bluuebunny/crossref_metadata_2025_split huggingface dataset:
The amount of DNA combined with TP53 mutations in liquid biopsy is associated with clinical outcome of renal cancer patients treated with immunotherapy and VEGFR-TKIs
Authors: Del Re Marzia , Crucitta Stefania , Paolieri Federico , Cucchiara Federico , Verzoni Elena , Bloise Francesco , Ciampi Raffaele , Mercinelli Chiara , Capuano Annalisa , Sportiello Liberata , Martinetti Antonia , Procopio Giuseppe , Galli Luca , Porta Camillo , Bracarda Sergio , Danesi Romano 
Published: August 2022

Abstract
Background
Despite the increasing number of treatment options, reliable prognostic/predictive biomarkers are still missing for patients affected by metastatic clear cell renal cell carcinoma (mccRCC).

Methods
Patients with mccRCC undergoing standard first line treatment were enrolled. Blood (12 ml) was drawn at treatment baseline and circulating free DNA (cfDNA) was extracted from plasma. Next-generation sequencing (NGS) was performed on cfDNA using the Oncomine Pan-Cancer Cell-Free Assay and clinical outcomes were correlated with liquid biopsy findings.

Results
A total of 48 patients were enrolled, 12 received immunotherapy and 36 received a vascular endothelial growth factor receptor (VEGFR) tyrosine kinase inhibitor (TKI). A cfDNA cut-off of 0.883 ng/μl stratified patients based on progression-free survival (PFS) and overall survival (OS) (p = 0.001 and p = 0.008, respectively). cfDNA amount was also correlated with best response (p = 0.006). Additional cfDNA cut-points divided patients into short, intermediate and long responders, with PFS of 4.87 vs 9.13 vs 23.1 months, respectively (p < 0.001). PFS resulted to be significantly shorter in carriers of mutant TP53 compared to not carriers (p = 0.04). Patients with high cfDNA levels and mutant TP53 have the worst PFS, while patients with low cfDNA amounts and no mutations in TP53 displayed the longest PFS (p = 0.004).

Conclusions
The present study demonstrates that cfDNA and TP53 are potential predictive biomarkers of response in mccRCC to be further explored in larger and/or prospective studies.
Gene expression and methylation profiles show the involvement of POMC in primary hyperparathyroidsm
Authors: Zhou Wen-Xuan , Wang Shu , Wu Ting-Chao , Cheng Ling-Chao , Du Yao , Wu Wei , Lin Chen , Li Xin-Ying , Hu Zhong-Liang 
Published: August 2022

AbstractPrimary hyperparathyroidism (PHPT) is mainly caused by parathyroid adenoma, which produces excess parathyroid hormones. Its pathogenic mechanisms have not yet been fully understood. To investigate the mechanism in the pathogenesis of PHPT, the transcriptome and genome-wide DNA methylation profiles of parathyroid adenoma were analyzed. The candidate genes that may be involved in the PHPT were verified via qRT-PCR, immunohistochemistry, western blot, and methylation-specific PCR. A total of 1650 differentially expressed genes and 2373 differentially methylated regions were identified. After the integration of its transcriptome and DNA methylation data, IL6, SYP, GNA01, and pro-opiomelanocortin (POMC) were the candidate genes that demonstrated a similar pattern between their mRNA expression and DNA methylation status. Of the 4 candidate genes, POMC, a pro-peptide which is processed to a range of bioactive peptide products like ACTH, was further confirmed to be expressed at low levels at both the mRNA and protein levels, which may be due to POMC promoter hypermethylation. Hypermethylation of the POMC promoter may contribute to its low expression, which may be involved in the pathogenesis of PHPT.
ExerG: adapting an exergame training solution to the needs of older adults using focus group and expert interviews
Authors: Ringgenberg Nathalie , Mildner Sarah , Hapig Marcia , Hermann Sarah , Kruszewski Katharina , Martin-Niedecken Anna Lisa , Rogers Katja , Schättin Alexandra , Behrendt Frank , Böckler Sonja , Schmidlin Stefan , Jurt Roman , Niedecken Stephan , Brenneis Christian , Bonati Leo H. , Schuster-Amft Corina , Seebacher Barbara 
Published: August 2022

Abstract
Background
Exergames are playful technology-based exercise programs. They train physical and cognitive functions to preserve independence in older adults (OAs) with disabilities in daily activities and may reduce their risk of falling. This study gathered in-depth knowledge and understanding of three different user groups’ experiences in and relevant needs, worries, preferences, and expectations of technology-based training, to develop an exergame training device for OAs.

Methods
We conducted a qualitative study using semi-structured focus group interviews of primary (OAs in geriatric or neurological rehabilitation) and secondary (health professionals) end users, as well as expert interviews of tertiary end users (health insurance experts or similar), exploring user perspectives on adjusting an existing exergame to OAs’ needs. Voice-recorded interviews were transcribed by researchers and analyzed using thematic analysis (TA) following an inductive, data-driven, iterative approach.

Results
We interviewed 24 primary, 18 secondary, and 9 tertiary end users at two rehabilitation centers in Austria and Switzerland. Our TA approach identified five to six themes per user group. Themes in the primary end user group reflected aspects of safety, training goals, individuality, game environment, social interactions, and physical and technical overload. Themes in the secondary end user group comprised facets of meaningfulness, distraction through the game environment, safety, gamification elements, the availability and accessibility of the exergame. Tertiary end users’ themes addressed aspects of financial reimbursement, suitable target populations, professional training for the handling of exergame devices, training goals, and concerns about the use of exergames in geriatric rehabilitation.

Conclusions
In conclusion, an exergame for OAs must be safe, motivating and fully adaptable to the target group while promoting the return to or preservation of autonomy and independence in daily life. Our findings contribute to developing hard- and software extensions for the ExerG training device. Further research is needed to expand the validity of our findings to larger populations.
PerSVade: personalized structural variant detection in any species of interest
Authors: Schikora-Tamarit Miquel Àngel , Gabaldón Toni 
Published: August 2022

AbstractStructural variants (SVs) underlie genomic variation but are often overlooked due to difficult detection from short reads. Most algorithms have been tested on humans, and it remains unclear how applicable they are in other organisms. To solve this, we develop perSVade (personalized structural variation detection), a sample-tailored pipeline that provides optimally called SVs and their inferred accuracy, as well as small and copy number variants. PerSVade increases SV calling accuracy on a benchmark of six eukaryotes. We find no universal set of optimal parameters, underscoring the need for sample-specific parameter optimization. PerSVade will facilitate SV detection and study across diverse organisms.
A survey of contextual factors and psychological needs satisfaction as correlates of youth athletes’ developmental outcomes in the Ethiopian sports academy context
Authors: Tadesse Tefera , Asmamaw Aemero , H/Mariam Sirak , Edo Beshir 
Published: August 2022

Abstract
Background
This study examined the contextual factors associated with psychological need satisfaction (PNS) and the predictability of the PNS components, together with the contextual factors, on the developmental outcomes of elite young athletes in the Ethiopian sports academies, and further identified differences in perception of PNS from a comparative perspective. The study used a cross-sectional survey design applying developmental and PNS theories as guiding frameworks. Samples of elite young Ethiopian athletes participated (n = 257, 47.47% were women with a mean age of 17.44 years and SD = 0.87, and 52.53% were men with a mean age of 18.25 years and SD = 1.14).

Results
Structural equation modeling showed that the three PNS domains, together with the five contextual factors positively predicted the three developmental outcomes measured (41–54% explained variance). Moreover, there were higher differences in PNS (0.55 ≤ Cohen’s d ≥ 0.71) among young athletes classified by the sport types.

Discussion
As per the findings of this study, young athletes may differ in the levels of PNS they obtained depending on the type of sports enrolled in sports academies. Also, the results of this study indicated that PNS attained may be modestly influenced by some contextual factors. It also evidenced that those developmental outcomes in elite young athletes are significantly positively associated with contextual and PNS factors. Stakeholders such as young athlete coaches, parents, sports psychologists, and administrators must consider the differing implications of program type during the elite young athletes’ participation in sports academics and the significant positive association between contextual factors, PNS, and developmental outcomes of elite young athletes.

Conclusions
In sum, the PNS of youth athletes may differ across sports types and the talent development of elite young athletes should emphasize the individual nature of the processes. Also, it can be concluded that the PNS components than the contextual factors had higher predictions of developmental outcomes.
Expanding ACMG variant classification guidelines into a general framework
Authors: Masson Emmanuelle , Zou Wen-Bin , Génin Emmanuelle , Cooper David N. , Le Gac Gerald , Fichou Yann , Pu Na , Rebours Vinciane , Férec Claude , Liao Zhuan , Chen Jian-Min 
Published: August 2022

Abstract
Background
The American College of Medical Genetics and Genomics (ACMG)-recommended five variant classification categories (pathogenic, likely pathogenic, uncertain significance, likely benign, and benign) have been widely used in medical genetics. However, these guidelines are fundamentally constrained in practice owing to their focus upon Mendelian disease genes and their dichotomous classification of variants as being either causal or not. Herein, we attempt to expand the ACMG guidelines into a general variant classification framework that takes into account not only the continuum of clinical phenotypes, but also the continuum of the variants’ genetic effects, and the different pathological roles of the implicated genes.

Main body
As a disease model, we employed chronic pancreatitis (CP), which manifests clinically as a spectrum from monogenic to multifactorial. Bearing in mind that any general conceptual proposal should be based upon sound data, we focused our analysis on the four most extensively studied CP genes, PRSS1, CFTR, SPINK1 and CTRC. Based upon several cross-gene and cross-variant comparisons, we first assigned the different genes to two distinct categories in terms of disease causation: CP-causing (PRSS1 and SPINK1) and CP-predisposing (CFTR and CTRC). We then employed two new classificatory categories, “predisposing” and “likely predisposing”, to replace ACMG’s “pathogenic” and “likely pathogenic” categories in the context of CP-predisposing genes, thereby classifying all pathologically relevant variants in these genes as “predisposing”. In the case of CP-causing genes, the two new classificatory categories served to extend the five ACMG categories whilst two thresholds (allele frequency and functional) were introduced to discriminate “pathogenic” from “predisposing” variants.

Conclusion
Employing CP as a disease model, we expand ACMG guidelines into a five-category classification system (predisposing, likely predisposing, uncertain significance, likely benign, and benign) and a seven-category classification system (pathogenic, likely pathogenic, predisposing, likely predisposing, uncertain significance, likely benign, and benign) in the context of disease-predisposing and disease-causing genes, respectively. Taken together, the two systems constitute a general variant classification framework that, in principle, should span the entire spectrum of variants in any disease-related gene. The maximal compliance of our five-category and seven-category classification systems with the ACMG guidelines ought to facilitate their practical application.
Pathological changes induced by Alzheimer’s brain inoculation in amyloid-beta plaque-bearing mice
Authors: Lam Suzanne , Hérard Anne-Sophie , Boluda Susana , Petit Fanny , Eddarkaoui Sabiha , Cambon Karine ,   The Brainbank Neuro-CEB Neuropathology Network, Letournel Franck , Martin-Négrier Marie-Laure , Faisant Maxime , Godfraind Catherine , Boutonnat Jean , Maurage Claude-Alain , Deramecourt Vincent , Duchesne Mathilde , Meyronet David , Fenouil Tanguy , de Paula André Mauès , Rigau Valérie , Vandenbos-Burel Fanny , Seilhean Danielle , Duyckaerts Charles , Boluda Susana , Plu Isabelle , Chiforeanu Dan Christian , Laquerrière Annie , Marguet Florent , Lannes Béatrice , Lhermitte Benoît , Picq Jean-Luc , Buée Luc , Duyckaerts Charles , Haïk Stéphane , Dhenain Marc 
Published: August 2022

AbstractAlzheimer's disease (AD) is characterized by intracerebral accumulations of extracellular amyloid-β (Aβ) plaques and intracellular tau pathology that spread in the brain. Three types of tau lesions occur in the form of neuropil threads, neurofibrillary tangles, and neuritic plaques i.e. tau aggregates within neurites surrounding Aβ deposits. The cascade of events linking these lesions and synaptic or memory impairments are still debated. Intracerebral infusion of human AD brain extracts in Aβ plaque-bearing mice that do not overexpress pathological tau proteins induces tau pathologies following heterotopic seeding of mouse tau protein. There is however little information regarding the downstream events including synaptic or cognitive repercussions of tau pathology induction in these models. In the present study, human AD brain extracts (ADbe) and control-brain extracts (Ctrlbe) were infused into the hippocampus of Aβ plaque-bearing APPswe/PS1dE9 mice. Memory, synaptic density, as well as Aβ plaque and tau aggregate loads, microgliosis, astrogliosis at the inoculation site and in connected regions (perirhinal/entorhinal cortex) were evaluated 4 and 8 months post-inoculation. ADbe inoculation produced the following effects: (i) memory deficit; (ii) increased Aβ plaque deposition in proximity to the inoculation site; (iii) tau pathology induction; (iv) appearance of neuropil threads and neurofibrillary tangles next to the inoculation site with a spreading to connected regions. Neuritic plaque pathology was detected in both ADbe- and Ctrlbe-inoculated animals but ADbe inoculation increased the severity close to and at distance of the inoculation site. (v) Finally, ADbe inoculation reduced synaptic density in the vicinity to the inoculation site and in connected regions as the perirhinal/entorhinal cortex. Synaptic impairments were correlated with increased severity of neuritic plaques but not to other tau lesions or Aβ lesions, suggesting that neuritic plaques are a culprit for synaptic loss. Synaptic density was also associated with microglial load.
Graphical abstract
Targeted policy intervention for reducing red meat consumption: conflicts and trade-offs
Authors: James William H.M. , Lomax Nik , Birkin Mark , Collins Lisa M. 
Published: August 2022

Abstract
Background
There are a range of policies and guidelines focused on meat consumption which aim to tackle health and environmental issues. Policies are often siloed in nature and propose universal limits on consumption. Despite this, there will be a number of conflicts and trade-offs between interest groups. This study explores secondary impacts associated with guidelines issued by the World Cancer Research Fund and assesses the utility of a targeted policy intervention strategy for reducing red meat consumption.

Methods
We used highly detailed consumption data of over 5,000 individuals from the National Diet and Nutrition Survey. We firstly compared individual consumption against the policy guidelines to identify demographic groups most likely to consume above recommended levels. We then synthetically modified the food diary data to investigate the secondary impacts of adherence to the recommendations by all individuals. We assessed changes in overall consumption, nutrient intake (iron, zinc, vitamin B12, vitamin B3, fat and saturated fat) and global warming potential. We also projected future impacts under various population projections.

Results
We found that certain demographic groups are much more likely to exceed the recommendations and would therefore benefit from a targeted intervention approach. Our results provide a baseline for which the impacts of any meat substitute diets can be assessed against. Whilst secondary health benefits may be realised by reducing intake of certain nutrients (e.g. fats), negative impacts may occur due to the reduced intake of other nutrients (e.g. iron, zinc). Reduced overall consumption is likely to have implications for the wider meat industry whilst complementary impacts would occur in terms of reduced greenhouse gas emissions. Impacts will be counteracted or maybe even reversed by any substitute products, highlighting the need to carefully consider the suitability and impacts of meat-replacements.

Conclusion
The future structure of the meat industry will depend on how conflicts and trade-offs are addressed and how more holistic policy ideas are implemented. This research provides a framework for using demographic and consumption data to reduce negative trade-offs and improve policy effectiveness.
How to evaluate surgical tourism service organizations in China: indicators system development and a pilot application
Authors: Zhang Dan , Yan Yue , Liao Mei-xia , Liu Ting-fang 
Published: August 2022

Abstract
Background
Surgical tourism is an emerging economic sector, with the most growth potential demonstrated in China's health industry before the COVID-19 pandemic. Surgical tourism accounts for a large part of medical tourism services in China, with high requirements in terms of quality and safety. By contrast, China suffers from insufficient measurement tools and theoretical research. The aim of this study was to develop a set of reliable and feasible indicators by augmenting the Donabedian model to evaluate the quality of surgical tourism services.

Methods
A literature review and focus group interview were used to generate indicators for the quality of surgical tourism services. The basic framework of the evaluation system was based on the structure–process–outcome Donabedian model. The screening and weight setting were conducted through an analytical hierarchy process (AHP) and a two-round Delphi consultation with 13 panelists. The validity and reliability of experts were tested by the experts' positive coefficient, authority coefficient, and coordination coefficient. The reliability of the questionnaire was assessed by a pre-test distributed within an International Medical Department of a public hospital in China.

Results
Based on the Donabedian quality theory, a novel evaluation system of surgical tourism service institutions was constructed with three dimensions, nine first-level items and 39 second-level items. The three dimensions consisted of the structure (0.315), process (0.287), and outcome (0.398), with several indicators for each dimension and each indicator was given a weight. Of the two rounds of Delphi consultation, the response rates were 86.67% and 100%. The coordination coefficient of expert opinions in the two rounds of consultation were 0.49 and 0.65 (p < 0.05). For the empirical study, the self-evaluation score of a public hospital was 86, which could rate as a two-star institution.

Conclusions
Our evaluation system identified three suitable quality dimensions of surgical tourism services to improve the safety and quality of practical healthcare. It reflects the access criterion of surgical tourism institutions, provides references for the best choice of surgical services for tourists, and can be applied by healthcare managers and policy makers to allocate resources more efficiently and promote more surgical tourism services with international standards.
Functional diversification and molecular mechanisms of FLOWERING LOCUS T/TERMINAL FLOWER 1 family genes in horticultural plants
Authors: Wang Shuang , Yang Yiman , Chen Fadi , Jiang Jiafu 
Published: August 2022

AbstractFlowering is an important process in higher plants and is regulated by a variety of factors, including light, temperature, and phytohormones. Flowering restriction has a considerable impact on the commodity value and production cost of many horticultural crops. InArabidopsis, theFT/TFL1gene family has been shown to integrate signals from various flowering pathways and to play a key role in the transition from flower production to seed development. Studies in several plant species of theFT/TFL1gene family have revealed it harbors functional diversity in the regulation of flowering. Here, we review the functional evolution of theFT/TFL1gene family in horticulture plants and its unique regulatory mechanisms; in addition, theFT/TFL1family of genes as an important potential breeding target is explored.
Linking the European Organisation for Research and Treatment of Cancer Item Library to the Common Terminology Criteria for Adverse Events
Authors: Gilbert Alexandra , Piccinin Claire , Velikova Galina , Groenvold Mogens , Kuliś Dagmara , Blazeby Jane M. , Bottomley Andrew 
Published: August 2022

PURPOSE The European Organisation for Research and Treatment of Cancer (EORTC) Item Library is an interactive online platform currently composed of 950 unique items (questions) derived from 67 patient-reported outcome (PRO) questionnaires. PROs complement clinician adverse event (AE) reporting classifications like the Common Terminology Criteria for Adverse Events (CTCAE). This work aims to create a standardized framework using the CTCAE to systematically classify symptomatic AEs from the EORTC Item Library through linking individual items to corresponding AEs. METHODS The EORTC Item Library items were searched for within the CTCAE (v5.0) and linked to an AE if they were described within the AE's title, description, or grading. Symptoms described in EORTC items but not located in the CTCAE were coded as missing symptoms. Other nonsymptom EORTC items, not described within the CTCAE were assigned a non-CTCAE descriptive classification. Further descriptive codes (eg, multiple issues) were allocated to enable descriptive analysis. Two raters independently coded 26.2% (n = 249) of the items. The remaining 701 items were coded by one rater and verified by the second, followed by discussion with two additional raters to reach consensus. RESULTS Overall, 625 (65.8%) EORTC items were linked to 208 different AEs. Three hundred sixty-nine items provide information about non-CTCAE cancer–related issues and were categorized into seven descriptive classifications, including body image; emotional impact of a symptom, diagnosis, or treatment; global health and quality of life; and impact on life and daily activities. Inter-rater agreement for independent coding was 79.1%. Bowel urgency and tenesmus were identified as missing symptoms in CTCAEv5.0. CONCLUSION The EORTC Item Library provides considerable coverage of CTCAE toxicities, along with other complementary issues important to patients with cancer. Using the CTCAE clinical framework to classify symptomatic PRO items may facilitate PRO selection and use in clinical trials and routine care.