bluuebunny/crossref_metadata_2025 huggingface dataset:
An In-Position Measurement Method of Point Replacing Surface for Triple Eccentric Butterfly Valve Precision Machining
Authors: Wang Dong , Feng Jingyang , Guo Minglong , Wei Zhaocheng , Gao Bin
Published: September 2023

The machining quality of sealing surface of triple eccentric butterfly valve is crucial to its the sealing performance. Especially, the measuring of sealing surface size is the key to assess the machining quality. Due to the special structure of triple eccentric butterfly valve, the sealing surface size of triple eccentric butterfly valve is difficult and inaccurate to measure in position, which makes it difficult to ensure the machining quality of triple eccentric butterfly valve sealing surface. This will affect the sealing performance of triple eccentric butterfly valve, and result in poor bidirectional sealing, non-interchangeability, and lower machining productivity of the bodies and discs. Based on the above problems, this paper proposes a new measuring method for sealing surface size, i.e., in-position measuring method of point replacing surface. The reliability of method is analyzed and proved from the level of design principle of triple eccentric butterfly valve. Further, the tooling fixture and in-position measuring device of sealing surface size are designed and manufactured based on the measuring method of the point replacing surface. Different from the existing assembling boring process, this paper designs and manufactures a new boring tooling fixtures and develops an integrated process of measuring and machining. After the preliminary measuring and machining test, the reproducibility of the results was good, parts interchangeability and bidirectional sealing could be realized. And the application of this machining process significantly shortened the machining time and increases the machining efficiency by 25%.
Preliminary metabolomics-based predictive models for myelosuppression in breast cancer patients with different anthracycline chemotherapy
Authors: Li Pan , Lao Si xian , qin Lulu , Guo Yi , Wu Yu feng , Jia Wen bin , Huang Min , Zhong Yan , Zhong Guo ping , Zeng Weiwei
Published: August 2023

Background:
Myelosuppression is a common adverse effect in breast cancer patients receiving anthracyclines combined with cyclophosphamide chemotherapy. Screening potential biomarkers and building predictive models have implications for clinical management of myelosuppression.
Methodology:
This study collected 103 breast cancer patients in Shenzhen, China, from September 2020 to January 2022, including two different chemotherapy (Epirubicin or Doxorubicin). The plasma samples were collected 48 hours after chemotherapy. Plasma metabolomics were measured using Ultra-High-Performance Liquid Chromatography-Tandem Q-Exactive. After identification of metabolites and screening of potential differential metabolites, we mapped the key pathways. Further, we established a LASSO-logistic predictive model for myelosuppression.
Results:
In the group of patients treated with doxorubicin, we identified 19 differential metabolites. These metabolites were primarily associated with 6 metabolic pathways, including sphingolipid metabolic pathway, glycine, serine and threonine metabolic pathway, glycerol phospholipid metabolic pathway, tryptophan metabolic pathway, primary bile acid biosynthesis pathway and purine metabolic pathway. From these, a final logistic regression model was developed, incorporating seven variables. This model exhibited an accuracy of 84.91% in predicting chemotherapy-related myelosuppression, with an impressive area under the ROC curve of 0.9571. Similarly, in patients who received epirubicin, we uncovered 20 differential metabolites that were linked to 14 metabolic pathways, encompassing taurine and hypotaurine metabolism, D-glutamine and D-glutamic acid metabolism, and more. A final logistic regression model was constructed, encompassing 12 variables. This model demonstrated an accuracy of 82.35% in predicting the occurrence of chemotherapy-related myelosuppression, with an area under the ROC curve reaching 0.9198.
Conclusion:
In this study, potential biomarkers and metabolic pathways related to myelosuppression were screened by non-targeted metabolomics. The prediction models of myelosuppression in different chemotherapy populations was constructed, and the models demonstrated robust discriminatory and predictive capabilities. Our novel findings suggested that metabolomics provided unique insights into formulating individualized medication strategies for anthracyclines combined with cyclophosphamide in breast cancer patients.
An UHPLC-QE-Orbitrap-MS method for accurate quantification of short-chain fatty acids in serum from an older Chinese population
Authors: Wang Sheng , Feng Rui , Kong Li , Zhou Rui , Hu Fang-ting , Sun Shu-Jing , Chen Guan-Jun , Tao Fang-Biao , Liu Kai-Yong
Published: September 2023

Short-chain fatty acids (SCFAs), such as acetic acid, propionic acid, lactic acid, β-hydroxybutyric acid, and crotonic acid, play key biological roles and are also strongly associated with the maintenance of health and the development of age-related diseases. However, an accurate method for SCFA detection in human serum is lacking. Herein, we developed an UHPLC-QE-Orbitrap MS method based on 3-nitrophenylhydrazine derivatization in negative electrospray ionization through parallel reaction monitoring mode for the simultaneous detection of 11 SCFAs in the serum, and the analysis was performed on an Agilent Proshell 120 EC-C18 column (2.1 mm × 100 mm, 2.7 µm). Three pairs of isomers—isobutyric and butyric acid, isovaleric and valeric acid, and isocaproic and caproic acid—were completely separated in 20 min in a single run. Our method exhibited satisfactory linearity (r > 0.99) for all analytes, and both intrabatch and interbatch accuracies (73.74–127.9%) and precisions (˂21%) were acceptable. The extraction recoveries of all analytes were 90.80–111.7%, and the IS-normalized matrix effects were 74.43–116.9%. This optimized method was successfully applied to a cohort of 1021 older Chinese individuals. Our results may further the understanding of the metabolic phenotypes associated with SCFAs in other populations.
Effects of SMILE and FS-LASIK on choroidal thickness and blood flow density in patients with myopia
Authors: Yang Shirui , Qian Tiantian , Tang Min , Zhang Jing , Hou Jie , Dong Yahui , Lei Yulin
Published: September 2023

Purpose: This study aimed to evaluate the changes in choroidal thickness and blood flow density after small-incision lenticule extraction (SMILE) and femtosecond laser-assisted in-situ keratomileusis (FS-LASIK) using an optical coherence tomography system (OCT).
Methods: In this study, patients who underwent myopia surgery between May 2021, and October 2022, were randomly selected. The patients were divided into two groups on the basis of surgical method: SMILE group and FS-LASIK group. The diopter, axial length of the eyeball, choroidal thickness, and blood flow density of the patients were tracked and measured before the surgery, and at 1 week, 1 month, and 3 months after the surgery.
Results: A total of 56 patients (112 eyes) were included in the study, with 35 individuals (70 eyes) in the SMILE group and 21 individuals (42 eyes) in the FS-LASIK group. The postoperative diopter of both groups showed a significant improvement (P < 0.05), and the axial length of the eyes was shorter than the baseline level (P < 0.05). After the operation, the choroidal thickness of the two groups showed a trend of first increasing and then decreasing at multiple measurement sites, and only few sites were basically stable after the thickness increased. No significant change was observed in the choroidal blood flow density between the two groups after the operation.
Conclusion: In this study, the axial length of the eye shortened after SMILE and FS-LASIK, the thickness of the choroid at only few sites increased and remained stable, and the choroidal blood flow density did not change significantly. The choroid was less affected after corneal refractive surgery.
The combined effects of temperature and exogenous bacterial sources on mortality in Crassostrea virginica under severe hypoxia
Authors: Steeves Laura , Winterburn Keryn , Coffin Michael R. S. , Babarro Jose M. F. , Guyondet Thomas , Comeau Luc A. , Filgueira Ramon
Published: August 2023

In aquatic environments, low dissolved oxygen concentrations can result in depressed bivalve defense systems while promoting anaerobic bacterial growth, ultimately leading to increased bivalve mortality rate. There are discrepancies between laboratory and field studies examining bivalve mortality under low oxygen conditions, possibly leading to an underestimation of the impact of hypoxic events. Indeed, laboratory studies typically exclude potentially influential factors that may affect survival, e.g., exogenous bacteria. In this study, adult oyster (Crassostrea virginica, 60 ± 5 mm shell length) survivability was investigated during severe hypoxia (< 0.1 mgO2L− 1) in combination with high temperature (20˚C vs. 28˚C), and the introduction of a secondary bacteria source (anoxic marine sediment). In addition, an experiment tested if the conventional methodological approach in these types of experiments, i.e., removing dead bivalves from the population, impacted survivability. Results demonstrate that at the highest tested temperature (28˚C) the effect of a secondary bacterial source did not significantly impact survival rates (time taken for half the population to die (LT50) (LT50: 9.7 ± 0.5 vs. 10.9 ± 0.4 days secondary bacterial source vs. no secondary bacterial source, respectively). However, at the lower temperature (20˚C) the presence of a secondary bacterial source did decrease survival rates (LT50: 9.8 ± 0.4 vs. 13.7 days bacterial source vs. no secondary bacterial source, respectively). Additionally, dead oyster removal increased oyster survivability in all treatments relative to when they were not removed. This study highlights the mechanisms by which mortality rates are underestimated in laboratory compared to field studies.
Comparative Evaluation of Mechanical Injury Methods for Establishing Stable Tracheal Stenosis Animal Models
Authors: Lin Hongbin , Ainiwaer Mailudan , Jiang Zheng , Wang Zhenyan , Liu Jun , Chen Fei
Published: September 2023

To compare the stability of different mechanical injury methods for establishing tracheal stenosis animal models with endoscopic assistance and explore the feasibility of tracheal stoma in the establishment of tracheal stenosis animal models.Twenty-one healthy adult New Zealand white rabbits were randomly divided into an experimental group and a control group. In the experimental group, eight rabbits underwent tracheal incision followed by steel brush scraping with endoscopic assistance. In the control group, nylon brush scraping was performed. The control group was further divided into two subgroups (Group A and Group B). Group A consisted of eight rabbits undergoing scraping without tracheal stoma, while Group B included five rabbits undergoing scraping followed by tracheal stoma. All experimental rabbits were observed under endoscopy for tracheal stenosis changes at 7 days, 14 days, and 21 days after scraping. On the 21st day, the rabbits were euthanized, and histological observations were conducted after HE staining of the specimens.All 16 rabbits in the group without tracheal stoma survived well. The experimental group showed significant stenosis compared to Group A of the control group (P<0.05). All rabbits in Group B of the control group died at different time points after the operation. HE and Masson staining of the narrowed tracheal specimens revealed a small amount of inflammatory cell infiltration in the submucosa, along with fibroblast proliferation and abundant deposition of collagen fibers.Compared to nylon brush scraping, steel brush scraping with endoscopic assistance is a more effective method for mechanically inducing stable and pronounced tracheal stenosis in animal models. However, the survival of experimental rabbits undergoing tracheal fistula remains challenging and requires further exploration.
Single DC-Link based 5-Level MLI topology for Renewable and grid Applications with fewer Switches
Authors: TIWARI ANURAG
Published: September 2023

This article describes a 5-level single DC source multilevel inverter(SDS-MLI) with fewer components and optimum efficiency. MultipleDC source MLI topologies are presently deemed unsuitable for arange of applications, such as renewable energy (RE) conversion systemsand grid applications, while single DC source MLI topologies aremore suitable. Existing MLI circuits have more active/passive components,but the SDS-MLI design employs a level-doubling network,requires fewer components, and reduces the DC-link voltage for gridapplications. The SDS-MLI uses one capacitor, six switches, and aDC supply. A primary control method enforces a well-known phasedisposition carrier arrangement to actualize the presented configuration.Existing systems are evaluated based on the number of activeand passive components, their efficiency, capacitor voltage, and voltagestress. In comparison to existing topologies, SDS-MLI has fewercomponents, a lower capacitor voltage, and less TSVs to achieve anefficiency of 98.66%. MATLAB/Simulink and experimental setups areused to verify the SDS-MLI architecture. On the basis of experimentalsetup and simulation, the number of load voltage & load currentwaveforms under various situations such as variable load, varied inputsupply, different frequencies, and different modulation indexes are shown.
Biodegradable flexible foam: novel material based on cassava TPS obtained by extrusion
Authors: Alban-Bolaños Pedro , Ayala-Aponte Alfredo Adolfo , Villada-Castillo Héctor Samuel , Rodríguez-Herrera Raúl , Ávalos-Belmonte Felipe , Solanilla-Duque José Fernando
Published: September 2023

Thermoplastic foams made from petrochemical polymers are commonly commercialized in the market, which, due to their chemical nature, require hundreds of years to degrade and therefore end up accumulating and polluting the environment. Therefore, the present research sought to develop a biodegradable foam from thermoplastic cassava starch, biodegradable polyester and wheat gluten. Initially, an extreme vertex blend design was run, which comprised 60 to 70% thermoplastic starch (TPS), 30 to 40% biodegradable polyester and 0 to 5% wheat gluten, the foam was obtained by extrusion and evaluated for expansion rate, bulk density, damping index and morphology. A thin layer of rubber latex was applied to the foamed material with the most outstanding properties in order to reduce moisture adsorption, and its biodegradability was also evaluated. The results indicated that with the addition of 70% TPS, 30% polyester and 0% wheat gluten it was possible to obtain by extrusion a flexible thermoplastic foam with high radial expansion rate and low bulk density. Impregnation of the foam with natural rubber latex created an impermeable layer that helped to decrease moisture adsorption; however, there was an increase in compressibility. Also, it was found that this foam met the biodegradability condition, since it presented a percentage of mineralization in relative terms of 97.59% in less than 180 days.
Home- and Community-based Care in the New Generation of Medicaid Administrative Data
Authors: Wang Sijiu , Konetzka R. Tamara
Published: August 2023

This study aimed to assess the quality of Home and Community-Based Services (HCBS) data elements within the Transformed Medicaid Statistical Information System Analytical File (TAF) and to devise strategies for improving its research usability. Analyzing Medicaid TAF data from 2016 to 2018, we conducted a retrospective data quality analysis, focusing specifically on HCBS-related data elements. Through secondary data analysis, we identified significant challenges, including considerable missingness and inconsistencies that hamper the effective use of TAF for research purposes. Despite these issues, we developed three approaches that enabled us to identify 94% of 1915(c) waiver claims as HCBS. Our study also revealed considerable cross-state variations in data quality, prompting specific recommendations for utilizing HCBS data within TAF. Ultimately, the study concludes that while challenges exist, applying our recommended strategies can yield data of acceptable quality for most states, particularly in identifying HCBS usage and classifying them into service categories. Given the growing importance of home-based care, there is a pressing need to prioritize improvements in TAF's HCBS data quality to better inform policy and practice.
RETRACTED: Long-Term Time-Series Analysis of Precipitation in Semi-Arid Agra District: Unveiling Climatic Trends from 1922 to 2022
Authors: Gardner Bob Stanley , Soren David Durjoy Lal , Chauhan Nelia Lois , Biswas Brototi , Gardner Shalomin
Published: September 2023

The authors have requested that this preprint be removed from Research Square.
Comparative Analysis of Summer Atmospheric Heat Sources Over the Qinghai-Xizang Plateau from Different Reanalysis Data and Radiosonde Data
Authors: Lei Runzhi , Yu Ye , Li Jianglin
Published: September 2023

The thermal effect of the Qinghai-Tibet Plateau (QTP) affects the regional and global weather and climate. Although some studies have evaluated the vertically integrated atmospheric heat sources (< Q1>) calculated from different reanalysis datasets, an evaluation of the vertical distribution of atmospheric heat sources (Q1) is lacking. In this study, data from 14 radiosonde (TK) sites in the eastern QTP were interpolated to 1o×1o grids using the objective analysis method. The summer Q1 calculated using gridded TK data based on the "inverse algorithm" was compared to those of ERA-Interim, ERA5, JRA55, and CRA40. The applicability of the four reanalysis datasets over QTP was discussed from the perspective of the vertical distribution of Q1. The results show that the vertical profiles of meteorological elements of the four reanalysis datasets correlate well with that of TK, with a correlation coefficient of 0.99. However, the vertical velocities (ω) of the four reanalysis datasets differ greatly, with ω_ERA5 correlating best with ω_TK and having the smallest root mean square error (RMSE). The meridional and zonal mean Q1 and its components (local temperature change, temperature advection, and vertical shear of potential temperature) calculated using ERA5 correlate best with those estimated using TK, and the RMSE is the smallest. The ω and Q1 calculated using high-resolution reanalysis data correlate better with those from TK and have a lower RMSE. Under the same spatial and temporal resolution, ω_ERA5 and Q1_ERA5 correlate best with those of TK, and the RMSEs are the smallest. Among the four reanalysis datasets, ERA5 is more suitable for Q1 analysis in summer on the Eastern QTP.
Exploring causal correlations between inflammatory cytokines and stroke and its subtypes: a Mendelian randomization study
Authors: guo yu , Sun Huaiyu , Shuai Hou , Zhang Wuqiong , Liu Huiqing , Zhu Lixia , Meng Hongmei
Published: September 2023

Background: The causal relationship between inflammatory factors and stroke subtypes remains unclear. This study aimed to analyze the causal relationship between 41 inflammatory factors and these two factors using Mendelian randomization (MR).
Methods: We performed a two-sample MR analysis to assess the causal effects of 41 inflammatory cytokines on stroke and its subtypes and conducted a genome-wide association study (GWAS) data. The inverse-variance weighted (IVW) method was adopted as the main MR method, and we performed a series of two-sample Mendelian randomizations and related sensitivity analyses.
Results:The study indicated some suggestive evidences: using the IVW approach, we found that lower possible levels of IL-4 were positively associated with the occurrence of stroke (odds ratio [OR] = 0.93, 95% confidence interval [CI]:0.88-0.99, p = 0.014), higher interleukin (IL)-1β, IL-12p70 levels may be positively correlated with the occurrence of stroke (OR = 1.09, 95% CI:1.01-1.18, p = 0.027; OR = 1.08, 95% CI:1.02-1.15, p = 0.015). For IS, results showed that lower levels of IL-4, tumor necrosis factor-related apoptosis-inducing ligand were positively associated with the occurrence of possible ischemic stroke (IS) (OR = 0.92, 95% CI:0.87-0.98, p = 0.006; OR = 0.95, 95% CI:0.91-1.00, p = 0.031), higher levels of IL-1β, IL-12p70 and vascular endothelial growth factor (VEGF) may be positively correlated with the occurrence of IS (OR = 1.09, 95% CI:1.00-1.19, p = 0.042; OR = 1.07, 95% CI:1.01-1.15, p = 0.035; OR = 1.06, 95% CI:1.00-1.12, p = 0.034). We found that lower IL-17 levels may be positively associated with an increased risk of intracerebral hemorrhage (ICH) (OR = 0.51, 95% CI:0.28-0.93, p = 0.028). For subtypes of stroke, IS and ICH, higher levels of growth regulated oncogene-α, beta nerve growth factor, IL-18, macrophage colony-stimulating factor, and induced protein 10 upregulated the risk factors while lower levels of IL-2ra and IL-17 upregulated the risk factors.
Conclusion: Our findings confirmed that inflammatory factors play a crucial role in the occurrence of stroke and may provide a new direction for stroke treatment.
Multi-classification-assisted diagnosis of multi-scale lung adenocarcinoma pathological maps based on Scalenet101
Authors: Huang Zijie , Li Jianjun , Yang Liyuan , GUO Jing , Yao Zhen
Published: August 2023

Among all types of cancers, lung cancer is the deadliest cancer with a high mortality rate. Early diagnosis of lung cancer enables its timely and effective treatment, which can help reduce the risk of death. The aim of this research is to propose a deep learning approach for classifying and detecting lung adenocarcinoma tissues. The method was an improved Scalenet101 based on class activation mapping. (I) Scalenet101 classified lung adenocarcinoma tissue images into cancer, stromal and normal categories with the help of the Sigmoid. Then, the performance of Scalenet101 was validated using the pre-trained downstream techniques such as AlexNet, VGG16, VGG19, and ResNet50. (ii) Multi-scale fusion and weight fitting were performed to obtain multi-classification activation maps, which could improve the interpretability and accuracy in lung cancer evaluation. The performance of this model was tested using benchmark lung adenocarcinoma tissue images from WSSS4LUAD. The results showed that the model achieved an absolute classification accuracy of over 93.86% and an F1 score of over 95.44%.
Distinct changes to pancreatic volume rather than pancreatic autoantibody positivity: Insights into immune checkpoint inhibitors induced diabetes mellitus
Authors: Wei Hung-Hui , Lai Ying-Chieh , Lin Gigin , Lin Cheng-Wei , Chang Ya-Chu , Chang Wen-Cheng , Liou Miaw-Jene , Chen I-Wen
Published: September 2023

Background:
Immune checkpoint inhibitors (ICI) are promising treatment options for various cancers. However, their use is associated with immune-related adverse events (irAEs), including ICI-induced diabetes mellitus (ICI-DM). This study aimed to investigate the clinical features of ICI-DM, with a particular focus on alterations to pancreatic volume.
Methods:
We conducted a retrospective review of 2829 patients who received ICI treatment at the Chang Gung Memorial Hospital, Linkou, between January 2014 and December 2021. New-onset diabetes or diabetic ketoacidosis (DKA) was identified in ten patients receiving ICI therapy. Pancreatic volumes were assessed by manual segmentation of computed tomography (CT) images before and after ICI-DM diagnosis.
Results:
Among these ten patients, nivolumab was the most commonly used ICI (50.0%), followed by pembrolizumab (30.0%) and atezolizumab (20.0%). One patient received combination therapy with nivolumab and ipilimumab. The median age was 63.01 years (range: 40.1 − 87.8). ICI-DM developed after a median of 13.5 cycles (range: 2 − 42) of ICI treatment or 9.85 months (range:1.5 − 21.3) since ICI initiation. The initial presentation was DKA in 60.0% of patients. All patients had low or undetectable C-peptide levels (range: <0.033 − 0.133 nmol/L) and were negative for most type 1 diabetes mellitus (T1DM)-related autoantibodies; only one patient tested positive for glutamic acid decarboxylase antibodies. CT imaging revealed significant pancreatic atrophy, with a median pancreatic volume decrease of 19.92% (P = 0.038) from baseline and sustained significant decline at last follow-up (median − 37.14%, P = 0.012).
Conclusions:
ICI-DM is often accompanied by pancreatic atrophy and approximately two-thirds of patients initially present with DKA. Although most patients with ICI-DM do not have T1DM-related autoantibodies, awareness of decreased pancreatic volumes with CT imaging is valuable for predicting diabetic emergencies in patients treated with ICIs.
Trial registration:
This study was approved by the Institutional Review Board of the Chang Gung Memorial Hospital (No.202201766B0).
Detection of retene in Proterozoic strata: a new understanding of its environmental indicator significance
Authors: Wang Jian , Xu Shijing , Wu Nan , Xu Qinghai , Liu Xianfeng
Published: September 2023

Retene is generally recognized as a diagenetic product of abietane-structured diterpenoids originating from terrestrial higher plants (such as conifers) that evolved after the Devonian period. In this study, retene was detected in the Proterozoic strata of the Tarim Basin and the Western Hubei area of the lower Yangtze Platform in China. A gas chromatography-mass spectrometry analysis of 28 Proterozoic (Sinian and Nanhua system) sediment samples collected from China demonstrates that these Proterozoic marine carbonate strata, although absent of input from higher plants, were rich in retene compounds. This finding indicates that diterpenoids, a type of retene precursor, can also be synthesized by Proterozoic algae and bacteria and that terrestrial higher plants are not the only sedimentary provenance of retene. So, retene can no longer serve as a biomarker to distinguish marine and continental sedimentary environments. However, no known retene precursors, such as dehydroabietin, dehydrabietane, simonellite, and tetrahydroretene, were detected in the samples. Therefore, the existence of other unknown types of retene precursors derived from algae or bacteria remains to be investigated.
Investigating the Association between Low-Density Lipoprotein Cholesterol and Pancreatic Cancer Risk: A Mendelian Randomization Study
Authors: Huang Yalong , Peng Yiyun , Yang Guoyuan , Wan Haohao , Fan Wanqi , Ma Yuntao
Published: September 2023

Objective
Mendelian randomization is a method that utilizes genetic variants that are randomly assigned at conception to investigate causal relationships between an exposure (such as low-density lipoprotein cholesterol) and an outcome (such as pancreatic cancer). This study employs a Mendelian randomization approach to investigate the potential relationship between low-density lipoprotein cholesterol (LDL-C) levels and the risk of developing pancreatic cancer.
Methods
The study data were derived from a genome-wide association study (GWAS) meta-analysis dataset, which included 115,078 samples for LDL-C and 218,187 samples for pancreatic cancer. This study utilized several Mendelian randomization (MR) methods, including the inverse variance weighted (IVW), weighted median, weighted mode, and MR-Egger approaches, to examine the potential causal relationship between LDL-C and the risk of developing pancreatic cancer. The odds ratio was used as the measure of association between LDL-C and pancreatic cancer in the MR analyses. MR-PRESSO and leave-one-out sensitivity analyses were conducted to detect horizontal pleiotropy and assess the robustness of the results.
Results
To investigate the causal relationship between LDL-C and pancreatic cancer risk, this study utilized 46 single nucleotide polymorphisms (SNPs) associated with LDL-C as instrumental variables, which were extracted from GWAS (R2 < 0.001, P < 5x10− 8). The F-statistics of all included SNPs were above 10, indicating the absence of weak instrument bias and confirming the reliability of the results. The IVW analysis revealed an odds ratio (OR) of 0.66 [95% confidence interval (CI): 0.44–0.98; P < 0.05], indicating a potential protective effect of LDL-C against pancreatic cancer. Weighted mode and weighted median analyses also demonstrated similar causal relationships with ORs of 0.49 [95% CI: 0.27–0.91, P < 0.05] and 0.47 [95% CI: 0.26–0.82, P < 0.05], respectively. However, the simple mode regression analysis and MR-Egger intercept test did not yield similar results with P > 0.05, suggesting no statistical significance. The funnel plot and MR-Egger intercept did not indicate horizontal pleiotropy or heterogeneity (P = 0.31), further supporting the reliability of the study's findings.
Conclusion
The results of this Mendelian randomization study suggest that high levels of LDL-C may have a protective effect against the development of pancreatic cancer. These findings highlight the potential importance of LDL-C levels in pancreatic cancer prevention and may inform future studies and interventions aimed at reducing pancreatic cancer incidence.
Experiences of and recommendations for LGBTQ+-affirming substance use services: A qualitative study with LGBTQ+ people who use opioids and other drugs
Authors: Paschen-Wolff Margaret M. , DeSousa Avery , Paine Emily Allen , Hughes Tonda L. , Campbell Aimee N.C.
Published: September 2023

Background
Lesbian, gay, bisexual, transgender, queer, and other LGBTQ populations (LGBTQ+; e.g., non-binary individuals) have higher rates of substance use (SU) and disorders (SUD) compared to heterosexual and cisgender populations. Such disparities can be attributed to minority stress, including stigma and discrimination in healthcare settings. LGBTQ+-affirming SU treatment and related services remain limited. The purpose of this qualitative study was to characterize LGBTQ + people’s experiences in SU services and recommendations for LGBTQ+- affirming care.
Methods
We conducted demographic surveys (characterized using descriptive statistics) and individual qualitative interviews with N = 23 LGBTQ + people. We employed a flexible coding approach to describe participants’ experiences with stigma, discrimination, and support within SU services; and participant recommendations for how to make such services LGBTQ+-affirming at the patient-, staff-, and organizational-level. We highlighted components of minority stress and mitigators of adverse stress responses throughout our thematic analysis.
Results
Patient-level experiences included bullying, name-calling, sexual harassment, and physical distancing from peers; and support via community-building with LGBTQ + peers. Staff-level experiences included name-calling, denial of services, misgendering, lack of intervention in peer bullying, and assumptions about participants’ sexuality; and support via staff advocacy for LGBTQ + patients, holistic treatment models, and openly LGBTQ + staff. Organizational-level experiences included stigma in binary gendered program structures; and support from programs with gender-affirming groups and housing, and in visual cues (e.g., rainbow flags) of affirming care. Stigma and discrimination led to minority stress processes like identity concealment and stress coping responses like SU relapse; support facilitated SU treatment engagement and retention. Recommendations for LGBTQ+-affirming care included non-discrimination policies, routine pronoun sharing, LGBTQ+-specific programming, hiring LGBTQ + staff, routine staff sensitivity training, and gender-inclusive program structures.
Conclusions
LGBTQ + people experience stigma and discrimination within SU services; supportive and affirming care is vital to reducing treatment barriers and promoting positive health outcomes. The current study offers concrete recommendations for how to deliver LGBTQ+-affirming care, which could reduce SU disparities and drug overdose mortality overall.
ONT read assembly of the Black Rhino genome
Authors: Kraaijeveld Ken , Bossers Koen , Petrusevski Nikola , Pieterman Stef , Sonsbeek Linda G.R. Bruins-van , Wittink Floyd
Published: September 2023

Objectives: The black rhinoceros (Diceros bicornis) is an endangered mammal for which a captive breeding program is part of the conservation effort. Black rhinos in zoo's often suffer from chronic infections and heamochromatosis. Furthermore, breeding is hampered by low male fertility. To aid a research project studying these topics, we sequenced and assembled the genome of a captive male black rhino using ONT sequencing data only.
Data description: This work produced over 100 Gb whole genome sequencing reads from whole blood. These were assembled into a 2.47 Gb draft genome consisting of 834 contigs with an N50 of 29.53 Mb. The genome annotation was lifted over from an available genome annotation for black rhino, which resulted in the retrieval of over 99% of gene features. This new genome assembly will be a valuable resource in for conservation genetic research in this species.
The Causal Effect of COVID-19 on Chronic Mastoiditis: A Bidirectional Two-Sample Mendelian Randomization-Based Study
Authors: Chen Siyuan , Deng Qin , Lv Hao , Wu Xiaomin , Xu Yingying , Xu Yu
Published: September 2023

Background
In the aftermath of COVID-19, individuals are experiencing long-term complications of the disease, making it imperative to study its organismal consequences. Although there have been sporadic studies with conflicting results on the relationship between COVID-19 and chronic mastoiditis (CM), a comprehensive investigation of this relationship is necessary, as CM can result in severe intracranial infections.
Methods
COVID-19 traits of varying severity were selected as exposures while chronic mastoiditis was selected as the outcome. Bidirectional univariable Mendelian randomization analyses were performed after rigorous screening of instrumental variables. Subsequently, mediation analyses were conducted to further investigate the underlying mechanisms.
Results
Univariable MR analysis suggested that there was a significant positive association between the infected COVID-19 and CM risk (OR = 2.574613, 95% CI 1.326495-4.997100, p = 0.005189). By contrast, the causal effect of hospitalized COVID-19 on CM (OR = 1.336397, 95% CI 1.060450–1.684149, p = 0.013995), as well as the causal effect of severe COVID-19 on CM (OR = 1.145725, 95% CI 0.978811–1.341102, p = 0.090380), are insignificant. Moreover, through mediation analysis, we found that “E-selectin levels” was the mediator of the causal effects of infected COVID-19 on CM (Indirect β = 0.673348, 95% CI, 0.081898–1.264798, the mediated proportion of 70.3%, p = 0.049373).
Conclusion
For the first time, we conducted a study to investigate the causal effects between three COVID-19 traits and chronic mastoiditis. Our findings indicate a significant causal effect of COVID-19 infection on CM. By contrast, the causal effects of hospitalized COVID-19 and severe COVID-19 on CM are insignificant. Moreover, we initially identified “E-selectin levels” as the mediator of the causal effect of infected COVID-19 on CM. Our finding enriches the types of COVID-19 sequelae and helps to prevent mastoiditis caused by COVID-19 in the early stage, thereby eliminating the possibility of intracranial infection and other serious complications.
Security Robustness Evolution of Split Edge-Cloud Neural Networks
Authors: DOUCH SALMANE , ABID MOHAMED RIDUAN , ZINE-DINE KHALID , BOUZIDI DRISS , BENHADDOU DRISS
Published: September 2023

Cloud computing, with its novel presence at the cloud Edge, proves indispensable to the success of the fifth (5G) and sixth-generation (6G) networks. This due to the myriad set of expected applications and required stringent constraints on latency and bandwidth, e.g., eHealth and Automotive vehicles which fall under the 5G URLLC (Ultra Reliable and Low Latency Communication) set. In order to reduce bandwidth usage at the Cloud core network and allow for faster latency responses, edge computing proposes a new servicing paradigm consisting of bringing computation and intelligence near where the end users reside, i.e., at the edge of the cloud. This is achieved by the edge infrastructure’s ability to support a variety of intelligent and computational jobs at the radio access network (RAN) level. However, many AI tasks, particularly those involving deep learning, pose a challenge as they require significantly more memory and processing capacity, which cannot be provisioned at the edge. Only cloud data centers can do. To address this issue, different edge intelligence methods, such as quantization, pruning, distributed inference, etc., have been proposed in the literature. This research investigates split neural networks (SNN), a neural network architecture with numerous early exits. SNN greatly decreases memory and computing, making it a promising NN architecture for edge devices and applications. Moreover, as the use of these SNNs grows, it becomes increasingly essential to study and validate their safety properties, notably their tolerance to small perturbations, before deploying them in safety-critical applications. This paper presents, as far as we know, the first exploratory work on the robustness assessment of split Edge Cloud neural networks. We evaluated SNN robustness using auto_LiRPA an advance neural network verification tool that is base on bounds calculation. We also compared the relative robustness of SNN to a normal NN, considering the many parameters that influence SNN’s robustness. Our experiment results show that SNN not only reduces the average inference time by 3/4. But it also proved to be four to ten times more resilient against adversarial attacks than normal NN.
Synthesis of lead-free Cu/CuFeO 2 /CZTS thin film as a novel photocatalytic hydrogen generator from wastewater and solar cell applications
Authors: Ali Amira H. , Ahmed Ashour M. , Abdelhamied M. M. , Abdel-Khaliek Ahmed A. , Khalik S. Abd El , Abass Safaa M. , Shaban Mohamed , Hasan Fuead , Rabia Mohamed
Published: September 2023

The sewage water is tested as a source of hydrogen production with high efficiency value of 25.44% using Cu/CuFeO2 (delafossite)/CZTS (Cu2ZnSnS4, kesterite) as an investigated photocatalyst. The X-ray diffraction (XRD) analysis of the investigated photocatalyst (Cu/CuFeO2/CZTS) revealed a compact crystalline material as witnessed by the diffraction peaks with high intensities. From the optical characterization, the recorded band gap values of Cu/CuFeO2/CZTS, Cu/CuFeO2, and CZTS are 1.15, 1.97, and 1.43 eV, respectively, inferring an obvious enhancement in the optical properties of the investigated photocatalyst, Cu/CuFeO2/CZTS. The photoelectrochemical (PEC) performance of the investigated photocatalyst for hydrogen (H2) generation was examined in wastewater. The current-time characteristic and the PEC behavior of Cu/CuFeO2/CZTS in dark and under light illumination using various power densities or monochromatic wavelengths, and different temperatures were studied. The current densities (JPh) under light illumination and (Jo) in dark were − 8.0 and − 0.7 mA cm− 2, respectively. The H2 generation rate for Cu/CuFeO2/CZTS electrode was 0.049 mA/h. The thermodynamic parameters, respectively, ΔS*, ΔE, and ΔH* were 28.76 kJ mol− 1 K− 1, 21.0, and 18.28 kJ mol− 1 at 390 nm. The findings of the work hold great promise for addressing the energy production and the hindrances of sewage treatment at the same time.
Role of follicular CD8+ T cells labeled with B cell helper immunotypes in multiple sclerosis and a murine model
Authors: Ding Jia-Qi , Zhang Jun-Qi , Zhao Si-Jia , Jiang Dong-Bo , Lu Jia-Rui , Yang Shu-Ya , Wang Jing , Sun Yuan-Jie , Huang Yi-Nan , Hu Chen-Chen , Zhang Xi-Yang , Zhang Jia-Xing , Liu Tian-Yue , Han Chen-Ying , Qiao Xu-Peng , Guo Jun , Zhao Cong , Yang Kun
Published: September 2023

Background
Multiple sclerosis (MS) has been considered to be a T cell-dependent autoimmune disease of the central nervous system (CNS), and so does the experimental autoimmune encephalomyelitis (EAE) model. Recent studies have revealed a specific subset of CD8 T cells, known as CD8 follicular T cells (CD8+CXCR5+ T), are involved in antiviral, anti-tumor immunity, and systemic autoimmunity. While the role of CD8+CXCR5+ T cells in MS and EAE remains unclear.
Methods
We detected CD8+CXCR5+ T cell frequency in the peripheral blood of relapsing-remitting MS patients and healthy controls by flow cytometry and analyzed its correlation with disease activity. To show the dynamic changes and locations of CD8+CXCR5+ T cells in secondary lymphoid organs and CNS from EAE mice, flow cytometry and multiplexed immunohistochemistry were performed. RNA-seq, co-culture experiments and in vivo adoptive transfer were then conducted to reveal the phenotypes and functions of CD8+CXCR5+ T cells.
Results
Expansion of CD8+CXCR5+ T cells in MS patients and EAE mice was detected during the acute phase. In relapsing MS patients, elevated frequencies of circulating CD8+CXCR5+ T cells were positively correlated with new gadolinium-enhancement lesions of CNS. In EAE mice, CD8+CXCR5+ T cells infiltrated in ectopic lymphoid structures of spinal cords and germinal centers of spleens were positively correlated with clinical score and highly expressed ICOS, CD40L, IL-21 and IL-6. In vitro co-culture experiments and CD8+CXCR5+ T-adoptive mice both confirmed the ability of CD8+CXCR5+ T cells to provide B cell help and contribute to disease progression.
Conclusions
CD8+CXCR5+ T cells which bridged cytotoxic T cells and B cells in MS might be a promising target for developing disease-modifying treatments in the future.
A pair of compound heterozygous IARS2 variants manifesting West syndrome and electrolyte disorders in a Chinese patient
Authors: Zhou Feiyu , Yi Gui , Liu Xiangyu , Sheng Wenchao , Shu Jianbo , Li Dong , Cai Chunquan
Published: September 2023

Background: Aminoacyl -tRNA synthetases (ARSs) are evolutionarily conserved enzymes that ensure the accuracy of the translation process. Isoleucyl-tRNA synthetase 2 (IARS2) gene is a type of ARS that encodes mitochondrial isoleucine-tRNA synthetase. Pathogenic variants in the IARS2 gene are associated with mitochondrial disease which involves a number of patients presenting broad clinical phenotypes. These clinical phenotypes include West syndrome, Leigh syndrome, and Cataract (CA), growth hormone deficiency(G), sensory neuropathy (S), sensorineural hearing loss(S), and skeletal dysplasia syndrome (CAGSSS). Only 29 cases have been reported worldwide, by this case, we further expand the clinical spectrum of IARS2 pathogenic variants.
Methods: Whole exon sequencing was performed on the child with West syndrome. Three-dimensional structure reconstruction and thermodynamic stability prediction were performed to further analyze the relationship between variation and phenotype.
Conclusions: This study further expands the clinical spectrum of IARS2 pathogenic variants. The case summaries help raise clinical awareness of IARS2-associated disease and reduce misdiagnosis.
Single-cell analysis reveals endothelial cell heterogeneity in colorectal cancer: Tip cells drive enhanced angiogenesis and reduced antigen presentation
Authors: Xie Zhenyu , Niu Liaoran , Du Kunli , Chen Ling , Zheng Gaozan , Dai Songchen , Dan Hanjun , Duan Lili , Dou Xinyu , Feng Fan , Zhang Jian , Zheng Jianyong
Published: August 2023

This study aims to uncover the heterogeneity of endothelial cells (ECs) in colorectal cancer (CRC) and their crucial role in angiogenesis, with a special focus on tip cells. Using single-cell RNA sequencing to profile ECs, our data suggests that CRC ECs predominantly exhibit enhanced angiogenesis and decreased antigen presentation, a shift in phenotype largely steered by tip cells. We also observed that an increase in the density and proportion of tip cells correlates with CRC occurrence, progression, and poorer patient prognosis. Furthermore, we identified endothelial cell-specific molecule 1 (ESM1), specifically expressed in tip cells, sustains a VEGFA-KDR-ESM1positive feedback loop, promoting angiogenesis and CRC proliferation and migration. We also spotlight a unique long-tail effect in VEGFA expression: while VEGFAis primarily expressed by epithelial cells, the highest level of VEGFAexpression is found in individual myeloid cells. Moreover, we observed that effective PD-1 blockade immunotherapy significantly reduced tip cells, disrupting the VEGFA-KDR-ESM1positive feedback loop in the process. Our investigation into the heterogeneity of ECs in CRC at a single-cell level offers important insights that may contribute to the development of more effective immunotherapies targeting tip cells in CRC.
The frequency and pathogenicity of BRCA1 and BRCA2 variants in the general Japanese population.
Authors: Idogawa Masashi , Mariya Tasuku , Tanaka Yumi , Saito Tsuyoshi , Nakase Hiroshi , Tokino Takashi , Sakurai Akihiro
Published: August 2023

Hereditarybreast and ovarian cancer syndrome (HBOC) resulting from pathogenic variants of BRCA1 or BRCA2 is the most common and well-documented hereditary tumor. Although founder mutations have been identified in population-based surveys in various countries, the types of variants are not uniform across races and regions. Recently, the Tohoku Medical Megabank Organization (ToMMo) released whole-genome sequence data including approximately 54,000 individuals from the general population of theTohoku area in Japan. We analyzed these data and comprehensively identified the prevalence of BRCA1/2 pathogenic and truncating variants. Interestingly, our analysis showed that most of the top BRCA1/2pathogenic variants believed to be founder mutations do not match reports from other countries. We believe that an accurate understanding of the unique distribution and characteristics of pathogenic BRCA1/2variants in Japan through this analysis will enable better surveillance and intervention for HBOC patients, not only in Japan but also worldwide.
Li-storage of Li2ZnTi3O8@C-N anodes with high-performance in a wide temperature range
Authors: Li Jiayi , Zhang Xue , Xu Haoran , Ma Wenzhao , Wang Lijuan
Published: September 2023

Spinel Li2ZnTi3O8 (LZTO) with a zero volumetric change, exhibits high safety as an anode of lithium-ion batteries. Nevertheless, the low electrical conductivity restricts its wide application. A facile one-step solid-state route has been used to synthesize LZTO@C-N composites with different N content. The existence of N-doped carbon improves the diffusion coefficients of Li+ ions and the electronic conductivity, and reduces the charge-transfer resistance and the side reactions between electrolyte and LZTO. The N content can affect the lattice constants and the appearance the new phases. The LZTO@C-N-2 composite with the proper N content of 2.2 w.% possesses the best electrochemical performance in wide temperature range from 0 to 55°C. Discharging at 2 A g− 1 and charging at 0.5 A g− 1, 219.7 and 214.8 mAh g− 1 are obtained for LZTO@C-N-2 at the 1st and 150th cycles, respectively, with small capacity fade at 25°C. 290.3 and 151 mAh g− 1 are delivered at the 1st and 150th cycles for LZTO@C-N-2 at 55°C, respectively. Even at 0°C, the LZTO@C-N-2 composite still shows good rate capability. The simple synthetic route and good electrochemical performance enable LZTO@C-N-2 to be a potential anode of LIBs.