bluuebunny/crossref_metadata_2025 huggingface dataset:
Microbial Carbon Oxidation in Seawater Below the Hypoxic Threshold
Authors: Wolf Sarah , Jayawickrama Clare , Carlson Craig A. , Deutsch Curtis , II Edward W. Davis , Chan Francis , Giovannoni Stephen J.
Published: February 2024

Global oxygen minimum zones (OMZs) often reach hypoxia but seldom reach anoxia. Recently it was reported that Michaelis Menten constants (Km) of oxidative enzymes are orders of magnitude higher than respiratory Km values, and in the Hypoxic Barrier Hypothesis it was proposed that, in ecosystems experiencing falling oxygen, oxygenase enzyme activities become oxygen-limited long before respiration. We conducted a mesocosm experiment with a phytoplankton bloom as an organic carbon source and controlled dissolved oxygen (DO) concentrations in the dark to determine whether hypoxia slows carbon oxidation and oxygen decline. Total oxygen utilization (TOU) in hypoxic treatment (ca. 8.7 µM O2) was 21.7% lower than the oxic treatment (ca. 301.3 µM O2) over the first 43 days of the experiment. In addition, following the restoration of fully oxic conditions to the hypoxic treatment, TOU accelerated, demonstrating that oxidative processes are sensitive to DO concentrations found in large volumes of the ocean. Microbial amplicon-based community composition diverged between oxic treatments, indicating a specialized microbiome that included Thioglobaceae (SUP05 Gammaproteobacteria), OM190 (Planctomycetota), related to annamox bacteria, ABY1 (Patescibacteria), and SAR86 subclade D2472, thrived in the hypoxic treatment, while Actinobacteria and SAR11 were sharply inhibited. Our findings support the hypothesis that oxygenase kinetics might slow the progression of ocean deoxygenation in oxygen-poor regions and be a factor in the evolution of microbial taxa adapted to hypoxic environments.
Primary drug-coated balloon angioplasty with provisional stenting versus primary stenting for the treatment of de novo coronary artery lesions: REC-CAGEFREE I trial rationale and design
Authors: Gao Chao , He Xinqiang , Liu Yunpeng , Liu Jianzheng , Jiang Zhiwei , Zhu Bin , Qin Xing , Xia Yunlong , Zhang Tingting , Wang Ping , Zhang Ruining , Onuma Yoshinobu , Xia Jielai , Wang Duolao , Serruys Patrick , Tao Ling
Published: February 2024

Background
Percutaneous coronary intervention (PCI) with primary stenting, which stands for stent implantation regardless of obtaining satisfactory results with balloon angioplasty, has superseded conventional plain old balloon angioplasty with provisional stenting. With drug-coated balloon (DCB), primary DCB angioplasty with provisional stenting has shown non-inferiority to primary stenting for de novo coronary small vessel disease. However, the long-term efficacy and safety of such a strategy to the primary stenting on clinical endpoints in de novo lesions without vessel diameter restrictions remain uncertain.
Study design
The REC-CAGEFREE I is an investigator-initiated, multicenter, randomized, open-label trial aimed to enroll 2270 patients with acute or chronic coronary syndrome from 43 interventional cardiology centers in China to evaluate the non-inferiority of primary paclitaxel‐coated balloons angioplasty to primary stenting for the treatment of de novo, non-complex lesions without vessel diameter restrictions. Patients who fulfill all the inclusion and exclusion criteria and have achieved a successful lesion pre-dilatation will be randomly assigned to the two arms in a 1:1 ratio. Protocol-guided DCB angioplasty and bailout stenting after unsatisfactory angioplastyare mandatory in the primary DCB angioplasty group. The second-generation sirolimus-eluting stent will be used as a bailout stent in the primary DCB angioplasty group and the treatment device in the primary stenting group. The primary endpoint is the incidence of Device-oriented Composite Endpoint (DoCE) within 24 months after randomization, includingcardiac death, target vessel myocardial infarction, and clinically and physiologically indicated target lesion revascularization.
Discussion
The ongoing REC-CAGEFREE I trial is the first randomized trial with a clinical endpoint to assess the efficacy and safety of primary DCB angioplasty for the treatment of de novo, non-complex lesions without vessel diameter restrictions. If non-inferiority is shown, PCI with primary DCB angioplasty could be an alternative treatment option to primary stenting.
Design of the STRIVE-IPF Trial- Study of Therapeutic Plasma Exchange, Rituximab, and Intravenous Immunoglobulin for Acute Exacerbations of Idiopathic Pulmonary Fibrosis
Authors: Kulkarni Tejaswini , Criner Gerard , Kass Daniel , Rosas Ivan , Scholand Mary Beth , Dilling Daniel , Summer Ross , Duncan Steven
Published: February 2024

Background: Acute exacerbations of idiopathic pulmonary fibrosis (AE-IPF) affect a significant proportion of patients with IPF. There are limited data to inform therapeutic strategies for AE-IPF, despite its high mortality. We discuss the rationale and design of STRIVE-IPF, a randomized, multi-center, open-label Phase IIb clinical trial to determine the efficacy of combined therapeutic plasma exchange (TPE), rituximab, and intravenous immunoglobulin (IVIG), in comparison to treatment as usual (TAU), among patients with acute IPF exacerbations.
Methods: The STRIVE-IPF trial will randomize 51 patients among five sites in the United States. The inclusion criteria have been designed to select a study population with AE-IPF, as defined by American Thoracic Society criteria, while excluding patients with an alternative cause for a respiratory decompensation. The primary endpoint of this trial is six-month survival. Secondary endpoints include supplement oxygen requirement and six-minute walk distance which will be assessed immediately prior to treatment and after completion of therapy on day 19, as well as at periodic subsequent visits.
Discussion: The experimental AE-IPF therapy proposed in this clinical trial was adapted from treatment regimens used in other antibody-mediated diseases. The regimen is initiated with TPE, which is expected to rapidly reduce circulating autoantibodies, followed by rituximab to reduce B-cells and finally IVIG, which likely has multiple effects, including affecting feedback inhibition of residual B-cells by Fc receptor occupancy. We have reported potential benefits of this experimental therapy for AE-IPF in previous anecdotal reports. This clinical trial has the potential to profoundly affect current paradigms and treatment approaches to patients with AE-IPF.
Trial Registration ClinicalTrials.gov identifier: NCT03286556
Aerosol-type Classification Based on AERONET Version 3 Data: A Case Study of Two Major Cities in Pakistan
Authors: Zeeshan Muhammad
Published: February 2024

In the Earth’s atmosphere, aerosols are one of the most variable components that significantly impact Earth's climate and largely vary in their forms. This study investigates the temporal distribution of atmospheric particles over two mega-cities in Pakistan for the period 2015–2023, offering an aerosol-type classification based on the Particle Linear Depolarization Ratio (PLDR) and Single-Scattering Albedo (SSA) at 1020 nm, retrieved by the AERONET (Aerosol Robotic Network) Version 3.0 Level 2.0 inversion products. Results reveal that Lahore has comparatively higher average values for Aerosol Optical Depth (AOD 440nm) and Ångstroṁ Exponent (AE 440-870nm) than Karachi. The contribution of fine (coarse) −mode aerosols to the total volume concentration dominates at lower (higher) PLDR values. The dust ratio (Rd) parameter indicated that coarse-mode aerosols are dominated at both sites with occurrence rates of 86% at Lahore, and 99% at Karachi, respectively. Pure dust (PD) particles have a higher frequency of occurrence (43.16%) and pollution-dominated mixture (PDM) aerosols (44.14%) in the atmosphere of Lahore and Karachi, respectively, but dust-dominated mixture (DDM) have a lower frequency of occurrence (33.91% and 29.63%, respectively). Annual incidence rates for dust-free pollution aerosols (SA, MA, WA, and NA) are lower (25.62% at Lahore, 27.87% at Karachi) at both sites as compared to dust-containing (28.47% at Lahore, 30.43% at Karachi) aerosol type. Weakly absorbing (WA) and non-absorbing (NA) aerosols are dominated as compared to strong absorbing (SA) and moderately absorbing (MA) aerosols. In addition, seasonally, winter season is strongly affected by PD (85.42%) and DDM (54.39%), spring seasons by WA (55.53%) and PDM (68.61%), summer by NA (Lahore: 64.94%, and Karachi: 57.22%), and autumn seasons by WA (Lahore: 51.56%, and Karachi: 49.46%) aerosols, over Lahore and Karachi, respectively.
Optimizing Mendelian Randomization for Drug Prediction: Exploring Validity and Research Strategies
Authors: Zhang Miaoran , Xie Zhihao , Tian Aowen , Su Zhiguo , Wang Wenxuan , Qi Baiyu , Yang Jianli , Wen Jianping , Chen Peng
Published: February 2024

Mendelian randomization (MR) plays an increasingly important role in drug discovery, yet its full potential and optimized framework for accurately predicting drug targets have not been firmly established. This study aimed to evaluate the efficacy of multiple MR models in predicting effective drug targets and to propose the optimal selection of models and instrumental variables for MR analyses. We meticulously constructed datasets using approved drug indications and a range of IVs, encompassing cis-expression quantitative trait loci (eQTLs) and protein quantitative trait loci (pQTLs). Our analytical approach incorporated diverse models, including Wald’s ratio, inverse-variance weighted (IVW), MR‒Egger, weighted median, and MRPRESSO, to evaluate MR's validity in drug target identification. The findings highlight MR efficacy, demonstrating approximately 70% accuracy in predicting effective drug targets. For the selection of instrumental variables, tissue-specific eQTLs in disease-related tissues emerged as superior IVs. We identified a r2 threshold below 0.3 as optimal for excluding redundant SNPs. To optimize the MR model, we recommend IVW as the primary computational model, complemented by the weighted median and MRPRESSO for robust analyses. This finding is consistent with current findings in the literature. Notably, a P value of < 0.05, without false discovery rate correction, is the most effective for identifying significant drug targets. With the optimal strategies we summarized, we identified new potential therapeutic targets for IBD and its subtypes, including ERAP1, HLA-DQA1, IRF5 and other genes. This study provides a refined, optimized strategy for MR application in drug discovery. Our insights into the selection of instrumental variables, model preferences, and parameter thresholds significantly enhance MR's predictive capacity, offering a comprehensive guide for future drug development research.
Seismic resilience assessment of cable-stayed bridges based on composite copula models
Authors: Yang Guojun , ZHANG Tieyao , TIAN Li , DU Yongfeng , TANG Guangwu , MAO Jianbo
Published: February 2024

The seismic vulnerability of cable-stayed bridges, as crucial transportation nodes with numerous components, has always been a focal point of concern. The paper introduces a vulnerability assessment method for cable-stayed bridge system with the consideration of multi-component based on Pair Copula and Vine Copula models. The seismic resilience of cable-stayed bridges is evaluated by considering the degradation of bridge performance. In this approach, Pair Copula and Vine Copula models are iteratively applied to assess the vulnerability of each component of the cable-stayed bridge, resulting in an overall system vulnerability assessment. Additionally, performance degradation curves for the cable-stayed bridge during a downtime period are defined, and seismic resilience is assessed to simulate the impact of secondary disasters and other post-earthquake damages, leading to a reduction in bridge performance and affecting seismic resilience. The effectiveness of the proposed method is demonstrated using an actual cable-stayed bridge, illustrating its applicability. The study investigates the adverse effects of the degradation process on the seismic resilience of cable-stayed bridges. The results indicate that the method is highly applicable for obtaining the system vulnerability of cable-stayed bridges, providing a more practical assessment of their seismic resilience. This approach serves as a theoretical reference for future assessments of the seismic resilience of cable-stayed bridges.
Determinants of FinTech Service Utilization and Access Factors: Case of Palestine
Authors: Habash Nojoud
Published: February 2024

This study addresses the challenges of accessibility to financial technology (FinTech) services in emerging markets, focusing on Palestine. The purpose is to examine the determinants influencing access to and usage of FinTech services in this context, amidst the unprecedented disruptions faced by the conventional financial system due to decentralization and the removal of physical barriers in the dynamic landscape of FinTech. The study employs a robust multinomial Generalized Linear Model regression analysis. The analysis is based on a nationally representative secondary survey dataset on financial inclusion from the year 2022. Theory of Planned Behavior (TPB) is utilized to dissect the factors influencing FinTech usage, adding a distinctive layer to existing literature, particularly within the specific context of a developing country like Palestine. The study reveals significant insights into the challenges of financial inclusion in Palestine. Economic conditions and individual income levels emerge as formidable obstacles impacting both the accessibility and utilization of FinTech services. These factors intertwine with motivational and attitudinal behaviors among the surveyed population, that individual motivation plays a more potent role than attitude in steering the decision-making process surrounding FinTech adoption. This study introduces original contributions to the existing literature by applying TPB to dissect the determinants of FinTech usage within the specific context of a developing country, Palestine. The study explores the intricate interplay between economic conditions, individual income levels, motivational factors, and attitudinal behaviors in shaping FinTech access and usage.
The Interaction Between the Recent Evolution of Working from Home and Online Shopping
Authors: Mohammadi Motahare , Davatgari Amir , Asgharpour Sina , Shabanpour Ramin , Mohammadian Abolfazl , Derrible Sybil , Pendyala Ram , Salon Deborah
Published: February 2024

The growing behaviors of work-from-home (WFH) and online shopping hold significant potential for reducing traffic congestion and emissions. Understanding the frequency and the interplay between these two behaviors is important for successful implementation. This study investigates the recent trends of WFH and online shopping and the underlying factors influencing individuals’ decisions on these two behaviors. Focusing on non-grocery online shopping, this study uses comprehensive survey data collected across the United States during October and November 2021. We develop a Generalized Structural Equation Model (GSEM) to jointly examine WFH and online shopping frequency and their interaction. Moreover, the study investigates the psychological aspects of WFH and online shopping, introducing four stochastic latent constructs—WFH comfort, WFH unproductiveness, online shopping enjoyment, and online shopping inconvenience using the attitudinal variables. Results indicate a positive causal relationship, suggesting that increased WFH promotes online shopping engagement. Perceived comfort and productivity at home affect WFH frequency shaped by factors like home workspace, commuting time, childcare responsibilities, and telecommunications with co-workers. Likewise, perceived convenience and enjoyment significantly affect online shopping, influenced by aspects such as timesaving, and the delivery and return process. Technological tools at home also play a role in WFH frequency. Demographic factors like age, race, income, physical disability, and mode choice habits correlate with WFH and online shopping incidence, while job category and employer flexibility influence WFH frequency. These insights can help policymakers to regulate remote work and online shopping activities as they continue to grow.
Expressional and prognostic value of CRLF3 in liver hepatocellular carcinoma patients via integrated bioinformatics analyses and experiments
Authors: 王 幸幸 , Huang Zhen , Huang Lili , Huang Cong , Zhang Xiaoying , Zhang Xiantu
Published: February 2024

BACKGROUND: Liver hepatocellular carcinoma (LIHC) exhibits a notable prevalence and fatality rate, posing a significant risk to human well-being. 1. The orphan cytokine receptor-like factor 3 (CRLF3), which exhibits evolutionary conservation, has been associated with hematopoiesis in vertebrates, human diseases, and neuroprotection in insects 2,3. However, there is a dearth of research investigating the role of CRLF3 in LIHC and the underlying mechanisms involved.
METHODS: The researchers utilized the TCGA database to examine the putative regulatory association between the expression of CRLF3 mRNA and LIHC.The Human Protein Atlas (HPA) has made available visual representations of the expression patterns of the CRLF3 protein. To determine the protein expression levels of CRLF3 in LIHC and adjacent normal tissues, immunohistochemistry techniques were employed.The study employed the Kaplan-Meier method, Cox regression, and logistic regression to evaluate the association between CRLF3 mRNA expression levels and survival outcomes and prognosis. In this study, the researchers employed GO and Kyoto KEGG pathway enrichment analyses, as well as GSEA, to investigate the potential regulatory role of CRLF3. The biological function of CRLF3 was identified using the ssGSEA technique.
RESULTS: The primary objective of this study is to assess the levels of expression exhibited by various members of the CRLF family in LIHC and analyze their potential influence on prognosis. The mRNA expression levels of CRLF3 exhibited a significant increase in LIHC tissues, both at the transcript and protein levels. Furthermore, research has demonstrated that patients exhibiting elevated levels of CRLF3 in LIHC experience diminished OS, DSS, and PFI. Several clinicopathologic parameters, including clinical T stage, pathologic stage, histologic grade, and AFP concentration, have been seen to exhibit associations with CRLF3 expression in LIHC. The study used multivariate survival analysis to establish that CRLF3 served as an independent predictive factor. Additional enrichment analysis was conducted, which demonstrated that the PI3K Akt, Wnt, FcεRI-mediated NF-κB activation, activation of the intestinal immune network for the IgA production, interactions between immune cells and microRNAs in the tumor microenvironment, and JAK/STAT signaling pathways exhibited significant enrichment in the group with high CRLF3 expression. The ssGSEA analysis revealed a significant positive connection between the expression of CRLF3 and the presence of T helper 2 (Th2) and T helper cells.
CONCLUSIONS: Increased CRLF3 in LIHC is strongly linked to decreased survival and immune infiltration invasion. Based on the findings of our study, it is suggested that CRLF3 has the potential as a prognostic marker for unfavorable outcomes and might serve as a viable target for immunotherapeutic interventions in the management of LIHC.
Single-centre experience on the safety and efficacy of thoracoscopy under local anaesthesia for the management of intrathoracic infections
Authors: Fujita Kohei , Saito Zentaro , Ito Takanori , Imakita Takuma , Oi Issei , Kanai Osamu , Yamamoto Yuki , Hata Hiroaki , Sawai Satoru , Tanizawa Kiminobu
Published: February 2024

Objectives: Thoracoscopy under local anaesthesia is widely performed to diagnose malignancies and infectious diseases. However, few reports have described the use of this procedure for diagnosing and treating intrathoracic infections. This study aimed to evaluate the safety and efficacy of thoracoscopy under local anaesthesia for the management of intrathoracic infections.
Results: Data from patients who underwent thoracoscopy procedures performed by chest physicians under local anaesthesia at our hospital between January 2018 and December 2023 were retrospectively reviewed. We analysed their demographic factors, reasons for the examinations, diseases targeted, examination lengths, anaesthetic methods used, diagnostic and treatment success rates, as well as any adverse events. Thirty patients were included. Of these, 12 (40%) had thoracoscopies to diagnose infections, and 18 (60%) had them to treat pyothorax.
In terms of diagnosing pleurisy, the causative microorganism of origin was identified via thoracoscopy in only three of 12 (25.0%) patients. For diagnosing pyothorax, the causative microorganism wasidentified in 7 of 18 (38.9%) patients. Methicillin-resistant Staphylococcus aureus was the most common causative microorganism identified. The treatment success rates were very high, ranging between 94.4–100%, whereas the identification rate of the causative microorganisms behind infections was low, ranging between 25.0–38.9%. The most frequent adverse events included perioperative hypoxaemia and pain. There were two (6.7%) serious adverse events of grade ≥ 3, but none resulted in death.
Sunflower meal valorization through enzyme-aided fractionation and production of emerging prebiotics
Authors: Simović Milica , Banjanac Katarina , Veljković Milica , Semenčenko Valentina , Lopez-Revenga Paula , Montilla Antonia , Moreno F. Javier , Bezbradica Dejan
Published: February 2024

Sunflower meal, a plentiful and underutilized oil industry by-product, is currently discarded as waste or used as cheap component of animal feed with poor protein content and high content of complex carbohydrates. To harness its great potential for valorization, we propose an efficient method through enzyme-aided fractionation yielding 47.8% of hemicellulosic fraction, with simultaneous generation of various other potentially valuable fractions (including polyphenol-rich fraction, protein isolate, pectin, and lignin). According to the monomeric composition the main type of extracted hemicellulose was xylan with the common feature of a backbone of β-(1→4)-linked xylose residues, with a common substitution with arabinose moieties and some glucuronic acid residues. Subsequently, the xylan fraction underwent enzymatic treatment using commercial xylanase (ROHALASE® SEP-VISCO) to produce highly valuable compounds - emerging prebiotics xylo-oligosaccharides (XOS). Under optimized reaction conditions (70°C, pH 6 and enzyme concentration of 0.005% v/v using 5% w/v xylan solution) a yield of XOS with a polymerization degree DP<50 reached approximately 52.3% after 2 hours (majority of obtained product had DP<6 with predominance of XOS2 and XOS3 and without significant xylose generation).
RIP3 orchestrates oxidative stress and pyroptosis in doxorubicin-induced cardiotoxicity through regulation of AKT/Nrf2 signaling cascade
Authors: Wang Zhenyi , Yang Yitong , Wang Nisha , Lu Linhe , Xu Chennian , Ren Jun , Yang Lifang
Published: February 2024

This study was designed to explore the role of RIP3 in DOX-induced cardiotoxicity and its underlying molecular mechanisms.Ourresults demonstrate that RIP3 exacerbates DOX-inducedcardiotoxicity through promoting oxidative stress and pyroptosis by regulating the AKT/Nuclear factor erythroid 2-related factor 2 (Nrf2) pathway. Inhibition of RIP3 by using GSK-872 attenuated DOX-induced cardiac remodeling and contractile dysfunction. Moreover, by using GSK-872 in vivo, the results revealed that inhibition of RIP3 alleviated DOX-induced cardiotoxicity by the resulting inhibition of oxidative stress and pyroptosis. Besides, inhibition of RIP3 increased the protein levels of AKT and Nrf2 in DOX-treatedmouse hearts. Furthermore, the AKT inhibitor LY294002 lessened RIP3 reduction-offered protection against DOX-induced H9c2 cell injury by moderating oxidative stress and pyroptosis. Taken together, these data demonstrate that RIP3 activation orchestrates DOX-induced cardiotoxicity through elevated oxidative stress and pyroptosis in an AKT/Nrf2-dependent manner. Those findings highlight the clinical relevance and therapeutic potential of targeting RIP3for the treatment of DOX-induced cardiotoxicity.
CT Hounsfield Unit value as a Treatment Response Indicator for Spinal Metastatic Lesions in Patients with Non-Small-Cell Lung Cancer
Authors: Taniwaki Hiroshi , Dohzono Sho , Sasaoka Ryuichi , Takamatsu Kiyohito , Hoshino Masatoshi , Nakamura Hiroaki
Published: February 2024

This study aimed to determine the impact of computed tomography (CT)-measured increased Hounsfield unit (HU) values in the spinal metastatic lesions on the overall survival of patients with non-small-cell lung cancer (NSCLC), as well as to analyze the factors associated with HU increase in metastatic bone lesions. A total of 85 patients were included in this study between 2016 and 2021. HU values were evaluated in the metastatic bone lesions at the time of diagnosis of spinal metastasis (baseline), and at 3, 6, and 12 months after diagnosis. Patients were divided into two groups based on the median increase in HU between baseline and after 3 months of treatment in metastatic bone lesions. The Kaplan-Meier method was used to assess overall survival. Based on the median value of HU change (124), 42 and 43 patients were included in the HU responder and non-responder groups, respectively. The median overall survival was significantly longer in the HU responder group than in the HU non-responder group (13.7 vs. 6.4 months, P < 0.001). Multiple linear regression analysis revealed that the use of antiresorptive agents and molecularly targeted therapies were significant factors associated with an increase in HU. HU increase in spinal metastatic lesions after 3 months of treatment correlated with a significantly longer overall survival in patients with NSCLC. Thus, HU measurement may not only serve as an easy and quantitative method to evaluate the treatment response in spinal metastatic lesions, but can also predict the overall survival.
Investigation of the Pathogenic Variants Induced Sjogren’s Syndrome in Turkish Population
Authors: Terzi Ulku , Ates Ilker , Erden Abdulsamet , Suzen Sinan , Irham Lalu Muhammad
Published: February 2024

Sjögren’s syndrome is a chronic autoimmune disorder of unspecified etiology implicating exocrine glands. SS patients illustrate dry eyes and mouth, joint pain, fever and neurological symptoms. Hormones, immune dysregulation, and environmental and genetic factors play the primary roles in the development of the disease. Previous studies reported that HLA-II, STAT4, BAFF and TINIP1 polymorphisms have a pivotal role in SS development, however, the variant on each gene has not been investigated in the Turkish population. Therefore, this study aims to identify and evaluate the association between four variants of the four mentioned genes above and the development of Sjögren's syndrome. This study recruited 40 healthy subjects and 115 patients with Sjögren's syndrome in a Turkish population. All genomic variants were detected using the PCR-RFLP technique. We observed that SNP rs1130380, rs7574865, rs9514828, and rs17728338 were associated with SS development. We herein highlighted that the subjects with 1/2 or 2/2 Allele (%) had a higher susceptibility to SS development than those with the 1/1 Allele. Furthermore, the allele frequency of each variant was then assessed in multiple continents, including African, American, European, and Asian cohorts. Interestingly, our data shows that upregulating variants are at higher frequencies compared to European American and Asian populations, which implies that Turkish populations might be relatively susceptible to SS development related to these variants. The results indicated that all variants were significantly associated with the development of the SS disease in the Turkish population.
Cell adhesion molecule CD44 is dispensable for reactive astrocyte activation during prion disease
Authors: Bradford Barry M. , Walmsley-Rowe Lauryn , Reynolds Joe , Verity Nicholas , Mabbott Neil
Published: February 2024

Prion diseases are fatal, infectious, neurodegenerative disorders resulting from accumulation of misfolded cellular prion protein in the brain. Early pathological changes during CNS prion disease also include reactive astrocyte activation with increased CD44 expression, microgliosis, as well as loss of dendritic spines and synapses. CD44 is a multifunctional cell surface adhesion and signalling molecule which is considered to play roles in astrocyte morphology and the maintenance of dendritic spine integrity and synaptic plasticity. However, the role of CD44 in prion disease was unknown. Here we used mice deficient in CD44 to determine the role of CD44 during prion disease. We show that CD44-deficient mice displayed no difference in their response to CNS prion infection when compared to wild type mice. Furthermore, the reactive astrocyte activation and microgliosis that accompanies CNS prion infection was unimpaired in the absence of CD44. Together, our data show that although CD44 expression is upregulated in reactive astrocytes during CNS prion disease, it is dispensable for astrocyte and microglial activation and the development of prion neuropathogenesis.
Severity and Mortality in Maintenance Hemodialysis Patients Infected with COVID-19 Omicron Strain: a Single-Centered, Retrospective Study in China
Authors: Song Jie , Yu Yan , Liu Hong , Wu Huilin , Zhao Junyong , Yuan Fang
Published: February 2024

Purpose
The aim of this study was to observe the characteristics of COVID-19 infected maintenance hemodialysis (MHD) patients, identify the risk factors for severe illness and mortality in this population, and establish a preliminary risk prediction model for severe COVID-19 infection of MHD patients.
Methods
We included patients who underwent long-term maintenance hemodialysis and were hospitalized for COVID-19 infection at our hospital from December 2022 to March 2023. We retrospectively analyzed their demographic characteristics, clinical manifestations, laboratory tests, hemodialysis-related information, treatment strategies and complications. The patients were divided into severe (heavy and critical) and non-severe (mild and moderate) groups. Logistic regression and Cox proportional hazards analysis were used to identify the risk factors for severe COVID-19 progression.
Results
The presence of cerebrovascular disease, elevated NLR, fibrinogen, and D-dimer are independent risk indicators for severe COVID-19 infection in MHD patients in early stage. The presence of diabetes, cerebrovascular disease, and elevated D-dimer and NLR were associated with mortality.
Conclusion
MHD patients have a high probability of developing into severe and critical COVID-19 infection, and NLR, fibrinogen, and D-dimer can serve as early warning indicators for severe and critical progression of COVID-19 infection. The presence of diabetes, cerebrovascular disease, elevated NLR and D-dimer levels attribute to worse clinical outcomes and increased mortality.
The Origin of Sensory Representation: What we can learn from congenital limb deficiencies: a case-control study
Authors: Uysal Hilmi , Gülbetekin Evrim , Şavklıyıldız Ayhan , Gül Hatice
Published: February 2024

Background
There are arguments regarding the ontological or embryological origin of sensory representation in the literature. This study aimed to understand the origin of somatosensory organization by comparing participants with congenital limb deficiencies with healthy controls.
Methods
Four participants with congenital limb deficiencies (three participants with bilateral amelia, one participant with tetramelia, 19–31 years old, two females, two males), 15 healthy controls (three males, 12 females; mean age, 19.57 ± 1.34 years) in the quantitative electroencephalography (QEEG) experiment, and 10 healthy controls (seven male, three female; mean age, 23.9 ± 2.21 years) in the functional magnetic resonance imaging (fMRI) experiment, participated in this study. fMRI and QEEG data were recorded to determine the somatosensorial organization in both participants with congenital limb deficiency and healthy controls. For the QEEG data, one sample t-tests were conducted to evaluate whether the spectral power in the CZ, C3, and C4 electrodes in the participants with congenital limb deficiencies differed from that in healthy controls when they were touched on their cheek, shoulder, and foot. In fMRI recordings, the face and hand regions were stimulated using a non-magnetic stick with cotton attached. For the fMRI data, individual level and group level interferences were examined with one and two sample t-tests, respectively. Moreover, masked regions of interest were systematically compared using the Mann-Whitney U-test.
Results
Our findings showed that the somatotopic structure of participants with congenital limb deficiency and healthy controls have some common patterns and striking differences. In the QEEG results, the cortical activity was lower in participants with congenital limb deficiency than the activity in healthy controls during tactile stimulation and the participant with tetramelia had lower cortical activity levels than both the participants with amelia and healthy controls (p < 0.05). Furthermore, the representation of the face showed activation predominantly towards the upper somatosensory cortex according to the fMRI results.
Conclusions
Differences in the somatosensory organization of individuals with congenital limb deficiency and healthy controls show that both ontology and plasticity may have played a role in this status.
Moving forward: Scaling-up the integration of an HIV and hypertension program in Akwa Ibom State, Nigeria
Authors: Mishra Shivani , Aifah Angela , Henry Daniel , Uzoigwe Nina , Udoh Emem , Idang Esther , Munagala Jahnavi , Onakomaiya Deborah , Kanneh Nafesa , Ekanem Anyiekere , Attah Eno Angela , Ogedegbe Gbenga , Ojji Dike
Published: February 2024

Background
As people living with HIV experience increased life expectancy, there is a growing concern about the burden of comorbid non-communicable diseases, particularly hypertension. This policy brief describes the current policy landscape in Akwa Ibom State, Nigeria, the research activities, and five policy recommendations rooted in an ongoing research study designed to integrate hypertension management into HIV care across primary health centers in the state.
Analysis
The policy brief was developed in four steps: review of existing policies, using the reviewed policies to inform research activities, solicitation of stakeholder recommendations via focus group discussions, and formulation of the resulting five policy recommendations for integrating hypertension management into HIV care programs in Akwa Ibom. The key analysis for this brief emerged from the thematic analyses of stakeholder responses.
Policy Implications
The five policy recommendations for integrating hypertension management in HIV care in Akwa Ibom State, Nigeria are: 1) build capacity by leveraging retired community nurses as mentors; 2) emphasize community engagement; 3) develop consistent training programs on hypertension management for health workers; 4) expand health insurance accessibility; and 5) formally integrate hypertension management into primary healthcare centers in Akwa Ibom State.
Toward Hospital Resilience: a Qualitative Study on the identification of Hospital Shocks during Disruption era in Indonesia
Authors: Sari Nurmala , Omar Mayeh , Pasinringi Syahrir A , Zulkifli Andi , Sidin Andi Indahwaty , Kapalawi Irwandy , Thamrin Yahya , Saleh Lalu Muhammad , Ayuningtyas Dumilah
Published: February 2024

Background:
Hospital resilience has been well recognized among healthcare managers and providers as disruption of hospital services threatens their business environment. However, the shocks identified in the recent hospital resilience concept are mainly related to disaster situations. This study aims to identify potential shocks the hospitals face during the disruption in Indonesia.
Method:This qualitative study is conducted in Makassar, Indonesia in August-November 2022. Data was collected through in-depth interviews with hospital managers and resilience experts using a semi-structured interview guide. Overall 20 key informants were interviewed. Data were analyzed by thematic analysis.
Results:
The study identified seven shocks to hospitals during the disruption era: policy, politics, economics, hospital management shifting paradigm, market and consumer behavior change, disaster, and conflicts. It also identified barriers to making hospitals resilient, such as inappropriate organizational culture, weak cooperation across sectors, the traditional approach of hospital management, inadequate managerial and leadership skills, and human resources capabilities, a lack of business mindset and resistance to change.
Conclusion: This study provides a comprehensive understanding of hospital shocks during disruptions. This would serve as a guide to redesigning the instruments and capabilities needed for a resilient hospital.
Annexin-A5 monomer as a membrane repair agent for the treatment of renal ischemia-reperfusion injury
Authors: Dong Yushan , Jia Zhuoxuan , Kang Bijun , Zhang Wenjie
Published: February 2024

Background: Renal ischemia-reperfusion injury (IRI) is one of the causes of acute kidney injury. Annexin A5 (AnxA5) as a calcium-dependent cell membrane binding protein has shown good protective effects in various organ IRI models. This study explored the therapeutic effect of exogenous AnxA5 monomer protein on renal IRI and its potential mechanism.
Methods: In vivo, different doses of AnxA5 were injected intravenously to treat bilateral renal IRI models in SD rats. This model confirms the protective effect of AnxA5 on the structure and function of the kidneys. In vitro, HK-2, the renal tubular epithelial cells, was subjected to hypoxia for 12 hours, followed by restoration of normal oxygen supply to simulate IRI. In vitro experiments have demonstrated the mechanism of action of AnxA5 by measuring cell activity and permeability. The comparison of the mutant AnxA5 protein M23 and the application of calcium-free culture medium further validated the protective effect of AnxA5 by forming a network structure.
Results: In vivo, AnxA5 monomer improved kidney function damage caused by IRI and prevented the deterioration of the pathological structure. In vitro, AnxA5 protected cell viability, reduced cell membrane permeability, and inhibited cell apoptosis induced by IRI treatment. However, AnxA5 lost its protective effect in the calcium-free culture medium and the M23 that lack the ability of forming a two-dimensional network structure could not reduce cell membrane permeability and lost its protective effect on cell viability, indicating that the formation of a two-dimensional network structure of AnxA5 is critical to the repair of the cell membrane.
Conclusions: Exogenous AnxA5 monomer could prevent renal IRI by binding to the damaged renal tubular epithelial cell membrane, forming a two-dimensional network structure to maintain cell membrane integrity, and ultimately prevent cell death.
Devising Breast Cancer Diagnosis Protocol through Machine Learning
Authors: Mujtaba Tooba
Published: February 2024

Breast cancer is a life threatening disease and have serious implications to health. It is further categorized on the bases of receptors including ER+ and HER2-.
Breast cancer is a multifaceted disease that has many subcategories characterized by unique genetic features. This research focuses on two important subgroups of receptors, including ER+ and HER2-. We conducted an analysis of gene expression data obtained from reliable source (Array Express: E-GEOD-52194, E-GEOD-75367, and E-GEOD-58135) in order to reveal the complex molecular details of these subtypes. The computational pipeline we used identified 396 genes that exhibited distinct patterns of gene expression in ER+ and HER2- breast cancers. The diagnostic and prognostic significance of these genes was evaluated using machine learning methods, namely SVM and decision tree models. Metrics like as accuracy, sensitivity, and specificity provide insights into their usefulness. Furthermore, the use of the STRING database for network analysis revealed significant signaling pathways and biological processes associated with the development of ER+ and HER2- breast cancer. The results of our research enhance our comprehension of these subcategories, which might possibly facilitate more accurate diagnoses and focused treatment interventions. This work provides valuable information on the genetic foundations of ER+ and HER2- breast cancer, which has potential implications for enhancing patient treatment and outcomes.
Development of a novel nomogram for predicting delayed methotrexate excretion following high-dose methotrexate in adult patients with hematologic malignancies
Authors: Ikeda Daisuke , Isezaki Tatsuya , Narita Kentaro , Yuyama Satoshi , Oura Mitsuaki , Uehara Atsushi , Tabata Rikako , Takeuchi Masami , Matsue Kosei
Published: February 2024

Purpose: High-dose methotrexate (HDMTX) is integral in treating hematologic malignancies but carries risks of severe toxicities due to prolonged MTX exposure. However, knowledge of delayed MTX excretion is primarily derived from pediatric and adolescent cohorts, with the reported predictors being presented as rough dichotomous values. This study aimed to identify risk factors for delayed MTX excretion exclusively in adult patients with hematologic malignancies and develop a more applicable predictive nomogram based on continuous clinical and laboratory variables.
Methods: 517 HDMTX cycles in 194 patients were retrospectively analyzed. Delayed MTX excretion was defined as either MTX concentration ≥1.0 μmol/L at 48 h or ≥0.1 μmol/L at 72 h after HDMTX initiation. Multivariate logistic regression analysis was used to construct the nomogram internally validated with the bootstrap method.
Results: Delayed MTX excretion was observed in 24.0% of cycles. Six significant predictors were identified: relapsed/refractory disease (Odds ratio [OR] 2.03), fewer HDMTX cycles (OR 0.771), treatment intent (OR 2.13), lower albumin (OR 0.563) and creatinine clearance levels (OR 0.993), and increased γ-glutamyl transpeptidase levels (OR 1.004, all P <0.05). These were incorporated into a web-based nomogram as continuous variables with good prediction accuracy (area under the curve, 0.73) and without significant overfitting. Delayed MTX excretion increased risks of developing acute kidney injury, even solely at the 72 h timepoint (OR 2.57, P = 0.025), without providing any benefit of clinical outcomes.
Conclusion: This study comprehensively characterized MTX elimination failure following HDMTX in adult patients and could pave the way for individualized risk prediction.
The comparison of eight-week high-intensity interval training VS. moderate-intensity continuous training on inflammatory and metabolic biomarkers in type II diabetes: a pilot randomized controlled trial
Authors: Alizadeh Sahar , Avandi Mohsen , Fico Brandon G. , Mahdieh Nahid , Hedayati Mehdi , Rambod Camelia , Bakhshandeh Hooman
Published: February 2024

Purpose: Low-grade chronic inflammation has been linked with several health complications like type II diabetes. Given that exercise potentially has anti-inflammatory effects, this study was designed to compare the impact of 8-week high-intensity interval training (HIIT) and moderate-intensity continuous training (MICT) on specific inflammatory and metabolic markers among a group of diabetic patients to examine how the intensity of exercise influences inflammation-related biomarkers.
Methods: An open-labeled, parallel, randomized, controlled trial was conducted at a cardiovascular center. Twenty-seven participants (15 females, mean age: 51±6.2years, BMI: 29.4±3.9kg/m2) were allocated into three equal groups (n=9): HIIT, MICT, and control (CON). Blood samples were collected at baseline, 24 and 72 hours after the last training session. Plasma levels of calprotectin, myeloperoxidase (MPO), interleukin 6 (IL-6) (primary endpoints), and insulin were measured.
Results: Comparing the data over time, none of the biomarkers showed significant differences between the study groups. IL-6 decreased over time in both training groups similarly (p˂0.001). Despite small improvements in anthropometric measures and maximal oxygen consumption (VO2max) among training groups compared to the CON group, the two training protocols had almost similar impacts on the investigated inflammatory and metabolic markers.
Conclusions Our findings indicate no statistically significant difference in inflammatory and metabolic measures between the two training groups, so neither of the training protocols is superior. However, both training groups exhibited improvements compared to the control group in glucose, triglyceride, and waist-to-hip ratio.
Trial registration: IRCT20181129041797N1 (date: 25 Dec. 2108). The full protocol of our study is also available on www.irct.ir
Microwave ablation for benign thyroid nodules with cosmetic problems and related factors for post-ablative complete relief: a two-center retrospective study
Authors: Li Xiao-Long , Chen Zi-Tong , Jin Yun-Jie , Xu Ben-Hua , Xu Ya-Dan , Cao Qiong , Bo Xiao-Wan , Wen Jie-Xian , Ji Zheng-Biao , Fan Pei-Li , Xu Hui-Xiong
Published: February 2024

Purpose: To investigate the efficacy of ultrasound (US)-guided percutaneous MWA for benign thyroid nodules with cosmetic problems and related factors for post-ablative complete relief (CR).
Methods: This retrospective study reviewed thyroid nodule efficacy in patients with cosmetic problems who underwent MWA from January 2021 to May 2023. Patients were followed up at 1, 3, and 6 months after MWA. Pre-treatment clinical characteristics, conventional ultrasound (US) and contrast-enhanced ultrasound (CEUS) features were analyzed to explore their correlation with cosmetic problems of CR (i.e., cosmetic score 1 or 2 at the 6-months follow-up). Univariable and multivariable regression analyses were carried out to identify variables associated with CR, and the related nomogram was established. Calibration curve and decision curve analysis were used to evaluate the nomogram performance.
Results: 118 patients with 118 nodules were included in the study. During the 1-, 3- and 6-month follow-up, the mean volume reduction ratios (VRR) were 2%, 36% and 73%, respectively. 22.0% (26/118), 57.6% (68/118), and 89.8% (106/118) patients achieved CR of cosmetic problems at 1, 3, and 6 months after MWA. In multivariable analysis, three variables (i.e., non-hashimoto’s thyroiditis [HT] [OR: 90.036, P= 0.001], nodule location not close to danger triangle area [OR: 66.812, P= 0.003], early hyperenhancement on CEUS [OR: 0.035, P = 0.024]) were found to be closely associated with CR of cosmetic problems at 6 months after MWA. A nomogram model was constructed, and its accuracy was well validated (i.e., C-index=0.914).
Conclusion: MWA was effective and safe for treating benign thyroid nodules with cosmetic problems. Moreover, non-HT, nodule location not close to danger triangle area, and early hyperenhancement on CEUS were associated with CR of cosmetic problems after MWA.