such as nutritional profiling, pH tolerance, and osmotolerant, are revealed. The genomic characterization of N. dimidiatum and B. papendorfii provides the basis for the future functional studies to gain further insights as to what makes these fungi persist in plants and why they are pathogenic to humans., (© 2023. The Author(s) under exclusive licence to Sociedade Brasileira de Microbiologia.)

HDV is a defective virus that uses the HBV surface antigen to enter hepatocytes. It is associated with an accelerated course of liver fibrosis progression and an increased risk of hepatocellular carcinoma. Negative HDV RNA 24 weeks after the end of therapy has been proposed as an endpoint but late relapses make this endpoint suboptimal, hence HBsAg loss appears to be more appropriate. Current HBV antiviral agents have poor activity against HDV hence the search for improved therapy. Drugs only active against HDV, such as lonafarnib, have shown efficacy in combination with nucleoside analogues and peginterferon, but do not lead to HBsAg loss. HBsAg loss sustained 24 weeks after the end of therapy with negative HBV DNA is termed functional cure. Agents that are being investigated for functional cure include those that inhibit replication such as entry inhibitors, polymerase inhibitors and capsid assembly modulators but seldom lead to functional cure. Agents that reduce HBV antigen load such as RNA interference and inhibitors of HBsAg secretion are promising. Immunomodulators on their own seldom achieve functional cure, hence these agents in combination to assess the optimal combination are being investigated. Consequently, agents leading to functional cure of HBV are ideal for both HBV and HDV., (© 2022 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background & Aims: Hepatitis B core-related antigen (HBcrAg) is a new biomarker for chronic hepatitis B (CHB) whose performance has not been critically or systematically appraised. Herein, we performed a systematic review to determine its clinical utility., Methods: We evaluated the biological pathway of HBcrAg and performed a systematic review of PubMed for clinical trials, cohort studies, and case-control studies that evaluated the clinical utility of HBcrAg. The effectiveness of HBcrAg in predicting HBV-specific clinical events (e.g. HBeAg seroconversion, phases of CHB, HBsAg loss, treatment response, and relapse after stopping therapy) was examined using receiver-operating characteristic curves. The correlation coefficients of HBcrAg with HBV DNA, quantitative HBsAg (qHBsAg), HBV RNA, and cccDNA were summarised from published studies. Median values were used as estimates., Results: HBcrAg consists of three precore/core protein products: HBcAg, HBeAg, and a 22 kDa precore protein. HBcrAg assays have been associated with false-positive rates of 9.3% and false-negative rates of between 12-35% for CHB. The new iTACT-HBcrAg is more sensitive but does not reduce the false-positive rate. A PubMed search found 248 papers on HBcrAg, of which 59 were suitable for analysis. The clinical performance of HBcrAg was evaluated using AUROC analyses, with median AUROCs of 0.860 for HBeAg seroconversion, 0.867 for predicting HBeAg(-) hepatitis, 0.645 for HBsAg loss, 0.757 for treatment response, and 0.688 for relapse after stopping therapy. The median correlation coefficient (r) was 0.630 with HBV DNA, 0.414 with qHBsAg, 0.619 with HBV RNA and 0.550 with cccDNA. Correlation decreased during antiviral therapy, but combined biomarkers improved performance., Conclusions: HBcrAg has a mixed performance and has a poor correlation with HBsAg loss and antiviral therapy, hence HBcrAg results should be interpreted with caution., Impact and Implications: Hepatitis B core-related antigen (HBcrAg) has been used to assess management of patients with chronic hepatitis B (CHB) without a systematic and critical Sreview of its performance. Our finding that HBcrAg had a false-positive rate of 9% and a false-negative rate of 12-35% raises concerns, although larger studies are needed for validation. A systematic review showed that the performance of HBcrAg was variable depending on the CHB endpoint; it was excellent at predicting HBeAg seroconversion and HBeAg-negative chronic hepatitis (vs. chronic infection), which should be its main use, but it was poor for relapse after stopping antiviral therapy and for HBsAg loss. HBcrAg results should be interpreted with considerable caution, particularly by physicians, researchers, guideline committees and agencies that approve diagnostic tests., (Copyright © 2022 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.)

Background: We describe the epidemiology, clinical characteristics, and outcomes of multisystem inflammatory syndrome in children (MIS-C) among children from Negeri Sembilan, Malaysia., Methods: A retrospective, multicentre, observational study was performed among children ≤15 years old who were hospitalized for MIS-C between January 18, 2021 and June 30, 2023. The incidence of MIS-C was estimated using reported SARS-CoV-2 cases and census population data. Descriptive analyses were used to summarize the clinical presentation and outcomes., Results: The study included 53 patients with a median age of 5.7 years (IQR 1.8-8.7 years); 75.5% were males. The overall incidence of MIS-C was approximately 5.9 cases per 1,000,000 person-months. Pediatric intensive care unit (PICU) admission was required for 22 (41.5%) patients. No mortalities were recorded. Children aged 6-12 years were more likely to present with cardiac dysfunction/shock (odds ratio [OR] 5.43, 95% confidence interval [CI] 1.67-17.66), whereas children below 6 years were more likely to present with a Kawasaki disease phenotype (OR 5.50, 95% CI 1.33-22.75). Twenty patients (37.7%) presented with involvement of at least four organ systems, but four patients (7.5%) demonstrated single-organ system involvement., Conclusion: An age-based variation in the clinical presentation of MIS-C was demonstrated. Our findings suggest MIS-C could manifest in a spectrum, including single-organ involvement. Despite the high requirement for PICU admission, the prognosis of MIS-C was favorable, with no recorded mortalities., (© 2023 Japan Pediatric Society.)

Introduction: The COVID-19 pandemic has reached a phase where many have been infected at least once. Healthcare workers were not spared from being infected. This study aimed to determine the period prevalence of COVID-19 among the paediatric healthcare workers in Negeri Sembilan as the country transitioned into an endemic phase of the pandemic. Additionally, we investigate potential sociodemographic and occupational characteristics associated with SARS-CoV-2 infection among healthcare workers., Materials and Methods: A cross-sectional study was conducted among the healthcare workers in the paediatric department at three public specialist hospitals in Negeri Sembilan between 15 and 21 April 2022. Data were collected through a self-administered questionnaire., Results: Out of the 504 eligible healthcare workers, 493 participated in this study (response rate 97.8%). The overall prevalence of COVID-19 (11 March 2020-15 April 2022) among healthcare workers was 50.9%. The majority (80.1%) were infected during the Omicron wave two months before the survey. Household contacts accounted for 35.9% of infection sources. The proportion of non-doctors in the COVID-19-infected group was significantly higher compared to the non-infected group (74.1% vs 64.0%, p=0.016). The COVID-19-infected group had a higher proportion of schoolgoing children (44.6% vs 30.6%, p=0.001) and children who attended pre-school/sent to the babysitter (49.0% vs 24.4%, p<0.001). There were no significant differences between infection rates among the healthcare workers working in the tertiary hospital and the district hospitals. There were also no significant differences in the proportion of COVID-19- infected doctors and nurses when analysed by seniority., Conclusion: Our study provided an estimate on the prevalence of COVID-19 among paediatric healthcare workers in Negeri Sembilan and the factors associated with infection, which captures the extent and magnitude of this pandemic on the state's paediatric department. Most infections resulted from household contact, with a higher proportion of infected healthcare workers having young children.

Background: Community-based exercise is a continuation and complement to inpatient rehabilitation for Parkinson's disease and does not require a professional physical therapist or equipment. The effects, parameters, and forms of each exercise are diverse, and the effect is affected by many factors. A meta-analysis was conducted to determine the effect and the best parameters for improving motor symptoms and to explore the possible factors affecting the effect of community-based exercise.  METHODS: We conducted a comprehensive search of six databases: PEDro, PubMed/Medline, CENTRAL, Scopus, Embase, and WOS. Studies that compared community-based exercise with usual care were included. The intervention mainly included dance, Chinese martial arts, Nordic walking, and home-based exercise. The primary outcome measure was the Unified Parkinson's Disease Rating Scale part III (UPDRS-III) score. The mean difference (95% CI) was used to calculate the treatment outcomes of continuous outcome variables, and the I 2 statistic was used to estimate the heterogeneity of the statistical analysis. We conducted subgroup analysis and meta-regression analysis to determine the optimal parameters and the most important influencing factors of the exercise effect.  RESULTS: Twenty-two studies that enrolled a total of 809 subjects were included in the analysis. Exercise had a positive effect on the UPDRS-III (MD = -5.83; 95% CI, -8.29 to -3.37), Timed Up and Go test (MD = -2.22; 95% CI -3.02 to -1.42), UPDRS ((MD = -7.80; 95% CI -10.98 to -6.42), 6-Minute Walk Test (MD = 68.81; 95% CI, 32.14 to 105.48), and Berg Balance Scale (MD = 4.52; 95% CI, 2.72 to 5.78) scores. However, the heterogeneity of each included study was obvious. Weekly frequency, age, and duration of treatment were all factors that potentially influenced the effect., Conclusions: This meta-analysis suggests that community-based exercise may benefit motor function in patients with PD. The most commonly used modalities of exercise were tango and tai chi, and the most common prescription was 60 min twice a week. Future studies should consider the influence of age, duration of treatment, and weekly frequency on the effect of exercise., Prospero Trial Registration Number: CRD42022327162., (© 2022. The Author(s).)

The Harvey rat sarcoma (HRAS) proto-oncogene belongs to the RAS family and is one of the pathogenic genes that cause cancer. Deleterious nsSNPs might have adverse consequences at the protein level. This study aimed to investigate deleterious nsSNPs in the HRAS gene in predicting structural alterations associated with mutants that disrupt normal protein-protein interactions. Functional and structural analysis was employed in analyzing the HRAS nsSNPs. Putative post-translational modification sites and the changes in protein-protein interactions, which included a variety of signal cascades, were also investigated. Five different bioinformatics tools predicted 33 nsSNPs as "pathogenic" or "harmful". Stability analysis predicted rs1554885139, rs770492627, rs1589792804, rs730880460, rs104894227, rs104894227, and rs121917759 as unstable. Protein-protein interaction analysis revealed that HRAS has a hub connecting three clusters consisting of 11 proteins, and changes in HRAS might cause signal cascades to dissociate. Furthermore, Kaplan-Meier bioinformatics analyses indicated that the HRAS gene deregulation affected the overall survival rate of patients with breast cancer, leading to prognostic significance. Thus, based on these analyses, our study suggests that the reported nsSNPs of HRAS may serve as potential targets for different proteomic studies, diagnoses, and therapeutic interventions focusing on cancer.

The effects of dielectric-barrier discharge (DBD) plasma treatment (20 s to 120 s treatment time with 40 kV, 12 kHz) induced mild oxidation on the gelling properties, and related structural changes of glycinin were investigated. The gelling ability of glycinin was improved by the mild oxidation induced by the plasma treatment. Treated glycinin gels exhibited a continuous and uniform network microstructure. Samples treated for 120 s had a 2.07-, 3.99- and 2.03-fold increase in hardness, chewiness, and resilience compared to the 20 s treated samples. Structural analyses showed that primary and secondary structures of glycinin were unaffected. The tertiary structure was shifted, accompanied by a decrease in free sulfhydryl (-SH) content. At the same time, carbonyl content and average particle diameter were increased by DBD treatment. The DBD treatment facilitated the generation/exchange of intermolecular disulfide bonds and enhanced gelling properties of glycinin. It is concluded that controlled plasma-induced protein oxidation can improve protein functionality., 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 B.V.)

Adipic acid, an industrially-important chemical that can be sustainably derived from biomass and post-consumer nylon, is traditionally overlooked as a linker for MOFs. Herein, we report the first direct one-pot method for synthesising UiO-66 MOFs with an unprecedented 69 mol% adipate content, as well as the feasibility of these materials for MOF defect engineering by rapid and selective adipate thermolysis.

Background: In recent years, major advance in molecular biology and genomic technologies have led to an exponential growth in biological information. As the deluge of genomic information, there is a parallel growth in the demands of tools in the storage and management of data, and the development of software for analysis, visualization, modelling, and prediction of large data set., Main Body: Particularly in plant biotechnology, the amount of information has multiplied exponentially with a large number of databases available from many individual plant species. Efficient bioinformatics tools and methodologies are also developed to allow rapid genome sequence and the study of plant genome in the 'omics' approach. This review focuses on the various bioinformatic applications in plant biotechnology, and their advantages in improving the outcome in agriculture. The challenges or limitations faced in plant biotechnology in the aspect of bioinformatics approach that explained the low progression in plant genomics than in animal genomics are also reviewed and assessed., Conclusion: There is a critical need for effective bioinformatic tools, which are able to provide longer reads with unbiased coverage in order to overcome the complexity of the plant's genome. The advancement in bioinformatics is not only beneficial to the field of plant biotechnology and agriculture sectors, but will also contribute enormously to the future of humanity., (© 2022. The Author(s).)

In parallel to the uncontrolled use of antibiotics, the emergence of multidrug-resistant bacteria, like Acinetobacter baumannii , has posed a severe threat. A. baumannii predominates in the nosocomial setting due to its ability to persist in hospitals and survive antibiotic treatment, thereby eventually leading to an increasing prevalence and mortality due to its infection. With the increasing spectra of drug resistance and the incessant collapse of newly discovered antibiotics, new therapeutic countermeasures have been in high demand. Hence, recent research has shown favouritism towards the long-term solution of designing vaccines. Therefore, being a realistic alternative strategy to combat this pathogen, anti- A. Baumannii vaccines research has continued unearthing various antigens with variable results over the last decade. Again, other approaches, including pan-genomics, subtractive proteomics, and reverse vaccination strategies, have shown promise for identifying promiscuous core vaccine candidates that resulted in chimeric vaccine constructs. In addition, the integration of basic knowledge of the pathobiology of this drug-resistant bacteria has also facilitated the development of effective multiantigen vaccines. As opposed to the conventional trial-and-error approach, incorporating the in silico methods in recent studies, particularly network analysis, has manifested a great promise in unearthing novel vaccine candidates from the A. baumannii proteome. Some studies have used multiple A. baumannii data sources to build the co-functional networks and analyze them by k-shell decomposition. Additionally, Whole Genomic Protein Interactome (GPIN) analysis has utilized a rational approach for identifying essential proteins and presenting them as vaccines effective enough to combat the deadly pathogenic threats posed by A. baumannii . Others have identified multiple immune nodes using network-based centrality measurements for synergistic antigen combinations for different vaccination strategies. Protein-protein interactions have also been inferenced utilizing structural approaches, such as molecular docking and molecular dynamics simulation. Similar workflows and technologies were employed to unveil novel A. baumannii drug targets, with a similar trend in the increasing influx of in silico techniques. This review integrates the latest knowledge on the development of A. baumannii vaccines while highlighting the in silico methods as the future of such exploratory research. In parallel, we also briefly summarize recent advancements in A. baumannii drug target research., Competing Interests: 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 © 2022 Tan and Lahiri.)

Objective: To compare the efficacy between vesselplasty and percutanous kyphoplasty (PKP) in the treatment of Kümmell disease., Methods: The clinical data of patients with Kümmell disease from July 2018 to December 2019 were retrospectively analyzed. According to the different therapeutic methods, the patients were divided into vesselplasty group and PKP group. There were 20 patients in vesselplasty group, including 2 males and 18 females, aged from 54 to 83 years with an average of (67.40±7.44)years, 1 case of T 10 fracture, 3 cases of T 12 fracture, 9 cases of L 1 fractures, 5 cases of L 2 fractures and 2 cases of L 3 fractures. There were 20 patients in PKP group, including 3 males and 17 females, aged from 56 to 81 with an average of(67.20±7.01) years, 2 cases of T 10 fracture, 1 case of T 11 fracture, 6 cases of T 12 fracture, 10 cases of L 1 fracture and 1 case of L 3 fracture. Visual analogue scale(VAS), Cobb angle, anterior vertebral height were recorded before operation, 1 day after operation and 1 year after operation. Oswestry Disability Index(ODI) was recorded before operation, 1 month after operation and 1 year after operation. And bone cement leakage rate was compared between two groups after operation., Results: All the patient were followed up for more than 1 year. In vesselplasty group, VAS score was 1.20±0.41, ODI was(13.50±3.10)%, Cobb angle was(17.20±3.12)° and anterior vertebral height was(20.20±1.35) mm at 1 year after operation. In PKP group, VAS score was 1.15±0.40, ODI was (13.20±3.00)%, Cobb angle was (17.10±3.19)° and anterior vertebral height was (20.10±1.37) mm at 1 year after operation. These index was significantly better than pre-operation through intra-group comparison( P <0.05), and there was no statistically difference between the two groups( P >0.05). There were 20 cases (20 vertebrae) in vesselplasty group, of which 1 case had bone cement leakage at the upper endplate, with a leakage rate of 5%(1/20). In PKP group, there were 20 cases (20 vertebrae), 3 cases of upward endplate leakage(3/7), 1 case of downward endplate leakage(1/7), 1 case of leakage to the front of the vertebral body(1/7), 2 cases of leakage to the side of the vertebral body(2/7), with a leakage rate of 35% (7/20). The difference between two groups was statistically significant( P <0.05)., Conclusion: Vesselplasty in the treatment of Kümmell disease can better reduce leakage rate of bone cement and reduce complications.

Background: The authors hypothesized that patients developing immune-related adverse events (irAEs) while receiving immune checkpoint inhibition (ICI) for recurrent/metastatic head and neck cancer (HNC) would have improved oncologic outcomes., Methods: Patients with recurrent/metastatic HNC received ICI at 2 centers. Univariate and multivariate logistic regression, Kaplan-Meier methods, and Cox proportional hazards regression were used to associate the irAE status with the overall response rate (ORR), progression-free survival (PFS), and overall survival (OS) in cohort 1 (n = 108). These outcomes were also analyzed in an independent cohort of patients receiving ICI (cohort 2; 47 evaluable for irAEs)., Results: The median follow-up was 8.4 months for patients treated in cohort 1. Sixty irAEs occurred in 49 of 108 patients with 5 grade 3 or higher irAEs (10.2%). ORR was higher for irAE+ patients (30.6%) in comparison with irAE- patients (12.3%; P = .02). The median PFS was 6.9 months for irAE+ patients and 2.1 months for irAE- patients (P = .0004), and the median OS was 12.5 and 6.8 months, respectively (P = .007). Experiencing 1 or more irAEs remained associated with ORR (P = .03), PFS (P = .003), and OS (P = .004) in multivariate analyses. The association between development of irAEs and prolonged OS persisted in a 22-week landmark analysis (P = .049). The association between development of irAEs and favorable outcomes was verified in cohort 2., Conclusions: The development of irAEs was strongly associated with an ICI benefit, including overall response, PFS, and OS, in 2 separate cohorts of patients with recurrent/metastatic HNC., (© 2021 American Cancer Society.)

The effect of dielectric barrier discharge (DBD) plasma treatment times from 2 to 5 min at 40 kV on IgG/IgE binding capacity and functionality of soybean glycinin was examined. A substantial reduction in the binding capacity (91.64% for IgG and 81.49% for IgE) was obtained after 5 min of plasma treatment, as determined by western-blot and ELISA analyses. Further studies demonstrated that the elimination of antigenicity and allergenicity of glycinin was directly related to plasma-induced structural changes on two aspects. A conformational alteration caused by oxidation of peptide bond amino groups, accompanied with an oxidation of Trp, Tyr, and Phe amino acid residues, which was confirmed by surface hydrophobicity, multi-spectroscopic analysis, and amino acid analysis. The cleavage of polypeptide chains inevitably partially diminished the linear epitopes, resulting in a primary decline in IgG/IgE binding capacity. Additionally, an increase in the solubility from 10.78 ± 0.35 to 65.96 ± 1.86% and significant increase in the emulsifying ability from 21.08 ± 2.64 to 160.29 ± 4.12 m 2 /g were observed after treatment of the plasma for 2 min. The present results confirm the potential use of DBD for the production of hypoallergenic soy protein-based products and improving their technical functions such as solubility and emulsifying ability., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Electrochemical reduction of CO 2 on copper-based catalysts has become a promising strategy to mitigate greenhouse gas emissions and gain valuable chemicals and fuels. Unfortunately, however, the generally low product selectivity of the process decreases the industrial competitiveness compared to the established large-scale chemical processes. Here, we present random solid solution Cu 1- x Ni x alloy catalysts that, due to their full miscibility, enable a systematic modulation of adsorption energies. In particular, we find that these catalysts lead to an increase of hydrogen evolution with the Ni content, which correlates with a significant increase of the selectivity for methane formation relative to C 2 products such as ethylene and ethanol. From experimental and theoretical insights, we find the increased hydrogen atom coverage to facilitate Langmuir-Hinshelwood-like hydrogenation of surface intermediates, giving an impressive almost 2 orders of magnitude increase in the CH 4 to C 2 H 4 + C 2 H 5 OH selectivity on Cu 0.87 Ni 0.13 at -300 mA cm -2 . This study provides important insights and design concepts for the tunability of product selectivity for electrochemical CO 2 reduction that will help to pave the way toward industrially competitive electrocatalyst materials.

The present study investigated the effects of dielectric-barrier-discharge (DBD) plasma treatment (12 kHz, 40 kV) at 1, 2, 3, and 4 min on the reduction of the immunoglobulin G (IgG) binding capacity of β-lactoglobulin (β-LG). The IgG binding capacity of β-LG was reduced by 58.21% following a plasma treatment time of 4 min, as confirmed by western-blot and ELISA analyses. The reduction in IgG binding capacity of β-LG was directly related to a stepwise change in its structure. The initial drop in the IgG binding capacity of β-LG was found to be caused by conformational alteration, free sulfhydryl exposure and cross-linkage of molecules induced by oxidation of NH-/NH 2 - functional groups of peptide bonds and of sensitive amino acid residues (Tyr, Trp) as confirmed by SDS-PAGE, surface hydrophobicity and multi-spectroscopic analyses. Plasma treatment of more than 3 min resulted in cleavage of disulfidebonds and fragmentation of β-LG that was confirmed by LC-MS/MS analysis, which resulted a further decline in the IgG binding capacity of β-LG. Plasma treatment therefore has great potential as a substitute treatment for enzymatic hydrolysis for the production of hypoallergenic milk protein-based products., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Background: The veracity of the proportional hazards (PH) requirement is rarely scrutinized in most areas of cancer research, although fulfilment of this assumption underpins widely-used Cox survival models. We sought to critically appraise the existence of prognostic factors with time-dependent effects and to characterize their impact on survival among CLM patients., Methods: Consecutive patients who underwent liver resection with curative intent for CLM at the Singapore General Hospital were identified from a prospectively-maintained database. We evaluated PH of 55 candidate variables, and parameters which departed significantly from proportionality were included in Cox models that incorporated an interaction term to account for time-dependent effects. As sensitivity analyses, we fitted Weibull mixture 'cure' models to handle long plateaus in the tails of survival curves, and also analyzed the restricted mean survival time., Results: 318 consecutive patients who underwent curative liver resection for CLM between Jan 2000 and Nov 2016 were included in this analysis. Hazard ratios for tumor grade (poorly-versus well- and moderately-differentiated) were found to decrease from 3.135 (95% CI: 1.637-6.003) at 12 months to 2.048 (95% CI: 1.038-4.042) after 24 months, and ceased to be significant at 26 months. Compared to left-sided tumors, a right-sided tumor location was found to portend worse prognosis for the first 10 months after resection but subsequently confer a survival benefit due to a crossing of survival curves. Corroborating this observation, long-term cure fractions were estimated to be 25.5% (95% CI: 17.4%-33.6%) and 34.2% (95% CI: 17.4%-50.9%) among patients with left-sided and right-sided primary disease respectively., Conclusion: Primary tumor sidedness and grade appear to exert time-varying prognostic effects in CLM patients undergoing curative liver resection., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

The role of central nervous system (CNS) prophylaxis with high-dose methotrexate (HDMTX) in DLBCL is controversial. In this retrospective study, we evaluated the efficacy of prophylactic HDMTX on isolated CNS relapse, concomitant CNS and systemic relapse, systemic relapse, and survival outcomes in 226 patients with newly diagnosed DLBCL and high-risk CNS International Prognostic Index (CNS-IPI) score treated with RCHOP. The three-year risk of isolated CNS relapse was significantly lower in patients who received HDMTX, at 3.1% compared to 14.6% (P = 0.032) in those who did not. However, neither concomitant CNS-systemic relapse rates, systemic relapse rates, nor three-year PFS and OS were significantly different between treatment groups in multivariable analysis. Among propensity score-matched patients (N = 102), HDMTX was also associated with significantly lower isolated CNS relapse rates (HR 0.06, 95% CI 0.004-0.946, P = 0.046). HDMTX was well tolerated with manageable toxicities when given at a dose of 3 g/m 2 by day 3 of RCHOP chemotherapy. Using propensity score matching and multivariable regression to yield treatment groups with well-balanced covariates, we showed that prophylactic HDMTX improved isolated CNS relapse rates but did not decrease concomitant CNS-systemic relapse rates, systemic relapse rates, or improve survival outcomes., (© 2021. The Author(s).)

Patient-derived tumor organoids (TOs) are emerging as high-fidelity models to study cancer biology and develop novel precision medicine therapeutics. However, utilizing TOs for systems-biology-based approaches has been limited by a lack of scalable and reproducible methods to develop and profile these models. We describe a robust pan-cancer TO platform with chemically defined media optimized on cultures acquired from over 1,000 patients. Crucially, we demonstrate tumor genetic and transcriptomic concordance utilizing this approach and further optimize defined minimal media for organoid initiation and propagation. Additionally, we demonstrate a neural-network-based high-throughput approach for label-free, light-microscopy-based drug assays capable of predicting patient-specific heterogeneity in drug responses with applicability across solid cancers. The pan-cancer platform, molecular data, and neural-network-based drug assay serve as resources to accelerate the broad implementation of organoid models in precision medicine research and personalized therapeutic profiling programs., Competing Interests: Declaration of interests A.A.K., A.A.S, A.B., B.D.L., B.M., B.M.L, C.-S.H., C.I., G.K., J.F.P., J.V.M., J.R.D., K.E.M., K.P.W., L.F.L, M.K., M.M.S., T.A.R, V.S.-F., J.V., and Y.Z are employees and shareholders of Tempus Labs. A.C., B.E.D., J.M.S., and M.A.S. are employees of Tempus Labs. A.A.K., A.A.S, B.M., B.M.L., M.K., M.M.S., V.S.-F., J.V., and Y.Z. are inventors on patents related to organoid technology. K.P.W. is a Senior Group Leader at A(∗)STAR. A.A.S. holds a faculty position at the University of Illinois at Chicago., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

The emergence and spread of antimicrobial resistance have been of serious concern to human health and the management of bacterial infectious diseases. Effective treatment of these diseases requires the development of novel therapeutics, preferably free of side effects. In this regard, natural products are frequently conceived to be potential alternative sources for novel antibacterial compounds. Herein, we have evaluated the antibacterial activity of the epicarp extracts of the Malaysian cultivar of yellow rambutan fruit (Nephelium lappaceum L.) against six pathogens namely, Bacillus subtilis, methicillin-resistant Staphylococcus aureus (MRSA), Streptococcus pyogenes, Pseudomonas aeruginosa, Klebsiella pneumoniae and Salmonella enterica. Among a series of solvent extracts, fractions of ethyl acetate and acetone have revealed significant activity towards all tested strains. Chemical profiling of these fractions, via HPLC, LC-MS and GC-MS, has generated a library of potentially bioactive compounds. Downstream virtual screening, pharmacological prediction, and receptor-ligand molecular dynamics simulation have eventually unveiled novel potential antibacterial compounds, which can be extracted for medicinal use. We report compounds like catechin, eplerenone and oritin-4-beta-ol to be computationally inhibiting the ATP-binding domain of the chaperone, DnaK of P. aeruginosa and MRSA. Thus, our work follows the objective to propose new antimicrobials capable of perforating the barrier of resistance posed by both the gram positives and the negatives.

With a continuous threat of antimicrobial resistance on human health worldwide, efforts for new alternatives are ongoing for the management of bacterial infectious diseases. Natural products of land and sea, being conceived to be having fewer side effects, pose themselves as a welcome relief. In this respect, we have taken a scaffolded approach to unearthing the almost unexplored chemical constituents of Malaysian red seaweed, Gracilaria edulis . Essentially, a preliminary evaluation of the ethyl acetate and acetone solvent extracts, among a series of six such, revealed potential antibacterial activity against six MDR species namely, Klebsiella pneumoniae , Pseudomonas aeruginosa , Salmonella enterica , methicillin-resistant Staphylococcus aureus (MRSA), Streptococcus pyogenes , and Bacillus subtilis . Detailed analyses of the inlying chemical constituents, through LC-MS and GC-MS chromatographic separation, revealed a library of metabolic compounds. These were led for further virtual screening against selected key role playing proteins in the virulence of the aforesaid bacteria. To this end, detailed predictive pharmacological analyses added up to reinforce Eplerenone as a natural alternative from the plethora of plausible bioactives. Our work adds the ongoing effort to re-discover and repurpose biochemical compounds to combat the antimicrobial resistance offered by the Gram-positive and the -negative bacterial species., Competing Interests: 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 © 2021 Asghar, Tan, Shahid, Yow and Lahiri.)

Matrix metalloproteinase-1 (MMP-1) is associated with many types of cancers, including oral, colorectal, and brain cancers. This paper describes the fabrication of an MMP-1 immunosensor based on a gold nanoparticle/polyethyleneimine/reduced graphene oxide (AuNP/PEI/rGO)-modified disposable screen-printed electrode (SPE). A microwave-assisted single-step method was employed for the simultaneous reduction of gold and graphene oxide in a PEI environment to avoid AuNP agglomeration. The crystal structure, chemical composition, optical properties, and interior morphology of the materials were probed by X-ray diffraction, Raman spectroscopy, UV-visible spectrometry, and transmission electron microscopy techniques. To assemble a label-free MMP-1 immunosensor layer-by-layer, 3-mercaptopropionic acid was utilized due to its strong sulfur-gold bonding ability, and its tail end was attached to a carboxyl group, allowing the MMP-1 antibody (anti-MMP-1) to be subsequently cross-linked using the traditional N-(3-dimethylaminopropyl) and N' ethylcarbodiimide hydrochloride method. Differential pulse voltammetry analysis showed a linear relationship with MMP-1 concentration in the range of 1-50 ng ml-1 with an R2 value of ∼0.996 (n = 5, RSD < 5%). This immunosensor was successfully applied for MMP-1 detection in urine, saliva, bovine serum, and cell culture media (HSC-3 & C6) of oral and brain cancers showing results comparable to those of the credible ELISA method.

The risks of non-alcoholic fatty liver disease (NAFLD) include obese and non-obese stresses such as chronic hepatitis C virus (HCV) infection, but the regulatory determinants remain obscure. Apolipoprotein J (ApoJ) served as an ER-Golgi contact-site chaperone near lipid droplet (LD), facilitating HCV virion production. We hypothesized an interplay between hepatic ApoJ, cholesterol esterification and lipid deposit in response to NAFLD inducers. Exposures of HCV or free-fatty acids exhibited excess LDs along with increased ApoJ expression, whereas ApoJ silencing alleviated hepatic lipid accumulation. Both stresses could concomitantly disperse Golgi, induce closer ApoJ and sterol O-acyltransferase 2 (SOAT2) contacts via the N-terminal intrinsically disordered regions, and increase cholesteryl-ester. Furthermore, serum ApoJ correlated positively with cholesterol and low-density lipoprotein levels in normal glycaemic HCV patients, NAFLD patients and in mice with steatosis. Taken together, hepatic ApoJ might activate SOAT2 to supply cholesteryl-ester for lipid loads, thus providing a therapeutic target of stress-induced steatosis.