bluuebunny/crossref_metadata_2025 huggingface dataset:
Compromised VEGFA secretion in Yap deficient alveolar epithelial type 1 cells lung impairs alveolar development and vascularization and aggravates hypoxia-induced pulmonary hypertension
Authors: He Xi , Gao Ruo-nan , Wang Ai-ping , Chen Lin-yan , Guo Yong-zhe , Zhang Jing , Zhang Yu-rong , Xu Yi-wei , Zhang Xin-tao , Huang Yu , Zhao Ziwen
Published: June 2023

Disorders of lung development may result in secondary pulmonary arterial hypertension (PAH), a complex condition marked by elevated pulmonary arterial pressure and impaired function of the right ventricle. Yes-associated protein (YAP), a pivotal mediator of the Hippo pathway, has gained growing recognition as a vital component in the signaling network that regulates cell behavior during lung development. However, the roles of Yap in both alveolar development and vascularization as well as its involvement in the pathogenesis of PAH remain unknown. By investigating mice with a conditional deletion of YAP specifically in alveolar epithelial type 1 (AT1) cells, we demonstrate that Yap deficiency results in impaired alveolar development and vascularization, which aligns with the exacerbation of hypoxia-induced PAH. These pathological changes occur concomitant with compromised endothelial growth factor A (VEGFA) secretion, a known angiogenic factor required for alveolar development and lung angiogenesis. Rescue experiments confirmed that VEGFA acts as a downstream target of Yap and plays a crucial role in both alveolar development and vascularization. Taken together, these data bear significant implications for comprehending the intricate mechanisms governing alveolar development and pulmonary vascular remodeling, thereby holding great promise for advancing our understanding of Group 3 PAH.
Bayesian estimation of gene constraint from an evolutionary model with gene features
Authors: Zeng Tony , Spence Jeffrey , Mostafavi Hakhamanesh , Pritchard Jonathan
Published: June 2023

Measures of selective constraint on genes have been used for many applications including clinical interpretation of rare coding variants, disease gene discovery, and studies of genome evolution. However, widely-used metrics are severely underpowered at detecting constraint for the shortest ∼25% of genes, potentially causing important pathogenic mutations to be overlooked. We developed a framework combining a population genetics model with machine learning on gene features to enable accurate inference of an interpretable constraint metric, shet. Our estimates outperform existing metrics for prioritizing genes important for cell essentiality, human disease, and other phenotypes, especially for short genes. Our new estimates of selective constraint should have wide utility for characterizing genes relevant to human disease. Finally, our inference framework, GeneBayes, provides a flexible platform that can improve estimation of many gene-level properties, such as rare variant burden or gene expression differences.
General and local predictors of mandibular cortical bone morphology in adult females and males: The seventh survey of the Tromsø Study
Authors: Teterina Anna , Niratisairak Sanyalak , Morseth Bente , Bolstad Napat
Published: June 2023

Objectives To analyze factors predicting mandibular cortical width (MCW) and mandibular cortical index (MCI) in adult females and males.
Material and Methods Data on 427 females and 335 males aged 40-84 from The Tromsø study: Tromsø7 were used. T-score, age, menopausal status (for females), remaining teeth, and periodontal status were analyzed in linear and logistic regression analyses as predictors of MCW and MCI, respectively.
Results T-score, age, and the number of remaining teeth significantly predicted MCW in females but not males. Standardized β coefficients were 0.286, -0.231, and 0.131, respectively. The linear regression model explained 24% of MCW variation in females. MCI in females was significantly predicted by T-score, age, and remaining teeth with the Wald values of 9.65, 6.17, and 5.83, respectively. The logistic regression model explained 16.3% - 23% of the variation in MCI in females. In males, T-score was the only significant predictor of the eroded cortex, and the logistic model explained only 4.3% – 5.8% of the variation in MCI.
Conclusions T-score showed a stronger relationship with MCW and MCI than other factors in females, which supports using those indices for osteoporosis screening. In males, T-score and other factors did not show relationships with MCW. T-score was the only significant predictor of MCI in males, yet to a lesser extent than in females, discouraging further studies of MCW and MCI for osteoporosis screening in males.
Clinical relevance: Understanding factors affecting mandibular cortical morphology is essential for further investigations of MCW and MCI usefulness for osteoporosis screening in females and males.
PDIA4: A Novel ER Stress Protein Regulating Hepatic Lipogenesis in Non-Alcoholic Fatty Liver Disease
Authors: Su Sheng-Chiang , Chen Ying-Chen , Chien Chu-Yen , Chiang Chi-Fu , Lin Fu-Huang , Kuo Feng-Chih , Huang Chia-Luen , Li Peng-Fei , Liu Jhih-Syuan , Lu Chieh-Hua , Ho Li-Ju , Hsieh Chang-Hsun , Hung Yi-Jen , Shieh Yi-Shing , Lee Chien-Hsing
Published: June 2023

Hepatic steatosis is a histological characteristic of non-alcoholic fatty liver disease (NAFLD). Hepatocytes are enriched with the endoplasmic reticulum (ER), essential for lipid metabolism. ER stress modulates lipogenesis and hepatic steatosis in hepatocytes, indicating an involvement of unfolded protein response (UPR) components in the NAFLD pathogenesis. Our previous study demonstrated that serum levels of protein disulfide isomerase A4 (PDIA4) correlate with the components of NAFLD. Therefore, this study aimed to evaluate PDIA4 role in NAFLD development. We treated HepG2 cells with palmitate to generate an obesity-associated NAFLD cell model and a high-fat diet-induced obesity-associated NAFLD mouse model. We demonstrated that human serum PDIA4 concentration is an independent risk factor for the fatty liver index and is upregulated in the liver tissues of DIO mice and human NAFLD tissue arrays. ER stress and PDIA4 expression increase in palmitate-exposed HepG2 cells. Moreover, palmitate triggers lipid accumulation and increases intracellular triglyceride (TG) levels in HepG2 cells in a dose-dependent manner. PDIA4 silencing suppresses palmitate-induced hepatic steatosis in HepG2 cells. PDIA4 mediates hepatic steatosis through direct interaction and proteolytic activation of sterol regulatory element-binding protein 1c (SREBP1c), further inducing the expression of stearoyl-CoA desaturase-1 (SCD1) and hepatic lipogenesis in palmitate-treated HepG2 cells. Additionally, ATF6 acts as an upstream modulator of palmitate-induced PDIA4 upregulation, and its depletion suppresses the stimulatory effect of palmitate on PDIA4 expression and steatosis in HepG2 cells. Our findings indicate a pathological role of PDIA4 in the development of obesity-associated NAFLD.
Human peripheral blood mononuclear cells display a temporal evolving inflammatory profile after myocardial infarction and modify myocardial fibroblasts phenotype
Authors: Miquelestorena-Standley Elodie , Silva Ana Valéria Vinhais , Monnier Marina , Chadet Stéphanie , Piollet Marie , Héraud Audrey , Lemoine Roxane , Bochaton Thomas , Derumeaux Geneviève , Roger Sébastien , Ivanes Fabrice , Angoulvant Denis
Published: June 2023

Pathophysiological response after acute myocardial infarction (AMI) is described as a three-stage model involving temporal phenotypic modifications of both immune cells and fibroblasts: a primary inflammatory phase, followed by a reparative phase and a fibrous scar maturation phase. Purinergic receptors, particularly the P2Y11 receptor, have been reported to be involved in the regulation of inflammation after ischemia and could act for the resolution of inflammation after AMI. For the first time, we characterized the immuno-inflammatory and P2Y11 expression profiles of peripheral blood mononuclear cells (PBMC) from AMI patients and analyzed the consequences of presenting these cells to cardiac fibroblasts in vitro. PBMC from 178 patients were collected at various times after reperfused ST-segment elevation AMI, from H0 to M12. Expression level of P2RY11 and genes involved in tolerogenic profile of dendritic cells and T cell polarization were evaluated by RT-PCR. P2Y11 protein expression was assessed by flow cytometry. PBMC and human cardiac fibroblasts (HCF) were cocultured and α-SMA/vimentin ratio was analyzed by flow cytometry. Within the first 48 hours after AMI, expression levels of HMOX1, STAT3 and CD4 increased while IDO1 and TBX21/GATA3 ratio decreased. Concomitantly, the expression of P2RY11 increased in both T and B cells. In vitro, PBMC collected at H48 after AMI induced an increase in α-SMA/vimentin ratio in HCF. Our results suggest that human PBMC display an evolving inflammatory profile with reparative characteristics the first two days after AMI and secrete soluble mediators leading to the myofibroblastic differentiation, thus participating to myocardial fibrosis.
Diagnostic Criteria of Dual Diagnosis Fatty Liver Disease is Better for Fatty Liver Research
Authors: Cheng Yu-Ming , Hsieh Tsung-Han , Wang Chia-Chi , Kao Jia-Horng
Published: June 2023

Background/purpose:
Metabolic Associated Fatty Liver Disease (MAFLD) was proposed to replace “non-alcoholic fatty liver disease (NAFLD) with new diagnostic criteria. The group meeting two diagnostic criteria is called “Dual diagnosis Fatty Liver Disease (DuFLD)”. The clinical characteristics of “DuFLD” remain unknown.
Methods
This study included participants from the Taiwan Bio-Bank cohort, where NAFLD was defined as hepatic steatosis in liver ultrasound with exclusion of other known chronic liver diseases. Metabolic dysfunction (MD) was defined as having any of following three criteria: overweight/obesity, type 2 diabetes mellitus (DM), or ≥ 2 metabolic risk abnormalities in lean/normal weight subjects. NAFLD fibrosis score (NFS) > 0.675 was defined as advanced liver fibrosis and atherosclerosis was diagnosed if having plaques on carotid duplex ultrasound.
Results
8038 participants (age 55.86 ± 10.12; males 41.07%) diagnosed as NAFLD were included in the final analysis. Of them, 7377 (91.8%) participants with MD were categorized as “DuFLD”, 661 (8.2%) participants without MD were categorized as “NAFLD without MD”. Using propensity score matching for age and sex, “DuFLD” patients had worse metabolic profiles, higher NFS and percentage of carotid plaques than those with “NAFLD without MD”. Multivariate analysis showed age, HT, DM and BMI were positively associated with advanced liver fibrosis, but inverse association with fatty liver index in patients with “DuFLD”.
Conclusions
This population-based study suggests that “DuFLD”, a group with high homogeneity, better identifies higher risk population of advanced liver fibrosis, suggesting the diagnostic criteria of “DuFLD” is better for fatty liver research and future drug development.
Prevalence of senile dementia in adult over 65 years of age: a cross-sectional survey of Hunan Province, China
Authors: Zhou Sijing , Luo Bangan , Zhang Xi , Wang Dongxin
Published: June 2023

Objective
To investigate the status, influencing factors and care burden of senile dementia in the population over 65 years old in Hunan Province. To provide the basis for the prevention and treatment of senile dementia.
Method
From April to May 2021, a total of 5979 residents aged ≥65 years old were selected from 30 districts and counties in Hunan Province using the Simplified Community Dementia Scale (CSI-D)/Dementia Early Screening Questionnaire (AD8) as screening tools. Community diagnosis is performed by a neurologist or psychiatrist in combination with the Simple Mental State Examination Scale (MMSE)/Montreal Cognitive Assessment Scale (MOCA). c2 test and the multi-factor logistic regression analysis the influence factors of senile dementia.
Results
The prevalence rate of senile dementia was 13.98%. Old age (OR =1.312, 95%CI: 1.231~1.399), chronic diseases (OR = 1.296, 95%CI: 1.091~1.540), especially hypertension, cerebrovascular disease, ischemic heart disease, living in rural areas (OR =1.688, 95%CI: 1.300 ~2.190) was a risk factor, and high education level (OR=0.678, 95%CI: 0.604~0.762) was a protective factor. The care burden of senile dementia is relatively large, 27.66% of senile dementia patients cause mild to severe distress to their family members or nannies, 12.65% of patients need different degrees of care such as day care or long-term nursing home.
Conclusion
The prevalence rate of senile dementia is high in Hunan Province and the burden of family care is heavy. The society should pay close attention to the physical and mental health of the elderly population and take active intervention measures to improve the prevention and treatment level of dementia in the elderly population.
Embracing Family Presence: Exploring the Reason of Family Decision Making Dependence on in-hospital Palliative Care for Cancer Patients
Authors: Krisdianto Boby Febri , Dahlia Debie , Waluyo Agung
Published: June 2023

Purpose:The implementation of home-based palliative care has been recognized as a commendable care model. However, it is noteworthy that families residing in Indonesia exhibit a propensity to predominantly seek palliative care services within hospital environments for their family members afflicted with palliative cancer. Therefore, this research’s aims is to explore the family members' perceived in their decision-making process of caring for the patients at the home of palliative cancer patients.
Method This study qualitative study used a descriptive phenomenological approach. Data were obtained through in-depth interviews with 10 Indonesian family members of the palliative cancer patients refusing the discharge and analyzed by using the Collaizi method. Furthermore, the Inclusion criteria were a dominant family who cares patient and lives with patient.
Results Three themes emerged in this study; are (1) lack of support in the decision-making, (2) Families rely on hospitalsand (3) pain and chronic sorrow.
Conclusions Nurses should engage in collaborative partnerships with healthcare providers to inform about patient condition and goal of care. Nurse also need to facilitate families' decision-making processes regarding home palliative care.
Implications for cancer survivors: The implications of this study align with the nursing profession's commitment to patient-centred care and the promotion of shared decision-making. By actively involving family members in the decision-making process and supporting their emotional well-being, nurses can contribute to enhancing the overall quality of care for palliative cancer patients in the home setting.
Safety and efficacy of clonidine hydrochloride extended –release (CLON-XR) for treatment of attention deficit hyperactivity disorder in Chinese children and adolescents: a multi-center, placebo-controlled, randomized, double-blind study
Authors: Du Yasong , Ke Xiaoyan , Gao Feng , Chen Wenxiong , Wu Weige , Li Yaping , Du Lijun , Ye Ying , Zhu Haijian , Cai Linhui , Xie Liyan
Published: June 2023

Background
While clonidine hydrochloride extended-release tablets (CLON-XR) have been approved by FDA for the treatment of ADHD, clinical data regarding its safety and efficacy in Chinese children and adolescents is limited. This present study is the first placebo-controlled, randomized, double-blind clinical trial of CLON-XR in the treatment of ADHD children and adolescents in China.
Methods
A total of 75 children with ADHD aged 6 to 17 were randomly assigned to the experimental group and placebo group in the ratio of 2:1, and received treatment for 6 weeks. Data from the Swanson Nolan and Pelham Version-IV (SNAP-IV) and the Clinical Global Impression (CGI) were evaluated. Safety measures included treatment-emergent adverse events (TEAEs), vital signs, laboratory assessments and electrocardiograms.
Results
ADHD symptoms had been significantly improved after treatment of CLON-XR since the first week. At week 5, the decrease in SNAP-IV total scores in CLON-XR group (17.5 ± 11.86) was statistically significantly more than that in the placebo group (10.3 ± 11.43; p < 0.05), and the degree of improvement in the SNAP-IV hyperactivity/ impulsivity and inattention subscale and the CGI scale in the experimental group from baseline to week 5 was also statistically significantly higher than that in the placebo group (p < 0.05). CLON-XR was effective in the treatment of ADHD, regardless of age and gender. The incidence of TEAEs in CLON-XR group was comparable to that in placebo group, and the TEAEs were mild and the dropout rate was low (5.3%).
Conclusions
The nonstimulant medication CLON-XR can significantly improve the core symptoms (attention deficit and hyperactivity/impulsivity) and overall function in ADHD patients with no addiction, mild adverse reactions, and good compliance and tolerability. It has the potential to improve sleep efficiency and can be considered a recommended drug for the treatment of ADHD children and adolescents in China.
Transarterial chemoembolization plus lenvatinib with or without programmed death-1 inhibitors for unresectable hepatocellular carcinoma: A negative result
Authors: Ding Zongren , Fang Guoxu , Zhang Bing , Zeng Yongyi
Published: June 2023

Introduction: Our aim was to explore whether programmed death receptor-1 (PD-1) inhibitors would improve the prognosis of unresectable hepatocellular carcinoma (HCC) treated with transarterial chemoembolization (TACE) plus lenvatinib.
Methods: In this single-center retrospective study, patients with unresectable HCC who underwent TACE and were administered lenvatinib with or without PD-1 inhibitors were enrolled and divided into the TACE + lenvatinib group and TACE + lenvatinib + PD-1 group. Overall survival (OS), progression-free survival (PFS) and tumor response were assessed by the Response Evaluation Criteria in Solid Tumors (RECIST v1.1 and mRECIST). Treatment-related adverse events (AEs) were evaluated according to the Common Terminology Criteria for Adverse Events (CTCAE, version 5.0).
Results: In total, 35 eligible patients with unresectable HCC were included; 82.9% of patients had Hepatitis B virus (HBV)infection, and 88.6% of patients had liver cirrhosis. A total of 88.6% of patients had multiple tumors, and the median diameter of the largest tumor was 10.1 cm. A total of 14.3% of patients had extrahepatic metastasis, and 51.4% of patients had portal vein tumor thrombus. The percentages of BCLC stages A, B and C were 5.7%, 28.6% and 65.7%, respectively. There were 16 patients in the TACE + lenvatinib group and 19 patients in the TACE + lenvatinib + PD-1 group. The median follow-up time was 7.7 months (ranging from 1.7–31.6 months). Neither group reached the median overall survival. Under RECIST v1.1 criteria, the median PFS was 10.4 and 7.9 months in the TACE + lenvatinib and TACE + lenvatinib + PD-1 groups (HR, 1.13; 95% CI, 0.45–2.84; P = 0.80), the objective response rates (ORR) were 31.3% and 31.6% (p > 0.05), and the disease control rates (DCR) were 93.8% and 78.9% (p > 0.05), respectively. Under mRECIST criteria, the median PFS was 10.4 and 10.1 months (HR, 0.98; 95% CI, 0.38–2.54, P = 0.97), the ORR was 62.5% and 63.2% (p > 0.05), and the DCR was 93.8% and 73.7% (p > 0.05), respectively. Overall, AEs were relatively similar between the two groups.
Conclusion: PD-1 inhibitors did not improve the PFS and tumor response of unresectable HCC treated with TACE plus lenvatinib. Hepatitis B infection, liver cirrhosis, portal vein tumor thrombus, multiple tumors and large tumor diameter may be potential factors that affect the efficacy of PD-1 inhibitors but need further validation.
The Patch-type Multi-lead Electrocardio Multiparameter Monitoring Diagnostic Instruments and Their New-type Wireless Remote Connected Ecosystem
Authors: Zhang Yue , Wu Bo , Liu Shuntian , Zhao Tongbing , Tan Zhaoping , Zhu Xiaoqiang , Yan Xiaohong , Qi Xiaomin , Tang Jinhai , Li Wei , Li Zejiang
Published: June 2023

Wearable ECG, respiration, blood pressure, blood oxygen, body temperature, blood sugar multiparameter monitoring devices with wireless remote monitoring function is of great significance for the assessment of cardiovascular health and detection of acute myocardial ischemia and yocardial infarction,and clinical management of critically ill patients or surgical patients1,2,3,4,5. However, due to the large size of traditional devices, traditional cardiac function monitoring methods cannot provide wireless remote monitoring1,2,3,6,7,8. Here we report a wearable patch-type multi-lead ECG multiparameter monitoring instrument3,4,5 and its new-type wireless remote connected ecosystem9,10,11,12 for wireless remote cardiac function assessment. We describe innovations in the design and material manufacturing of the devices that allow a complete one-time remote real-time examination of the patient's left ventricle and its posterior wall, right ventricle from different angles. We propose an new-type wireless remote connected ecosystem based on the B/S architecture (Browser-Server Mode) of the Wide Area Network covering all clinical application scenarios and medical services items13 of the cardiac cardiovascular system. We developed a complete set of AI detection and diagnosis models that automatically classifies common 28 categories of cardiovascular health and disease. This technology can realize wireless remote cardiac function monitoring and diagnosis, greatly improving the accuracy of ECG multiparameter monitoring diagnosis.
Extraction of flavonoids from the rind of Passiflora edulis f. Flavicarpa by pressurized solvent extraction and aqueous two-phase systems
Authors: Pinto Paloma Lira , Siqueira Ana Cristina de Abreu , de Sant’Ana Hosiberto Batista , de Brito Edy Sousa , Silva Ivanildo
Published: June 2023

As the rind of passion fruit is rich in flavonoids, it can be used as an alternative to obtain these compounds. This study extracted flavonoids from passion fruit rinds by pressurized solvent extraction. The obtained extract was submitted to aqueous two-phase extraction formed by ethanol and salts for the recovery of flavonoids. Passion fruit rind (PFR) was submitted to pressurized solvent extraction (PSE) using ethanol/water solution at 60:40 (v/v) as a solvent for the extraction of bioactive compounds, showing a polyphenol content of 5.48 gGAE∙kg− 1 PFR. Then, aqueous two-phase systems (ATPS) showed that flavonoids and sugars partitioned into opposite phases. The recovery of flavonoids in the top phase was above 98% w/w, and the recovery of sugars in the bottom phase was above 97% w/w. LC‒MS was used to evaluate the flavonoid profile in the top phase of ATPS, and the major flavonoids detected were lucenin-2, vicenin, isoorientin, apigenin, schaftoside and vitexin. According to the flavonoid profile by LC‒MS and the values of recovery of flavonoids, ATPS proved to be an effective technique for recovery of flavonoids from PSE extraction.
Comparative Transcriptome Analysis Reveals Candidate Genes For Cold Stress Response and Early Flowering in Pineapple
Authors: Yow Ashley G. , Laosuntisuk Kanjana , Young Roberto , Doherty Colleen J. , Gillitt Nicholas , Perkins-Veazie Penelope , Xiang Qiu-Yun Jenny , Iorizzo Massimo
Published: June 2023

Pineapple originates from tropical regions in South America and is therefore significantly impacted by cold stress. Periodic cold events in the equatorial regions where pineapple is grown may induce early flowering, also known as precocious flowering, resulting in monetary losses due to small fruit size and the need to make multiple passes for harvesting a single field. Currently, pineapple is one of the most important tropical fruits in the world in terms of consumption, and production losses caused by weather can have major impacts on worldwide exportation potential and economics. To further our understanding of and identify mechanisms for low-temperature tolerance in pineapple, and to identify the relationship between low-temperature stress and flowering time, we report here a transcriptomic analysis of two pineapple genotypes in response to low-temperature stress. Using meristem tissue collected from precocious flowering-susceptible MD2 and precocious flowering-tolerant Dole-17, we performed pairwise comparisons and weighted gene co-expression network analysis (WGCNA) to identify cold stress, genotype, and floral organ development-specific modules. Dole-17 had a greater increase in expression of genes that confer cold tolerance. The results suggested that low temperature stress in Dole-17 plants induces transcriptional changes to adapt and maintain homeostasis. Comparative transcriptomic analysis revealed differences in cuticular wax biosynthesis, carbohydrate accumulation, and vernalization-related gene expression between genotypes. Cold stress induced changes in ethylene and abscisic acid-mediated pathways differentially between genotypes, suggesting that MD2 may be more susceptible to hormone-mediated early flowering. The differentially expressed genes and module hub genes identified in this study are potential candidates for engineering cold tolerance in pineapple to develop new varieties capable of maintaining normal reproduction cycles under cold stress. In addition, a total of 461 core genes involved in development of reproductive tissues in pineapple were also identified in this study. This research provides an important genomic resource for understanding molecular networks underlying cold stress response and how cold stress affects flowering time in pineapple.
Identification and validation of disulfidptosis-related subtypes and the prognostic model in hepatocellular carcinoma
Authors: Huang Qiming , Li Tiewen , Liu Sisi , Chen Difei , Du Yemei , Jie Lei , Ma Yang , Hong Ru-Tao
Published: June 2023

Background
Disulfidptosis is a newly discovered form of cell death. The latest reports have revealed potential mechanisms for disulfide-mediated cell damage, including actin cytoskeleton proteins and cellular scaffold proteins, which are susceptible to disulfide stress. Accumulation of disulfides in cells results in the breakdown of the actin network and cell death. However, the prognostic role and regulatory mechanism of disulfidptosis-related genes in hepatocellular carcinoma remain unclear.
Methods
The differential expression, copy number variation, and prognostic relevance of 10 genes associated with disulfidptosis were analyzed. Based on the expression levels of the disulfidptosis-related genes, unsupervised clustering analysis was performed to classify the samples into three subtypes, and their gene expression, biological functions, and immune cell infiltration were analyzed. Subsequently, the common differentially expressed genes were screened and a gene prognostic model was established. Samples with high-risk scores showed higher immune cell infiltration and expression of immune checkpoint genes.
Results
Firstly, we found that four genes (LRPPRC, NCKAP1, RPN1, SLC7A11) showed significant prognostic ability for overall survival in HCC patients. Subsequently, using consensus clustering analysis, the samples were divided into three clusters(A, B and C cluster) based on the expression levels of the four prognostic disulfidoptosis genes, where the prognostic of B cluster was worse, and the cell cycle pathway activation was significantly enriched. Furthermore, the immune cell infiltration abundance was calculated, significant differences in TME were observed among the three subtypes. Additionally, among the common differentially expressed genes among the three subtypes, lasso regression was used to screen six survival-related genes, and a prognostic model was established. Finally, our results suggest that the risk score may serve as a useful tool for predicting sensitivity to immunotherapy and drug treatment in HCC patients.
Conclusion
These findings highlight the significant clinical implications of the sulfide death pathway and provide new insights into guiding personalized immune therapy strategies for patients with hepatocellular carcinoma.
Coagulase-negative Staphylococci from Bovine Milk: Virulent gene detection, and Antibiogram Profiles
Authors: Getahun Yared Abate , Abey Solomon Lulie , Beyene Achenef Melaku , Belete Mequanint Addisu , Tessema Tesfaye Sisay
Published: June 2023

Background Coagulase-negativeStaphylococcusspecies are an emerging cause of intramammary infection, posing a significant economic and public health threat. The cross-sectional study was conducted to isolate and assess virulence factors and antibiogram profiles of coagulase-negativeStaphylococcusspecies in 290 milk samples collected from February to August 2022. Species isolation and identification were performed by plate culturing and biochemical tests and single-plex PCR was used for the detection of virulent genes. The antimicrobial susceptibility profile of each coagulase-negativeStaphylococcusspecies isolate was determined by the Kirby-Bauer disc diffusion test. Results Coagulase-negativeStaphylococcusspecies were isolated in 28.6%, (83/290) of the samples. Of these, theS. epidermidis,S. sciuri,S. warneri,S. haemolyticus,S. simulans,S. chromogens,S. cohnii, andS. captisspecies were isolated at the rates of 11, 5.2, 3.4, 3.1, 3.1, 1, 1, and 0.7% respectively. Coagulase-negative Staphylococcusspecies carried 26.5, 22.1, 21.7, 9.6, 9.6 and 8.4% of theica D,Pvl,Mec A,hlb,Sec, andhlavirulent genes respectively. All the isolates showed a high percentage (100%) of resistance to Amoxicillin, Ampicillin, and Cefotetan and 37.5% of resistance to Oxacillin. The majority (54.2%) of coagulase-negative isolates also showed multidrug resistance. Conclusion The present study revealed that coagulase-negativeStaphylococcusspecies isolates were found carriage of one or more virulent and enterotoxin genes responsible for intramammary and food poisoning infections. The majority of the isolates (54.2%) were also found multidrug resistant. Thus, urgent disease control and prevention measures are warranted to reduce the deleterious impact of coagulase-negative species. This study is the first to document the detection of virulent and food poisoning genes in coagulase-negativeStaphylococcusspecies from milk in Ethiopia.
Gender Differences in Severity and Parental Estimation of Adolescent’s Pandemic-Related Stress in the United States
Authors: Simkus Andrew , Holtz Kristen , Twombly Eric , Wanty Nicole
Published: June 2023

Background: Research has consistently shown that female adolescents have experienced worse pandemic-related stress compared to males. A parent’s ability to accurately track their child’s stress levels likely increases the likelihood a problem is acknowledged and addressed as it arises. Therefore, we assessed how parents’ estimation of their adolescent children’s self-reported pandemic-related stress related to the child’s gender.
Methods: We performed cross-sectional secondary analysis using the nationally representative Population Assessment of Tobacco and Health study datasets from Wave 5 (2018-2019) and Wave 5.5 (July 2020-December 2020) among respondents aged 12-17. We conducted four logistic regression models to explore the relationship between child gender and parental underestimation of their child’s pandemic-related stress. We controlled for sociodemographic factors and personal characteristics associated with pandemic-related stress including, whether the adolescent had been diagnosed with COVID-19, the extent social distancing measures were practiced, school performance, previous year anxiety, depression, and overall mental health ratings, sleep trouble, TV screen time, and past year substance use.
Results: Even when controlling for these factors, female child gender was significantly and positively associated with parental underestimation of their child’s pandemic-related stress (Underestimated stress: OR = 1.25 95 % CI = [1.07-1.46]).
Conclusions: Informing parents that female adolescents were significantly more likely to have their levels of pandemic-related stress underestimated at home may encourage parents to take extra effort when checking in on their daughters’ mental health needs, which in turn may lead to more female adolescents receiving the familial and professional support they require.
Listening to music while running does not impair lateral balance or increase ground impact forces in non-fatigued novice treadmill runners
Authors: Cunningham Neil James , Zordan Rachel
Published: June 2023

Novice runners have neither acquired the skill of running nor embedded an efficient biomechanical technique. Removing auditory cues for feedback by listening to music was theorised to impair the ability to register or respond to heavy or uncoordinated step impacts, potentially exposing the novice runner to increased forces transmitted through to the lower limb. The primary objective was to determine whether removing auditory feedback cues affected biomechanical running gait stability in novice runners as measured by step width and step width variability. Secondary objectives included analysis of the effect of listening to music on ground reaction force (GRF) and running symmetry. In a sample of novice runners (n = 23), repeated measure analysis found no significant differences across all outcome variables comparing music and non-music conditions. Novice runners who listen to music were not exposed to higher GRF or obvious balance impairment while running on treadmills in a non-fatigued state.
Integration of small RNAs, transcriptome and degradome sequencing reveals the mechanism of high photosynthetic efficiency in Medicago ruthenica (L.)
Authors: Shi Fengling , Gao Cuiping , Zhang Yutong , Yan Wei , Qiao Yu , Gao Xia , Tang Fang , Yi Fengyan
Published: June 2023

Background
Medicago ruthenica, a superior leguminous forage, is strongly drought-resistant and has wide adaptability. It is closely related to Medicago sativa (a commonly cultivated forage). Characterized by its high tolerance to environmental stress, M. ruthenica is a valuable genetic resource. However, its low yield limits its large-scale promotion and utilization. Leaf morphology, an important agronomic trait, is closely related to forage yield and photosynthetic efficiency.
Results
In this study, leaf width and leaf area were found significantly positively correlated with forage yield in M. ruthenica. Specifically, the cultivar M. ruthenica ‘Mengnong No.1’ (MN No.1) with a larger leaf area had higher photosynthetic efficiency. Furthermore, the key miRNA-target gene networks associated with high photosynthetic efficiency of M. ruthenica were identified using small RNAs and transcriptome sequencing. Totally, 63 differentially expressed miRNAs (DEMs) were identified, including some known miRNAs (miR408, miR171, and miR398, etc.). These known miRNAs corresponded to 55 target genes; 6 miRNA-target gene pairs had negatively correlated expression patterns. Degradome sequencing analysis further confirmed the authenticity of miR408-targeted cleavage of LAC5; namely, the miR408-LAC5 module may mediate the mechanism of high photosynthetic efficiency formation in M. ruthenica.
Conclusions
This study for the first time proposed that leaf morphology as a key trait affecting the high-yielding plant type of M. ruthenica. The key gene modules screened in this study may provide new insights into the elucidation of photosynthetic efficiency mechanism and the bio-design breeding of legume forages in the future.
Predictors of Efficacy of Anamorelin in Non-small-cell Lung Cancer Patientswith Cachexia: A Retrospective Study
Authors: Ishioka Yoshiko , Tanaka Hisashi , Makiguchi Tomonori , Fujishima Syunsuke , Nunomura Yasuhito , Sakamoto Hiroaki , Shiratori Toshihiro , Taima Kageaki , Tasaka Sadatomo
Published: June 2023

PURPOSE: Anamorelin, a ghrelin receptor agonist, has recently been approved in Japan for the treatment of cachexia in patients with lung and gastrointestinal cancer. However, only a few studies have investigated whether anamorelin is actually useful in clinical settings. We therefore investigated its efficacy in terms of patient characteristics.
METHODS: We retrospectively evaluated 40 patients with non-small-cell lung cancer with cachexia who were prescribed anamorelin at our department between July 2021 and November 2022. A logistic regression analysis was used to analyze the association between patients’ background characteristics and early discontinuation (within 4 weeks).
RESULTS: The early discontinuation group included 11 patients (27.5%). An Eastern Cooperative Oncology Group Performance Status (ECOG-PS) of ≥2 (odds ratio 7.85, 95% confidence interval 1.43-43.21, p=0.018) was associated with early discontinuation. Eighteenpatients (45.0%) were able to continue administration for 12 weeks, and the mean change in body weight was +2.31 kg, which was a significant change (p=0.027). The mean changesin lean body mass and soft lean mass were +1.97 kg (p=0.14) and +1.26 kg (p=0.15), respectively.
CONCLUSION: The study confirmed that anamorelin was unlikely to be useful in patients with a poor general condition (ECOG-PS ≥2).
The Added Value of Systematic Sampling in In-Bore Magnetic Resonance Imaging Guided Prostate Biopsy
Authors: Drori Tomer , Zilberman Dorit , Portnoy Orith , Dotan Zohar , Rosenzweig Barak , Lazarovich Alon
Published: June 2023

We sought to quantify the additive value of systematic biopsy (SB) using in-bore magnetic resonance (MR)-guided prostate biopsy (IBMRGpB) by retrospectively reviewing the records of 189 patients who undergone IBMRGpB. Endpoints included clinically significant and non-clinically significant cancer diagnosis. SB detected clinically significant disease in 67 (35.5%) patients. Five (2.65%) patients whose targeted biopsies found benign or non-clinically significant disease had clinically significant disease on SB. SB from the lobe contralateral to the lesion detected clinically significant disease in 15 (12%) patients. The size of the prostate was larger, and the percentage of lesions located in the peripheral zone of the prostate was higher in patients with SB-detected clinically significant disease. The location of the main lesion in the peripheral zone of the prostate was a predictor for clinically significant disease in multivariate analysis (OR = 8.26, p = 0.04), a finding supported by a subgroup analysis of biopsy-naïve patients (OR = 10.52, p = 0.034). The addition of SB during IBMRGpB increased the diagnosis of clinically significant as well as non-clinically significant prostate cancer. The location of the main lesion in the peripheral zone emerged as a positive predictive factor for clinically significant disease on SB. These findings may enhance patient-tailored management.
Flax for seed or fibre use? Flax capsules from ancient Egyptian sites (3rd millennium BC to 2nd century AD) compared with modern genebank flax accessions
Authors: Karg Sabine , Spinazzi-Lucchesi Chiara , Diederichsen Axel
Published: June 2023

In order to determine whether ancient Egyptians had already selected and cultivated very specialized flax types according to their purpose for textile or oil production we compared archaeobotanical flax finds that are kept at the Botanical Museum of the Free University in Berlin, Germany with diverse genebank accessions kept at the Plant Gene Resources of Canada (PGRC). The main result was that fibre flax was most probably already cultivated in Egypt during the the 3rd millennium BC, whereas in all later periods an intermediate flax and/or oil type was in use. The collaboration between archaeobotanists and genebank curators shows how knowledge about ancient usage of plants can be generated by interpreting observations made on ancient findings using characterization data obtained from diverse genebank material.
Modified pine needles as a formaldehyde scavenger for urea-formaldehyde resin in plywood production
Authors: Dukarska Dorota , Kawalerczyk Jakub , Kmieciak Jakub
Published: June 2023

The aim of presented work was to investigate whether it is possible to use ground pine needles as a formaldehyde-scavenging filler for urea-formaldehyde resin in the production of plywood. The scope of the research included determinations of both optimal amount of introduced filler and the effect of its modification (silanization, hydrothermal and alkaline treatments). Properties of adhesives such as viscosity, gel time and pH were investigated and their morphology was assessed using scanning electron microscopy. Manufactured plywood were tested in terms of wet shear strength, tendency to delamination and formaldehyde emission. It was found that the addition of pine needles lowers the pH and reduces gel time of the adhesive. Moreover, it was shown that despite a significant reduction in formaldehyde emission, the addition of non-modified needles causes a decrease in bonding quality of plywood. Based on the results, 10 parts by weight of needles per 100 parts by weight of resin can be considered as optimal loading. The use of ground needles modified hydrothermally and with silane allows to minimize the negative effect on the strength of glue lines and leads to further reduction of formaldehyde emission. Therefore, it can be concluded that pine needles powder has a strong potential for the application as formaldehyde-scavenging filler for urea-formaldehyde adhesive in plywood production.
Undifferenced and combined time transfer method between stations considering the characteristics of the atomic clock
Authors: Lyu Dong , Liu Genyou , Liao Wei , Zhang Bo , Lyu Minghui
Published: June 2023

The authors have requested that this preprint be removed from Research Square.
Predictive factors associated with favourable neurological outcomes after extracorporeal cardiopulmonary resuscitation for out-of-hospital cardiac arrest: a retrospective multicentre cohort study
Authors: Tominaga Naoki , Takiguchi Toru , Seki Tomohisa , Hamaguchi Takuro , Nakata Jun , Yamamoto Takeshi , Tagami Takashi , Inoue Akihiko , Hifumi Toru , Sakamoto Tetsuya , Kuroda Yasuhiro , Yokobori Shoji
Published: June 2023

Background: Knowledge of the relative contributions of various factors to patient outcomes is crucial for optimal patient selection for extracorporeal cardiopulmonary resuscitation (ECPR) after out-of-hospital cardiac arrest (OHCA). However, evidence pertaining to their effects on neurological outcomes is limited. In this study, we investigated the predictive factors associated with favourable neurological outcomes after ECPR for OHCA.
Methods: We performed a secondary analysis of the SAVE-J II data, a retrospective multicentre registry study involving 36 participating institutions in Japan. Between 2013 and 2018, 2157 patients with OHCA who underwent ECPR were enrolled in SAVE-J II. Adult patients (aged ≥ 18 years) with OHCA, who underwent ECPR before admission to the intensive care unit (ICU), were included in our secondary analysis. Our primary outcome was a favourable neurological outcome at hospital discharge, defined as a Cerebral Performance Category (CPC) score of 1 or 2. We used a multivariate logistic regression model to examine the association between predictive factors measured at the incident scene or upon hospital arrival, and favourable neurological outcomes.
Results: A total of 1823 patients met study inclusion criteria. Multivariable analysis revealed that shockable rhythm at the scene of the OHCA (odds ratio (OR), 2.72; 95% confidence interval (CI), 1.43−5.38) and upon hospital arrival (OR, 2.56; 95% CI, 1.57−4.26), as well as unsustained return of spontaneous circulation (ROSC) (OR, 1.94; 95% CI, 1.02−3.61), gasping (OR, 4.67; 95% CI, 2.80−7.82), and pupillary reflex on arrival (OR, 3.06; 95% CI, 1.82−5.14) were significantly associated with favourable neurological outcomes.
Conclusions: This retrospective multicentre cohort study suggests that shockable rhythm, unsustained ROSC, gasping, and pupillary reflex were associated with particularly favourable neurological outcomes in patients with OHCA undergoing ECPR.
Thermodynamic equilibrium of Al 2 SiO 5 polymorphs in the triple point as a function of rock and fluid composition
Authors: Artimenko Margaret V.
Published: June 2023

For decades the geologists have discussed whether the Al2SiO5 polymorphs (andalusite, kyanite and sillimanite) can co-exists in thermodynamic equilibrium in a real rock at P–T conditions of the triple point or not. A triple-point rock sample was not so far identified reliably in nature. The thermodynamic-potentials minimization technique allows us to determine the bulk rock and fluid composition, other minerals in the assemblage, and other factors that could influence the stability of aluminosilicates. All three polymorphs were predicted to occur simultaneously in a mineral assemblage at P–T conditions of the triple point. Simple mineral assemblages consisting of plagioclase ± quartz ± paragonite ± graphite, biotite ± muscovite ± quartz ± magnetite ± graphite were studied in order to determine the conditions of the stable coexistence of the Al2SiO5 polymorphs. The study demonstrates how the hydrogen-, oxygen- and carbon-content in fluid can define the mineral assemblage and the coexistence of the Al2SiO5 polymorphs in it. The effect of such elements as Na, Fe, Mg, Mn, Ti and P was studied using bulk compositions of natural rock samples. A series of restrictions on the bulk composition of the host rock was identified.
A Simple and Effective Method of Cross-Lingual Plagiarism Detection
Authors: Avetisyan Karen , Malajyan Arthu , Ghukasyan Tsolak , Avetisyan Arutyun , Dou Chunxia
Published: June 2023

We present a simple cross-lingual plagiarism detection method applicable to a large number of languages. The presented approach leverages open multilingual thesauri for candidate retrieval task and pre-trained multilingual BERT-based language models for detailed analysis. The method does not rely on machine translation and word sense disambiguation when in use, and therefore is suitable for a large number of languages, including under-resourced languages. The effectiveness of the proposed approach is demonstrated for several existing and new benchmarks, achieving state-of-the-art results for French, Russian, and Armenian languages.
A New Data-Driven Stock Selection Model Framework Using Portfolio Theory
Authors: Chakraborty Joyita , Chakraborty Shoubhik
Published: June 2023

Stock filtering and selection in a portfolio is a critical problem given the large number of stocks across industries, market capitalizations, tenures, product types; the amount of information regarding their financial health and performance, valuation, company management and the different degrees of uncertainty and volatility associated with each of them. Previous studies propose theoretical models considering mean- variance method and several risk constraints. This paper describes a practical methodology of filtering and selecting stocks with solid fundamentals and available at an attractive valuation, out of thousands of available stocks in the index. Along with Piotroski F-score that considers three parameters- profitability, liquidity, and operating efficiency, we develop two new scores based on comprehensive data analysis- Custom and Valuation score, to gauge the company’s fundamental performance and valuation/expensiveness of the stock price. We consider NSE, India for all analysis, and NIFTY as the index for comparing market performance. We crawl data (source: Bloomberg) of 2,000 exchange-traded stocks for FY 2013–2017 and filter it down to 47 best stocks. Further, we narrow down to 10 final stocks keeping in mind diversification across industry segments, market capitalization and attractiveness of the firm. For validation, we check the performance of these 10 final stocks between 1st April, 2017 and 12th February, 2018. We find that our basket of stocks performed significantly better and give 9.5 times higher returns than market returns. Finally, we also validate the performance as of today with metrics like compounded sales growth, compounded profit growth, stock price CAGR, and Return on Equity.