bluuebunny/crossref_metadata_2025_split huggingface dataset:
Exploration of Signature Genes and Their Correlation with Immune Cell Infiltration in Cirrhosis
Authors: Li Yuxin , Zhang Wenjie , Mao Lina , Ma Yue , Wang Qiangsong , Zhao Yuanyuan 
Published: March 2024

Abstract
Early diagnosis of cirrhosis is crucial for improving patient prognosis. This study aims to investigate signature genes and their correlation with immune cell infiltration in cirrhosis. We utilized a liver cirrhosis patient dataset obtained from the GEO database to identify differentially expressed genes (DEGs). Weighted gene co-expression network analysis (WGCNA), least absolute shrinkage and selection operator (LASSO), and random forest analysis were employed to identify signature genes, including RGS1, DEFB1, and ANOS2P. Subsequently, gene set enrichment analysis (GSEA) revealed that these signature genes are associated with positive correlations with allograft rejection and the focal adhesion pathway. Moreover, CIBERSORT analysis suggested potential involvement of these signature genes in immune cell infiltration within cirrhotic conditions. This study enhances our understanding of cirrhosis pathogenesis and may contribute to the development of early diagnostic tools and therapeutic strategies.
Short-term lipopolysaccharide treatment leads to astrocyte activation in LRRK2 G2019S knock-in mice without loss of dopaminergic neurons
Authors: Ngo Hoang Kieu Chi , Le Hoang , Ayer Samuel J. , Crotty Grace F. , Schwarzschild Michael A. , Bakshi Rachit 
Published: March 2024

Abstract
Background
The G2019S mutation of LRRK2, which enhances kinase activity of the protein, confers a substantial risk of developing Parkinson’s disease (PD). However, the mutation demonstrates incomplete penetrance, suggesting the involvement of other genetic or environmental modulating factors. Here, we investigated whether LRRK2 G2019S knock-in (KI) mice treated with the inflammogen lipopolysaccharide (LPS) could model LRRK2 PD.
Results
We found that short-term (2 weeks) treatment with LPS did not result in the loss of dopaminergic neurons in either LRRK2 G2019S KI or wild-type (WT) mice. Compared with WT mice, LRRK2 G2019S-KI mice showed incomplete recovery from LPS-induced weight loss. In LRRK2 G2019S KI mice, LPS treatment led to upregulated phosphorylation of LRRK2 at the autophosphorylation site Serine 1292, which is known as a direct readout of LRRK2 kinase activity. LPS treatment caused a greater increase in the activated astrocyte marker glial fibrillary acidic protein (GFAP) in the striatum and substantia nigra of LRRK2 G2019S mice than in those of WT mice. The administration of caffeine, which was recently identified as a biomarker of resistance to developing PD in individuals with LRRK2 mutations, attenuated LPS-induced astrocyte activation specifically in LRRK2 G2019S KI mice.
Conclusions
Our findings suggest that 2 weeks of exposure to LPS is not sufficient to cause dopaminergic neuronal loss in LRRK2 G2019S KI mice but rather results in increased astrocyte activation, which can be ameliorated by caffeine.
A vehicle-to-infrastructure communication privacy protocolused Blockchain
Authors: Harrabi Samira , Jaafar Ines Ben , Omrani Oumaima 
Published: March 2024

Abstract
Since several decade, the Internet of Things IoT hasattracted enormous interest in the research communityand industry. However, IoT technologies has completelytransformed vehicular ad hoc networks (VANETs) intothe "Internet of Vehicles" IoV. In IoV networks, we needto integrate many different technologies, services andstandards. However, the heterogeneity and large numberof vehicles will increase the need of data security.The IoV security issues are critical because of the vulnerabilitiesthat exist during the transmission of informationthat expose the IoV to attacks. Each attack hasa security procedure. Many protocols and mechanismsexist to combat or avoid this communication securityproblem. One of these protocols is VIPER (a Vehicleto-Infrastructure communication Privacy EnforcementpRotocol). In our work, we try to improve this protocolby using Blockchain technology and certificationauthority.
Ramucirumab for advanced hepatocellular carcinoma in the current real world: A Japanese single-arm study post-REACH-2 (The R-evolution Study)
Authors: Kobayashi Kazufumi , Ogasawara Sadahisa , Itobayashi Ei , Okubo Tomomi , Itokawa Norio , Nakamura Kazuyoshi , Moriguchi Michihisa , Watanabe Shunji , Ikeda Masafumi , Kuroda Hidekatsu , Kawaoka Tomokazu , Hiraoka Atsushi , Yasui Yutaka , Kuzuya Teiji , Sato Rui , Kanzaki Hiroaki , Koroki Keisuke , Inoue Masanori , Nakamura Masato , Kiyono Soichiro , Kanogawa Naoya , Kondo Takayuki , Nakamoto Shingo , Ozawa Yoshihito , Tsuchiya Kaoru , Atsukawa Masanori , Aikata Hiroshi , Aramaki Takeshi , Oka Shiro , Morimoto Naoki , Kurosaki Masayuki , Itoh Yoshito , Izumi Namiki , Kato Naoya 
Published: March 2024

Abstract
Background
This study aimed to complement the results of the REACH-2 study by prospectively evaluating the safety and efficacy of ramucirumab in advanced hepatocellular carcinoma (HCC) in a real-world setting.
Methods
This was an open-label, nonrandomized, multicenter, prospective study conducted at 13 institutions in Japan (jRCTs031190236). The study included Child–Pugh Class A patients with advanced HCC who had received pretreatment with atezolizumab plus bevacizumab (Atez/Bev) or lenvatinib. Ramucirumab was introduced as a second-line treatment after Atez/Bev or lenvatinib and as a third-line treatment after Atez/Bev and lenvatinib.
Results
Between May 2020 and July 2022, we enrolled 19 patients, including 17 who received ramucirumab. Additionally, seven patients received lenvatinib, another seven patients received Atez/Bev, and three patients received Atez/Bev followed by lenvatinib as prior treatment. The primary endpoint was a 6-month progression-free survival (PFS) rate, which was 14.3%. The median PFS and overall survival were 3.7 and 12.0 months, respectively. The most common grade ≥ 3 adverse events (AEs) were hypertension (23.5%), proteinuria (17.6%), and neutropenia (11.8%). The discontinuation rate due to AEs was 29.4%. Six patients progressed from Child–Pugh A to B after treatment with ramucirumab. Thirteen patients were eligible for post-ramucirumab treatment, including systemic therapy.
Conclusions
Despite the limited number of patients, the efficacy of ramucirumab was comparable to that observed in the REACH-2 study when used after lenvatinib and Atez/Bev. However, the incidence of AEs was higher than that in the REACH-2 study.
The ER stress related gene panel guide the prognosis and chemosensitivity in acute myeloid leukemia
Authors: Ren Simei , Peng Hongwei , Long Luyao , Guo Jie , Dai Qi , Sun Li , Yang Lin 
Published: March 2024

Abstract

Background
Acute myeloid leukemia possess high heterogeneity and current European Leukemia Net (ELN) risk stratification system cannot be applicable to all AML patients and needs about 3 weeks testing cycle. The aim of this study was to develop a applicable prognostic tool that may overcome the above shortcomings.
Methods
We used AML patients collected in clinic and TCGA database to explore the role of ER stress in response to chemotherapy. Patients from the TCGA database were used as the training cohort, and two GEO datasets were used as external validation cohorts. Univariate /multivariate COX and LASSO regression was exemplified to establish the prognostic model. Kaplan-Meier and time-dependent ROC were used to assess and compare the efficiency of the model with ELN stratification and other models. R package "pRRophetic" was utilized to assess drug sensitivity.
Results
In the training cohort, we selected 5 ER stress-related genes to predict chemosensitivity and establish the ERS-5 prognostic model. The model successfully predicted the overall survival of patients; p < 0.0001, HR = 4.86 (2.79–8.44); AUC = 0.83. The model was verified in validation cohorts and could further stratify the risk of various AML subgroups. It also complemented the ability of ELN to predict the response of patients with AML to main chemotherapeutic drugs. Finally, a “ERS-5” risk score was construced by the nomogram based on the ERS-5 model and age.
Conclusions
The ERS-5 model allowed more rapid (about 3 hours) and accurate risk stratification and complemented the ability of ELN to assess chemosensitivity.
Situational Analysis of Maternal and Infant Mortality in Kazakhstan
Authors: Sabyrdilda Zhanar , Kosherbayeva Lyazzat , Qumar Ainur , Akhtayeva Nazgul , Abikulova Akmaral , Akhmetzhan Anuar 
Published: March 2024

Abstract

Background: Previous studies from Western countries showed an association between maternal and infant mortality with sociomedical problems. The social environment influencing the health status of mothers and infants is thus seen to be a function of the economic resources and forms of production of different regions. This is the first study that includes the study of preventable mortality from Pregnancy, childbirth and perinatal period and Congenital malformations in Kazakhstan in the context of regions. For 2015-2019 maternal mortality decreased by 16.5% in the Republic of Kazakhstan. However, since the start of the pandemic in 2020, the maternal mortality ratio has increased by 2.7 times.
This study aimed to provide the latest policy in maternal and infant mortality, and analyze their mortality ratios.
Methods: An appraisal was conducted of regulatory documents related to the maternal and child health last ten years in the Kazakhstan health system. To identify changes in avoidable mortality ratio trends for the period 2011-2021, join point regression was used to calculate the average annual percentage change for every age group by using the Join Point Regression Program, Version 4.9.1.0.
Results: Crude mortality associated with pregnancy and childbirth and the postpartum period were high in the 30-34 age group from 2015 to 2018. From 2019 to 2021, there has been an increase in mortality in the 35-39 age group from 0.48 (95% CI: - 0.06; 1.03) to 4.37 (95% CI: 2.83; 5.91) per 100,000 women. In general, in all age groups, there is a twofold increase in mortality in the period from 2018-2021.
Treatable mortality from pregnancy, childbirth and the puerperium fluctuated from 2015-2019 between 0.34 to 0.37 after which rose till 1.07 in 2021 per 100.000 population. The highest increase can be seen in Atyrau, South and East Kazakhstan, Karagandy and Almaty regions. The treatable mortality decreased in Kyzylorda, Akmola regions in the 2015-2021 period.
Conclusion: Several regions need to step up efforts to reduce maternal mortality, which remains high nationally compared to OECD countries.
This is the first study to examine the prevention of deaths from pregnancy, childbirth, and the perinatal period, as well as the development of birth defects in Kazakhstan by region, which helps physician decision-makers reconsider possible approaches to providing care at the primary health care level.
Experimental investigation on the physco-mechanical and protective properties of concrete incorporating Layered double hydroxide (LDH)
Authors: Shohide Mostafa A. 
Published: March 2024

Abstract
The main perspective of this paper is enhancing the physico-mechanical and protective characteristics of concrete. This was achieved by incorporation Layered double hydroxide (LDH) in mix design of concrete with different doses. The concrete specimens were prepared with LDH percentages (0.5, 1.0, 1.5, and 2) % by the cement weight. After the characterization of LDH, the prepared concrete specimens were investigated as follows: the workability and density of the fresh concrete, effect of the addition of LDH on the compressive strength of hardened concrete were determined. The protective performance of concrete was evaluated by determining water absorption, contact angle, and chloride permeability. The obtained results detected that the physico-mechanical and protective performance of concrete are enhanced gradually by the addition of LDH up to 1.5%. After this percent, LDH is agglomerate and therefore unable to disperse uniformly.
Comparison of esketamine and remifentanil in combination with propofol in patients with septic shock receiving invasive mechanical ventilation: a randomized controlled trial
Authors: Li Yuting , Li Hongxiang , Zhang Yuhan , Zhang Chaoyang , Gao Meng , Zhang Liying , Wang Youquan , Fu Yao , Zhang Dong 
Published: March 2024

Abstract

Background Analgesics and sedatives may affect the hemodynamics of patients with septic shock and produce adverse reactions. The purpose of this study was to compare the analgesic and sedative effect of esketamine and remifentanil in combination with propofol in patients with septic shock receiving invasive mechanical ventilation. Methods In this single-center, prospective, randomized, controlled pilot study, patients with septic shock in the intensive care unit (ICU) receiving invasive mechanical ventilation were randomized to receive esketamine or remifentanil in combination with propofol intravenously. The target Critical-Care Pain Observation Tool (CPOT) score was < 3 points and Richmond Agitation and Sedation Scale (RASS) score was − 2 ~ 0 points. The primary outcome was dosage of norepinephrine. Secondary outcomes included mechanical ventilation time, dosage of propofol, intestinal dysfunction rate, ICU length of stay, hospital length of stay, hospital mortality and 28-day survival rate. Adverse events during the interventional period were also recorded. Results A total of 120 patients were enrolled in the study. Sixty patients were assigned to each group. The median (IQR) dosage of norepinephrine of remifentanil group was 4.09(1.52,8.85) mg/kg while that of esketamine group was 1.72(1.01,3.97) mg/kg. The dosage of norepinephrine of esketamine group was less than that of remifentanil group(P = 0.007). There were no significant differences between two groups with respect to adverse event rate, intestinal dysfunction rate, dosage of propofol, mechanical ventilation time, ICU length of stay, hospital length of stay and hospital mortality(P > 0.05). Kaplan-Meier survival analysis showed that there was no significant difference in 28-day survival rate between two groups(P = 0.225). Conclusions Esketamine may decrease the dosage of norepinephrine in patients with septic shock receiving invasive mechanical ventilation. It is beneficial for stabilizing hemodynamics and appears to be an effective and safe agent for patients with septic shock requiring invasive mechanical ventilation. Further large scale studies are still required to confirm these results.
Non-uptake of COVID-19 vaccines and reasons for non-uptake among healthcare workers in Uganda: a cross-sectional study
Authors: Kyakuwa Nasimu , Abaasa Andrew , Mpooya Simon , Kalutte Hamza , Atuhairwe Christine , Perez Laurent , Kikaire Bernard 
Published: March 2024

Abstract
Background
Vaccines play a crucial role in eradicating and containing disease outbreaks. Therefore, understanding the reasons behind vaccine refusal and associated factors is essential for improving vaccine acceptance rates. Our objective was to examine the determinants of COVID-19 vaccine non-uptake and explore the reasons for non-uptake among healthcare workers in Uganda.
Methods
Between July and August 2021, we conducted a cross-sectional study among healthcare workers in primary healthcare facilities in Entebbe Municipality, Uganda. Participants were recruited using convenience sampling, and consenting individuals received credentials to access an electronic database and complete a structured questionnaire. Survey questions were based on the '3Cs' model of vaccine hesitancy, focusing on confidence, convenience, and complacency factors. We employed counts, percentages, and simple logit models to summarize the reasons for non-uptakeof COVID-19 vaccines and to identify associated factors.
Results
The study recruited 360 healthcare workers, 61.7% of whom were female, with an average age of 31 years (SD=7.9). Among them, 124 (34.4%) healthcare workers did not receive any COVID-19 vaccine. Non-uptake of COVID-19 vaccines was independently associated with several factors, including age [35+ years adjusted odds ratio (aOR)=0.30, 95% CI: 0.13-0.66 compared with 18-24 years], facility ownership [government, aOR=0.22 (0.10-0.49) compared with private not-for-profit], previous testing for coronavirus [yes, aOR=0.35 (0.19-0.65)], and previous involvement in COVID-19 vaccine activities [yes, aOR=0.17 (0.10-0.29)].
The primary reasons cited for non-uptake of COVID-19 vaccines were related to a lack of confidence in the vaccines, such as concerns about side effects (79.8%) and the need for more time to understand the vaccines (89.5%), as well as the importance of weighing benefits and risks (84.7%) before being vaccinated. A smaller proportion, approximately 23%, cited reasons related to complacency and lack of convenience in accessing vaccination services.
Conclusion
The high proportion of non-uptake of COVID-19 vaccines among this population primarily stems from a lack of confidence and trust in the vaccines, coupled with insufficient time allowed for users to make informed decisions. This underscores the urgent need for ongoing monitoring and trend analysis of vaccine non-uptake to guide the development and implementation of strategies aimed at building and sustaining vaccine confidence.
Predictors of prolonged length of stay in PICU of infants with severe bronchiolitis: are initial blood gases helpful?
Authors: Laruelle Baptiste , Rambaud Jerome , Léger Pierre-Louis , Bakayoko Awa , Essid Aben , Mbieleu Blaise , Tissiere Pierre , Bergounioux Jean , Zini Justine 
Published: March 2024

Abstract
Purpose
Every year between November and January, the epidemic of acute viral bronchiolitis causes massive admissions to pediatric intensive care units. One of the challenges is to identify infants who will require invasive ventilation or have a prolonged length of stay in intensive care units.
Methods
We conducted a multicenter retrospective study on three PICU wards in France to evaluate the different risk factors for prolonged hospitalization in pediatric intensive care and for invasive ventilation. We focused particularly on the blood gas parameters (pH, PCO2, and bicarbonate) before and after PICU admission.
Results
We included 268 patients between October 2018 and April 2019. Mean age was 62 days, 7% of infants had chronic conditions (bronchopulmonary dysplasia, congenital heart disease, etc.). The median length of stay in PICU was 4 days, 83% of infants required noninvasive ventilation and 6% required invasive ventilation. Variables associated with prolonged length of stay in PICU were an age less than 30 days, a severe comorbidity, onset of symptoms less than 3 days before admission, initial FiO2 above 30%, presence of apneas or bradycardia, hemodynamic failure, and presence of bacterial coinfection. The pH, PCO2 and bicarbonate after PICU admission were correlated with PICU length of stay whereas none of the blood gas parameters before admission.
Conclusion
Blood gas after PICU admission may be useful to predict the length of stay in PICU in patients whose clinical condition is difficult to evaluate.
Anopheles arabiensis larval habitats characterization and Anopheles species diversity in water bodies from Jozini, KwaZulu-Natal Province.
Authors: Marubini Elelwani Elliot , Musekiwa Alfred , Maposa Innocent , Mazarire Theresa , Sekgele Windy , Mabaso Nondumiso , Dlamini Dumsani , Md Hetani , Kuonza Lazarus , Munhenga Givemore 
Published: March 2024

Abstract

Introduction: The South African government is now implementing winter larviciding as a supplementary vector control tool. To achieve effective larviciding programme there is a need to understand the distribution of the larval habitats of vectors and their corresponding ecology. This study aimed to determine larval breeding habitats of anophelines and characterize the physicochemical properties of water that promote the proliferation of Anopheles arabiensisimmature stages of this species.
Methods: A desktop survey of water bodies was carried out followed by a physical search of potential Anophelesbreeding habitats. Anopheline larvae were sampled from water habitats in January and April 2021. At each positive habitat, physicochemical characteristics of the water including pH, electrical conductivity, total dissolved solids and salinity were measured. The collected Anopheles larvae were reared to adults and identified to genus and species level using morphological and molecular techniques. Factors associated with the presence of Anopheles arabiensislarvae in the breeding habitats were determined.
Results: Desktop survey identified 72 potential water bodies and only 38 were physically identified as potential anopheline larval habitats. Of these 84% (n=32/38) were positive for Anopheles larvae. A total of 598 Anopheles larvae collected, of which 59.4% (n=355/598) emerged into adults. Morphological identification of these adults, showed that the Anopheles gambiaecomplex accounted for 70% (n=250/355) of the collections. Polymerase chain reaction species of the Anopheles gambiaecomplex showed predominance of Anopheles merus 56% (n=83/147) in January, and predominance of Anopheles arabiensis in April, 91% (n=80/88). All physicochemical parameters differed significantly between the breeding sites (p<0.05 in all instances), except for electrical conductivity (p =0.07). The aquatic habitats surveyed showed that the impermanency of the breeding sites, neutral to alkaline pH, moderate salinity and low total dissolved solids were associated with the occurrence of Anopheles arabiensis larvae.
Conclusion: This study showed that Anopheles arabiensis primarily breed in small temporary water habitats characterized by neutral pH. Larviciding that targets Anopheles arabiensis should focus on temporary water bodies with neutral, moderate salinity and low total dissolved solids.
Identification of 4 Novel Variants in 19 Families with Congenital Cataracts
Authors: Sun Hai-Sen , Huang Teng , Xu Yi-Tong , Wang Ya-Qi , Zhang Shen-Rong , Xu Jia-Lin , Zhu Kai-Yi , Huang Wen-Kai , Huang Xiu-Feng , Li Jin 
Published: March 2024

Abstract
Background
Congenital cataracts (CC) are one of the leading causes of impaired vision or blindness in children, of which approximately 8.3–25% are inherited. More than 100 cataract-related genes have been identified globally.
Purpose
To identify the gene variants associated with congenital cataracts.
Methods
This study included a total of 58 patients from 19 pedigrees with congenital cataracts. All probands were initially screened by whole-exome sequencing(WES), and some pedigrees were validated by co-segregation analysis using Sanger sequencing.
Results
Pathogenic variants were detected in 10 families, with a positivity rate of 52.6%. Variants in various genes were identified, including GJA3, CRYGD, BFSP2, CRYAA, and CRYBA1. Importantly, this study identified novel variants in CRYBA4, IARS2, ARL2, and CRYBB3.
Conclusions
Our research findings have revealed multiple gene variant sites associated with cataracts in the 10 families studied, providing clinical guidance for better understanding and management of the disease.