bluuebunny/crossref_metadata_2025_split huggingface dataset:
Evaluation of cultural competency in a South African cluster randomised controlled trial: lessons learned for trial reporting standards
Authors: Siegfried Nandi Louise , Hopewell Sally , Erasmus-Claassen Lesley-Ann , Myers Bronwyn 
Published: October 2022

Abstract
Background
Failure to consider relevant cultural, ethnic and diversity parameters (and the intersection between these parameters) during trial protocol development and trial conduct may negatively impact recruitment, intervention development and delivery, and participant adherence and retention, potentially reducing overall internal validity. This case study aimed to evaluate the utility and comparability between the 9-item Gibbs Framework to measure cultural competency and the GRIPP-2(Short Form (SF)) 5-point checklist to assess patient and public involvement in the context of a complex clinical trial conducted in an African setting.

Methods
We identified and collated all relevant publications, source and procedural data related to the trial and integrated the documents into a dynamic trial timeline. Two independent investigators applied and scored the Gibbs Framework and the GRIPP-2(SF) checklist to the four publications arising from the trial, noting functionality and comparability between tools. Where cultural competency was not met, a third investigator screened all procedural and source data and identified if cultural competency had been achieved but not reported in the publications, or if the trial had not met appropriate cultural competency based on the documentation.

Results
Application of the Gibbs Framework found that the trial scored ‘2’ for seven of the nine Gibbs items, indicating full cultural competency for those questions. The Framework indicated that the trial research question was not driven by the articulated needs of patients, and neither were patients, caregivers and clinical providers involved in the development of the intervention. Comparability with the GRIPP-2(SF) checklist showed that the Gibbs performed better on evaluation of partnerships with the community, identification of culturally competent data sources and target populations, and appointment of trial staff in an inclusive manner.

Conclusions
Comprehensive evaluation of the trial’s cultural competency required scrutiny of both published manuscripts and source and procedural data, suggesting that there is a gap in current trial reporting standards with respect to cultural competence.

Trial registration
PACTR201610001825403. Registered on 17 October 2016.
Enteral versus parental nutrition after pancreaticoduodenectomy under enhanced recovery after surgery protocol: study protocol for a multicenter, open-label randomized controlled trial (ENE-PAN trial)
Authors: Takeda Yoshinori , Mise Yoshihiro , Kishi Yoji , Sugo Hiroyuki , Kyoden Yusuke , Hasegawa Kiyoshi , Takahashi Yu , Saiura Akio 
Published: October 2022

Abstract
Background
Infectious complications are the main causes of morbidity after pancreaticoduodenectomy (PD). Early enteral nutrition (EN) is a reasonable form of nutritional support that aims to mitigate the occurrence and severity of infectious complications by maintaining gut immunity. However, it remains unclear whether EN is beneficial for patients who underwent PD and are under enhanced recovery after surgery (ERAS) protocol.

Methods
A multicenter (six hospitals), open-label, randomized controlled trial will be started in July 2022. A total of 320 patients undergoing open PD will be randomly assigned to an EN group or a peripheral parental nutrition (PPN) group in a 1:1 ratio. The stratification factors will be the hospital, age (≥ 70 or not), and preoperative diagnosis (pancreatic cancer or not). In the EN group, enteral nutrition will start on postoperative day (POD) 1 at 200–300 ml/day via the percutaneous tube placed operatively. The volume of the diet will be increased to 400–600 ml/day on POD 2 and depend on the surgeon’s decision from POD 3. In the PPN group, PPN will be delivered after surgery. In both groups, oral feeding will start on POD 3. Each treatment will be finished when patients’ oral food intake reaches 60% of the nutritional requirement (25–30 kcal/day). The primary endpoint will be the occurrence of postoperative infectious complications within 90 days of surgery. The secondary endpoints will be all complications, including major ones such as Clavien–Dindo grade 3 or more and clinically relevant postoperative pancreatic fistula. Data will be analyzed per the intention to treat.

Discussion
This will be the first, large, and well-designed RCT that aims to determine whether EN is beneficial for patients who underwent PD under the ERAS protocol. According to the results of this study, either EN or PPN would be adopted as the standard nutritional support for patients undergoing PD.

Trial registration
jRCT1030210691. Registered on March 23, 2022.
Identification of microbial taxa present in Ctenocephalides felis (cat flea) reveals widespread co-infection and associations with vector phylogeny
Authors: Manvell Charlotte , Berman Hanna , Callahan Benjamin , Breitschwerdt Edward , Swain William , Ferris Kelli , Maggi Ricardo , Lashnits Erin 
Published: October 2022

Abstract
Background
Ctenocephalides felis, the cat flea, is the most common ectoparasite of cats and dogs worldwide. As a cause of flea allergy dermatitis and a vector for two genera of zoonotic pathogens (Bartonella and Rickettsia spp.), the effect of the C. felis microbiome on pathogen transmission and vector survival is of substantial medical importance to both human and veterinary medicine. The aim of this study was to assay the pathogenic and commensal eubacterial microbial communities of individual C. felis from multiple geographic locations and analyze these findings by location, qPCR pathogen prevalence, and flea genetic diversity.

Methods
16S Next Generation Sequencing (NGS) was utilized to sequence the microbiome of fleas collected from free-roaming cats, and the cox1 gene was used for flea phylogenetic analysis. NGS data were analyzed for 168 individual fleas from seven locations within the US and UK. Given inconsistency in the genera historically reported to constitute the C. felis microbiome, we utilized the decontam prevalence method followed by literature review to separate contaminants from true microbiome members.

Results
NGS identified a single dominant and cosmopolitan amplicon sequence variant (ASV) from Rickettsia and Wolbachia while identifying one dominant Bartonella clarridgeiae and one dominant Bartonella henselae/Bartonella koehlerae ASV. Multiple less common ASVs from these genera were detected within restricted geographical ranges. Co-detection of two or more genera (Bartonella, Rickettsia, and/or Wolbachia) or multiple ASVs from a single genus in a single flea was common. Achromobacter, Peptoniphilus, and Rhodococcus were identified as additional candidate members of the C. felis microbiome on the basis of decontam analysis and literature review. Ctenocephalides felis phylogenetic diversity as assessed by the cox1 gene fell within currently characterized clades while identifying seven novel haplotypes. NGS sensitivity and specificity for Bartonella and Rickettsia spp. DNA detection were compared to targeted qPCR.

Conclusions
Our findings confirm the widespread coinfection of fleas with multiple bacterial genera and strains, proposing three additional microbiome members. The presence of minor Bartonella, Rickettsia, and Wolbachia ASVs was found to vary by location and flea haplotype. These findings have important implications for flea-borne pathogen transmission and control.

Graphical Abstract
Adenosquamous carcinoma of the pancreas: two case reports and review of the literature
Authors: Paramythiotis Daniel , Kyriakidis Filippos , Karlafti Eleni , Didangelos Triantafyllos , Oikonomou Ilias-Marios , Karakatsanis Anestis , Poulios Christos , Chamalidou Eleni , Vagionas Anastasios , Michalopoulos Antonios 
Published: October 2022

Abstract
Background
Among the total reported cases of pancreatic duct adenocarcinomas, around 1–2.9% are adenosquamous carcinomas of the pancreas. Due to limited data, preoperative diagnosis is a great challenge for physicians, and it is usually set post-operational, based on the pathologist report. We operated on two cases of adenosquamous carcinoma of the pancreas, which we present alongside the operation and treatment planning.

Case report
A 69-year-old Caucasian female and a 63-year-old Caucasian male presented themselves with jaundice in our department. The abdomen computed tomography and magnetic resonance imaging scans revealed lesions of the pancreas. A pancreas–duodenumectomy was performed in both patients, and the post-operational histology analysis revealed adenosquamous carcinoma of the pancreas head. The patients were discharged in good condition and received further chemotherapy treatment after surgery.

Conclusions
Two case reports of adenosquamous carcinoma of the pancreas are described here, which both underwent surgery resection. The limited available literature on this topic substantially limits the knowledge and guidance on treatment. A summarization of the available literature is attempted, alongside a description of possible fields of future research.
Activation of arcuate nucleus glucagon-like peptide-1 receptor-expressing neurons suppresses food intake
Authors: Singh Ishnoor , Wang Le , Xia Baijuan , Liu Ji , Tahiri Azeddine , El Ouaamari Abdelfattah , Wheeler Michael B. , Pang Zhiping P. 
Published: October 2022

Abstract
Background
Central nervous system (CNS) control of metabolism plays a pivotal role in maintaining energy balance. In the brain, Glucagon-like peptide 1 (GLP-1), encoded by the proglucagon ‘Gcg’ gene, produced in a distinct population of neurons in the nucleus tractus solitarius (NTS), has been shown to regulate feeding behavior leading to the suppression of appetite. However, neuronal networks that mediate endogenous GLP-1 action in the CNS on feeding and energy balance are not well understood.

Results
We analyzed the distribution of GLP-1R-expressing neurons and axonal projections of NTS GLP-1-producing neurons in the mouse brain. GLP-1R neurons were found to be broadly distributed in the brain and specific forebrain regions, particularly the hypothalamus, including the arcuate nucleus of the hypothalamus (ARC), a brain region known to regulate energy homeostasis and feeding behavior, that receives dense NTSGcg neuronal projections. The impact of GLP-1 signaling in the ARC GLP-1R-expressing neurons and the impact of activation of ARC GLP-1R on food intake was examined. Application of GLP-1R specific agonist Exendin-4 (Exn-4) enhanced a proportion of the ARC GLP-1R-expressing neurons and pro-opiomelanocortin (POMC) neuronal action potential firing rates. Chemogenetic activation of the ARC GLP-1R neurons by using Cre-dependent hM3Dq AAV in the GLP-1R-ires-Cre mice, established that acute activation of the ARC GLP-1R neurons significantly suppressed food intake but did not have a strong impact on glucose homeostasis.

Conclusions
These results highlight the importance of central GLP-1 signaling in the ARC that express GLP-1R that upon activation, regulate feeding behavior.
Gaussian processes based extended target tracking in polar coordinates with input uncertainty
Authors: Guo Yunfei , Yang Dongsheng , Ren Lei , Yan Lei 
Published: October 2022

AbstractGaussian processes (GP) based extended target tracking (ETT) technique has attracted the attention of scientists since it can accurately estimate the kinematic states as well as the contour states of irregular-shape targets. Most traditional GP methods consider the ETT problem with a linear measurement model in Cartesian coordinates and ignore the input uncertainty of GP for simplicity. In many applications, however, measurements are generated with high-resolution sensors in polar coordinates. More importantly, the ignorance of input uncertainty in GP will exacerbate the tracking performance in these cases. In order to track an irregular-shape extended target in polar coordinates with input uncertainty, an improved GP-based probabilistic data association (IGP-PDA) algorithm is developed that includes the following enhancements: Firstly, a nonlinear measurement model is used and the unbiased converted measurement technique is invoked for the ETT problem. Secondly, the analytical form of statistical properties of the input uncertainty due to measurements noise and predicted error is derived. Thirdly, an IGP-PDA taking into account measurement origin uncertainty as well as input uncertainty is proposed, and three sub-optimal implementations are provided. Last, the posterior Cramer-Rao lower bound of ETT with input uncertainty is derived. Simulation results verify the effectiveness of the proposed method.
MED12 mutation as a potential predictive biomarker for immune checkpoint inhibitors in pan-cancer
Authors: Zhou Yong , Tan Yuan , Zhang Qin , Duan Qianqian , Chen Jun 
Published: October 2022

AbstractImmune checkpoint inhibitors (ICIs) therapy elicits admirable anti-tumor responses across many types of cancer. Growing evidence point to a link to Mediator complex subunit 12 (MED12) and DNA damage repair (DDR) and TGF-β signing, while the clinical data on the association of MED12 and ICIs response are lacking. In this study, clinical and whole-exome sequencing (WES) data from published studies were merged as a WES cohort to explore the association between MED12 mutation (MED12-Mut) and ICIs efficiency across cancers. Then, Memorial Sloan Kettering Cancer Center (MSKCC) cohort was used for validating our findings. The Cancer Genome Atlas (TCGA) cohort was used to perform anti-tumor immunity and prognosis analysis. In the WES cohort (n = 474), significant differences were detected between MED12-Mut and MED12-wildtype (MED12-Wt) patients regarding durable clinical benefit (DCB, 80.00% vs. 53.67%, P = 0.022). In addition, significantly prolonged PFS was observed in MED12-Mut patients (mPFS: not reached, NR vs. 5.87 months, HR: 0.38, 95% CI 0.17–0.85, log-rank P = 0.015), After taking into account age, gender, metastasis, treatment and TMB status, the result of multivariable Cox proportional hazards regression showed significantly better PFS (HR:0.40, 95% CI 0.18–0.92; P = 0.031). In the MSKCC cohort (n = 1513), overall survival advantage was achieved in MED12-Mut patients (mOS: 41 vs. 19 months, HR:0.54, 95%CI 0.34–0.85; log-rank P = 0.007), after taking into account same factors in WES cohort, this link still existed (HR: 0.60, 95% CI: 0.38–0.96, P = 0.033), Notably, TMB was also found significantly higher in MED12-Mut patients in both WES and MSKCC cohort. Further tumor-infiltrating lymphocytes and DDR-related gene analysis revealed anti-tumor immunity in MED12-Mut patients. Totally, MED12-Mut successfully predicted better clinical outcomes in ICIs-treated pan-cancer cohort, indicating that MED12-Mut could serve as a potential predictive biomarker for immune checkpoint inhibitors in pan-cancer.
Influence of COVID-19 pandemic on the decision making of patients in undergoing gamma knife radiosurgery
Authors: Shen Chiung-Chyi , Jiang Rong-San , Yang Men-Yin , You Weir-Chiang , Sun Ming-Hsi , Sheu Meei-Ling , Pan Liang-Yi , Sheehan Jason , Pan Hung-Chuan 
Published: October 2022

Abstract
Purpose
Gamma knife radiosurgery (GK) is a commonly used approach for the treatment of intracranial lesions. Its radiation response is typically not immediate, but delayed. In this study, we analyzed cases from a prospectively collected database to assess the influence of COVID-19 pandemic on the decision making in patients treated by gamma knife radiosurgery.

Methods
From January 2019 to August 2021, 540 cases of intracranial lesions were treated by GK with 207 cases before COVID-19 pandemic as a control. During the COVID-19 pandemic, 333 cases were similarly treated on patients with or without the COVID-19 vaccination. All the GK treated parameters as well as time profile in the decision making were analyzed. The parameters included age, sex, characteristic of lesion, targeted volume, peripheral radiation dose, neurological status, Karnofsky Performance Status (KPS), time interval from MRI diagnosis to consultation, time interval from the approval to treatment, frequency of outpatient department (OPD) visit, and frequency of imaging follow-up.

Results
Longer time intervals from diagnosis to GK consultation and treatment were found in the pandemic group (36.8 ± 25.5/54.5 ± 27.6 days) compared with the pre-COVID control (17.1 ± 22.4/45.0 ± 28.0 days) or vaccination group (12.2 ± 7.1/29.6 ± 10.9 days) (p < 0.001, and p < 0.001, respectively). The fewer OPD visits and MRI examinations also showed the same trends. High proportion of neurological deficits were found in the pandemic group (65.4%) compared with the control (45.4%) or vaccination group (58.1%) (p < 0.001). The Charlson comorbidity in the pandemic group was 3.9 ± 3.3, the control group was 4.6 ± 3.2, and the vaccination group was 3.1 ± 3.1. There were similar inter-group difference (p < 0.001). In multiple variant analyses, longer time intervals from the diagnosis to consultation or treatment, OPD frequency and MRI examination were likely influenced by the status of the COVID-19 pandemic as they were alleviated by the vaccination.

Conclusions
The decision making in patients requiring gamma knife treatment was most likely influenced by the status of the COVID-19 pandemic, while vaccination appeared to attenuate their hesitant behaviors. Patients with pre-treatment neurological deficits and high co-morbidity undergoing the gamma knife treatment were less affected by the COVID-19 pandemic.
Bile pigments in emergency and critical care medicine
Authors: Seya Mizuki , Aokage Toshiyuki , Nojima Tsuyoshi , Nakao Atsunori , Naito Hiromichi 
Published: October 2022

AbstractBile pigments, such as bilirubin and biliverdin, are end products of the heme degradation pathway in mammals and are widely known for their cytotoxic effects. However, recent studies have revealed that they exert cytoprotective effects through antioxidative, anti-inflammatory, and immunosuppressive properties. All these mechanisms are indispensable in the treatment of diseases in the field of emergency and critical care medicine, such as coronary ischemia, stroke, encephalomyelitis, acute lung injury/acute respiratory distress syndrome, mesenteric ischemia, and sepsis. While further research is required before the safe application of bile pigments in the clinical setting, their underlying mechanisms shed light on their utilization as therapeutic agents in the field of emergency and critical care medicine. This article aims to summarize the current understanding of bile pigments and re-evaluate their therapeutic potential in the diseases listed above.
Synaptic proteomics reveal distinct molecular signatures of cognitive change and C9ORF72 repeat expansion in the human ALS cortex
Authors: Laszlo Zsofia I. , Hindley Nicole , Sanchez Avila Anna , Kline Rachel A. , Eaton Samantha L. , Lamont Douglas J. , Smith Colin , Spires-Jones Tara L. , Wishart Thomas M. , Henstridge Christopher M. 
Published: October 2022

AbstractIncreasing evidence suggests synaptic dysfunction is a central and possibly triggering factor in Amyotrophic Lateral Sclerosis (ALS). Despite this, we still know very little about the molecular profile of an ALS synapse. To address this gap, we designed a synaptic proteomics experiment to perform an unbiased assessment of the synaptic proteome in the ALS brain. We isolated synaptoneurosomes from fresh-frozen post-mortem human cortex (11 controls and 18 ALS) and stratified the ALS group based on cognitive profile (Edinburgh Cognitive and Behavioural ALS Screen (ECAS score)) and presence of a C9ORF72 hexanucleotide repeat expansion (C9ORF72-RE). This allowed us to assess regional differences and the impact of phenotype and genotype on the synaptic proteome, using Tandem Mass Tagging-based proteomics. We identified over 6000 proteins in our synaptoneurosomes and using robust bioinformatics analysis we validated the strong enrichment of synapses. We found more than 30 ALS-associated proteins in synaptoneurosomes, including TDP-43, FUS, SOD1 and C9ORF72. We identified almost 500 proteins with altered expression levels in ALS, with region-specific changes highlighting proteins and pathways with intriguing links to neurophysiology and pathology. Stratifying the ALS cohort by cognitive status revealed almost 150 specific alterations in cognitively impaired ALS synaptic preparations. Stratifying by C9ORF72-RE status revealed 330 protein alterations in the C9ORF72-RE +ve group, with KEGG pathway analysis highlighting strong enrichment for postsynaptic dysfunction, related to glutamatergic receptor signalling. We have validated some of these changes by western blot and at a single synapse level using array tomography imaging. In summary, we have generated the first unbiased map of the human ALS synaptic proteome, revealing novel insight into this key compartment in ALS pathophysiology and highlighting the influence of cognitive decline and C9ORF72-RE on synaptic composition.
Public views of community pharmacy services during the COVID-19 pandemic: a national survey
Authors: Bou-Saba Alein W. , Kassak Kassem M. , Salameh Pascale R. 
Published: October 2022

AbstractObjectiveTo assess public opinion about community pharmacy services in Lebanon during the COVID-19 pandemic.MethodA cross-sectional study using an online questionnaire was conducted between April and August of 2021. A link was shared randomly among the Lebanese population using WhatsApp and Facebook. Public perceptions were explored within 3 different indicators: general services (B) dispensing (C), and storage (D). Chi-square, Student’s test and ANOVA tests were used.p < 0.05 was considered statistically significant.ResultsOut of 491 responses, only 9.6% scored above the 75th percentile (19.3% for the general services, 2.4% for dispensing indicator and 12.6% for storage indicator). The main concerns focused on lack of medication and reduced opening hours; however, 67.1% of respondents preferred consulting the community pharmacist instead of visiting primary health care centers, doctor’s private clinic and hospitals. Higher mean values of indicators B, C and in the overall indicator were significantly found in the presence of a pharmacist compared to the support pharmacy workforce.ConclusionThe overall public perception was inadequate. Significant difference in terms of quality of services was detected in the presence and absence of a community pharmacist during the crisis. It is recommended that the Order of Pharmacist of Lebanon (OPL) and the Ministry of Public Health (MOPH) undergo further steps mainly to enforce the laws concerning dispensing and storage indicators, improve the services in terms of extending the opening hours, ensure the availability of medicines and increase public awareness.
Synchronization of small-scale seismic clusters reveals large-scale plate deformation
Authors: Karabulut Hayrullah , Bouchon Michel , Schmittbuhl Jean 
Published: October 2022

AbstractIt has long been observed that periods of intense seismic activity in a region alternate with periods of relative quiescence, but establishing whether or not this intermittency is driven by broad-scale physical processes occurring in the Earth, remains a challenge. Here, we address this question of long-range triggering by a large-scale analysis of evolution of the seismicity between 2003 and 2017 in the Anatolia region. Two multi-year periods of synchronous high seismicity rate in 27 seismicity clusters across the Anatolian plate are evidenced before a relatively uniform quiescence period. We argue that two remote tectonic processes are important for the timing of these activities: the 2004 M9.2 Sumatra earthquake and the 2008–2011 episode of slab rollback/deformation in the Hellenic subduction, even if a clear causal mechanism is still lacking.
Graphical Abstract