bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prognostic significance of tumor deposits in radically resected gastric cancer: a retrospective study of a cohort of 1915 Chinese individuals
Authors: Zhou Menglong , Yang Wang , Zou Wei , Yang Jianing , Zhou Changming , Zhang Zhiyuan , Wang Yaqi , Zhang Jing , Wang Yan , Li Guichao , Zhang Zhen , Xia Fan 
Published: September 2022

Abstract
Background
Tumor deposits (TDs) have been identified as an independent prognostic factor in gastric cancer (GC). However, the associated clinicopathological factors and how to simply and reasonably incorporate TD into the TNM staging system remain undetermined. The aim of the current study was therefore to assess the significance of TD among radically resected GC patients.

Methods
We retrospectively reviewed 1915 patients undergoing radical resection between 2007 and 2012. The patients were classified into two groups according to TD status (absent vs. present), and the clinicopathologic characteristics, DFS, and OS were compared. Associations of TD presence with other clinicopathologic factors were evaluated by logistic regression analysis. Univariate and multivariate Cox regression analyses were performed to determine the prognostic factors for DFS and OS in the primary cohort. Propensity score matching (PSM) was performed to reduce the possibility of selection bias according to the presence of TD. External validation of previously proposed modified staging systems incorporating TD was conducted.

Results
The detection rate of TD was 10.5% (201/1915). The presence of TD was significantly related to unfavorable clinicopathologic variables, including advanced T and N categories. According to the multivariate Cox regression analysis, the presence of TD was identified as an independent prognostic factor for DFS and OS in the primary cohort (both P < 0.001). In the after-PSM cohort, TD presence also significantly shortened DFS and OS. In the external validation, one system that incorporated TD into the pTNM stage had the best performance.

Conclusions
The presence of TD was significantly associated with poor survival in radically resected GC patients. The incorporation of TD into the TNM staging system can further improve the predictive capability. A multicenter cohort with a large sample size is needed to determine the appropriate method of incorporation.
Factors leading to falls in transfemoral prosthesis users: a case series of sound-side stumble recovery responses
Authors: Eveld Maura E. , King Shane T. , Zelik Karl E. , Goldfarb Michael 
Published: September 2022

Abstract
Background
Transfemoral prosthesis users’ high fall rate is related to increased injury risk, medical costs, and fear of falling. Better understanding how stumble conditions (e.g., participant age, prosthesis type, side tripped, and swing phase of perturbation) affect transfemoral prosthesis users could provide insight into response deficiencies and inform fall prevention interventions.

Methods
Six unilateral transfemoral prosthesis users experienced obstacle perturbations to their sound limb in early, mid, and late swing phase. Fall outcome, recovery strategy, and kinematics of each response were recorded to characterize (1) recoveries versus falls for transfemoral prosthesis users and (2) prosthesis user recoveries versus healthy adult recoveries.

Results
Out of 26 stumbles, 15 resulted in falls with five of six transfemoral prosthesis users falling at least once. By contrast, in a previously published study of seven healthy adults comprising 214 stumbles using the same experimental apparatus, no participants fell. The two oldest prosthesis users fell after every stumble, stumbles in mid swing resulted in the most falls, and prosthesis type was not related to strategy/fall outcomes. Prosthesis users who recovered used the elevating strategy in early swing, lowering strategy in late swing, and elevating or lowering/delayed lowering with hopping in mid swing, but exhibited increased contralateral (prosthetic-side) thigh abduction and trunk flexion relative to healthy controls. Falls occurred if the tripped (sound) limb did not reach ample thigh/knee flexion to sufficiently clear the obstacle in the elevating step, or if the prosthetic limb did not facilitate a successful step response after the initial sound-side elevating or lowering step. Such responses generally led to smaller step lengths, less anterior foot positioning, and more forward trunk flexion/flexion velocity in the resulting foot-strikes.

Conclusions
Introducing training (e.g., muscle strength or task-specific motor skill) and/or modifying assistive devices (e.g., lower-limb prostheses or exoskeletons) may improve responses for transfemoral prosthesis users. Specifically, training or exoskeleton assistance could help facilitate sufficient thigh/knee flexion for elevating; training or prosthesis assistance could provide support-limb counteracting torques to aid in elevating; and training or prosthesis assistance could help initiate and safely complete prosthetic swing.
Preclinical assessment of synergistic efficacy of MELK and CDK inhibitors in adrenocortical cancer
Authors: Laha Dipranjan , Grant Robert R.C. , Mishra Prachi , Boufraqech Myriem , Shen Min , Zhang Ya-Qin , Hall Matthew D. , Quezado Martha , De Melo Michelly Sampaio , Del Rivero Jaydira , Zeiger Martha , Nilubol Naris 
Published: September 2022

Abstract
Background
Adrenocortical cancer (ACC) is a rare and aggressive cancer with dismal 5-year survival due to a lack of effective treatments. We aimed to identify a new effective combination of drugs and investigated their synergistic efficacy in ACC preclinical models.

Methods
A quantitative high-throughput drug screening of 4,991 compounds was performed on two ACC cell lines, SW13 and NCI-H295R, based on antiproliferative effect and caspase-3/7 activity. The top candidate drugs were pairwise combined to identify the most potent combinations. The synergistic efficacy of the selected inhibitors was tested on tumorigenic phenotypes, such as cell proliferation, migration, invasion, spheroid formation, and clonogenicity, with appropriate mechanistic validation by cell cycle and apoptotic assays and protein expression of the involved molecules. We tested the efficacy of the drug combination in mice with luciferase-tagged human ACC xenografts. To study the mRNA expression of target molecules in ACC and their clinical correlations, we analyzed the Gene Expression Omnibus and The Cancer Genome Atlas.

Results
We chose the maternal embryonic leucine zipper kinase (MELK) inhibitor (OTS167) and cyclin-dependent kinase (CDK) inhibitor (RGB-286638) because of their potent synergy from the pairwise drug combination matrices derived from the top 30 single drugs. Multiple publicly available databases demonstrated overexpression of MELK, CDK1/2, and partnering cyclins mRNA in ACC, which were independently associated with mortality and other adverse clinical features. The drug combination demonstrated a synergistic antiproliferative effect on ACC cells. Compared to the single-agent treatment groups, the combination treatment increased G2/M arrest, caspase-dependent apoptosis, reduced cyclins A2, B1, B2, and E2 expression, and decreased cell migration and invasion with reduced vimentin. Moreover, the combination effectively decreased Foxhead Box M1, Axin2, glycogen synthase kinase 3-beta, and β-catenin. A reduction in p-stathmin from the combination treatment destabilized microtubule assembly by tubulin depolymerization. The drug combination treatment in mice with human ACC xenografts resulted in a significantly lower tumor burden than those treated with single-agents and vehicle control groups.

Conclusions
Our preclinical study revealed a novel synergistic combination of OTS167 and RGB-286638 in ACC that effectively targets multiple molecules associated with ACC aggressiveness. A phase Ib/II clinical trial in patients with advanced ACC is therefore warranted.
A novel cysteine protease inhibitor in Baylisascaris schroederi migratory larvae regulates inflammasome activation through the TLR4–ROS–NLRP3 pathway
Authors: Xu Jingyun , Gu Xiaobin , Xie Yue , He Ran , Xu Jing , Xiong Lang , Peng Xuerong , Yang Guangyou 
Published: September 2022

Abstract
Background
Giant pandas (Ailuropoda melanoleuca) are the obligate host of the parasitic roundworm Baylisascaris schroederi. The infection of giant pandas with B. schroederi is very common. At present, little is known about the mechanism of immune interaction between B. schroederi and the host. As an important component of innate immunity, the NOD-like receptor 3 (NLRP3) inflammasome plays an important role in host immune response and the occurrence and development of infectious diseases.

Methods
We analyzed the regulation of NLRP3 inflammasome activation in monocyte-derived macrophages (MDMs) by the recombinant B. schroederi migratory larvae cysteine protease inhibitor rBsCPI-1, knowing from a previous study that the CPI-1 is highly expressed in B. schroederi migratory larvae. We first determined the effects of rBsCPI-1 and excretory–secretory products of B. schroederi migratory larvae on cell proliferation using the CCK-8 and LDH release assays. We then analyzed NLRP3 inflammasome activation, pyroptosis and pro-inflammatory cytokine release by quantitative-PCR, western blotting and enzyme-linked immunosorbent assay. The signaling pathway of rBsCPI-1 to activate NLRP3 inflammasomes was analyzed in activation and inhibition experiments. Finally, the effects of rBsCPI-1 on inflammasome activation in mice immunized with rBsCPI-1 were analyzed.

Results
The activation and inhibition experiments revealed that rBsCPI-1 induced inflammasome activation through the TLR4–ROS–NLRP3 signaling pathway, with reactive oxygen species (ROS) not only functioning as an activator of the NLRP3 inflammasome, but also an activation product of the NLRP3 inflammasome. rBsCPI-1 promoted the activation and assembly of the NLRP3 inflammasome, which further converted the pro-inflammatory cytokines interleukin (IL)-1β and IL-18 into mature active forms. At the same time, caspase-1 cleaved gasdermin D to trigger cell pyroptosis. The results of animal immunization experiments further confirmed that rBsCPI-1 could induce the activation of the NLRP3 inflammasome.

Conclusions
rBsCPI-1 activates the inflammasome through the TLR4–ROS–NLRP3 signaling pathway and further induces the pyroptosis of MDMs and release of pro-inflammatory factors IL-1β and IL-18, thus promoting the occurrence and development of the inflammatory response in the host.

Graphical abstract
Association of Alzheimer’s disease polygenic risk scores with amyloid accumulation in cognitively intact older adults
Authors: Luckett Emma S. , Abakkouy Yasmina , Reinartz Mariska , Adamczuk Katarzyna , Schaeverbeke Jolien , Verstockt Sare , De Meyer Steffi , Van Laere Koen , Dupont Patrick , Cleynen Isabelle , Vandenberghe Rik 
Published: September 2022

Abstract
Background
Early detection of individuals at risk for Alzheimer’s disease (AD) is highly important. Amyloid accumulation is an early pathological AD event, but the genetic association with known AD risk variants beyond the APOE4 effect is largely unknown. We investigated the association between different AD polygenic risk scores (PRS) and amyloid accumulation in the Flemish Prevent AD Cohort KU Leuven (F-PACK).

Methods
We calculated PRS with and without the APOE region in 90 cognitively healthy F-PACK participants (baseline age 67.8 (52–80) years, 41 APOE4 carriers), with baseline and follow-up amyloid-PET (time interval 6.1 (3.4–10.9) years). Individuals were genotyped using Illumina GSA and imputed. PRS were calculated using three p-value thresholds (pT) for variant inclusion: 5 × 10−8, 1 × 10−5, and 0.1, based on the stage 1 summary statistics from Kunkle et al. (Nat Genet 51:414–30, 2019). Linear regression models determined if these PRS predicted amyloid accumulation.

Results
A score based on PRS excluding the APOE region at pT = 5 × 10−8 plus the weighted sum of the two major APOE variants (rs429358 and rs7412) was significantly associated with amyloid accumulation (p = 0.0126). The two major APOE variants were also significantly associated with amyloid accumulation (p = 0.0496). The other PRS were not significant.

Conclusions
Specific PRS are associated with amyloid accumulation in the asymptomatic phase of AD.
Constraints and prospects of utilising mountain pastures in Gilgit-Baltistan, Pakistan
Authors: Hameed Asif , Tariq Muhammad , Buerkert Andreas , Schlecht Eva 
Published: September 2022

AbstractIn the mountain regions of northern Pakistan, pasture-based animal husbandry is a substantial element of people’s livelihood. To study the implications of herding strategies on rangeland utilization patterns, individual interviews with 90 herders and 10 group interviews with five to eight herders per group, respectively, were conducted in three valleys each of Pakistan’s Gilgit-Baltistan region. Data collection targeted number and species of animals kept, livestock management practices and seasonal pasture use and included GIS-based participatory mapping of spring, summer, autumn and winter pastures of yak, small ruminants and cattle. Households kept 10 yaks on average, along with 4 cattle and 15 small ruminants. Herding practices varied between valleys and seasons and were influenced by topographic as well as social factors. Full-time herding led to a more uniform distribution of yaks on pastures than part-time herding and unattended grazing, but in small ruminants promoted higher animal numbers near campsites. Many livestock keepers perceived rangeland degradation as a veritable challenge and identified lack of herding labour as one important problem. Training programmes for young herders, strengthening of group herding schemes and prevention of lowland pasture conversion into farmland were suggested as effective countermeasures.
Identifying performance factors of long-term care facilities in the context of the COVID-19 pandemic: a scoping review protocol
Authors: Létourneau Josiane , Bélanger Emilie , Sia Drissa , Beogo Idrissa , Robins Stephanie , Kruglova Katya , Jubinville Maripier , Tchouaket Eric Nguemeleu 
Published: September 2022

Abstract
Background
Long-term care facilities (LTCFs) have been severely affected by the COVID-19 pandemic with serious consequences for the residents. Some LTCFs performed better than others, experiencing lower case and death rates due to COVID-19. A comprehensive understanding of the factors that have affected the transmission of COVID-19 in LTCFs is lacking, as no published studies have applied a multidimensional conceptual framework to evaluate the performance of LTCFs during the pandemic. Much research has focused on infection prevention and control strategies or specific disease outcomes (e.g., death rates). To address these gaps, our scoping review will identify and analyze the performance factors that have influenced the management of COVID-19 in LTCFs by adopting a multidimensional conceptual framework.

Methods
We will query the CINAHL, MEDLINE (Ovid), CAIRN, Science Direct, and Web of Science databases for peer-reviewed articles written in English or French and published between January 1, 2020 and December 31, 2021. We will include articles that focus on the specified context (COVID-19), population (LTCFs), interest (facilitators and barriers to performance of LTCFs), and outcomes (dimensions of performance according to a modified version of the Ministère de la santé et des services sociaux du Québec conceptual framework). Each article will be screened by at least two co-authors independently followed by data extraction of the included articles by one co-author and a review by the principal investigator.

Results
We will present the results both narratively and with visual aids (e.g., flowcharts, tables, conceptual maps).

Discussion
Our scoping review will provide a comprehensive understanding of the factors that have affected the performance of LTCFs during the COVID-19 pandemic. This knowledge can help inform the development of more effective infection prevention and control measures for future pandemics and outbreaks. The results of our review may lead to improvements in the care and safety of LTCF residents and staff.

Scoping review registration
Research Registry researchregistry7026
eHealth literacy measurement tools: a systematic review protocol
Authors: Délétroz Carole , Allen Marina Canepa , Sasseville Maxime , Rouquette Alexandra , Bodenmann Patrick , Gagnon Marie-Pierre 
Published: September 2022

Abstract
Background
Improving eHealth literacy (eHL) is one of the biggest challenges currently facing the global healthcare community. Indeed the use of digital services has the potential to engage patients in care as well as improve the effectiveness of chronic disease self-management, it remains highly dependent on a patient’s specific skills and experiences in the health care systems. Although eHealth literacy has gained momentum in the past decade, it remains an underresearched area, particularly eHealth literacy measurement. The aim of the review is to identify patient-reported outcome measures (PROMs) of eHealth literacy for adult populations and to summarize the evidence on their psychometric properties.

Methods
We will conduct a systematic literature review of the tools used to measure eHealth literacy for adult population. The search strategy aims to find published studies. A three-step search strategy will be used in this review. Published studies will be searched in CINAHL, PubMed, PsycINFO, and Web of Science from inception until end. Grey literature will be searched to find theses. Database search strategies will be formulated and tested with the assistance of an expert Health Sciences Librarian. The selection of studies will be done by two independent reviewers. Disagreements will be resolved through consensus, and a third reviewer will solve discrepancies. Furthermore, two reviewers will independently evaluate the methodological rigor of the instruments development and testing and assign a grade using the standardized Consensus-based Standards for the Selection of Health Measurement Instruments (COSMIN) checklist. Disagreements will be discussed with a third reviewer, expert in psychometrics.
Extracted data will be aggregated and analyzed to produce a set of synthesized findings that will be used to develop evidence-informed recommendations in regard of eHL instruments. We will present a synthesis of all instruments, their psychometric properties, and make recommendations for eHL instrument selection in practice. Reporting will be informed by the Preferred Reporting Items for Systematic Reviews and Meta-Analysis and a PRISMA flow diagram.

Discussion
This systematic review will summarize the evidence on the psychometric properties of PROMs instruments used to measure eHL and will help clinicians, managers, and policy-makers to select an appropriate instrument.

Systematic review registration
PROSPERO CRD42021232765
Combined left thoracoscopic and median sternotomy approach to resect aortopulmonary mediastinal paraganglioma following feeding artery embolization: a case report
Authors: Itagaki Kota , Notsuda Hirotsugu , Suzuki Tomoyuki , Tanaka Ryota , Kamada Hiroki , Omata Kei , Tezuka Yuta , Ota Hideki , Okada Yoshinori , Saiki Yoshikatsu 
Published: September 2022

Abstract
Background
Aortopulmonary mediastinal paragangliomas are rare. Complete resection of the tumor is desirable regardless of tumor size in view of the risk of sudden death induced by adjacent organ compression and poor prognosis after partial resection or untreated observation. Due to the hypervascularity of the tumor, the risk of intraoperative bleeding is significant, and cardiopulmonary bypass is often required for complete resection.

Case presentation
The patient was diagnosed as having bilateral carotid body tumors and supposedly an aortic body tumor at the age of 43 and eventually underwent resections of bilateral carotid body tumors at the age of 52. The pathology of the carotid body tumors was compatible with paraganglioma on both sides. A familial succinate dehydrogenase subunit D mutation was subsequently identified. Five years later, a contrast-enhanced computed tomography scan showed an enlarged tumor of 45 mm in size in the aortopulmonary mediastinum. Based on the previously known genetic mutation, the tumor was thought to be a paraganglioma. After confirming with an endocrinologist that the aortic body tumor was non-functional, radiologists performed preoperative embolization of the feeding vessels. Subsequently, a surgical team consisting of thoracic and cardiovascular surgeons resected the aortic body tumor using a video-assisted small left thoracotomy approach combined with a median sternotomy approach. The procedure was completed without cardiopulmonary bypass or blood transfusion. The patient was discharged home on postoperative day 9 uneventfully.

Conclusions
After conduction of preceding interventional embolization of multiple feeding vessels, we employed a video-assisted thoracoscopic surgical approach to dissect the aspects of the tumor adjacent to the esophagus, descending thoracic aorta, and left pulmonary artery, followed by a median sternotomy approach to dissect the other aspects of the tumor adjacent to the ascending aorta, aortic arch, right pulmonary artery, and trachea. There have been no reports on scheduled preoperative embolization of feeding vessels to an aortopulmonary mediastinal paraganglioma. Multidisciplinary approach was effective for complete resection of this challenging rare mediastinal tumor.
Network Physiology of Exercise: Beyond Molecular and Omics Perspectives
Authors: Balagué Natàlia , Hristovski Robert , Almarcha Maricarmen , Garcia-Retortillo Sergi , Ivanov Plamen Ch. 
Published: September 2022

AbstractMolecular Exercise Physiology and Omics approaches represent an important step toward synthesis and integration, the original essence of Physiology. Despite the significant progress they have introduced in Exercise Physiology (EP), some of their theoretical and methodological assumptions are still limiting the understanding of the complexity of sport-related phenomena. Based on general principles of biological evolution and supported by complex network science, this paper aims to contrast theoretical and methodological aspects of molecular and network-based approaches to EP. After explaining the main EP challenges and why sport-related phenomena cannot be understood if reduced to the molecular level, the paper proposes some methodological research advances related to the type of studied variables and measures, the data acquisition techniques, the type of data analysis and the assumed relations among physiological levels. Inspired by Network Physiology, Network Physiology of Exercise provides a new paradigm and formalism to quantify cross-communication among diverse systems across levels and time scales to improve our understanding of exercise-related phenomena and opens new horizons for exercise testing in health and disease.