bluuebunny/crossref_metadata_2025 huggingface dataset:
A generalized disjunctive programming model for the static bike sharing rebalancing problem with demand intervals
Authors: Ikonen Teemu J. , Heljanko Keijo , Harjunkoski Iiro
Published: March 2024

Solving a static bike sharing rebalancing problem requires finding the minimum-cost route for rebalancing vehicles, subject to meeting the demand at the bike sharing stations of the system. In this work, we study the variant of the problem where the demand is specified by intervals, which adds flexibility to the routing of the rebalancing vehicles. We propose a generalized disjunctive programming (GDP) model to represent the problem and its reformulation into a mixed-integer linear programming (MILP) model. We use demand splitting to duplicate stations that require multiple visits. The model is designed for single-vehicle routing but can be used jointly with a clustering approach proposed in the literature for multi-vehicle routing. The model can solve to optimality 86.8\% of benchmark instances with 70 stations within two hours of computing time. On test cases derived from real process data, the model is more than two orders of magnitude faster than the reference model in the literature.
Accuracy of the National Violent Death Reporting System in Identifying Unintentional Firearm Deaths to Children by Children
Authors: Fischer Samuel , Miller Matthew , Barber Catherine , Azrael Deborah
Published: March 2024

Background: In assigning manner of death (MOD) for inclusion on death certificates, medical examiners and coroners have six options: natural, accident, suicide, homicide, undetermined, and pending. Unfortunately, they do not always apply uniform criteria in assigning manner. Previous research indicates surveillance statistics based on death certificates, such as the National Vital Statistics System, grossly miscount firearm accidents. The National Violent Death Reporting System (NVDRS) has taken steps to reduce variability in manner of death coding by providing uniform criteria for assigning an “abstractor manner of death” (AMD). A previous study found good accuracy of AMD coding for firearm accidents, 2003-2006, but a more recent study reported that the NVDRS undercounted self- and other-inflicted firearm accidents in which both the victim and shooter were under age 15.
Findings: We replicated the recent study’s population, identifying 924 NVDRS incidents from 2009-2018 in which both victim and shooter’s age was under 15 and AMD was homicide, suicide, unintentional or undetermined (there were no legal intervention deaths to children). We assigned a researcher-adjudicated MOD (RMD) by reviewing incident narratives, following NVDRS coding guidelines. RMD was compared with AMD and with manner recorded on the death certificate (MOD). Based on RMD as the gold standard, the sensitivity, specificity, and predictive values positive and negative of the AMD for childhood firearm accidents were, respectively 90%, 99%, 98% and 96%; 86% (24/28) of false negatives were coded by abstractors as homicides. By contrast, death certificate manner had relatively poor sensitivity of 63%.
Conclusions: In our sample of 924 deaths, the abstracter manner of death generally agreed with researcher-adjudicated manner of death, though not perfectly, missing 10% of researcher-adjudicated accidents, mostly because abstractors coded accidents as homicides. A sizable minority of false negatives were accidents where the narrative explicitly noted that adult negligence contributed to a child’s unintentional shooting death. While AMD coding in NVDRS is excellent, it could be improved if NVDRS coding guidelines explicitly affirmed that prosecution for negligent manslaughter is not a counterindication to an AMD of accident, provided the firearm was not used to intentionally harm, threaten, or coerce an individual.
How Do Precarious Workers Protect Their Rights? A Case of Chinese Live Streamers
Authors: Xie Chenmin , Xiang Jun , Fu Libing
Published: March 2024

With the rapid development of the Internet, many precarious works relying on platforms have emerged, and the protection of the rights of this group is often infringed upon because of its uncertainty and mobility. But we have no way of knowing whether and to what extent the rights of workers are effectively protected when they have disputes with companies. This study analyses 741 judgment documents using live streamers as a case to explore the different scenarios of protected precarious workers and unprotected workers. The study finds that employees are best protected by a labour contract and should not sign a contract (or agreement) with a company for too long; in terms of company choice, smaller companies reflect better protection of their labour rights and interests. The study is intended to serve as a reference for those who are about to engage in precarious work as well as those who are currently engaged in precarious work, and to contribute to a more standardised and better development of precarious work.
Prevalence of MAFLD in the U.S. Based on NHANES 2009-2018: Differences in Demographic Characteristics, Physical Indices and Lifestyle Conditions
Authors: Ye Dan , Wang Jiaofeng , Shi Jiaheng , Ma Yiming , Li Yanglei , Li Qingshang , Hu Xiaona , Chen Jie , Bao Zhijun
Published: March 2024

Background and Aims: The incidence of metabolic dysfunction-associated fatty liver disease (MAFLD) is high among U.S. adults, but studies on its occurrence in different ethnic and age groups are limited. The aim of the present study was to assess MAFLD occurrence among the United States (U.S.) adults by considering demographic characteristics, physical indices, and lifestyle conditions.
Methods: This study utilized the National Health and Nutrition Examination Survey (NHANES) data 2009-2018 from 23,546 participants aged ≥20 years. Variables such as age, sex, race, body mass index (BMI), waist circumference (WC), blood pressure, sedentary behavior, sleep, and depression were analyzed.
Results: Among 9933 participants, 3562 had MAFLD (34.1%), with notably higher percentages of Mexican-Americans (54.1%) and lower percentages of blacks (20.5%). The incidence of MAFLD was significantly greater (P<0.001) in males (39%) than in females (29.2%), which was particularly evident within the 36-40 years age group. The MAFLD incidence exhibited an age-dependent pattern, initially increasing and subsequently declining (except for whites). Compared to white MAFLD patients, black MAFLD patients exhibited greater BMI, WC, systolic blood pressure (SBP), and diastolic blood pressure (DBP) values, whereas values for these measures were lower among Mexican-American patients. Logistic regression analysis adjusting for age and sex revealed that depression was more common among MAFLD patients (P<0.001), except for severe depression (P>0.05). Notably, the MAFLD incidence was not significantly associated with sedentary behavior or sleep duration.
Conclusions: The MAFLD incidence varies across different racial, age, and sex groups, and targeted interventions are essential for reducing the burden of MAFLD. However, further research is necessary to explore the correlations among MAFLD incidence, sleep patterns, and an inactive lifestyle.
Determinants and willingness to practice obstetric analgesia among women attending antenatal clinic at Dr. Bogalech Gebre Memorial General Hospital Central Ethiopia, 2022
Authors: Geltore Teketel , Alemu Getachew , Taye Ayanos , Sileshi Eden , Bekele Merkin , Foto lakew
Published: March 2024

Background: Contraction is possibly, the most painful experience which is manifested by most women, and the experience of labor pain is exclusive to individual women, hence then, it is only parturient who can label the extent of pain she is going through. This study aimed to evaluate factors influencing the willingness to receive labor analgesia among women attending the antenatal clinic at Dr. Bogalech Gebre Memorial General Hospital Central Ethiopia in 2022.
Methods: A cross-sectional study was conducted involving 398 randomly selected participants. Data was collected using a structured questionnaire through face-to-face interviews from January to March 2023. Information was inputted in EpiData 4.2 and transferred to SPSS version 20 for analysis. Both bivariate and multivariate binary logistic regressions were conducted to determine factors related to pregnant women's willingness to choose labor analgesia. COR and AOR were computed to assess the association between variables.
Results: A total of 398 (94%) pregnant women participated in this study. Overall, 117 (29.4%) of the pregnant women had practiced labor pain management. Being a housewife (AOR: 8.35, 95% CI: 2.07, 33.63. p <). Women who live in urban (AOR: 2.60, 95% CI: 1.29, 5.29).Having had (AOR: 1.70, 95% CI: 1.00, 2.60). The short duration of labor time (AOR: 1.84, 95% CI: 1.15, 2.96) was significantly associated factors with willingness to practice labor analgesia.
Conclusion and Recommendation: We conclude that the willingness of pregnant mothers' toward obstetric analgesia practice was low in the study area. Being a housewife, residence, awareness, and short duration of labor were statistically significant with the willingness of the mothers to practice labor analgesia. Pregnant women in the present study had poor knowledge of obstetric analgesia methods in general. Hence, all responsible bodies have to work on the provision of appropriate health education specifically labor pain management options, and reducing the worries and misunderstandings of parturient to scale up its methods and practice.
Causal Relationship Between Immune Cells and Female Infertility: A Mendelian Randomisation Study
Authors: XIE Yafei , ZHANG Zeling , YIN Qiaozhi
Published: March 2024

Background: Observational and retrospective studies have demonstrated that aberrant immune responses and dysregulation of immune cell populations may be implicated in female infertility. However, the precise relationship between distinct subtypes of immune cells and female infertility remains elusive.
Method: In this study, we conducted a two-sample Mendelian randomization (MR) analysis to examine the causal relationship between 731 immune phenotypes and female infertility. The inverse variance weighting method was employed as the primary estimator, complemented by MR-Egger and weighted median approaches. To address potential bias from single nucleotide polymorphisms (SNPs), we utilized MR-PRESSO. Additionally, Cochran's Q test and MR-Egger intercept analysis were performed to detect heterogeneity and horizontal pleiotropy.
Results: We detected a causal role of fourteen immune phenotypes with female infertility, including CD11c+ CD62L- monocyte AC (OR=1.042,95%CI=1.002-1.083,P=0.037), CD62L-CD86+myeloid DC AC (OR=1.048,95%CI=1.010-1.088,P=0.013),CD62L-CD86+myeloid DC %DC(OR=1.052,95%CI=1.012-1.094,P=0.010), HLA DR++ monocyte AC(OR=1.038,95%CI=1.000-1.078,P=0.049),Activated&restingTregAC(OR=0.900,95%CI=1.838-0.959,P=0.001), Activated&secreting Treg%CD4 Treg(OR=1.009,95%CI=1.001-1.017,P=0.028),CD25hi%CD4+(OR=0.936,95%CI=0.895-0.978,P=0.004),TCRgd AC(OR=1.053,95%CI=1.003-1.106,P=0.039),HLA DR+CD4+%T cell(OR=0.922,95%CI=0.869-0.978,P=0.007),HLA DR+NKAC(OR=0.926,95%CI=0.864-0.993,P=0.031),CD28-DN(CD4-CD8-)%T cell(OR=1.048,95%CI=1.000-1.098,P=0.049),CD19 on IgD+ CD38- unsw mem(OR=1.056; 95%CI=1.026-1.087; p=0.0002),CD24 on IgD+ CD38- unsw mem(OR=0,967,95%CI=0.937-0.997,P=0.033) and CD25 on IgD+CD38- unsw mem(OR=0,977,95%CI=0.964-1.000,P=0.049).
Conclusion:The study demonstrates a causal association between 14 genetically determined immune cell phenotypes and female infertility, thereby identifying novel drug targets for the prevention and treatment of this condition.
Assessing CMIP6 uncertainties at global warming levels
Authors: Evin Guillaume , Ribes Aurélien , Corre Lola
Published: March 2024

IPCC reports and climate change impact studies generally exploit ensembles of climate projections based on different socio-economic pathways and climate models, which provide the temporal evolution of plausible future climates. However, The Paris Agreement and many national and international commitments consider adaptation and mitigation plans targeting future global warming levels. Model uncertainty and scenario uncertainty typically affect both the crossing-time of future warming levels and the climate features at a given global warming level. In this study, we assess the uncertainties in a multi-model multi-member CMIP6 ensemble (MME) of seasonal and regional temperature and precipitation projections. In particular, we show that the uncertainties of regional temperature projections are considerably reduced if considered at a specific global warming level, with a limited effect of the emission scenarios and a reduced influence of GCM sensitivity. We also describe in detail the large uncertainties related to the different behavior of the GCMs in some regions.
The role of systemic inflammatory indices in predicting nausea and vomiting in pregnancy and the need for hospitalization
Authors: Dereli Murat Levent , Özkan Sadullah , Üçok Belgin Savran , Topkara Serap , Sucu Sadun , Fıratlıgil Fahri Burçin , Kurt Dilara , Kurt Ahmet , Çelen Şevki , Üstün Yaprak Engin
Published: March 2024

Purpose
To investigate the role of the systemic immune-inflammation index (SII), systemic inflammatory response index (SIRI) and pan-immune inflammation value (PIV) in predicting nausea and vomiting in pregnancy (NVP)
Methods
Women diagnosed and managed for NVP at a large tertiary hospital between 2016 and 2021 were retrospectively analyzed. After applying the inclusion criteria, a total of 278 eligible patients with NVP and 278 gestational age-matched healthy pregnant women were included. Patients with NVP were divided into mild (n = 58), moderate (n = 140) and severe NVP (n = 80). Patients with moderate and/or severe NVP who were at high risk for hospitalization were pooled and assigned to an inpatient treatment group. The groups were then compared.
Results
SII and PIV were significantly higher in the NVP group than in the control group, while SII, SIRI and PIV were significantly higher in the inpatient treatment group than in the mild NVP group. The comparison of overall performance in predicting NVP development showed that SII was better than PIV (p < 0.001), while there was no significant superiority between SII, SIRI and PIV in predicting inpatient treatment needs. An SII with a cut-off value of > 1207x103/µL (47.48% sensitivity, 82.01% specificity) had the highest discriminatory power for predicting a pregnancy in which NVP will develop.
Conclusions
Our results suggest an association between high SII and PIV and an increased risk of future NVP. These markers can be used as a first-trimester screening test to improve treatment planning of pregnancies at high risk of HG.
Tumor-site directed A1R expression enhances CAR T cell function and improves efficacy against solid tumors
Authors: Darcy Phillip , Sek Kevin , Chen Amanda , Cole Thomas , Armitage Jesse , Tong Junming , Yap Kah Min , Munoz Isabelle , Dunbar Phoebe , Giuffrida Lauren , Henderson Melissa , meyran deborah , Nguyen Dat , Huang Yu-Kuan , de Menezes Maria N. , Derrick Emily , Chan Cheok Weng , Todd Kirsten , Chan Jack , Li Jasmine , Lai Junyun , Petley Emma , Mardiana Sherly , Bosco Anthony , Waithman Jason , Parish Ian , Mølck Christina , Stewart Gregory , Kats Lev , House Imran , Beavis Paul
Published: March 2024

The efficacy of Chimeric Antigen Receptor (CAR) T cells against solid tumors is limited by immunosuppressive factors in the tumor microenvironment (TME) including adenosine, which
suppresses CAR T cells through activation of the A2A receptor (A2AR). To overcome this, CAR T cells were engineered to express A1R, a receptor that signals inversely to A2AR. Using murine and human CAR T cells, constitutive A1R overexpression was demonstrated to significantly enhance CAR T cell effector function albeit at the expense of CAR T cell persistence. Through a novel CRISPR/Cas9 “knock-in” approach we demonstrated that CAR T cells engineered to express A1R in a tumor-localized manner, led to enhanced anti-tumor efficacy dependent on the
transcription factor IRF8. This data provides a novel approach for enhancing CAR T cell efficacy in solid tumors and provides proof of principle for site-directed expression of factors that promote effector T cell differentiation.
Assessing biochemical and clinical analysis results of infertile male patients in comparison with spermiogram results
Authors: Sarikaya Selcuk , Kiliccalan Ibrahim , Caglar Emel , Serdar Muhittin , Bedir Selahattin , Ozgurtas Taner
Published: March 2024

Infertility is recently a common health problem among the populations. Our study aims to reveal the clinical outcomes of infertile male patients that were evaluated comparatively according to spermiogram results. Male infertility patients between the ages of 18–50 with regular health records were included in the study. Men under the age of 18, over the age of 50 and who did not seek children were excluded from the study. Demographic data, questionnaire scores, hormonal parameters and spermiogram results were examined and comparatively analyzed. 133 patients were included. Patietns with abnormal spermiogram results had higher mean FSH(mIU/mL) and LH(mIU/mL) values. Patients with normal spermiogram results had higher sperm concentration(mil/mL) and sperm motility(%a + b).(p < 0.05) Azoospermia patients had highest mean FSH(mIU/mL) and WBC(*10^3cells/uL) values and teratozoospermia patients had the lowest.(p < 0.05) Patients with normal results had lowest mean LH(mIU/mL) values while azoospermia patients had the highest.(p < 0.05) Asthenoteratozoospermia patients had highest mean LYM(*10^3cells/uL) values while patients with normal results had the lowest.(p < 0.05) Although statistically significant differences were not observed in terms of trace element analysis and many laboratory results, our study is important due to limited number of studies for especially trace element analysis in infertile male patients.
What the textbooks don’t teach about the reality of running a digitally enabled health study: a qualitative interview study
Authors: Bradway Meghan , Garbarron Elia , Larbi Dillys , Breivik Elin , Muzny Miroslav , Årsand Eirik
Published: March 2024

Background: Most studies do not produce their intended outcomes on time or within budget. However, it is challenging to identify the facilitators and barriers to successful study management when the “behind the scenes action” of especially digitally enabled health research studies are akin to a black box. Therefore, it is necessary to explore first-hand experience of the facilitators and barriers to managing digitally enabled health studies. The goal of such studies is to produce new knowledge and/or developed tools that can be translated to real-world benefits for the health and care sector, individuals, and other stakeholders. These studies now exist in a time that encourages collaborative research activities with interdisciplinary research partnerships, industry collaboration, end-user involvement and insights for policy. These expectations require teams with different work cultures, methodologies, technologies, and approaches to work together, resulting in significant benefits but also challenges.
Methods: We interviewed 15 research team members from eight digitally enabled health studies about their experience and perception of the management of their studies. A semi-structured interview guide was used to explore concepts related to study activity management, team dynamics, and resources and technologies used to manage research activities. An adductive thematic analysis was performed on the transcripts.
Results: Five main themes were identified: 1) Project Team, 2) Study management, which included management technologies, 3) Study plan, 4) Intervention, 5) Participants. This paper focuses on the first two main themes. Sub-themes included: Roles and responsibilities, Methods, Changes, Challenges and solutions and Expectations vs. reality. Sub-themes were applicable to all main themes. Therefore, results were presented as knowledge gained from the interaction between sub-themes within each theme, i.e. referred to as “comprehensive insights” in the results section of this paper.
Conclusion: This interview study provides new knowledge about the realities of working in collaborative, digitally enabled, health research studies, and demonstrates several opportunities for improved understanding of study management. More realistic and thorough understanding of the complex system in which digitally enabled health research exists can be applied to better prepare experienced researchers and newly graduated students entering the field, as well as improve existing strategies for management.
SESAME - Self-supervised framework for Extractive queStion Answering over docuMent collEctions
Authors: Batista Vitor Alcantara , Gomes Diogo Silva Magalhães , Evsukoff Alexandre Gonçalves
Published: March 2024

Question Answering is one of the most relevant areas in the field of Natural Language Processing, rapidly evolving with promising results due to the increasing availability of suitable datasets and the advent of new technologies, such as Generative Models. This article introduces SESAME, a Self-supervised framework for Extractive queStion Answering over docuMent collEctions. SESAME aims to enhance open-domain question answering systems (ODQA) by leveraging domain adaptation with synthetic datasets, enabling efficient question answering over private document collections with low resource usage. The framework incorporates recent advances with large language models, and an efficient hybrid method for context retrieval. We conducted several sets of experiments with Machine Reading for Question Answering (MRQA) 2019 Shared Task datasets, FAQuAD - a Brazilian Portuguese reading comprehension dataset, Wikipedia, and Retrieval-Augmented Generation Benchmark, to demonstrate SESAME's effectiveness. The results indicate that SESAME's domain adaptation using synthetic data significantly improves QA performance, generalizes across different domains and languages, and competes with or surpasses state-of-the-art systems in ODQA.Finally, SESAME is an open-source tool, and all code, datasets and experimental data is available for public use in our repository.
Therapeutic inhibition of glycolysis preferentially targets pathogenic monocyte subsets and attenuates CNS inflammation in flavivirus encephalitis
Authors: King Nicholas , Wishart Claire , Spiteri Alanna , Tan Jian , Macia Laurence
Published: March 2024

Infiltrating monocytes play a dual role in central nervous system (CNS) diseases, both driving and attenuating inflammation. However, it is unclear how metabolic pathways preferentially fuel protective or pathogenic processes and whether these can be therapeutically targeted to enhance or inhibit these opposing functions. Here, we employed single-cell RNA-sequencing and metabolic protein flow analysis of brain and bone marrow (BM) to map the metabolic signatures of monocyte-derived cells (MCs) to their functions during lethal West Nile virus encephalitis. Using trajectory analysis, we showed progression of BM monocytes through 3 metabolic profiles before their migration to the brain where they differentiated into metabolically distinct MC populations. These included a single pro-inflammatory HIF1-α MC cluster that diverged into two disparate populations: an inducible nitric oxide synthase-positive (iNOS+) M1-like MC, with high glycolysis and amino acid metabolic scores, and a glycolytically quiescent, MHC-II+ antigen-presenting MC. Daily in vivo glycolysis inhibition with 2-deoxy-D-glucose significantly reduced CNS leukocyte numbers, reducing neuroinflammation and disease signs without increasing viral load. Reduced leukocyte numbers were not due to decreased myelopoiesis, but a preferential decrease in iNOS+, compared to antigen-presenting MC, highlighting different glycolytic dependencies between these subsets. Importantly, HIF1-a was independent of glycolysis, enabling continued antigen-presenting MC differentiation, while glycolysis inhibition did not impair generation of an effective antiviral response by cervical node T cells. Together, this integrative approach unveils the tight coupling of MC function and metabolism in viral CNS disease, highlighting novel metabolic therapeutic intervention points, potentially with anti-viral therapy, during severe or uncontrolled inflammation.
Detecting atypical sentinel lymph nodes in early-stage cervical cancer using a standardized technique with a hybrid tracer
Authors: Vila Joana Amengual , Colomer Anna Torrent , Bas Catalina Sampol , Duarte Adriana Quintero , Coll Mario Ruiz , Merlo Jorge Rioja , Cordoba Octavi
Published: March 2024

Background
Since October 2018, lymph node (LN) status has become part of the International Federation of Gynaecology and Obstetrics (FIGO) staging, given that it is one of the most important prognostic factors among women with cervical cancer (CC).
The aim of this study was to determine the rate of atypical lymphatic drainage in patients with clinical early-stage CC using a hybrid tracer (ICG-99mTc nanocolloid).
Methodology
A prospective, observational, descriptive, single-centre study conducted at Son Espases University Hospital between January 2019 and October 2023. Patients with clinical early-stage CC who underwent SLN mapping during surgical staging were included. External iliac and obturator nodes were defined as common SLN locations. Para-aortic, common iliac, presacral, internal iliac, and parametrial nodes were defined as uncommon (atypical) locations.
Results
Thirty-nine cases of CC were included. Overall SLN detection rate was 97.4%, with 89.5% bilaterally. Positive SLNs were found in 21.1% of patients. Atypical lymphatic drainage was present in 8 out of 38 (21.1%). Of the total SLNs (146), 10.3% corresponded to an atypical zone (the most frequent, common iliac vessels). SLNs in the atypical area had a higher proportion of metastasis than the usual area (37.5% vs. 16.7%; p=0.327).
Parametrial nodes were detected in 17.9% of patients; two of these (5.2%) with the presence of metastases. In all cases where a parametrial SLN was detected, drainage was also observed to a SLN in a common location. There was no involvement of parametrial lymphatic channels or parametrial nodes in any patient (7/8, 87.5%) with metastatic pelvic SLNs.
Conclusion
SLN biopsy can detect unusual drainage in a significant proportion of patients with CC. SLNs in atypical locations have a higher percentage of metastatic involvement, which consequently improves staging and tailoring therapy. Our series suggests that lymphatic drainage from the cervical tumour to the pelvic nodes could be a direct route that bypasses parametrial nodes.
We suggest that SLN mapping performed by a standardized surgical technique using a hybrid tracer (ICG-99mTc) could help in the identification of the "true sentinel lymph node" and ensure no empty node packet is obtained.
BCAP29/31 as a Poor Prognostic Biomarker for Head and Neck Squamous Carcinoma: Impacting the TGFβ1/Smad- EMT Pathway
Authors: Zhang Shurong , Gao Lihua , Gao Wen , Zhu Xiaoyu , Liao Yuxuan , Ma Xinyu , Wang Hongyi , Zhou Dawei , Zhang Bo , Chen Liangjian
Published: March 2024

Objectives This study aimed to investigate the possible mechanism of action of BCAP29/31 in head and neck squamous cell carcinoma (HNSC) and to provide clues for finding new therapeutic targets for HNSC.
Materials and methods We performed several data analyses including Kyoto Encyclopedia of the Genome (KEGG) and Gene Ontology (GO) analyses, immune infiltration, and single-cell analyses using databases such as TIMER2.0, TISIDB, STRING, Metascape, and GRNdb. The possible mechanism of action of BCAP29/31 in HNSC was investigated and validated using Q-PCR real-time fluorescence quantitative analysis.
Results BCAP29/31 manifested a trend of overexpression and a certain mutation rate in HNSC. BCAP29/31 are each other's members of the protein interactions network and are associated with calcineurin binding and vesicle transport function. BCAP29/31 demonstrated the same trend correlating with CD8+ T and B cells, and abnormal associations with endothelial cell and macrophage infiltration levels.
Conclusion The overexpression of BCAP29/31 is correlated with poor prognosis in HNSC and may affect the TGFβ1/Smad epithelial-mesenchymal transition (EMT) process. Overexpression of BCAP29/31 may be a factor causing the aberrant level of immune infiltration in HNSC. In conjunction with existing clinical treatment options, knockdown of BACP29/31 or targeted elimination of tumor-associated macrophage M2 tumor-associated macrophages (TAM M2) may help improve anti-PD-1/PD-L1 efficacy.
Clinical Relevance Our study elucidated the mechanism of action in which BCAP29/31 may be involved in HNSC. The results supported the use of BCAP29/31 as a poor prognostic biomarker for HNSC and offered new insights to improve the efficacy of anti-PD-1/PD-L1 therapies in HNSC in the future.
Likelihood of a novel pathogenic LDLR mutant allele inherited preferentially within an Indian family with familial hypercholesterolemia
Authors: Reddy Lakshmi Lavanya , Shah Swarup A. V , Paradkar Minal , Ponde Chandrashekhar K , Rajani Rajesh , Pillai Sudhir , Pradhan Dibyabhaba , Singh Harpreet Singh , Ashavaid Tester F
Published: March 2024

Background & Aims:
Familial hypercholesterolemia (FH) is an autosomal dominant disorder characterized by increased levels of low-density lipoprotein cholesterol (LDL-C). LDL receptor (LDLR) gene mutations is the primary genetic cause thereby necessitating the screening of family members for early detection and management. We aim to report an Indian family with FH harboring a novel pathogenic nonsense mutation in LDLR gene with a strong likelihood of preferential transmission.
Methods
EDTA blood samples were collected from the available family members upon obtaining written informed consent. Genotyping for LDLR mutation was performed by PCR amplification and Sanger sequencing. 11 of the 16 family members were clinically affected and identified as having dyslipidemia. A novel mutation (c.743_744delinsAA) in exon 5 of LDLR gene was identified in the proband and 05 of the investigated family members that were dyslipidemic. In silico tools predicted, the novel mutation to be pathogenic and deleterious.
Conclusions
The present case study of an Indian family with FH identifies a novel pathogenic LDLR mutation (c.743_744delinsAA), which is predicted to induce non-decay mediated mRNA decay (NMD). Based on the inheritance pattern of the mutant LDLR allele, across the 3 generations, there seem to be a strong likelihood of preferential transmission of mutant allele indicating genetically-biased fertilization over the wild-type allele. This case report for a first time suggests a strong likelihood of preferential transmission in FH and underscores the importance of genetic testing for FH diagnosis as well as cascade screening for early detection, risk stratification and implementation of preventive strategies.
Declining number of general practitioners can impair influenza vaccination uptake in Italy
Authors: Domnich Alexander , Lapi Francesco , Orsi Andrea , Grattagliano Ignazio , Rossi Alessandro , Cricelli Claudio , Icardi Giancarlo
Published: March 2024

Background
As in many other countries, seasonal influenza vaccination coverage in Italian older adults is insufficient. In Italy, most influenza vaccine doses are administered by general practitioners (GPs), whose number has been declining in recent years. In parallel, the number of patients per GP and consequent GP workload increased dramatically. In this longitudinal study, we aimed to test whether influenza vaccination coverage may be affected by the increased GP workload.
Methods
The study outcome was the influenza vaccination coverage rate in adults aged ≥ 65 years and registered in 20 Italian regions over the last 23 years. The independent variable of interest was GP workload, proxied as the proportion of GPs with more than 1,500 patients, which is an imposed normative ceiling. By adopting an econometric approach, different specifications of fixed- and random-effects panel regression models were run to assess the association of interest, when adjusted for potential confounders.
Results
Over the last two decades, most regions showed a negative association between influenza vaccination coverage rates and the density of GPs with a high number of patients. This latter negative association was confirmed (P < 0.05) in different panel model specifications. In particular, in the fully adjusted two-way fixed-effects model, which explained 72.6% of the variance, each 10% increase in the number of GPs with more than 1,500 patients was associated with a 1.7% decrease in influenza vaccination coverage. However, this association was present only in region-years where at least 18% of GPs were deemed overloaded.
Conclusions
In the upcoming years, the number of Italian GPs is projected to decline further. At the same time, the aging Italian population will determine an even greater workload for GPs. This study demonstrated that increased GP workload may partially explain the spatiotemporal variation in influenza vaccination uptake in the Italian elderly. With the imperative of increasing or at least maintaining influenza vaccination coverage rates, several short- and mid-term initiatives should be implemented in order to optimize GP workload during seasonal immunization campaigns.
Disease pattern and mortality rate among patients admitted to the Intensive Care Unit in Arbaminch General Hospital, Southern Ethiopia
Authors: Daniel Tigabu , Abera Yonas , Yihune Menaye
Published: March 2024

Background: Disease patterns in intensive care Unit is differ from place to place. Cardiac disease, septic shock, trauma, and acute abdomen are the common causes of admission. The mortality rate in the Intensive Care Unit (ICU) was higher than that in the other hospital units. Our aim was to assess the common admission diagnosis and mortality rate among Intensive Care Unit (ICU) patients in the Arbaminch General Hospital.
Methods: A retrospective cross-sectional study was conducted based on a review of the records and charts of patients admitted from January 1, 2019, to January 1, 2021. Descriptive statistics were also calculated. An independent variable effect on the mortality rate was observed.
Result: The most common admission diagnoses were cardiac and other medical diseases, septic shock and ARDS followed by acute abdomen and other surgical diseases. The overall mortality rate was 40.7%. On multivariate logistic regression analysis, no significant mortality rate affecting factors were identified.
Conclusion: Cardiac and other medical diseases were the most common admissions diagnoses, with an overall mortality rate of 40.7%. No significant association was found between the mortality rate and independent variables in the multivariate logistic regression.
Nanopore direct RNA sequencing provides additional insight into transcriptome differentiation during transition to the aquatic environment of amphibious liverwort Riccia fluitans L. (Marchantiales)
Authors: Maździarz Mateusz , Krawczyk Katarzyna , Kurzyński Mateusz , Paukszto Łukasz , Szablińska-Piernik Joanna , Szczecińska Monika , Sulima Paweł , Sawicki Jakub
Published: March 2024

Background
Riccia fluitans, an amphibious liverwort, exhibits a fascinating adaptation mechanism to transition between terrestrial and aquatic environments. Utilizing nanopore direct RNA sequencing, we try to capture the complex epitranscriptomic changes undergo in response to land-water transition.
Results
A significant finding is the identification of 45 differentially expressed genes (DEGs), with a split of 33 downregulated in terrestrial forms and 12 upregulated in aquatic forms, indicating a robust transcriptional response to environmental changes. Analysis of N6-methyladenosine (m6A) modifications revealed 173 m6A sites in aquatic and only 27 sites in the terrestrial forms, indicating a significant increase in methylation in the former, which could facilitate rapid adaptation to changing environments. The aquatic form showed a global elongation bias in poly(A) tails, which is associated with increased mRNA stability and efficient translation, enhancing the plant's resilience to water stress. Significant differences in polyadenylation signals were observed between the two forms, with nine transcripts showing notable changes in tail length, suggesting an adaptive mechanism to modulate mRNA stability and translational efficiency in response to environmental conditions. This differential methylation and polyadenylation underline a sophisticated layer of post-transcriptional regulation, enabling Riccia fluitans to fine-tune gene expression in response to its living conditions.
Conclusions
These insights into transcriptome dynamics offer a deeper understanding of plant adaptation strategies at the molecular level, contributing to the broader knowledge of plant biology and evolution. These findings underscore the sophisticated post-transcriptional regulatory strategies Riccia fluitansemploys to navigate the challenges of aquatic versus terrestrial living, highlighting the plant's dynamic adaptation to environmental stresses and its utility as a model for studying adaptation mechanisms in amphibious plants.
Prognosis and management of chronic obstructive pulmonary disease in a real-world setting: A 5-year follow-up analysis of a multi-institutional registry
Authors: Takano Tomotsugu , Tsubouchi Kazuya , Hamada Naoki , Ichiki Katsuyuki , Torii Ryo , Takata Shohei , Kawakami Satoru , Nakagaki Noriaki , Yoshida Makoto , Kitasato Yasuhiko , Tobino Kazunori , Harada Eiji , Ishii Hiroshi , Wataya Hiroshi , Maeyama Takashige , Fujita Masaki , Yatera Kazuhiro , Okamoto Masaki , Yabuuchi Hidetake , Kiyomi Fumiaki , Tokunaga Shoji , Nakanishi Yoichi , Okamoto Isamu
Published: March 2024

Background
We conducted a prospective observational study to elucidate the long-term prognosis and management of chronic obstructive pulmonary disease (COPD) in Japan in the mid-2010s in clinical practice.
Methods
This prospective cohort study included 29 facilities. A total of 427 patients clinically diagnosed with COPD, enrolled between September 2013 and April 2016, were analysed. Interstitial pneumonia was excluded through a central multidisciplinary discussion. Follow-up data were collected for up to 5 years after patient registration.
Results
In total, 67 patients clinically diagnosed with COPD did not have airflow limitations (AFL) at the time of registration. In the cohort with AFL (n=370), 266 patients completed a 5-year follow-up, while 58 patients died during the 1556.7 person-years of observation. The overall 5-year survival rate was 85.2%. Stratified by % forced expiratory volume in one second (FEV1), survival rates were 93.4% in the 50 ≤ %FEV1 group, 82.5% in the 30 ≤ %FEV1 < 50 group, and 66.1% in the %FEV1 < 30 group. The prognosis of the subpopulation without AFL was poor with 5-year survival of 83.0%. This subpopulation exhibited respiratory symptoms, low vital capacity and total lung capacity, and emphysematous changes.
Conclusions
Our study presents the 5-year survival and real-world clinical practice scenario of a prospective cohort of patients clinically diagnosed with COPD in Japan in the mid-2010s. Overall, 13% of the patients in this cohort did not show AFL at registration with respiratory symptoms, distinct spirometric patterns, and poor prognosis.
Umbilical Artery Atherosclerosis as the Risk Factor for Anorectal Malformation
Authors: Diposarosa Rizki , Pamungkas Kurniawan Oki , Anita Melian , Wikanadi Sinung
Published: March 2024

Background: Anorectal malformation (ARM) is a congenital anomaly in which the anus and rectum are not normally developed. The causes of this anomaly are thought to be multifactorial. Umbilical cord pathology is related to various congenital anomalies and atherosclerosis of the umbilical artery may induce negative effects on the fetus, therefore, this study analyzed the correlation between umbilical artery atherosclerosis and the incidence of ARM.
Method: This case-control study was conducted between November 2020 and March 2021. Umbilical cord samples were taken from neonates with/without ARM and evaluated for the presence of umbilical artery atherosclerosis. Spearman analysis was utilized to determine any correlations.
Result: Umbilical cord samples from 30 newborns without ARM and 30 newborns with ARM were analyzed revealing that 10 newborns with ARM had initial atherosclerotic lesions in their umbilical artery.
Conclusion: The incidence of an initial atherosclerotic lesion instead of an atherosclerotic lesion in the patients with ARM was significantly correlated with the incidence of ARM.
Onion Peel Extract/Copper Oxide Nanoparticles as Corrosion Inhibitors for Carbon Steel in Hydrochloric Acid; Extraction, Characterization, Electrochemical Study, and Theoretical Explorations
Authors: Darweesh Mona , Emam Sanaa M. , Wahba Adel , Ayad Mohamed I. , El-Nahass Marwa , Abdelhamied Amany , Hammad Wafaa
Published: March 2024

The effectiveness of onion peel extract, (OPE), for carbon steel in one molar (1 M) hydrochloric acid solution was illustrated utilizing weight loss (WL) techniques, potentiodynamic polarization (PDP), electrochemical impedance spectroscopy (EIS), and surface morphological examination. Also, this process was characterized using Fourier transform infrared (FT-IR), energy dispersive X-ray spectroscopy (EDX), thermogravimetric analysis (TGA), atomic force microscopy (AFM), and scanning electron microscope (SEM). The protective efficiency rises as OPE concentration rises and decreases with corrosive solution temperature, according to weight loss measurements. Polarization curves display that OPE behaves as a mixed-type inhibitor in hydrochloric acid. The adsorption process mechanism is supported by EIS, which demonstrates that charge-transfer resistance rises, and double-layer capacitance falls with inhibitor concentration. OPE adhering to carbon steel follows the Langmuir isotherm, through a physical adsorption process and the inhibitor molecules were shown to have spontaneously adsorbed onto the carbon steel based on the negative values of Gibb's free energy of adsorption. The synergistic effect of copper oxide nanoparticles, CuO-NPs in combination with OPE on the inhibition corrosion of carbon steel was evaluated. The results showed that the inhibition efficiency of OPE increases in the presence of CuO-NPs due to synergistic interactions of OPE extract molecules with CuO-NPs. The electron-donating capacity of the chemical component of the OPE has been shown in theoretical studies employing quantum chemistry methods.
Manifestations and Biomarkers to Predict Mortality Risk in Adults with Invasive Streptococcus dysgalactiae
Authors: Hanada Shigeo , Wajima Takeaki , Takata Misako , Morozumi Miyuki , Shoji Michi , Iwata Satoshi , Ubukata Kimiko
Published: March 2024

Purpose: The incidence of invasive Streptococcus dysgalactiae subsp. equisimilis (iSDSE) infections is increasing in developed countries, but studies on the risk factors for death in iSDSE infection are scant. Here, we aimed to clarify risk factors and predictors of mortality in adults with iSDSE infection.
Methods: A multicentre observational study of adults with iSDSE infection (n = 588) was conducted to investigate the effects of host factors, disease severity, biomarkers, and antibiotic regimens, and bacterial factors on 28-day mortality.
Results: The overall mortality rate was 10.4%, with a significant increase in those aged ≥60 years. Most of the patients (97.4%) had some underlying diseases. The mortality rate (70.4%) of patients with severe disease was significantly higher than that of patients with mild-to-moderate disease (4.3%). The risk factors for death identified using multivariate analysis were age ≥60 years (hazard ratio [HR], 3.4; 95% confidence interval [CI], 1.0–11.3, p = 0.042); severe disease (HR, 15.0; 95% CI 7.7–29.2, p < 0.001); bacteraemia without primary focus (HR, 20.5; 95% CI 2.8–152.3, p = 0.003); serum creatinine ≥2.0 mg/dL (HR, 2.2; 95% CI 1.2–4.0, p = 0.010); serum creatine kinase ≥300 IU/L (HR, 2.1; 95% CI 1.1–3.8, p = 0.019); and macrolide resistance (HR, 1.8; 95% CI 1.0–3.3, p = 0.048). Treatment regimens and emm types were not associated with poor outcomes.
Conclusion: Evaluation of clinical manifestations and biomarkers on admission is important to predict invasive SDSE infection prognosis.
Effects of grassland duration on butterfly communities and its relevance to grassland area
Authors: INOUE Taiki , KENTA Tanaka
Published: March 2024

Semi-natural grasslands, renowned for their rich biodiversity, are experiencing global decline, necessitating urgent conservation prioritization. Recently, researches have established that the vegetation history significantly influences grassland biodiversity. This study focuses on three vegetation types in and around ski-run grasslands of central Japan: (i) ancient or old grasslands persisting for 300 to several millennia, (ii) new grasslands recently converted from forests 43 to 72 years ago, and adjacent forests serving as control vegetation type. We examined the effect of grassland duration, in relation to its spatial area, on butterfly communities. Transects of 5 × 20 m were established at six to seven sites for each vegetation type to survey butterfly communities. In 2017, plant communities were similarly surveyed along the same transects (Inoue, Yaida et al., 2021). Species composition, species count, and overall butterfly abundance were not affected by grassland duration. Nevertheless, the species composition was affected by the spatial area of old grasslands within a 100 m radius of each transect, with an increase in the number of rare grassland species in extensive old grasslands. Minois dryas and Eurema mandarina were identified as indicator species of extensive old grasslands (>8000 m2 within 100 m radius of each transect), whereas no indicator species were detected in the other grassland sites. The abundances of M. dryas, Brenthis daphne, Melitaea ambigua, Curetis acuta, and Zophoessa callipteris were greater in areas where the areas of old grasslands within 100 m of each transect were greater. The previous study at these sites have shown that Sanguisorba officinalis (Rosaceae), the host plant of B. daphne, and Lespedeza bicolor (Fabaceae), the main host plant of E. mandarina and C. acuta, are indicators of old grasslands, explaining the dependency of these three butterfly species on old grasslands. Our findings suggest that extensive old grasslands should be accorded high conservation priority to preserve diversity of grassland butterflies.