bluuebunny/crossref_metadata_2025 huggingface dataset:
An integrative single-cell multi-omics profiling of human pancreatic islets identifies T1D associated genes and regulatory signals
Authors: Chen Shuibing , Zhao Zeping , Albanus Ricardo D'Oliveira , Taylor Henry , Tang Xuming , Han Yuling , Orchard Peter , Varshney Arushi , Zhang Tuo , Manickam Nandini , Erdos Michael , Narisu Narisu , Taylor D. Leland , Saavedra Xiaxia , Zhong Aaron , Li Bo , Zhou Ting , Naji Ali , Liu Chengyang , Collins Francis , Parker Stephen
Published: October 2023

Genome wide association studies (GWAS) have identified over 100 signals associated with type 1 diabetes (T1D). However, translating any given T1D GWAS signal into mechanistic insights, such as causal variants, their target genes, and the specific cell types involved, has been challenging. Here, we present a comprehensive multi-omic integrative analysis of single-cell/nucleus resolution profiles of gene expression and chromatin accessibility in healthy and autoantibody+ (AAB+) human pancreatic islets, and islets under T1D-stimulating conditions. We nominate effector cell types for all T1D GWAS signals and the regulatory elements and genes for three independent T1D risk variants acting through β cells at the DLK1/MEG3, RASGRP1, and TOX loci. Subsequently, we validated the functional impact of these genes and regulatory regions using isogenic human embryonic stem cells (hESCs) and found that loss of RASGRP1 or DLK1, as well as disruption of their regulatory regions, led to increased β cell apoptosis. Furthermore, β cells derived from isogenic hESCs carrying the T1D risk allele of rs3783355 associated with DLK1 showed elevated β cell death. Through RNA-seq and ATAC-seq analyses, we identified five genes upregulated in both RASGRP1-/- and DLK1-/- β-like cells, four of which are associated with T1D. This integrative approach combining single-cell multi-omics, GWAS, and isogenic hPSC-derived β-like cells illuminates cell type context, genes, single nucleotide polymorphisms (SNPs), and regulatory elements underlying T1D-associated signals, providing insights into the biological functions and molecular mechanisms involved.
Good Statistical Practice - Good Clinical Practice for Statisticians
Authors: Stocken Deborah D , Mossop Helen , Armstrong Emma , Lewis Steff , Dutton Susan J , Peckitt Claire , Gamble Carrol , Brown Julia MB
Published: October 2023

Background Statisticians are fundamental in ensuring clinical research, including clinical trials, are conducted with quality, transparency, reproducibility and integrity. Good Clinical Practice (GCP) is an international quality standard for the conduct of clinical trials research. Statisticians are required to undertake training on GCP but existing training is generic and, crucially, does not cover statistical activities. This results in statisticians undertaking training mostly unrelated to their role and variation in awareness and implementation of relevant regulatory requirements with regards to statistical conduct. The need for role-relevant training is recognised by the NHS Health Research Authority and the Medicines and Healthcare products Regulatory Agency (MHRA).Methods The Good Statistical Practice (GCP for Statisticians) project was instigated by the UK Clinical Research Collaboration (UKCRC) Registered Clinical Trials Unit (CTU) Statisticians Operational Group and funded by the National Institute for Health and Care Research (NIHR), to develop materials to enable role-specific GCP training tailored to statisticians. Training materials have been developed based on MHRA GCP and cover legislation and guidance for best practice across all clinical trial processes with statistical involvement, incorporating existing UKCRC guidance on analysis plans, validation of statistical programming and data sharing. The training has been developed to include exercises and real-life scenarios to bridge the gap between theory and practice. Comprehensive feedback from pilot work with UKCRC CTU and NIHR Statisticians has been incorporated.Results An accessible, comprehensive, piloted training package has been developed tailored to statisticians working in clinical research, particularly the clinical trials arena. The training is freely available for national and international adoption.Conclusion All research staff should have training in GCP yet the training undertaken by most academic statisticians is generic and does not cover activities related to their role. The Good Statistical Practice (GCP for Statisticians) project has developed and extensively piloted new, role-specific, comprehensive, accessible GCP training tailored to statisticians working in clinical research, particularly the clinical trials arena. This role-specific training will encourage best practice, leading to transparent and reproducible statistical activity, as required by regulatory authorities and funders.
A Scan of Pleiotropic Immune Mediated Disease Genes Identifies Novel Determinants of Baseline FVIII Inhibitor Status in Hemophilia-A
Authors: Howard Tom , Almieda Marcio , Diego Vincent , Viel Kevin , Luu Bernadette , Haack Karin , Raja Rajalingam , Ameri Afshin , Chitlur Meera , Rydz Natalia , Lillicrap David , Watts Raymond , Kessler Craig , Ramsey Christopher , Dinh Long , Kim Benjamin , Powell Jerry , Peralta Juan , Bouls Ruayda , Abraham Shirley , Shen Yu-Min , Murillo Carlos , Mead Henry , Lehmann Paul , Fine Eli , Escobar Miguel , Kumar Satish , Williams-Blangero Sarah , Kasper Carol , Almasy Laura , Cole Shelley , Blangero John , Konkle Barbara
Published: October 2023

Hemophilia-A (HA) is caused by heterogeneous loss-of-function factor (F)VIII gene (F8)-mutations and deficiencies in plasma-FVIII-activity that impair intrinsic-pathway-mediated coagulation-amplification. The standard-of-care for severe-HA-patients is regular infusions of therapeutic-FVIII-proteins (tFVIIIs) but ~30% develop neutralizing-tFVIII-antibodies called “FVIII-inhibitors (FEIs)” and become refractory. We used the PATH study and ImmunoChip to scan immune-mediated-disease (IMD)-genes for novel and/or replicated genomic-sequence-variations associated with baseline-FEI-status while accounting for non-independence of data due to genetic-relatedness and F8-mutational-heterogeneity. The baseline-FEI-status of 450 North American PATH subjects—206 with black-African-ancestry and 244 with white-European-ancestry—was the dependent variable. The F8-mutation-data and a genetic-relatedness matrix were incorporated into a binary linear-mixed model of genetic association with baseline-FEI-status. We adopted a gene-centric-association-strategy to scan, as candidates, pleiotropic-IMD-genes implicated in the development of either ³2 autoimmune-/autoinflammatory-disorders (AADs) or ³1 AAD and FEIs. Baseline-FEI-status was significantly associated with SNPs assigned to NOS2A (rs117382854; p=3.2E-6) and B3GNT2 (rs10176009; p=5.1E-6), which have functions in anti-microbial-/-tumoral-immunity. Among IMD-genes implicated in FEI-risk previously, we identified strong associations with CTLA4 assigned SNPs (p=2.2E-5). The F8-mutation-effect underlies ~15% of the total heritability for baseline-FEI-status. Additive genetic heritability and SNPs in IMD-genes account for >50% of the patient-specific variability in baseline-FEI-status. Race is a significant determinant independent of F8‑mutation-effects and non-F8-genetics.
Therapeutic Intervention of Neuroinflammatory Alzheimer Disease Model by Inhibition of Classical Complement Pathway with the Use of Anti-C1r Loaded Exosomes
Authors: Richards Terjahna , Perron Jeanette C. , Patel Ketan , Wurpel John , Reznik Sandra E. , Schanne Francis
Published: October 2023

Alzheimer’s disease (AD) is a complex neurodegenerative disease associated with memory decline, cognitive impairment, amyloid plaque formation and tau tangles. Neuroinflammation has been shown to be a precursor to apparent amyloid plaque accumulation and subsequent synaptic loss and cognitive decline. In this study, the ability of a novel, small molecule, T-ALZ01, to inhibit neuroinflammatory processes was analyzed. T-ALZ01, an inhibitor of complement component C1r, demonstrated a significant reduction in the levels of the inflammatory cytokines, IL-6 and TNF-α in vitro. An LPS-induced animal model, whereby animals were injected intraperitoneally with 0.5 mg/kg LPS, was used to analyze the effect of T-ALZ01 on neuroinflammation in vivo. Moreover, exosomes (nanosized, endogenous extracellular vehicles) were used as drug delivery vehicles to facilitate intranasal administration of T-ALZ01 across the blood-brain barrier. T-ALZ01 demonstrated significant reduction in degenerating neurons and the activation of resident microglia and astrocytes, as well as inflammatory markers in vivo. This study demonstrates a significant use of small molecule complement inhibitors via exosome drug delivery as a possible therapeutic in disorders characterized by neuroinflammation, such AD.
Can deep learning help in understanding the geodynamo?
Authors: Kuslits Lukács , Horváth András , Wesztergom Viktor , Beggan Ciaran , Rubóczki Tibor , Prácser Ernő , Czirok Lili , Bozsó István , Lemperger István
Published: October 2023

Machine learning (ML) is an emerging tool used in an ever-growing number of branches of contemporary geophysical research. To date however, rarely have such methods been applied specifically for the study of Earth’s internal magnetic field and the geodynamo. Prevailing methods currently used in inferring the characteristic properties and the probable time evolution of the geodynamo are based on two differing but connected approaches. They both directly rely on simplified applications of magnetohydrodynamics.
In this study, first attempts at applying a new kind of inference method are presented. Its long-term goal focuses on inferring concentrations of electric current densities inside the core as the direct sources of the magnetic field itself rather than addressing the fluid motions.
The method makes use of simplified models in which equivalent current loops represent local current systems emerging in computationally extremely intensive turbulent geodynamo simulations. These forward models were then utilized to produce synthetic magnetic field maps with a widely varying configurations of such current loops hypothetically placed inside a conductive outer core, along maps of real historical geomagnetic field model data both computed at the core-mantle boundary (CMB). The resulting maps were used as input training samples for an image processing deep neural network, which essentially learns to infer the parameters of all these modelled current systems based on the magnetic field maps.
Results presented here are focusing mainly on the feasibility of the method when applied for synthetic data and the quality parameters of these inferences. The overall distribution of loop currents can be recovered with a satisfying accuracy. However, the quality of the reconstruction of magnetic field properties is compromised by unrealistic values occasionally being inferred, and an inability to recover realistic secular time variations (SV). One example is shown of an inferred model obtained using CMB magnetic field maps. Main features of the maps of actual field values can be reproduced, and the corresponding inferred current loops tend to align in chain-like arrangements.
Assessment of diffuse bone marrow involvement on 18F-fluoro-D-glucose PET/computed tomography
Authors: Zhang Tong , Li Ping , Yang Funing , Wang Hongjia
Published: October 2023

Purpose
This study aims to investigate the role of bone marrow (BM) FDG uptake distribution by 18F-FDG PET/CT in assessing pathological status of BM with diffusely increased FDG uptake.
Methods
We retrospectively analyzed one hundred and thirty-four PET/CT scans with diffusely increased FDG uptake in BM, which involved forty-nine patients with malignant diseases of BM and eighty-five patients with benign disorders of BM. The maximum standardized uptake values (SUVmax) of axial skeletons (spine, ribs, sternum, pelvis), appendicular skeletons (proximal humerus, proximal femur, clavicle, scapula), and the range of humerus FDG uptake were measured, and the clinical and laboratory data were collected. Multivariate logistic regression analysis and receiver operating characteristic (ROC) curve were used to evaluate the risk factors for BM malignancies and discriminative ability of above indicators for pathology status of BM with diffusely increased FDG uptake.
Results
In patients with diffusely increased FDG uptake in BM, both the glucose metabolism in axial and appendicular skeletons were higher in BM malignancies than benign disorders. The multivariate logistic regression analysis (stepwise) revealed age (odds ratio [OR] 1.073; 95%CI, 1.031-1.117; P=0.001), femurs SUVmax (OR 2.058; 95%CI, 1.317-3.218; P=0.002), neutrophil count (OR 0.805; 95%CI, 0.718-0.902; P<0.001) and range of humerus FDG uptake (OR 11.335; 95%CI, 2.831-45.377; P=0.001) were associated with BM malignancies. Combined diagnosis had the highest ROC value (AUC 0.918; 95%CI, 0.864-0.973; P<0.001) with a sensitive of 89.8% and specificity of 85.9%.
Conclusion
Metabolic information of appendicular skeletons on FDG PET/CT was significant for assessing diffuse involvement in BM. Age combined femurs SUVmax, neutrophil count and range of humerus FDG uptake was reliable in differentiating BM malignancies from benign disorders.
Development of a low-frequency vibration-assisted turning device for nickel-based alloy
Authors: Shi Weichao , Zheng JianMing , Zhu LingJian , Chen Ting , Jing ZhangShuai , Peng Chao , Xue Rong , Li Qi
Published: October 2023

As a typical difficult-to-machine material which is widely used in aerospace and aviation field, the high quality and efficient machining of nickel-based alloys has always been the hotspot in mechanical machining. However, the problem of force and heat concentrations can reduce the machining stability of nickel-based alloys, leading to tool wear and work hardening, seriously affecting the flow direction and fracture of chips. Therefore, a novel low-frequency vibration-assisted turning device is developed by using adjustable dual eccentric mechanism in this paper. The chip separation conditions of low-frequency vibration turning is analyzed. The relationship between cutting parameters and cutting force, cutting temperature, tool wear, workpiece surface morphology, and tool life was studied through experiments. The experimental results demonstrate that the low-frequency vibration-assisted turning device can effectively suppress cutting force fluctuations, reduce cutting temperature, delay tool wear speed, improve surface quality, and increase tool life, meeting the high-quality and efficient machining requirements of nickel-based alloys. The research results will provide theoretical support for the problem of chip breakage in difficult to machine materials and the study of low-frequency vibration-assisted cutting technology.
CSPG-PTPσ blockade promote neurofilament growth and synaptic formation via regulating autophagy flux in spinal cord injury
Authors: Wang Hongyu , Feng Naibo , Liu Chungeng , Xie Yongheng , Zhou Zipeng , Zhao Haosen , Xiao Guozhi , Yang Dazhi
Published: October 2023

Chondroitin sulfate proteoglycans (CSPGs) play critical role in the pathology of spinal cord injury (SCI). CSPG can be induced by autophagy inhibition in astrocyte, however, CSPG impact on autophagy and its role in SCI was still unknown. We investigate intracellular sigma peptide (ISP) targeting protein tyrosine phosphatase σ (PTPσ), effect on autophagy and synaptic formation in SCI. We determined autophagy related protein light chain 3 (LC3) and p62, autophagosome-lysosome fusion related protein STX17 (syntaxin 17), and lysosome-associated membrane protein 2 (LAMP2), pre-synaptic marker synaptophysin (SYN) and postsynaptic density protein-95 (PSD-95) in vivo SCI and in vitro primary spinal neuron via western blot. The expression of LC3B and NeuN, LAMP2 and STX17, SYN and vesicular glutamate transporter 1(VGLUT1), neuronal growth-associated protein GAP-43 and neurofilament were determined via immunofluorescence (IF). The preserved neuron in the injured spinal cord were assessed via Nissl-staining and neurobehavioral function by Basso Mouse Scale (BMS) score. We found that ISP activated autophagy flux related level of LC3B and p62, autophagosome-lysosome fusion related LAMP2/STX17, excitatory synapse marker SYN/VGLUT1, axon growth related GAP-43/Neurofilament expression in SCI. ISP promote preserved number of motor neurons and improved neurobehavioral recovery after SCI. CSPG-PTPσ blockade restored autophagy flux, synaptic and neurofilament growth, and promote functional recovery in SCI. Our study extended CSPG-PTPσ role in autophagy flux regulation, synaptic function and functional recovery in SCI.
The Experiences of Parents of Children with Sickle Cell Disease in a Metropolis in Ghana
Authors: Bayuo Francis Borsongdeme , Boateng Edward Appiah , Apiribu Felix , Wondong Winifred Pogsaa , Asakeboba Philomena
Published: October 2023

Problem:
Sickle cell disease imposes complex demands on the lives of affected children and their families. In recent years, several studies have appraised the burden of care on parents of children with SCD in different parts of the world. This study explored the experiences of parents of children with SCD in a metropolis in Ghana, using the ABCX family stress model as the guiding theoretical framework.
Methods
The exploratory qualitative research approach was used. Thirteen (13) parents were purposively selected and engaged in individual, face-to-face interviews. The interviews were audio-recorded, transcribed verbatim, and analyzed using thematic content analysis.
Results
Three (3) major themes emerged namely, the perception of SCD by participants, the burden of care, and the resources used by parents. Participants had negative perceptions of SCD and were reluctant to give birth again due to the challenges of caring for a child with SCD. Resources used by participants were social support and coping strategies.
Conclusions
Genetic counseling before marriage should be highlighted in the awareness creation of SCD. Professional counseling services should be intensified to assist parents of children with SCD to promote their emotional health.
Implementing shared decision making support for cardiovascular disease prevention: Stakeholder interviews and case studies in Australian primary care
Authors: Bonner Carissa , Cornell Samuel , Pickles Kristen , Batcup Carys , de Wet Carl , Morgan Mark , Greaves Kim , O’Connor Denise , Hawkes Anna L , Crosland Paul , Chapman Niamh , Doust Jenny
Published: October 2023

Background:
Australian cardiovascular disease (CVD) prevention guidelines recommend absolute CVD risk assessment, but less than half of eligible patients have the required risk factors recorded due to fragmented implementation over the last decade. Co-designed decision support tools for general practitioners (GPs) and consumers have been developed that improve knowledge barriers to guideline-recommended CVD risk assessment and management. This study used a stakeholder consultation process to identify and pilot test the feasibility of implementation strategies for these decision support tools in Australian primary care.
Methods:
This work was based on the Multiphase Optimisation Strategy (MOST) framework and included: 1) stakeholder consultation to map existing implementation strategies (2018-20); 2) interviews with 29 Primary Health Network (PHN) staff from all Australian states and territories to identify new implementation opportunities (2021); 3) pilot testing the feasibility of low, medium, and high resource implementation strategies (2019-21). Framework Analysis was used for qualitative data and Google analytics provided decision support usage data over time.
Results:
Informal stakeholder discussions indicated a need to partner with existing programs delivered by the Heart Foundation and PHNs. PHN interviews identified the importance of linking decision support tools with GP education resources, quality improvement activities, and consumer-focused prevention programs. Participants highlighted the importance of taking account of general practice processes, such as business models, workflows, medical records and clinical audit software. Specific implementation strategies were identified as feasible to pilot during COVID-19: 1) low resource: adding website links to local health area guidelines for clinicians and a Heart Foundation toolkit for primary care providers; 2) medium resource: presenting at GP education conferences and integrating the resources into audit and feedback reports; 3) high resource: auto-populate the risk assessment and decision aids from patient records via clinical audit software.
Conclusions:
This research identified a wide range of feasible strategies to implement decision support tools for CVD risk assessment and management. The findings will inform the translation of new CVD guidelines in primary care. Future research will use economic evaluation to explore the added value of higher versus lower resource implementation strategies.
Inhibiting thinning in tube bending by considering a coupling effect of material compensation and friction under a boosting movement
Authors: Fang Hao , Wang Zhineng , Bin Guangfu , Lin Weiming , Lin Yaocheng , Tran Cong Trieu
Published: October 2023

Pressure die boost is an effective method to inhibit the thinning in the manufacturing process of aerospace tubes, and its mechanism is concerned by scholars at home and abroad. Finite element and experimental methods were conducted to analyze the tube thinning with and without boost. The effects of boosting velocity and friction on the outer wall thickness of the tube are studied. Results show that frictional force generated by the boost and the material compensation effect combine to resist the outer wall thinning during the bending process. When the boosting velocity is higher than the tube bending linear velocity, the frictional force of the boost generates a specific compressive stress, which weakens the tensile stress during the bending process of the outer wall. In the meantime, the boosting effect transfers the material from the feed section to the bending section, compensating for the thinning of the tube wall during the bending process. A new theoretical model of tube bending and thinning under boost conditions is proposed to explain this coupling effect. The relative error between the new theoretical model and the experimental value is less than 1.5%, and the accuracy is improved by 5.3% compared with the traditional no-boost condition. It overcomes the poor accuracy of the existing thinning model when fitting to boosted conditions and reveals the boosted effect's mechanism on the tube thinning.
Developing a Risk Assessment Tool for Cancer-related Venous Thrombosis in China: A modified Delphi-Analytic Hierarchy Process study
Authors: Qin Xiaoli , Gao Xiurong , Yang Yujie , Ou Shunlong , Luo Jing , Wei Hua , Jiang Qian
Published: October 2023

Objective
To develop a Risk Assessment Tool for Cancer-related Venous Thrombosis in China.
Methods
A modified two-round Delphi method was employed to establish consensus within a field to reach an agreement via a questionnaire or by interviewing a multidisciplinary panel of experts by collecting their feedback to inform the next round, exchanging their knowledge, experience, and opinions anonymously, and resolving uncertainties. Furthermore, The AHP (Analytic Hierarchy Process) was used to determine the final quality indicators' relative importance.
Results
The expert's positive coefficient was 85.19% in the first round and 82.61% in the second round, with authoritative coefficients of 0.89 and 0.92 in the respective surveys. The P-value of Kendall's W test was all less than 0.001 for each round, and the W-value for concordance at the end of the two rounds was 0.115. The final Risk Assessment Tool for Cancer-related Venous Thrombosis consisted of three domains, ten subdomains, and 39 indicators, with patient factors weighing 0.1976, disease factors weighing 0.4905, and therapeutic factors weighing 0.3119.
Conclusion
The tool is significantly valid and reliable with a strong authority and coordination degree, and it can be used to assess the risk of cancer-related VTE and initiate appropriate thrombophylactic interventions in China.
Artificial intelligence-based counting algorithm enables accurate and detailed analysis of the broad spectrum of spot morphologies observed in antigen-specific B cell ELISPOT and FluoroSpot assays
Authors: Karulin Alexey Y , Katona Melinda , Megyesi Zoltán , Kirchenbaum Greg A. , Lehmann Paul V.
Published: October 2023

Antigen-specific B cell ELISPOT and multicolor FluoroSpot assays, in which the membrane-bound antigen itself serves as the capture reagent for the antibodies that B cells secrete, inherently result in a broad range of spot sizes and intensities. The diversity of secretory footprint morphologies reflects the polyclonal nature of the antigen-specific B cell repertoire, with individual antibody-secreting B cells in the test sample differing in their affinity for the antigen, fine epitope specificity, and activation/secretion kinetics. To account for these heterogeneous spot morphologies, and to eliminate the need for setting up subjective counting parameters well-by-well, CTL introduces here its cutting-edge deep learning-based IntelliCount™ algorithm within the ImmunoSpot® Studio Software Suite which integrates CTL’s proprietary deep neural network. Here, we report detailed analyses of spots with a broad range of morphologies that were challenging to analyze using standard parameter-based counting approaches. IntelliCount™, especially in conjunction with high dynamic range (HDR) imaging, permits the extraction of accurate, high-content information of such spots, as required for assessing the affinity distribution of an antigen-specific memory B cell repertoire ex vivo. IntelliCount™ also extends the range in which the number of antibody-secreting B cells plated and spots detected follow a linear function; that is, in which the frequencies of antigen-specific B cells can be accurately established. Introducing high-content analysis of secretory footprints in B cell ELISPOT/FluoroSpot assays therefore fundamentally enhances the depth in which an antigen-specific B cell repertoire can be studied using freshly or cryopreserved primary cell material, such as peripheral blood mononuclear cells.
Polygenic risk score-assessment of drug induced hepatotoxicity in high-risk acute lymphoblastic leukemia
Authors: Aslam Sara , Sarwar Sumbal , Ahmed Mehboob , N.A. Shabana
Published: October 2023

Introduction: Genetic variations are associated with an increasing risk of asparaginase hepatotoxicity in acute lymphoblastic leukemia (ALL). The polygenetic risk assessment (PRS) of the representative genetic variants can contribute to increasing risk prediction to personalize the treatment. Herein, we estimated the single variants-phenotype and polygenetic-phenotype analysis.
Materials and methods: A total of 216 high-risk group acute lymphoblastic leukemia patients that have undergone remission induction therapy were recruited. The asparaginase hepatotoxicity assessment was based on serum characteristics and the presence of hepatomegaly. Genotyping was performed and genotype-phenotype associations were further evaluated to include four genetic contrast models (co-dominant, recessive, dominant and over-dominant) and polygenetic risk score.
Results:Our results demonstrated that SOD2 rs4880, PNPLA3 rs738409 and ABCC1 rs4148350 allele frequency had significantly protective impact whereas the ABCG2rs2231142 variant has risk causing impact with the hepatotoxicity as compared to the non-hepatotoxicity group. The genetic contrast analysis showed that SOD2rs4880 and PNPLA3 rs738409 variants were significantly associated with a recessive model, ABCC1 rs4148350 variant with the dominant model, ABCG2rs2231142 variant have shown no significant association with hepatotoxicity. The polygenetic risk score assessment demonstrated that the cumulative impact of a higher number of variants (4-8) has higher polygenic risk scores among the hepatotoxicity group. The receiver operating curve (ROC) demonstrated that the area under the ROC curve does not show statistical significance (p=0.07, CI= 0.26-0.49), suggesting the absence of bias in the analysis.
Conclusions: In conclusion, our PRS was strongly associated with asparaginase hepatotoxicity in ALL. The PRS provide means to identify those individuals at greater risk of hepatotoxicity and this information will contribute to personalizing treatment in the future
Modeling 4HeN clusters with wave functions based on neural networks
Authors: Freitas William , Vitiello Silvio Antonio , Abreu Bruno
Published: October 2023

A recently introduced neural network-based trial wave function, in combination with the variational Monte Carlo method, is applied to clusters of helium atoms of several sizes. Energies of clusters ranging from 11 to 24 atoms are reported in excellent agreement with those of the droplet model obtained with diffusion Monte Carlo. The abilities of neural networks to recognize patterns and relationships from distinct input features are explored, including identifying radial symmetry without explicitly considering it in the network inputs. The relation between data representation and the learning process is investigated, showing that high-quality data representations are critical for the efficient use of neural networks.
Triglyceride Glycemic Index and hearing threshold shifts of adults in the United States: A cross-sectional study
Authors: Pan Jia-ying , Chen Yuan , Lin Zhi-he , Lv Bo , Chen Lie , Feng Shao-yan
Published: October 2023

Background: Hearing Loss is a representative human sensory impairment,no studies have paid attention to the correlation between the Triglyceride-Glucose (TyG) index and hearing loss (HL) to date.We conducted this analysis to elucidate the correlation between the Triglyceride Glucose (TyG) index and hearing threshold shifts among US adults.
Methods: Our analysis included 1,226 adults (age range: 20 to 69 years old) from the 2015–2016 National Health and Nutrition Examination Survey (NHANES) data. TyG index was scored into three quartiles. HL referred to the case of pure-tone average (PTA) ≥ 20 dB at 0.5, 1, 2, 4 kHz in the better ear. Weighted univariate analysis, weighted multivariate linear regression analyses as well as smooth curve fittings evaluated the associations between TyG index and PTA hearing threshold shifts.
Results: TyG index is non-linearly related to speech-frequency and high-frequency PTA,which are inversely associated with the TyG index before reaching the turning point. With the TyG index exceeding the turning point, the speech-frequency and high-frequency PTA show an uptrend as the TyG index elevates.
Conclusion: In our analysis, both very low and very high TyG index levels show a relevance to increased speech-frequency and high-frequency PTA, consequently elevating the risk of HL.
An Assessment of Public Experiences and Expectations with Physicians: A Cross Sectional Study from Karachi, Pakistan
Authors: Irshad Hammad Atif , Mahar Muhammad Umar , Jahangir Arshia , Aamir Syed Roohan , Jamil Muhammad Abdullah , Ahsan Khizer , Taufiq Maliha , Ahmed Abdullah , Golani Shilpa , Amir Sehba , Kakar Wasila Gul , Ali Abida , Nafees Asaad Ahmed
Published: October 2023

Background: Although physicians are highly regarded members of society, patients are not always satisfied with their care, suggesting a mismatch between the public’s expectations and reality. Thus, the aim of this study was to determine the public’s expectations regarding roles and responsibilities of a physician, to assess patient experiences, and to evaluate factors associated with the two outcomes.
Methods: A cross-sectional study was conducted via face-to-face structured interviews from July 14th to August 2nd, 2023, in Karachi, Pakistan. 424 consenting adults were approached and enrolled by visiting public spaces (malls, parks, hospitals, and residential buildings). The questionnaire consisted of sociodemographic characteristics, a modified Exceptional Good Doctor Likert, hospital visit information, and Patient Picker-15 (PPE-15) sections. The Likert and PPE-15 sections were scored through pre-decided criteria for expectations and experience, respectively, and categorized using a median cut-off into high and low expectations and negative and positive experiences, respectively for simple and multiple logistic regression.
Results: A median score of 30.5/ 34 (IQR = 3.3) was found for expectations and 4/ 14 (IQR= 4) for experiences. Significant factors associated with high expectations were older age groups (OR=4.54 [1.18-17.50]) and higher monthly household incomes (0.40 [0.20-0.79]), while the odds of negative experiences were lower after visits to emergency departments (0.38 [0.18-0.84]) and private health care centers (0.31 [0.13-0.70]).
Conclusion: These results suggest that the public has high expectations from physicians, however their experiences are not always positive. Initiatives to develop a patient-centric ethos are needed for which we outline recommendations to both the public and physicians respectively.
High strength hydrogel using phenolated lignin
Authors: Hany Lubna Jahan Sarkar , Rahman M Mostafizur , Popy Razia Sultana , Ferdous Taslima , Sarker Ashis Kumar , Jahan M Sarwar
Published: October 2023

In this investigation, lignin was phenolated and lignin based PVA hydrogels was synthesized. The highest yield in phenolation was found to be 123% at 10% sulfuric acid charge and L/P ratio of 1/4 at 120°C. FTIR spectra showing the increasing intensity of the bending vibration of phenolic hydroxyl group (O–H) at 1356 cm− 1 indicated the successful phenolation of lignin. A remarkable difference was observed in hydrogel preparation between phenolated (PhL) and nonphenolated lignin (L). Phenolated lignin had 98% yield while nonphenolated lignin yielded 88% at 1:1 L/PVA ratio. At L/PVA ratio of 2:1, nonphenolated lignin did not form stable hydrogel and remained very soft galley like liquid after 24 h of reaction. However, phenolated lignin formed stable hydrogel up to 5:1 L/PVA ratio with 78% yield. L/PVA hydrogel had higher swelling ratio in comparison with PhL/PVA hydrogel. At the lignin to PVA ratio of 1:2, the swelling ratio was 3101% and 4417% for phenolated and nonphenolated lignin hydrogels.
Identification and characterization of TOR in Macrobrachium rosenbergii and its role in muscle protein and lipid production
Authors: Dai Xilin , Li Xuenan , Yin Danhui , Chen Xin , Wang Linwei , Pang Luyao , Fu Yuanshuai
Published: October 2023

The recent scarcity of fishmeal and other resources means that studies on the intrinsic mechanisms of nutrients in the growth and development of aquatic animals at the molecular level have received widespread attention. The target of rapamycin (TOR) pathway has been reported to receive signals from nutrients and environmental stresses, and regulates cellular anabolism and catabolism to achieve precise regulation of cell growth and physiological activities. In this study, we cloned and characterized the full-length cDNA sequence of the TOR gene of Macrobrachium rosenbergii (MrTOR). MrTOR was expressed in all tissues, with higher expression in heart and muscle tissues. In situ hybridization also indicated that MrTOR was expressed in muscle, mainly around the nucleus. RNA interference decreased the expression levels of MrTOR and downstream protein synthesis-related genes (S6K, eIF4E, and eIF4B) (P < 0.05) and the expression and enzyme activity of the lipid synthesis-related enzyme, fatty acid synthase (FAS), and increased enzyme activity of the lipolysis-related enzyme, lipase (LPS). In addition, amino acid injection significantly increased the transcript levels of MrTOR and downstream related genes (S6K, eIF4E, eIF4B, and FAS), as well as triglyceride and total cholesterol tissue levels and FAS activity. Starvation significantly increased transcript levels and enzyme activities of adenylate-activated protein kinase and LPS and decreased transcript levels and enzyme activities of FAS, as well as transcript levels of MrTOR and its downstream genes (P < 0.05), whereas amino acid injection alleviated the starvation-induced decreases in transcript levels of these genes. These results suggested that arginine and leucine activated the TOR signaling pathway, promoted protein and lipid syntheses, and alleviated the pathway changes induced by starvation.
The estimated mediating roles of anemia-related variables in the association between kidney function and mortality: a National Health and Nutrition Examination Survey (NHANES) study
Authors: Kim Yae Hyun , Lee Whanhee , Kim Kyun Young , Kim Yaerim , Ko Ara , Weon Boram , Lee Jeonghwan , Jin Wencheng , Kim Dong Ki , Kim Yon Su , Lim Chun Soo , Lee Jung Pyo
Published: October 2023

Background and objectives
Anemia is a common complication of chronic kidney disease (CKD). However, it is difficult to assess the contribution of anemia in CKD patients on long-term outcomes, such as mortality and morbidity, because kidney function affects outcomes directly and indirectly. This study evaluated the mediating effect of anemia in the relationship between CKD and clinical outcomes.
Design, setting, participants, and measurements
We used NHANES data from 1999 through 2014 and included adults aged ≥ 20 years. The percent mediating effect of four biomarkers indicative of anemia (hemoglobin [Hb], hematocrit [Hct], red cell distribution width [RDW], and mean corpuscular hemoglobin concentration [MCHC]) was examined by comparing the hazard ratios from a biomarker-adjusted model.
Results
Of the 38,951 participants, all-cause death occurred in 4,997. Cox proportional hazard models revealed a higher risk of all-cause mortality in the > 45 years and CKD groups than in the early CKD group. Together, the levels of Hb and Hct were inversely related to all-cause mortality, and RDW was related to mortality. The single mediation analysis showed that the mediation effects of anemia indicators on CKD and all-cause mortality in the elderly (> 65 years) population were greater than those in the general population. Similarly, in the multimediation analysis, the combined mediation effect of anemia was higher in the elderly (> 65 years) and CKD group than in the general population.
Conclusion
This study showed that the mediating effects of anemia increased proportionally to the CKD stage. Additionally, we suggest possible mechanism of anemia on CKD, which shed light on a new therapeutic ways although it is necessary to explore the effects of other potential mediating factors on kidney outcomes.
Construction of a prognostic model based on cuproptosis-related patterns for predicting survival, immune infiltration, and immunotherapy efficacy in breast cancer
Authors: Tang Yuanyuan , Lv Chunliu , Luo Zhenhua , Li Zan , Yu Junyi
Published: October 2023

Background
Breast cancer is now the most common and lethal malignancy among women worldwide. Cuproptosis is a newly identified copper-dependent programmed cell death and has been found to be closely associated with the development of cancer. However, reports describing cuproptosis regulatory mechanism on breast cancer are still lacking. In this study, we aimed to establish a prognostic model for patients with breast cancer to improve risk stratification.
Methods
The mRNA expression data was downloaded from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. Consensus clustering was utilized to identify patterns based on cuproptosis-related genes (CRGs). Significant modules and key genes were screened by WGCNA analysis and differentially expressed genes (DEGs) analysis. Cox regression was used to construct prognostic model, and time-dependent receiver-operating characteristic and Kaplan-Meier analyses were used to evaluate its prediction ability. Functional pathways, immune cell infiltration, tumor purity, tumor mutation, tumor heterogeneity and drug sensitivity prediction between the two risk groups were also analyzed.
Results
Two cuproptosis patterns with distinct prognosis were identified, and the top 21 DEGs that were most significantly and survival associated between the two patterns were screened for constructing our prognostic model. The risk score based on the prognostic model exhibited negative correlation with survival. Enrichment analysis showed that multiple immune related pathways were mainly enriched in the low-risk group. In addition, patients in the low-risk group presented more abundant immune cell infiltration, higher stromal component, lower tumor purity, cancer stemness, tumor mutational burden, and tumor heterogeneity, perhaps associated with their better prognosis. Finally, significant differences of IC50 were also observed between patients in high- and low-risk groups who received chemotherapy and targeted therapy drugs.
Conclusions
These findings in our study may provide evidence for further research and individualized management of breast cancer.
MIFormer: An Effective Semantic SegmentationNetwork for Foggy Weather conditions
Authors: Ge Shilei , Huo weiwei , Lu Bing , Gong Guoqing
Published: October 2023

Reliable operation is a key metric for autonomous driving, but the factors related to the environment such as weather and lighting can impair the perception capability of autonomous vehicles. Unsupervised adaptation in foggy circumstances is difficult due to the significant fluctuations in the scene's visibility caused by weather conditions, including smog, fog, and haze. This paper presents an effective network using multi-teacher intermediate domain adaptation (MIFormer), which offers a fresh approach to adapting semantic segmentation for the purpose of handling dense foggy scenes. This network integrates training from an intermediate domain to reduce the domain gap caused by heavy fog weather. To further increase segmentation accuracy, we propose three training strategies: Rare Class Sampling, Multi-teacher knowledge distillation, and Mixup improved by Uncertainty principle. We assess the performance of the suggested model across scenarios involving the adaptation from actual clear-weather scenes to real foggy scenes, as well as from synthetic non-foggy images to real foggy scenes. The results have demonstrated that MIFormer’s performance in semantic segmentation with foggy images is better than that with ResNet-38, BDL, CBST, MLST and FogAdapt. In particular, when adhering to the standard configurations and comparing against some mainstream methods, MIFormer achieves a segmentation performance of 69.1 mIoU adapted from GTA to foggy-Cityscapes and 61.8 mIoU adapted from Synthia to foggy-Cityscapes. Additionally, it can even segment rare classes effectively, such as train, bus, and truck.
Effectiveness of Conservative Treatment in Patients with AOSpine Type A2 and A3 Fractures of the Thoracic and Lumbar Spine Without Neurological Deficit: A Protocol for a Prospective Cohort Study
Authors: Grin Andrey , Pogonchenkova Irena , Karanadze Vasiliy , Lvov Ivan , Talypov Aleksandr , Kordonskiy Anton , Abdrafiev Rinat , Makarova Marina , Filippov Maksim , Manuilov Vadim
Published: October 2023

Introduction:
One of the important yet unresolved questions is the choice between conservative and surgical treatment for compressive and burst fractures. Published prospective studies to date have provided contradictory evidence. Hitchon et al. demonstrate the relative superiority of conservative treatment in the long term, Siebenga et al. favor surgery, and Shen et al. suggest no difference. Currently, according to the clinicaltrials.gov database, only two active multicenter cohort studies are dedicated to this issue, and three more were terminated in the years following the start of the COVID-19 pandemic. This fact indicates the high relevance and active interest of the surgical community in this issue.
Methods and analysis.
This study is a prospective cohort study. All enrolled subjects will be divided into two concurrent groups based on the treatment technique applied. The main group (prospective) will consist of patients who underwent conservative therapy. The control group (historical control) will be comprised of patients who underwent surgery previously at the Sklifosovsky Research Institute for Emergency Medicine. In total, 80 patients (40 per group) are planned to be enrolled in the study. The primary endpoint is the Oswestry Disability Index dynamics at the end of the 12-month follow-up. Secondary outcomes will be assessed using the SF-36 scale and EQ-5D-5L. Additional parameters will include sagittal balance of the spine, fusion results, total cost of treatment, and hospital stay over one year. Follow-up examinations will be performed at 3, 6, and 12 months.
Ethics and dissemination.
The current study will be conducted in accordance with the Helsinki Declaration of the World Medical Association. The provided protocol was approved by the local ethics committees of the Sklifosovsky Research Institute for Emergency Medicine (Approval No. 5–23 20.09.2023) and the Moscow Scientific and Practical Center for Medical Rehabilitation, Restorative and Sports Medicine (Approval No. 7/1 16.10.2023). The preliminary and final results of the study will be presented in peer-reviewed neurosurgery and spinal journals and at relevant international conferences.
Trial registration number
NCT06059820
Xylobiose treatment triggers a defense-related response and alters cell wall composition.
Authors: Dewangan Bhagwat Prasad , Gupta Arunima , Sah Rajan Kumar , Das Shouvik , Kumar Sandeep , Bhattacharjee Saikat , Pawar Prashant Anupama-Mohan
Published: October 2023

Plant cell wall-derived oligosaccharides, i.e., damage-associated molecular patterns (DAMPs), could be generated after pathogen attack or during normal plant development, perceived by cell wall receptors, and can alter immunity and cell wall composition. Therefore, we hypothesised that xylo-oligosaccharides (XOS) could act as an elicitor and trigger immune responses. To test this, we treated Arabidopsis with xylobiose (XB) and investigated different parameters. XB-treatment significantly triggered the generation of reactive oxygen species (ROS), activated MAPK protein phosphorylation, and induced callose deposition. The combination of XB (DAMP) and flg22 a microbe-associated molecular pattern (MAMP) further enhanced ROS response and gene expression of PTI marker genes. RNA sequencing analysis revealed that more genes were differentially regulated after 30 min compared to 24 h XB-treated leaves, which correlated with ROS response. Increased xylosidase activity and soluble xylose level after 30 min and 3 h of XB-treatment were observed which might have weakened the DAMP response. However, an increase in total cell wall sugar and a decrease in uronic acid level was observed at both 30 min and 24 h. Additionally, arabinose, rhamnose, and xylose levels were increased in 30 min, and glucose was increased in 24 h compared to mock-treated leaves. The level of jasmonic acid, abscisic acid, auxin, and cytokinin were also affected after XB treatment. Overall, our data revealed that the shortest XOS can act as a DAMP, which triggers the PTI response and alters cell wall composition and hormone level.
Management of Mucocele by Laser- A Case Report
Authors: Srivastava Dr. Vivek , Sahney Dr. Tanu , Sharma Dr. Aaron , Dr. Rameswari Acharya
Published: October 2023

Abstract:

Mucoceles are benign cystic lesions developing from minor salivary glands and commonly encountered in dental practice. Removal of mucoceles can be accomplished using various surgical methods, including scalpel excision, electrocautery, cryotherapy, and laser surgery. Diode lasers have been found to be a safe and effective treatment modality for mucocele removal due to their precise and minimally invasive nature. This article aims to discuss the use of diode lasers for excision of mucocele.

Keywords- Mucocele, Cystic lesion, Excision, Soft tissue diode laser, SiroLaser Blue.

Source of support- Nil

Conflict of interest- None declared

Ethical clearance- Approved by Intuitional Ethical Committee