bluuebunny/crossref_metadata_2025_split huggingface dataset:
The value of the preoperative Naples prognostic score in predicting prognosis in gallbladder cancer surgery patients
Authors: Yang Jie , Lv Lin , Zhao Fengqing , Mei Xiaoping , Zhou Hongkun , Yu Feijie 
Published: September 2023

Abstract
Purpose
The Naples prognostic score (NPS) is a comprehensive prognostic model that includes inflammatory and nutrition-related indicators and is increasingly used as a prognostic score for various malignant tumors. Given its predictive effect on prognosis in patients with gallbladder cancer, it is currently unclear. This study aimed to investigate the role of preoperative NPS in predicting prognosis in gallbladder cancer surgery patients.

Patients and methods
A retrospective analysis was performed for 135 patients who underwent radical surgery for gallbladder cancer without preoperative treatment between March 2011 and January 2020. NPS was calculated by measuring the preoperative total cholesterol value, serum albumin value, neutrophil–lymphocyte ratio (NLR), and lymphocyte-monocyte ratio (LMR). They were then divided into 3 groups (groups 0, 1, and 2) based on NPS scores. Survival analysis was performed using the Kaplan–Meier method and log-rank test. Univariate and multivariate Cox proportional hazards models were used to identify independent prognostic factors. Plot time-dependent receiver operating characteristic (ROC) curves to compare the prognostic value of scoring systems. Finally, a nomogram model was developed with independent prognostic factors.

Results
Multivariate analysis showed that NPS was an independent risk factor affecting OS (HR = 3.417, p < 0.05). The time-dependent ROC curve results showed that NPS had a better predictive value on survival prognosis than other indicators. The nomogram constructed according to independent factors such as NPS has a good predictive ability for OS.

Conclusion
As a simple and reliable tool, the NPS has important predictive value in the survival prognosis of gallbladder cancer patients. The nomogram model constructed by NPS will help determine prognosis and make individualized treatment decisions.
Functional diversity of c-di-GMP receptors in prokaryotic and eukaryotic systems
Authors: Khan Fazlurrahman , Jeong Geum-Jae , Tabassum Nazia , Kim Young-Mog 
Published: September 2023

AbstractCyclic bis-(3', 5')-dimeric guanosine monophosphate (c-di-GMP) is ubiquitous in many bacterial species, where it functions as a nucleotide-based secondary messenger and is a vital regulator of numerous biological processes. Due to its ubiquity, most bacterial species possess a wide range of downstream receptors that has a binding affinity to c-di-GMP and elicit output responses. In eukaryotes, several enzymes and riboswitches operate as receptors that interact with c-di-GMP and transduce cellular or environmental signals. This review examines the functional variety of receptors in prokaryotic and eukaryotic systems that exhibit distinct biological responses after interacting with c-di-GMP. Evolutionary relationships and similarities in distance among the c-di-GMP receptors in various bacterial species were evaluated to understand their specificities. Furthermore, residues of receptors involved in c-di-GMP binding are summarized. This review facilitates the understanding of how distinct receptors from different origins bind c-di-GMP equally well, yet fulfill diverse biological roles at the interspecies, intraspecies, and interkingdom levels. Furthermore, it also highlights c-di-GMP receptors as potential therapeutic targets, particularly those found in pathogenic microorganisms.
A prospective analysis of physical activity and mental health in children: the GECKO Drenthe cohort
Authors: Yang Lu , Corpeleijn Eva , Hartman Esther 
Published: September 2023

Abstract
Background
Mental health problems in young people have become a global health burden. The positive effects of physical activity on mental health in adults are well known but still not clear in children. The aim of this study was to investigate to what extent physical activity in early childhood would affect mental health in middle childhood.

Methods
From the Dutch GECKO Drenthe birth cohort, 850 children (51.5% boys) were enrolled in this analysis. Physical activity and sedentary time were measured at age 5–6 using ActiGraph GT3X. Mental health was assessed using the Strengths and Difficulties Questionnaire (SDQ) at age 5–6 and age 10–11. Multiple linear regression models were used to estimate the associations between physical activity, sedentary time and SDQ subscales, stratified by gender, adjusting for age, BMI, maternal education level, family size, accelerometer wear time and season, and additionally adjusting for SDQ scores at age 5–6 to take tracking of mental health over time into account.

Results
Greater physical activity volume at age 5–6 was associated with lower peer problems scores at age 10–11 in boys and girls. An increase in MVPA was associated with lower peer problems scores in boys (b = -0.445, -0.713 to -0.176) and girls (b = -0.354, -0.601 to -0.107), however, increased sedentary time was linked to higher peer problems scores in boys (b = 1.18, 0.455 to 1.906) and girls (b = 0.870, 0.191 to 1.550). For hyperactivity, higher levels of physical activity volume and MVPA were associated with higher hyperactivity scores in boys. Increased sedentary time was related to lower hyperactivity scores in boys. Further adjustment for SDQ scores at age 5–6 attenuated associations between physical activity and hyperactivity in boys but hardly changed the relationships with peer problems. No significant associations between physical activity and other SDQ subscales or total difficulties scores were observed, neither in boys nor in girls.

Conclusions
Children who are more physically active at age 5–6 have fewer peer problems at age 10–11, and for boys, greater activity levels at age 5–6 could be an indicator of hyperactivity at age 10–11.
miR155, TREM2, INPP5D: Disease stage and cell type are essential considerations when targeting clinical interventions based on mouse models of Alzheimer’s amyloidopathy
Authors: Gandy Sam , Ehrlich Michelle E. 
Published: September 2023

AbstractStudies of microglial gene manipulation in mouse models of Alzheimer’s disease (AD) amyloidopathy can cause unpredictable effects on various key endpoints, including amyloidosis, inflammation, neuritic dystrophy, neurodegeneration, and learning behavior. In this Correspondence, we discuss three examples, microRNA 155 (miR155), TREM2, and INPP5D, in which observed results have been difficult to reconcile with predicted results based on precedent, because these six key endpoints do not reliably track together. The pathogenesis of AD involves multiple cell types and complex events that may change with disease stage. We propose that cell-type targeting and timing of intervention are responsible for the sometimes impossibility of predicting whether any prospective therapeutic intervention should aim at increasing or decreasing the level or activity of a particular molecular target.
Physical injuries and burns among refugees in Lebanon: implications for programs and policies
Authors: Al-Hajj Samar , Moustafa Moustafa , El Hechi Majed , Chahrour Mohamad A. , Nasrallah Ali A. , Kaafarani Haytham 
Published: September 2023

Abstract
Background
Refugees are prone to higher risks of injury due to often austere living conditions, social and economic disadvantages, and limited access to health care services in host countries. This study aims to systematically quantify the prevalence of physical injuries and burns among the refugee community in Western Lebanon and to examine injury characteristics, risk factors, and outcomes.

Methods
We conducted a cluster-based population survey across 21 camps in the Beqaa region of Lebanon from February to April 2019. A modified version of the ‘Surgeons Overseas Assessment of Surgical Need (SOSAS)’ tool (Version 3.0) was administered to the head of the refugee households and documented all injuries sustained by family members over the last 12 months. Descriptive and univariate regression analyses were performed to understand the association between variables.

Results
750 heads of households were surveyed. 112 (14.9%) households sustained injuries in the past 12 months, 39 of which (34.9%) reported disabling injuries that affected their work and daily living. Injuries primarily occurred inside the tent (29.9%). Burns were sustained by at least one household member in 136 (18.1%) households in total. The majority (63.7%) of burns affected children under 5 years and were mainly due to boiling liquid (50%). Significantly more burns were reported in households where caregivers cannot lock children outside the kitchen while cooking (25.6% vs 14.9%, p-value = 0.001). Similarly, households with unemployed heads had significantly more reported burns (19.7% vs. 13.3%, p value = 0.05). Nearly 16.1% of the injured refugees were unable to seek health care due to the lack of health insurance coverage and financial liability.

Conclusions
Refugees severely suffer from injuries and burns, causing substantial human and economic repercussions on the affected individuals, their families, and the host healthcare system. Resources should be allocated toward designing safe camps as well as implementing educational awareness campaigns specifically focusing on teaching about heating and cooking safety practices.
The battle for mental well-being in Ukraine: mental health crisis and economic aspects of mental health services in wartime
Authors: Seleznova Violetta , Pinchuk Irina , Feldman Inna , Virchenko Volodymyr , Wang Bo , Skokauskas Norbert 
Published: September 2023

AbstractThe ongoing war in Ukraine is having profound impacts on both the local and global economy, as well as the infrastructure and overall well-being of the people. The prolonged duration of the conflict, coupled with its many related consequences such as total uncertainty, unfavorable economic conditions, and a distressing media backdrop, have a lasting impact on the mental health of the population. The ongoing war in Ukraine has exposed weaknesses in the national mental health care system and underscored the importance of mental health economics. To prevent further mental health problems, it is crucial to develop a comprehensive set of measures aimed at strengthening the capacity of the mental health care system in Ukraine. Currently, Ukraine’s mental health care system suffers from a lack of financial and human resources, which hinders its ability to provide adequate support to those in need. To address this issue, joint efforts between Ukrainian mental health stakeholders and the international governmental and non-governmental organizations are needed to provide support and capacity building for mental health services in Ukraine.
CHSY1 promotes CD8+ T cell exhaustion through activation of succinate metabolism pathway leading to colorectal cancer liver metastasis based on CRISPR/Cas9 screening
Authors: Sun Guangshun , Zhao Siqi , Fan Zhongguo , Wang Yuliang , Liu Hanyuan , Cao Hengsong , Sun Guoqiang , Huang Tian , Cai Hongzhou , Pan Hong , Rong Dawei , Gao Yun , Tang Weiwei 
Published: September 2023

Abstract
Background
The most common site of metastasis in colorectal cancer (CRC) is the liver and liver metastases occur in more than 50% of patients during diagnosis or treatment. The occurrence of metastasis depends on a series of events known as the invasive-metastasis cascade. Currently, the underlying genes and pathways regulating metastasis initiation in the liver microenvironment are unknown.

Methods
We performed systematic CRISPR/Cas9 screening using an in vivo mouse model of CRC liver metastasis to identify key regulators of CRC metastasis. We present the full results of this screen,which included a list of genes that promote or repress CRC liver colonization. By silencing these genes individually, we found that chondroitin sulfate synthase 1 (CHSY1) may be involved in CRC metastasis. We verified the function of CHSY1 and its involvement in liver metastasis of CRC through in vivo and in vitro experiments.

Result
The results of TCGA and CRISPR/Cas9 showed that CHSY1 was overexpressed in CRC primary and liver metastasis tissues and indicated a worse clinical prognosis. In vitro and in vivo experiments confirmed that CHSY1 facilitated the liver metastasis of CRC and CHSY1 induced CD8+ T cell exhaustion and upregulated PD-L1 expression. The metabolomic analysis indicated that CHSY1 promoted CD8+ T cell exhaustion by activating the succinate metabolism pathway leading to liver metastasis of CRC. Artemisinin as a CHSY1 inhibitor reduced liver metastasis and enhanced the effect of anti-PD1 in CRC. PLGA-loaded Artemisinin and ICG probe reduced liver metastasis and increased the efficiency of anti-PD1 treatment in CRC.

Conclusion
CHSY1 could promote CD8+ T cell exhaustion through activation of the succinate metabolic and PI3K/AKT/HIF1A pathway, leading to CRC liver metastasis. The combination of CHSY1 knockdown and anti-PD1 contributes to synergistic resistance to CRC liver metastasis. Artemisinin significantly inhibits CHSY1 activity and in combination with anti-PD1 could synergistically treat CRC liver metastases. This study provides new targets and specific strategies for the treatment of CRC liver metastases, bringing new hope and benefits to patients.
Palliative care for persons with late-stage Alzheimer’s and related dementias and their caregivers: protocol for a randomized clinical trial
Authors: Toles M. , Kistler C. , Lin F. C. , Lynch M. , Wessell K. , Mitchell S. L. , Hanson L. C. 
Published: September 2023

Abstract
Background
Limited access to specialized palliative care exposes persons with late-stage Alzheimer’s disease and related dementias (ADRD) to burdensome treatment and unnecessary hospitalization and their caregivers to avoidable strain and financial burden. Addressing this unmet need, the purpose of this study was to conduct a randomized clinical trial (RCT) of the ADRD-Palliative Care (ADRD-PC) program.

Methods
The study will use a multisite, RCT design and will be set in five geographically diverse US hospitals. Lead investigators and outcome assessors will be masked. The study will use 1:1 randomization of patient-caregiver dyads, and sites will enroll N = 424 dyads of hospitalized patients with late-stage ADRD with their family caregivers. Intervention dyads will receive the ADRD-PC program of (1) dementia-specific palliative care, (2) standardized caregiver education, and (3) transitional care. Control dyads will receive publicly available educational material on dementia caregiving. Outcomes will be measured at 30 days (interim) and 60 days post-discharge. The primary outcome will be 60-day hospital transfers, defined as visits to an emergency department or hospitalization ascertained from health record reviews and caregiver interviews (aim 1). Secondary patient-centered outcomes, ascertained from 30- and 60-day health record reviews and caregiver telephone interviews, will be symptom treatment, symptom control, use of community palliative care or hospice, and new nursing home transitions (aim 2). Secondary caregiver-centered outcomes will be communication about prognosis and goals of care, shared decision-making about hospitalization and other treatments, and caregiver distress (aim 3). Analyses will use intention-to-treat, and pre-specified exploratory analyses will examine the effects of sex as a biologic variable and the GDS stage.

Discussion
The study results will determine the efficacy of an intervention that addresses the extraordinary public health impact of late-stage ADRD and suffering due to symptom distress, burdensome treatments, and caregiver strain. While many caregivers prioritize comfort in late-stage ADRD, shared decision-making is rare. Hospitalization creates an opportunity for dementia-specific palliative care, and the study findings will inform care redesign to advance comprehensive dementia-specific palliative care plus transitional care.

Trial registration
ClinicalTrials.gov NCT04948866. Registered on July 2, 2021.
Effect of dexmedetomidine on postoperative delirium in patients undergoing awake craniotomies: study protocol of a randomized controlled trial
Authors: Li Muhan , Liu Minying , Cui Qianyu , Zeng Min , Li Shu , Zhang Liyong , Peng Yuming 
Published: September 2023

Abstract
Introduction
Postoperative delirium (POD) is a common complication, and it has a high incidence in neurosurgery patients. Awake craniotomy (AC) has been widely performed in patients with glioma in eloquent and motor areas. Most of the surgical procedure is frontotemporal craniotomy, and the operation duration has been getting longer. Patients undergoing AC are high-risk populations for POD. Dexmedetomidine (Dex) administration perioperatively might help to reduce the incidence of POD. The purpose of this study is to investigate the effect of Dex on POD in patients undergoing AC.

Methods
The study is a prospective, single-center, double-blinded, paralleled-group, randomized controlled trial. Patients undergoing elective AC will be randomly assigned to the Dex group and the control group. Ten minutes before urethral catheterization, patients in the Dex group will be administered with a continuous infusion at a rate of 0.2 µg/kg/h until the end of dural closure. In the control group, patients will receive an identical volume of normal saline in the same setting. The primary outcome will be the cumulative incidence and severity of POD. It will be performed by using the confusion assessment method in the first 5 consecutive days after surgery. Secondary outcomes include quality of intraoperative awareness, stimulus intensity of neurological examination, pain severity, quality of recovery and sleep, and safety outcomes.

Discussion
This study is to investigate whether the application of Dex could prevent POD in patients after undergoing AC and will provide strong evidence-based clinical practice on the impact of intraoperative interventions on preventing POD in AC patients.

Trial registration
ClinicalTrials.gov, NCT05195034. Registered on January 18, 2022.
Identification of candidate genes and chemicals associated with osteoarthritis by transcriptome-wide association study and chemical-gene interaction analysis
Authors: Mei Lin , Zhang Zhiming , Chen Ruiqi , Liu Zhongyue , Ren Xiaolei , Li Zhihong 
Published: September 2023

Abstract
Background
Osteoarthritis (OA) is a common degenerative joint disease and causes chronic pain and disability to the elderly. Several risk factors are involved, such as aging, obesity, genetic susceptibility, and environmental factors. We conducted a transcriptome-wide association study (TWAS) and chemical-related gene set enrichment analysis (CGSEA) to investigate the susceptibility genes and environmental factors.

Methods
TWAS analysis was conducted to identify the susceptibility genes by integrating the summary-level genome-wide association study data of knee OA (KOA) and hip OA (HOA) with the precomputed expression weights from the Genotype-Tissue Expression Project (Version 8). The FUSION software was used for both single-tissue and cross-tissue TWAS, which were combined using an aggregate Cauchy association test. The biological function and pathways of the TWAS genes were explored using the Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) databases, and the human cartilage mRNA expression profiles were utilized to validate the TWAS genes. CGSEA analysis was performed to scan the OA-associated chemicals by integrating the TWAS results with the chemical-related gene sets.

Results
There were 44 and 93 unique TWAS genes identified in 7 and 11 chromosomes for KOA and HOA, respectively, fourteen and four of which showed significantly differential expression in the mRNA profiles, such as CRHR1, LTBP1, WWP2, LMX1B, and PTHLH. OA-related pathways were found in the KEGG and GO analysis, such as TGF-beta signaling pathway, MAPK signaling pathway, hyaluronan metabolic process, and chondrocyte differentiation. Forty-five OA-associated chemicals were identified, including quercetin, bisphenol A, and cadmium chloride.

Conclusions
Several candidate OA-associated genes and chemicals were identified through TWAS and CGSEA analysis, which expanded our understanding of the relationship between genes, chemicals, and their impact on OA.
Automatic evaluation of atlantoaxial subluxation in rheumatoid arthritis by a deep learning model
Authors: Okita Yasutaka , Hirano Toru , Wang Bowen , Nakashima Yuta , Minoda Saki , Nagahara Hajime , Kumanogoh Atsushi 
Published: September 2023

Abstract
Background
This work aims to develop a deep learning model, assessing atlantoaxial subluxation (AAS) in rheumatoid arthritis (RA), which can often be ambiguous in clinical practice.

Methods
We collected 4691 X-ray images of the cervical spine of the 906 patients with RA. Among these images, 3480 were used for training the deep learning model, 803 were used for validating the model during the training process, and the remaining 408 were used for testing the performance of the trained model. The two-dimensional key points’ detection model of Deep High-Resolution Representation Learning for Human Pose Estimation was adopted as the base convolutional neural network model. The model inferred four coordinates to calculate the atlantodental interval (ADI) and space available for the spinal cord (SAC). Finally, these values were compared with those by clinicians to evaluate the performance of the model.

Results
Among the 408 cervical images for testing the performance, the trained model correctly identified the four coordinates in 99.5% of the dataset. The values of ADI and SAC were positively correlated among the model and two clinicians. The sensitivity of AAS diagnosis with ADI or SAC by the model was 0.86 and 0.97 respectively. The specificity of that was 0.57 and 0.5 respectively.

Conclusions
We present the development of a deep learning model for the evaluation of cervical lesions of patients with RA. The model was demonstrably shown to be useful for quantitative evaluation.
Development of a novel observed structured clinical exam to assess clinical ultrasound proficiency in undergraduate medical education
Authors: Kamilaris Andrew , Kramer Jeffrey A. , Baraniecki-Zwil Gwen , Shofer Frances , Moore Christy , Panebianco Nova , Chan Wilma 
Published: September 2023

Abstract
Objectives
A pilot study was performed to develop and test an observed structured clinical exam (OSCE) for clinical ultrasound in second-year medical students. The goal was to assess a longitudinal clinical ultrasound curriculum for medical students and to help determine readiness to perform ultrasound during clinical clerkships.

Methods
The OSCE contained 40 tasks over 30 min in a one-to-one examiner to examinee environment using standardized patients covering cardiac, pulmonary, and inferior vena cava (IVC) ultrasound exams along with 6 critical diagnoses. Examinees were assessed using a binary checklist approach. A two-way ANOVA analysis was performed to determine if there were differences between the day and session the OSCE was administered. Results are presented as mean ± standard deviation.

Results
One hundred fifty-two students were tested with an overall mean score of 64.9 ± 17.6%. Scores between the cardiac, IVC, and lung sections varied—67.8% ± 18.8%, 62.4% ± 26.2%, and 57.1% ± 20.6%, respectively. One hundred twenty-six (82.9%) answered at least one critical diagnosis incorrectly. Students in the late session performed better than the early session (1: 60% vs 2: 69%, p = .001).

Conclusions
Students performed better in later sessions. Additionally, the number of questions left blank at the end of the exam suggests that the length of the OSCE should be evaluated. Incorporating critical diagnoses was challenging for examinees. The proposed OSCE is a valuable assessment tool that could be adapted to assess student’s readiness to use clinical ultrasound prior to clerkships.