Search

To recover methane from waste activated sludge through anaerobic digestion (AD) is one promising alternative to achieve carbon neutrality for wastewater treatment plants. However, humic acids (HAs) are one of the major compositions in waste activated sludge, and their accumulation performs inhibition effects on AD. This study investigated the potentials of biochar (BC) in alleviating inhibition effects of HAs on AD. Results showed that although the accumulated HAs reduced methane yield by 9.37% compared to control, the highest methane yield, 132.6 mL CH 4 /g VSS, was obtained after adding BC, which was 45.9% higher than that in HA group. Mechanism analysis showed that BC promoted the activities of hydrolase such as protease and α-glucosidase, which were 69.7% and 29.7% higher than those in HA group, respectively. The conversion of short-chain fatty acids was accelerated. In addition, the evolutions of electroactive microorganisms like Clostridium_sensu_stricto_13 and Methanosaeta were consistent with the activitiies of electron transfer and the contents of cytochrome c. Furthermore, parts of HAs rather than all of them were adsorbed by BC, and the remaining free HAs and BC formed synergistic effects on methanogenesis, then both CO 2 reduction and acetoclastic methanogenesis pathways were improved. The findings may provide some solutions to alleviate inhibition effects of HAs on AD., 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.)

Background: A significant number of coronavirus disease 2019 (COVID-19) survivors are experiencing long COVID, with symptoms lasting beyond three months. While diverse long COVID symptoms are established, there are gaps in understanding its long-term trends, intensity, and risk factors, requiring further investigation., Aims: This study aimed to investigate the long COVID characteristics and associated factors by following COVID-19 survivors for one year post-infection and comparing them with healthy counterparts., Main Methods: In this longitudinal, correlational study, COVID-19 survivors diagnosed between November 2021 and February 2023 were monitored every three months for a year. Participants aged ≥18 years who had reported a positive COVID-19 test were recruited via social media and healthcare provider referrals., Key Findings: Out of 182 survivors who initially agreed to participate, 176 completed the study. The mean age was 47.56 years (SD = 16.2), and 51.1 % were female. There was a clinically significant decline in cognitive function and health-related quality of life over time, with symptoms like shortness of breath, reduced physical fitness, and increased health concerns. Those with severe acute COVID-19 symptoms experienced greater cognitive and physical declines and more shortness of breath a year later. Lower financial status was linked to poorer health-related quality of life and increased health concerns., Significance: A year post-infection, COVID-19's impact on cognitive function and health-related quality of life remains significant, affecting individuals and communities. Survivors with severe initial symptoms and economic disadvantages need more attention. Future research should identify additional predictors of severe long COVID., Competing Interests: Declaration of competing interest None to declare., (Copyright © 2024. Published by Elsevier Inc.)

A highly effective and enantioselective vinylogous Mannich reaction between benzothiazolimines and γ-butenolides catalyzed by a quinine based squaramide has been disclosed. A series of chiral benzothiazole amines containing a γ,γ-disubstituted butanolide scaffold bearing an adjacent chiral stereocenter have been successfully obtained in good to excellent yields (up to 91%) with excellent enantioselectivities (up to >99% ee) and diastereoselectivities (>20 : 1 dr) with broad substrate generality under mild conditions. The new scaffold integrated with both chiral benzothiazolimine and γ-butenolide moieties may provide a possibility for the development of new pharmaceutical entities.

Introduction: Assessment of BIA-ALCL prevalence is challenged by a lack of population-level data for the prevalence of breast implants in the wider population. Absence of such data obscures the true prevalence of BIA-ALCL and hinders informed consent consultations. We performed a systematic review to synthesise data from published studies reporting BIA-ALCL cases in defined patient populations to better inform the evidence base., Methods: PubMed and Embase were searched to obtain studies reporting the prevalence of BIA-ALCL in defined patient cohorts with breast implants where case prevalence was calculable. Study characteristics, the number of BIA-ALCL cases and total sample size were extracted and used to calculate the prevalence of BIA-ALCL per 100,000 implanted patients., Results: Of 1,477 publications identified by the search, 38 studies incorporating 28 cohort and 6 registry studies satisfied the inclusion criteria encompassing a total population sample of 17,038,371 patients and 1,170 BIA-ALCL patients. The prevalence of BIA-ALCL was found to be 30.54 per 100,000 implanted patients with textured implants (1 case per 3,274 implanted patients) and 6.70 per 100,000 implanted patients with implants of any-type (1 case per 14,925 implanted patients)., Conclusions: By synthesising the published literature, this work provides a determination of BIA-ALCL prevalence using study- and population-level data where the prevalence of breast implants is known. The accurate determination of BIA-ALCL prevalence is of fundamental importance for patients undergoing implant-related surgery to enable the provision of valid informed consent., Competing Interests: Conflict of Interest Statement: The authors declare no conflict of interests., (Copyright © 2024 by the American Society of Plastic Surgeons.)

Synaptic dysfunction is recognized as an early step in the pathophysiology of parkinsonism. Several genetic mutations affecting the integrity of synaptic proteins cause or increase the risk of developing disease. We have identified a candidate causative mutation in synaptic "SH3GL2 Interacting Protein 1" (SGIP1), linked to early-onset parkinsonism in a consanguineous Arab family. Additionally, affected siblings display intellectual, cognitive, and behavioral dysfunction. Metabolic network analysis of [ 18 F]-fluorodeoxyglucose positron emission tomography scans shows patterns very similar to those of idiopathic Parkinson's disease. We show that the identified SGIP1 mutation causes a loss of protein function, and analyses in newly created Drosophila models reveal movement defects, synaptic transmission dysfunction, and neurodegeneration, including dopaminergic synapse loss. Histology and correlative light and electron microscopy reveal the absence of synaptic multivesicular bodies and the accumulation of degradative organelles. This research delineates a putative form of recessive parkinsonism, converging on defective synaptic proteostasis and opening avenues for diagnosis, genetic counseling, and treatment., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Introduction: Over 6.8 million fractures occur annually in the US, with 10% experiencing delayed- or non-union. Anabolic therapeutics like PTH analogs stimulate fracture repair, and small molecule salt inducible kinase (SIK) inhibitors mimic PTH action. This study tests whether the SIK inhibitor YKL-05-099 accelerates fracture callus osteogenesis., Methods: 126 female mice underwent femoral shaft pinning and midshaft fracture, receiving daily injections of PBS, YKL-05-099, or PTH. Callus tissues were analyzed via RT-qPCR, histology, single-cell RNA-seq, and μCT imaging. Biomechanical testing evaluated tissue rigidity. A hydrogel-based delivery system for PTH and siRNAs targeting SIK2/SIK3 was developed and tested., Results: YKL-05-099 and PTH-treated mice showed higher mineralized callus volume fraction and improved structural rigidity. RNA-seq indicated YKL-05-099 increased osteoblast subsets and reduced chondrocyte precursors. Hydrogel-released siRNAs maintained target knockdown, accelerating callus mineralization., Discussion: YKL-05-099 enhances fracture repair, supporting selective SIK inhibitors' development for clinical use. Hydrogel-based siRNA delivery offers targeted localized treatment at fracture sites., 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 © 2024 Momenzadeh, Yeritsyan, Abbasian, Kheir, Hanna, Wang, Dosta, Papaioannou, Goldfarb, Tang, Amar-Lewis, Nicole Prado Larrea, Martinez Lozano, Yousef, Wixted, Wein, Artzi and Nazarian.)

Background and Purpose: Recently, artificial intelligence tools have been deployed with increasing speed in educational and clinical settings. However, the use of artificial intelligence by trainees across different levels of experience has not been well-studied. This study investigates the impact of artificial intelligence assistance on the diagnostic accuracy for intracranial hemorrhage and large-vessel occlusion by medical students and resident trainees., Materials and Methods: This prospective study was conducted between March 2023 and October 2023. Medical students and resident trainees were asked to identify intracranial hemorrhage and large-vessel occlusion in 100 noncontrast head CTs and 100 head CTAs, respectively. One group received diagnostic aid simulating artificial intelligence for intracranial hemorrhage only ( n = 26); the other, for large-vessel occlusion only ( n = 28). Primary outcomes included accuracy, sensitivity, and specificity for intracranial hemorrhage/large-vessel occlusion detection without and with aid. Study interpretation time was a secondary outcome. Individual responses were pooled and analyzed with the t test; differences in continuous variables were assessed with ANOVA., Results: Forty-eight participants completed the study, generating 10,779 intracranial hemorrhage or large-vessel occlusion interpretations. With diagnostic aid, medical student accuracy improved 11.0 points ( P < .001) and resident trainee accuracy showed no significant change. Intracranial hemorrhage interpretation time increased with diagnostic aid for both groups ( P < .001), while large-vessel occlusion interpretation time decreased for medical students ( P < .001). Despite worse performance in the detection of the smallest-versus-largest hemorrhages at baseline, medical students were not more likely to accept a true-positive artificial intelligence result for these more difficult tasks. Both groups were considerably less accurate when disagreeing with the artificial intelligence or when supplied with an incorrect artificial intelligence result., Conclusions: This study demonstrated greater improvement in diagnostic accuracy with artificial intelligence for medical students compared with resident trainees. However, medical students were less likely than resident trainees to overrule incorrect artificial intelligence interpretations and were less accurate, even with diagnostic aid, than the artificial intelligence was by itself., (© 2024 by American Journal of Neuroradiology.)

Objectives: Patients are increasingly being given direct access to their medical records. However, radiology reports are written for clinicians and typically contain medical jargon, which can be confusing. One solution is for radiologists to provide a "colloquial" version that is accessible to the layperson. Because manually generating these colloquial translations would represent a significant burden for radiologists, a way to automatically produce accurate, accessible patient-facing reports is desired. We propose a novel method to produce colloquial translations of radiology reports by providing specialized prompts to a large language model (LLM)., Materials and Methods: Our method automatically extracts and defines medical terms and includes their definitions in the LLM prompt. Using our method and a naive strategy, translations were generated at 4 different reading levels for 100 de-identified neuroradiology reports from an academic medical center. Translations were evaluated by a panel of radiologists for accuracy, likability, harm potential, and readability., Results: Our approach translated the Findings and Impression sections at the 8th-grade level with accuracies of 88% and 93%, respectively. Across all grade levels, our approach was 20% more accurate than the baseline method. Overall, translations were more readable than the original reports, as evaluated using standard readability indices., Conclusion: We find that our translations at the eighth-grade level strike an optimal balance between accuracy and readability. Notably, this corresponds to nationally recognized recommendations for patient-facing health communication. We believe that using this approach to draft patient-accessible reports will benefit patients without significantly increasing the burden on radiologists., (© The Author(s) 2024. Published by Oxford University Press on behalf of the American Medical Informatics Association. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Biochar has been used to enhance methane generation from anaerobic digestion through establishing direct interspecific electron transfer between microorganisms. However, the microbial communication is still inadequate, thereby limiting further methane production improvement contributed by biochar. This study investigated the roles of quorum-sensing molecules, acylated homoserine lactone (AHL), in anaerobic digestion of waste activated sludge aided by biochar. Results showed that the co-addition of separated biochar and AHL achieved best methane production performance, with the maximal methane yield of 154.7 mL/g volatile suspended solids, which increased by 51.9%, 47.2%, 17.9%, and 39.4% respectively compared to that of control, AHL-loaded biochar, sole AHL, and sole biochar groups. The reason was that the co-addition of separated biochar and AHL promoted the stages of hydrolysis and acidification, promoting the conversion of organic matters and short-chain fatty acids, and optimizing the accumulation of acetate acid. Moreover, the methanogenesis stage also performed best among experimental groups. Correspondingly, the highest activities of electron transfer and coenzyme F420 were obtained, with increase ratios of 33.2% and 27.2% respectively compared to that of control. Furthermore, biochar did more significant effects on the evolution of microbial communities than AHL, and the direct interspecific electron transfer between fermentative bacteria and methanogens were possibly promoted., 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.)

Objective: Mounting evidence suggests that histone deacetylases (HDAC) inhibitors reduce cartilage destruction in animal models of osteoarthritis (OA). Tumor necrosis factor (TNF)-α-blocking treatment for OA may provide effective joint protection by slowing joint damage. To investigate the effects of intraperitoneal administration of etanercept (a TNF-α inhibitor) on OA development in rats and changes in the nociceptive behavior of rats and expression of HDACs, RUNX2, and MMP13 in cartilage., Methods: Induction of OA in Wistar rats was accomplished through anterior cruciate ligament transection (ACLT). One or five milligrams (mg) of etanercept was administered intraperitoneally for 5 consecutive weeks after ACLT to the ACLT + etanercept (1 and 5 mg/kg) groups. Nociceptive behavior and changes in knee joint width were analyzed. Cartilage was evaluated histologically and immunohistochemically., Results: ACLT + etanercept significantly improved mechanical allodynia and weight-bearing distribution compared to ACLT alone. In OA rats treated with etanercept, cartilage degeneration and synovitis were significantly less pronounced than those in ACLT rats. OA-affected cartilage also showed reduced expression of HDAC 6, 7, RUNX-2, and MMP-13 in response to etanercept but increased expression of HDAC4., Conclusion: Our study demonstrated that etanercept therapy (1) attenuated the development of OA and synovitis in rats, (2) reduced nociception, and (3) regulated chondrocyte metabolism, possibly by inhibiting cell HDAC6 and HDAC7, RUNX2, and MMP13 and increasing HDAC4 expression. Based on new evidence, etanercept may have therapeutic potential in OA., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Introduction: This study investigates the role of hypoxia-related genes in the neuroprotective efficacy of Yang Xue oral liquid (YXKFY) in Alzheimer's disease (AD) and Parkinson's disease (PD). Methods and results: Using differential expression and weighted gene co-expression network analysis (WGCNA), we identified 106 and 9 hypoxia-associated genes in AD and PD, respectively, that are implicated in the transcriptomic and proteomic profiles. An artificial intelligence-driven hypoxia signature (AIDHS), comprising 17 and 3 genes for AD and PD, was developed and validated across nine independent cohorts ( n = 1713), integrating 10 machine learning algorithms and 113 algorithmic combinations. Significant associations were observed between AIDHS markers and immune cells in AD and PD, including naive CD4 + T cells, macrophages, and neutrophils. Interactions with miRNAs (hsa-miR-1, hsa-miR-124) and transcription factors (USF1) were also identified. Single-cell RNA sequencing (scRNA-seq) data highlighted distinct expression patterns of AIDHS genes in various cell types, such as high expression of TGM2 in endothelial cells, PDGFRB in endothelial and mesenchymal cells, and SYK in microglia. YXKFY treatment was shown to repair cellular damage and decrease reactive oxygen species (ROS) levels. Notably, genes with previously dysfunctional expression, including FKBPL, TGM2, PPIL1, BLVRB, and PDGFRB, exhibited significant recovery after YXKFY treatment, associated with riboflavin and lysicamine. Conclusion: The above genes are suggested to be central to hypoxia and neuroinflammation responses in AD and PD, and are potential key mediators of YXKFY's neuroprotective action., 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 © 2024 Chen, Cheng, Tang, Xu, Zhong, Gao, Cheng and Chen.)

This work reports the thermal and electron beam stabilities of a series of isostructural metal-organic frameworks (MOFs) of type MFM-300(M) (M = Al, Ga, In, Cr). MFM-300(Cr) was most stable under the electron beam, having an unusually high critical electron fluence of 1111 e - Å -2 while the Group 13 element MOFs were found to be less stable. Within Group 13, MFM-300(Al) had the highest critical electron fluence of 330 e - Å -2 , compared to 189 e - Å -2 and 147 e - Å -2 for the Ga and In MOFs, respectively. For all four MOFs, electron beam-induced structural degradation was independent of crystal size and was highly anisotropic, although both the length and width of the channels decreased during electron beam irradiation. Notably, MFM-300(Cr) was found to retain crystallinity while shrinking up to 10%. Thermal stability was studied using in situ synchrotron X-ray diffraction at elevated temperature, which revealed critical temperatures for crystal degradation to be 605, 570, 490 and 480 °C for Al, Cr, Ga, and In, respectively. The pore channel diameters contracted by ≈0.5% on desorption of solvent species, but thermal degradation at higher temperatures was isotropic. The observed electron stabilities were found to scale with the relative inertness of the cations and correlate well to the measured lifetime of the materials when used as photocatalysts., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Biochar produced from bio-wastes has been widely used to promote the performance of anaerobic digestion. Waste activated sludge (WAS) is considered as a kind of popular precursor for biochar preparation, but the abundant resources in WAS were neglected previously. In this study, the roles of biochar prepared from raw, pretreated, and fermented sludge on anaerobic digestion were investigated. That is, parts of carbon sources and nutrients like polysaccharides, proteins, and phosphorus were firstly recovered after sludge pretreatment or fermentation, and then the sludge residuals were used as raw material to prepare biochar. The methane yield improved by 22.1% with adding the biochar (AK-BC) prepared by sludge residual obtained from alkaline pretreatment. Mechanism study suggested that the characteristics of AK-BC like specific surface area and defect levels were updated. Then, the conversion performance of intermediate metabolites and electro-activities of extracellular polymeric substances were up-regulated. As a result, the activity of electron transfer was increased with the presence of AK-BC, with increase ratio of 21.4%. In addition, the electroactive microorganisms like Anaerolineaceae and Methanosaeta were enriched with the presence of AK-BC, and the potential direct interspecies electron transfer was possibly established. Moreover, both aceticlastic and CO 2 -reducing methanogenesis pathways were improved by up-regulating related enzymes. Therefore, the proposed strategy can not only obtain preferred biochar but also recover abundant resources like carbon source, nutrients, and bioenergy., 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.)

BACKGROUND Lipoprotein (a) [Lp(a)] is associated with atherosclerosis and cardiovascular mortality in patients with kidney failure. Aortic stiffness (AS), measured primarily by carotid-femoral pulse wave velocity (cfPWV), reflects vascular aging and precedes end-organ failure. This study aimed to evaluate the association between serum Lp(a) levels and cfPWV in patients undergoing peritoneal dialysis (PD). MATERIAL AND METHODS In this cross-sectional study, which included 148 patients with long-term PD for end-stage kidney failure, cfPWV was measured using a cuff-based method. AS was defined as a cfPWV exceeding 10 m/s, and an enzyme-linked immunosorbent assay was used to determine serum Lp(a) levels. Univariate and multivariate regression analyses were performed to identify the clinical correlates of AS. RESULTS There were 32 (21.6%) patients diagnosed with AS. Based on the multivariate logistic regression analysis, the odds ratio for AS was 1.007 (95% confidence interval, 1.003-1.011; P=0.001) for every 1 mg/L increase in Lp(a) levels. Multivariate linear regression analysis showed that Lp(a) (P<0.001), age (P=0.003), waist circumference (P=0.008), systolic blood pressure (P=0.010), and diabetes mellitus (P<0.001) were positively associated with cfPWV. The area under the receiver operating characteristic curve for Lp(a) in differentiating AS from non-AS was 0.770 (95% confidence interval, 0.694-0.835; P<0.0001). CONCLUSIONS Serum Lp(a) level was independently associated with cfPWV and AS in patients with PD.

Context: Despite making do-not-resuscitate or comfort care decisions during advance care planning, terminally ill patients sometimes receive life-sustaining treatments as they approach end of life., Objectives: To examine factors contributing to nonconcordance between end-of-life care and advance care planning., Methods: In this longitudinal retrospective cohort study, terminally ill patients with a life expectancy shorter than six months, who had previously expressed a preference for do-not-resuscitate or comfort care, were followed up after palliative shared care intervention. An instrument with eight items contributing to non-concordant care, developed through literature review and experts' consensus, was employed. An expert panel reviewed electronic medical records to determine factors associated with non-concordant care for each patient. Statistical analysis, including descriptive statistics and the chi-square test, examines demographic characteristics, and associations., Results: Among the enrolled 7871 patients, 97 (1.2%) received non-concordant care. The most prevalent factor was "families being too distressed about the patient's deteriorating condition and therefore being unable to let go" (84.5%) followed by "limited understanding of medical interventions among patients and surrogates" (38.1%), and "lack of patient participation in the decision-making process" (25.8%)., Conclusions: This study reveals that factors related to relational autonomy, emotional support, and health literacy may contribute to non-concordance between advance care planning and end-of-life care. In the future, developing an advance care planning model emphasizes respecting relational autonomy, providing emotional support, and enhancing health literacy could help patients receiving a goal concordant and holistic end-of-life care., Competing Interests: Conflict of interest The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Lesch-Nyhan syndrome (LNS) is a congenital defect disease that results in defective purine metabolism. It is caused by pathogenic variants of the HPRT gene. Its clinical symptoms mainly include high uric acid levels, gout, and kidney stones and damage. The mechanism of LNS has not been fully elucidated, and no cure exists. Animal models have always played an important role in exploring causative mechanisms and new therapies. This study combined CRISPR/Cas9 and microinjection to knock out the HPRT gene to create an LNS rabbit model. A sgRNA targeting exon 3 of HPRT gene was designed. Subsequently, Cas9 mRNA and sgRNA were injected into rabbit zygotes, and injected embryos were transferred to the uterus. The genotype and phenotype of rabbits were analyzed after birth. Four infant rabbits (named R1, R2, R3 and R4), which showed varying levels of gene modification, were born. The gene-editing efficiency was 100%. No wild-type sequences at the target HPRT gene were detected in R4 rabbit. Next, 6-thioguanine drug testing confirmed that HPRT enzymatic activity was deficient in R4 infant rabbit. HE staining revealed kidney abnormalities in all infant rabbits. Overall, an sgRNA capable of knocking out the HPRT gene in rabbits was successfully designed, and HPRT gene-modified rabbits were successfully constructed by using CRISPR/Cas9 technology and microinjection. This study provides a new nonrodent animal model for studying LNS syndrome.

Phosphorus is one of the important factors to successfully establish the microalgal-bacterial symbiosis (MABS) system. The migration and transformation of phosphorus can occur in various ways, and the effects of phosphate on the MABS system facing environmental impacts like heavy metal stress are often ignored. This study investigated the roles of phosphate on the response of the MABS system to zinc ion (Zn 2+ ). The results showed that the pollutant removal effect in the MABS system was significantly reduced, and microbial growth and activity were inhibited with the presence of Zn 2+ . When phosphate and Zn 2+ coexisted, the inhibition effects of pollutants removal and microbial growth rate were mitigated compared to that of only with the presence of Zn 2+ , with the increasing rates of 28.3% for total nitrogen removal, 48.9% for chemical oxygen demand removal, 78.3% for chlorophyll-a concentration, and 13.3% for volatile suspended solids concentration. When phosphate was subsequently supplemented in the MABS system after adding Zn 2+ , both pollutants removal efficiency and microbial growth and activity were not recovered. Thus, the inhibition effect of Zn 2+ on the MABS system was irreversible. Further analysis showed that Zn 2+ preferentially combined with phosphate could form chemical precipitate, which reduced the fixation of MABS system for Zn 2+ through extracellular adsorption and intracellular uptake. Under Zn 2+ stress, the succession of microbial communities occurred, and Parachlorella was more tolerant to Zn 2+ . This study revealed the comprehensive response mechanism of the co-effects of phosphate and Zn 2+ on the MABS system, and provided some insights for the MABS system treating wastewater containing heavy metals, as well as migration and transformation of heavy metals in aquatic 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 Elsevier Ltd. All rights reserved.)

Objective: To evaluate the efficacy endpoints of HbA1c and body weight loss after switching from the GLP-1 receptor agonists, semaglutide or dulaglutide, to treatment with the GIP/GLP-1 receptor agonist (RA) tirzepatide., Methods: Models were developed and validated to describe the HbA1c and weight loss time course for semaglutide (SUSTAIN 1-10), dulaglutide (AWARD-11) and tirzepatide (SURPASS 1-5, phase 3 global T2D program). The impact of switching from once weekly GLP-1 RAs to tirzepatide was described by simulating the efficacy time course. Semaglutide and dulaglutide doses were escalated in accordance with their respective labels., Results: Model-predicted mean decreases from baseline in HbA1c and body weight for semaglutide 0.5 mg, 1 mg, and 2 mg were 1.22 to 1.79% and 3.62 to 6.87 kg respectively, at Week 26. Model-predicted mean decreases from baseline in HbA1c and body weight for dulaglutide 1.5 mg, 3 mg and 4.5 mg were 1.53 to 1.84% and 2.55 to 3.71 kg respectively, at Week 26. After switching to tirzepatide 5, 10 and 15 mg HbA1c reductions were predicted to range between 1.95 to 2.46% and body weight reductions between 6.50 to 12.1 kg by Week 66., Conclusion: In this model-based simulation, switching from approved maintenance doses of semaglutide or dulaglutide to tirzepatide, even at the lowest approved maintenance dose of 5 mg, showed the potential to further improve HbA1c and body weight reductions.

The strong geometric frustration of the kagome antiferromagnets (KAFMs) can destabilise conventional magnetic order and lead to exotic electronic states, such as the quantum spin-liquid state observed in someS=12KAFM materials. However, the ground state of S  = 1 KAFM systems are less well understood. Spin nematic phases and valence bond solid ground states have been predicted to form but a paucity of experimental realisations restricts understanding. Here, the S  = 1 KAFM NH 4 Ni 2 Mo 2 O 10 H 3 is presented, which has the 3-fold symmetry of the kagome lattice but significant site depletion, with∼64%site occupancy. Frustration and a competition between exchange interactions are evidenced through the suppression of order below the Weiss temperature|θW|and observation of ferromagnetic and antiferromagnetic characteristics in the magnetisation data. A semi spin glass ground state is predicted based on the ac-field frequency dependence of the magnetic transition and ferromagnetic signal., (Creative Commons Attribution license.)

Background/purpose: Fibroblast growth factor (FGF) 5 is a member of the FGF family that functions as a regulator of tissue growth and regeneration. Aberrant FGF5 expression has been previously associated with the progression of a number of different malignancies. However, its potential role in oral cancer remains unclear. In this study, we explored the relationship between the expression of FGF5 protein in oral squamous cell carcinomas (OSCCs) and the clinicopathological parameters of OSCCs and whether the expression of FGF5 protein in OSCCs could be a prognostic factor for OSCC patients., Methods: The FGF5 protein expression was examined in 64 OSCC and 34 normal oral mucosal specimens by immunohistochemical staining. Stress induced upregulation and intracellular redistribution of FGF5 were verified using xenograft animal model and OSCC cell lines., Results: The mean FGF5 protein labelling index was significantly higher in OSCC than in normal oral mucosal samples, with high FGF5 protein labelling index (>58%) being correlated with advanced stage and poor survival of OSCC patients. Apart from the peri-cytoplasmic staining pattern characteristic of paracrine growth factors, FGF5 protein was localized as distinct punctate structures in the cytoplasm of advanced stage or stressed-induced cells. This redistribution and upregulation of FGF5 protein could be sustained after termination of the stress induction in cell line and xenograft animal models., Conclusion: FGF5 can be induced by cellular stress and risk factors of OSCC, where high expression levels of FGF5 is potentially a useful parameter for predicting OSCC progression and patient survival., Competing Interests: Declaration of competing interest The authors declare no conflicts of interest., (Copyright © 2023. Published by Elsevier B.V.)

Background: The outbreak of COVID-19 caused severe damage to public health globally and served as a stark reminder of the potential for future pandemics. Promoting protective behaviors to prevent the spread of any contagious disease thus remains a priority. Although research has shown that health beliefs can affect protective behaviors, few studies have examined the role of information-seeking in this relationship., Objectives: On the basis of the health belief model, this research focused on whether health beliefs affect personal protective behaviors through health information-seeking behaviors., Methods: This cross-sectional study with a causal-comparative design used an online questionnaire to investigate the Taiwanese public's health beliefs, protective behaviors, and information-seeking behaviors during the COVID-19 pandemic. Data were analyzed using descriptive statistics and multiple regression analysis., Results: Between September 2021 and January 2022, 322 valid questionnaires were collected. The results revealed that the effects of two health beliefs-self-efficacy and perceived benefits-on handwashing, social distancing, practicing good cough etiquette, and keeping one's environment clean and well ventilated were partially mediated by the frequency of official information-seeking., Discussion: Results of this study support the regular and timely promotion of pandemic prevention measures through official sites. Promoting official information-seeking can help enhance protective behaviors., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Dulaglutide 3.0 and 4.5 mg weekly doses were approved for additional glycemic control in adult patients with type 2 diabetes inadequately controlled with metformin and 0.75 or 1.5 mg weekly doses of dulaglutide. Effects such as nausea and vomiting are commonly reported with dulaglutide and other glucagon-like peptide-1 receptor agonist therapies. Based on a pharmacokinetic/pharmacodynamic model-informed approach, a stepwise dose-escalation scheme with 4-week intervals between dose increments was suggested to mitigate gastrointestinal events for dulaglutide. These gastrointestinal events are dose dependent and attenuate over time with repeated dosing. A Markov chain Monte Carlo pharmacokinetic/pharmacodynamic joint model was developed using AWARD-11 data (N = 1842) to optimize dulaglutide dose escalation to 3.0 and 4.5 mg to mitigate gastrointestinal events. Model simulations evaluated probabilities of nausea and vomiting events for various dosing scenarios in patients needing higher doses for additional glycemic control. The model indicated that patients may dose escalate from 1.5 to 3.0 mg, then 4.5 mg weekly after at least 4 weeks on each dose. No clinically meaningful differences in nausea or vomiting events were expected when patients escalated to 3.0 or 4.5 mg following initiation at 0.75 or 1.5 mg dulaglutide. Based on the findings of this model, a minimum 4-week duration at each dose before escalation was appropriate to reduce gastrointestinal events of dulaglutide, consistent with observed gastrointestinal events data from the AWARD-11 study and supporting the currently recommended dose-escalation regimen of dulaglutide doses of 3.0 and 4.5 mg for additional glycemic control., (© 2023 American College of Clinical Pharmacology.)

In order to meet the market demand and avoid the increase of operation amount and cleaning cost in the process of ultrafiltration, it is particularly important to find more practical and efficient methods to control and improve membrane fouling. In this study, the ions in the ultrafiltration process were regulated to affect membrane surface proteins composition (lactoferrin, α-lactalbumin, β-lactoglobulin A and β-lactoglobulin B) and delay membrane fouling. It was found that Na + (21 mmol/L), Zn 2+ (0.25 mmol/L) and K + (44 mmol/L) was added at 4 min, 8 min and 12 min, respectively during ultrafiltration process. The continuous regulation slowed down the decline rate of membrane flux and reduced the content of α-lactalbumin, β-lactoglobulin A and β-lactoglobulin B on the membrane surface analyzed by HPLC. This could reduce the irreversible membrane fouling of proteins cake resistance. Furthermore, the ions concentration was also investigated after filtration. The concentration of K + was increased significantly and other ions concentration was not significantly changed after continuous regulation such Na + , Mg 2+ , Zn 2+ and Ca 2+ compared to control. Therefore, dynamic ionic regulation of whey protein ultrafiltration process is a simple and effective method, which provides technical theoretical basis for optimizing and improving membrane technology., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2023 Elsevier B.V. All rights reserved.)