bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mutant PIK3CA is a targetable driver alteration in histiocytic neoplasms
Authors: Durham Benjamin H. , Hershkovitz-Rokah Oshrat , Abdel-Wahab Omar , Yabe Mariko , Chung Young Rock , Itchaki Gilad , Ben-Sasson Maayan , Asher-Guz Vered A. , Groshar David , Doe-Tetteh Seyram A. , Alano Tina , Solit David B. , Shpilberg Ofer , Diamond Eli L. , Mazor Roei D. 
Published: October 2023

Abstract
Langerhans cell histiocytosis (LCH) is an inflammatory myeloid neoplasm characterized by the accumulation of clonal mononuclear phagocyte system cells expressing CD1a and CD207. In the past decade, molecular profiling of LCH as well as other histiocytic neoplasms demonstrated that these diseases are driven by MAPK activating alterations, with somatic BRAFV600E mutations in &gt;50% of patients with LCH, and clinical inhibition of MAPK signaling has demonstrated remarkable clinical efficacy. At the same time, activating alterations in kinase-encoding genes, such as PIK3CA, ALK, RET, and CSF1R, which can activate mitogenic pathways independent from the MAPK pathway, have been reported in a subset of histiocytic neoplasms with anecdotal evidence of successful targeted treatment of histiocytoses harboring driver alterations in RET, ALK, and CSF1R. However, evidence supporting the biological consequences of expression of PIK3CA mutations in hematopoietic cells has been lacking, and whether targeted inhibition of PI3K is clinically efficacious in histiocytic neoplasms is unknown. Here, we provide evidence that activating mutations in PIK3CA can drive histiocytic neoplasms in vivo using a conditional knockin mouse expressing mutant PIK3CAH1047R in monocyte/dendritic cell progenitors. In parallel, we demonstrate successful treatment of PIK3CA-mutated, multisystemic LCH using alpelisib, an inhibitor of the alpha catalytic subunit of PI3K. Alpelisib demonstrated a tolerable safety profile at a dose of 750 mg per week and clinical and metabolic complete remission in a patient with PIK3CA-mutated LCH. These data demonstrate PIK3CA as a targetable noncanonical driver of LCH and underscore the importance of mutational analysis–based personalized treatment in histiocytic neoplasms.
Challenges for quality and utilization of real-world data for diffuse large B-cell lymphoma in REALYSA, a LYSA cohort
Authors: Ghesquières Hervé , Cherblanc Fanny , Belot Aurélien , Micon Sophie , Bouabdallah Krimo K. , Esnault Cyril , Fornecker Luc-Matthieu , Thokagevistk Katia , Bonjour Maxime , Bijou Fontanet , Haioun Corinne , Morineau Nadine , Ysebaert Loïc , Damaj Gandhi , Tessoulin Benoit , Guidez Stéphanie , Morschhauser Franck , Thiéblemont Catherine , Chauchet Adrien , Gressin Rémy , Jardin Fabrice , Fruchart Christophe , Labouré Gaëlle , Fouillet Ludovic , Lionne-Huyghe Pauline , Bonnet Antoine , Lebras Laure , Amorim Sandy , Leyronnas Cécile , Olivier Gaelle , Guieze Romain , Houot Roch , Launay Vincent , Drénou Bernard , Fitoussi Olivier , Detourmignies Laurence , Abraham Julie , Soussain Carole , Lachenal Florence , Pica Gian Matteo , Fogarty Patrick , Cony-Makhoul Pascale , Bernier Adeline , Le Guyader-Peyrou Sandra , Monnereau Alain , Boissard Frédéric , Rossi Cédric , Camus Vincent 
Published: October 2023

Abstract
Real-world data (RWD) are essential to complement clinical trial (CT) data, but major challenges remain, such as data quality. REal world dAta in LYmphoma and Survival in Adults (REALYSA) is a prospective noninterventional multicentric cohort started in 2018 that included patients newly diagnosed with lymphoma in France. Herein is a proof-of-concept analysis on patients with first-line diffuse large B-cell lymphoma (DLBCL) to (1) evaluate the capacity of the cohort to provide robust data through a multistep validation process; (2) assess the consistency of the results; and (3) conduct an exploratory transportability assessment of 2 recent phase 3 CTs (POLARIX and SENIOR). The analysis population comprised 645 patients with DLBCL included before 31 March 2021 who received immunochemotherapy and for whom 3589 queries were generated, resulting in high data completeness (&lt;4% missing data). Median age was 66 years, with mostly advanced-stage disease and high international prognostic index (IPI) score. Treatments were mostly rituximab, cyclophosphamide, doxorubicin hydrochloride, vincristine, and prednisone (R-CHOP 75%) and reduced dose R-CHOP (13%). Estimated 1-year event-free survival (EFS) and overall survival rates were 77.9% and 90.0%, respectively (median follow-up, 9.9 months). Regarding transportability, when applying the CT's main inclusion criteria (age, performance status, and IPI), outcomes seemed comparable between patients in REALYSA and standard arms of POLARIX (1-year progression-free survival 79.8% vs 79.8%) and SENIOR (1-year EFS, 64.5% vs 60.0%). With its rigorous data validation process, REALYSA provides high-quality RWD, thus constituting a platform for numerous scientific purposes. The REALYSA study was registered at www.clinicaltrials.gov as #NCT03869619.
Genome-wide association analysis of heifer livability and early first calving in Holstein cattle
Authors: Gao Yahui , Marceau Alexis , Iqbal Victoria , Torres-Vázquez Jose Antonio , Neupane Mahesh , Jiang Jicai , Liu George E. , Ma Li 
Published: October 2023

Abstract
Background
The survival and fertility of heifers are critical factors for the success of dairy farms. The mortality of heifers poses a significant challenge to the management and profitability of the dairy industry. In dairy farming, achieving early first calving of heifers is also essential for optimal productivity and sustainability. Recently, Council on Dairy Cattle Breeding (CDCB) and USDA have developed new evaluations of heifer health and fertility traits. However, the genetic basis of these traits has yet to be thoroughly studied.

Results
Leveraging the extensive U.S dairy genomic database maintained at CDCB, we conducted large-scale GWAS analyses of two heifer traits, livability and early first calving. Despite the large sample size, we found no major QTL for heifer livability. However, we identified a major QTL in the bovine MHC region associated with early first calving. Our GO analysis based on nearby genes detected 91 significant GO terms with a large proportion related to the immune system. This QTL in the MHC region was also confirmed in the analysis of 27 K bull with imputed sequence variants. Since these traits have few major QTL, we evaluated the genome-wide distribution of GWAS signals across different functional genomics categories. For heifer livability, we observed significant enrichment in promotor and enhancer-related regions. For early calving, we found more associations in active TSS, active Elements, and Insulator. We also identified significant enrichment of CDS and conserved variants in the GWAS results of both traits. By linking GWAS results and transcriptome data from the CattleGTEx project via TWAS, we detected four and 23 significant gene-trait association pairs for heifer livability and early calving, respectively. Interestingly, we discovered six genes for early calving in the Bovine MHC region, including two genes in lymph node tissue and one gene each in blood, adipose, hypothalamus, and leukocyte.

Conclusion
Our large-scale GWAS analyses of two heifer traits identified a major QTL in the bovine MHC region for early first calving. Additional functional enrichment and TWAS analyses confirmed the MHC QTL with relevant biological evidence. Our results revealed the complex genetic basis of heifer health and fertility traits and indicated a potential connection between the immune system and reproduction in cattle.
Metagenomic analysis of gut microbiome and resistome of Whooper and Black Swans: a one health perspective
Authors: Fu Yin , Zhang Kaihui , Shan Fa , Li Junqiang , Wang Yilin , Li Xiaoying , Xu Huiyan , Qin Ziyang , Zhang Longxian 
Published: October 2023

Abstract
Background
With the promotion of “One Health,” the health of animals and their impact on the environment have become major concerns recently. Widely distributed in China, the whooper swans (Cygnus cygnus) and black swans (Cygnus atratus) are not only important to the ecological environment, but they may also potentially influence public health security. The metagenomic approach was adopted to uncover the impacts of the gut microbiota of swans on host and public health.

Results
In this study, the intestinal microbiome and resistome of migratory whooper swans and captive-bred black swans were identified. The results revealed similar gut microbes and functional compositions in whooper and black swans. Interestingly, different bacteria and probiotics were enriched by overwintering whooper swans. We also found that Acinetobacter and Escherichia were significantly enriched in early wintering period swans and that clinically important pathogens were more abundant in black swans. Whooper swans and black swans are potential reservoirs of antibiotic resistance genes (ARGs) and novel ARGs, and the abundance of novel ARGs in whooper swans was significantly higher than that in black swans. Metagenomic assembly–based host tracking revealed that most ARG-carrying contigs originated from Proteobacteria (mainly Gammaproteobacteria).

Conclusions
The results revealed spatiotemporal changes in microbiome and resistome in swans, providing a reference for safeguarding public health security and preventing animal epidemics.
Insights into the use of telemedicine in primary care in times of the SARS-CoV-2 pandemic - a cross-sectional analysis based on the international PRICOV-19 study in Austria
Authors: Stummer Florian Odilo , Voggenberger Lisa , Gomez Pellin Maria de la Cruz , van Poel Esther , Willems Sara , Hoffmann Kathryn 
Published: October 2023

Abstract
Background
The SARS-CoV2 pandemic as well as the implementation of public health measures to decrease the spread of the virus re-sparked the call for “virtual” health or “distance” treatments. This paper aimed to assess the use of video consultations, the up-to-dateness of practice websites, and the views of GPs on whether eHealth is a positive aspect for the future of their practices in publicly -funded primary healthcare facilities in Austria.

Methods
The cross-sectional online questionnaire, part of the PRICOV-19 study, was conducted from December 2020 until July 2021. We randomly recruited 176 GP practices across Austria. Descriptive statistics as well as binary logistic regression models were applied to examine the associations between telemedicine use and practice factors.

Results
Compared with before the pandemic (3.8%), 7.6% of publicly funded GP practices have been using video consultations since the pandemic. In line with this, 93.9% of the practices had no increase in video consultation use. Fewer than half (44.3%) had an up-to-date webpage, and 27.8% assumed that the pandemic might have been a positive driver for eHealth in their practices. Positive associations with video consultation use could be found in practices with fewer patients aged 70 years and over than the average and more patients with chronic diseases than the average.

Conclusion
The use of video consultations in general practice and the readiness for other telemedicine approaches are both very low in Austria. Austria has to urgently follow the example of countries with a transparent and comprehensive national digital health strategy that includes video consultation. Without a proper payment system, patient inclusion, and support with regard to administrative and organizational aspects, no substantial change will occur in spite of an increase in need due to the pandemic and changes in the patient population.
General practice nurse trainees’ perspectives on general practice nursing as a career choice: qualitative findings from a vocational training scheme in the United Kingdom (UK)
Authors: Lewis Robin 
Published: October 2023

Abstract
Background
There is a shortage of general practice nurses worldwide to deal with an ever-increasing workload, and the need to attract new staff into general practice nursing is therefore vital. As part of this, a one-year Vocational Training Scheme (VTS) for new to general practice nurses was developed in 2020 by the South Yorkshire Primary Care Workforce and Training Hub.

Methods
The aim of the study was to examine the VTS trainees’ views on general practice nursing as a career. A pragmatic, convenience sample of trainees was recruited. Of the 21 trainees, 17 agreed to take part in the study. Data were collected from the trainees using a series of four regular, timed, online focus groups designed to follow the trainees’ trajectory on the programme over a 12-month period. The data were analysed using framework analysis.

Results
The timed nature of the focus groups meant that the analysis of the data was linked to the trainees’ trajectory over the course of the year. Three themes were generated from the data: ‘pathways into general practice’; ‘learning to be a GPN’; and ‘the future GPN’. In theme one, the trainees talked of the difficulties in accessing general practice as a new graduate, specifically the need for prior experience and how to get it. In the second, the transition to being a general practice nurse was discussed, and the expectation of being able to ‘hit the ground running’ once in post. The new graduate participants were also concerned over the opportunities for clinical supervision and support in the role after the programme. Finally, the participant s expressed concern over future opportunities for professional development and the prospects for a long-term career in general practice.

Conclusion
To address the worldwide workforce ‘crisis’ in general practice nursing, sustainable career pathways are needed to encourage new graduate nurses to consider working in general practice. Starting at university, changing the culture and providing the necessary infrastructure to support ongoing professional development in general practice nursing are key to its success.
Study on association factors of intestinal infectious diseases based-Bayesian spatio-temporal model
Authors: Zhan Yancen , Gu Hua , Li Xiuyang 
Published: October 2023

Abstract
Background
Intestinal infectious diseases (IIDs) are a significant public health issue in China, and the incidence and distribution of IIDs vary greatly by region and are affected by various factors. This study aims to describe the spatio-temporal trends of IIDs in the Chinese mainland and investigate the association between socioeconomic and meteorological factors with IIDs.

Methods
In this study, IIDs in mainland China from 2006 to 2017 was analyzed using data obtained from the China Center for Disease Control and Prevention. Spatio-temporal mapping techniques was employed to visualize the spatial and temporal distribution of IIDs. Additionally, mean center and standard deviational ellipse analyses were utilized to examine the spatial trends of IIDs. To investigate the potential associations between IIDs and meteorological and socioeconomic variables, spatiotemporal zero-inflated Poisson and negative binomial models was employed within a Bayesian framework.

Results
During the study period, the occurrence of most IIDs has dramatically reduced, with uneven reductions in different diseases. Significant regional differences were found among IIDs and influential factors. Overall, the access rate to harmless sanitary toilets (ARHST) was positively associated with the risk of cholera (RR: 1.73, 95%CI: 1.08-2.83), bacillary dysentery (RR: 1.32, 95%CI: 1.06-1.63), and other intestinal infectious diseases (RR: 1.88, 95%CI: 1.52-2.36), and negatively associated with typhoid fever (RR: 0.66, 95%CI: 0.51-0.92), paratyphoid fever (RR: 0.71, 95%CI: 0.55-0.92). Urbanization is only associated with hepatitis E (RR: 2.48, 95%CI: 1.12-5.72). And GDP was negatively correlated with paratyphoid fever (RR: 0.82, 95%CI: 0.70-0.97), and bacillary dysentery (RR: 0.77, 95%CI: 0.68-0.88), and hepatitis A (RR: 0.84, 95%CI: 0.73-0.97). Humidity showed positive correlation with some IIDs except for amoebic dysentery (RR: 1.64, 95%CI: 1.23-2.17), while wind speed showed a negative correlation with most IIDs. High precipitation was associated with an increased risk of typhoid fever (RR: 1.52, 95%CI: 1.09-2.13), and high temperature was associated with an increased risk of typhoid fever (RR: 2.82, 95%CI: 2.06-3.89), paratyphoid fever (RR: 2.79, 95%CI: 2.02-3.90), and HMFD (RR: 1.34, 95%CI: 1.01-1.77).

Conclusions
This research systematically and quantitatively studied the effect of socioeconomic and meteorological factors on IIDs, which provided causal clues for future studies and guided government planning.
Interleukin-21 modulates balance between regulatory T cells and T-helper 17 cells in chronic hepatitis B virus infection
Authors: Cai Yun , Ji Hailei , Zhou Xin , Zhao Kai , Zhang Xiaoping , Pan Liang , Shi Ruihua 
Published: October 2023

Abstract
Background
Chronic HBV infection is always accompanied by differences in the balance between regulatory T cells (Tregs) and T-helper 17 (Th17) cells in infection phases. IL-21 plays an important role in the progression of chronic HBV infection. Thus, the aim of our study was to investigate the role of the regulatory function of IL-21 in maintaining the balance between Tregs and Th17 cells in chronic HBV infection.

Methods
Twenty-five chronic HBV-infected patients in the immune-tolerant (IT) phase and 23 chronic hepatitis B (CHB) patients were recruited in this study. Cytokines production was measured by ELISA. The mRNA expression levels were determined by qPCR. CD4+T cells were stimulated with or without IL-21. Tregs and Th17 cells were measured by flow cytometry. pSTAT3 and STAT3 expression was assessed by Western blotting.

Results
The concentration of IL-21 in the serum of CHB were significantly higher than that in the serum from IT patients, and IL-21 and IL-21R levels in the PBMCs from CHB were higher than those from IT patients. IL-21 promoted Th17 cells differentiation and function but inhibited Treg cells differentiation and function by activating STAT3 signaling pathways, upregulating RORγt expression, downregulating Foxp3 expression, by increasing IL-17and IL-22 secretion, and decreasing TGF-β secretion in chronic HBV infection. The proportion of Tregs and TGF-β concentrations in CHB was significantly lower than that in IT patients. Furthermore, the percentage of Th17 cells and the IL-17 concentration in CHB was markedly higher than that in IT patients, causing a reduction in the Tregs/Th17 ratio in CHB patients.

Conclusions
Our results suggest that IL-21 may contribute to inflammation in chronic HBV infection by modulating the balance between Treg and Th17 cells.
The evolution of age-specific smoking cessation rates in the United States from 2009 to 2017: a Kalman filter based approach
Authors: Le Thuy T. T. , Warner Kenneth E. , Mendez David 
Published: October 2023

Abstract
Background
Tracking the US smoking cessation rate over time is of great interest to tobacco control researchers and policymakers since smoking cessation behaviors have a major effect on the public’s health. Recent studies have employed dynamic models to estimate the US cessation rate through observed smoking prevalence. However, none of those studies has provided annual estimates of the cessation rate by age group. Hence, the primary objective of this study is to estimate annual smoking cessation rates specific to different age groups in the US from 2009 to 2017.

Methods
We employed a Kalman filter approach to investigate the annual evolution of age-group-specific cessation rates, unknown parameters of a mathematical model of smoking prevalence, during the 2009–2017 period using data from the 2009–2018 National Health Interview Surveys. We focused on cessation rates in the 25–44, 45–64 and 65 + age groups.

Results
The findings show that cessation rates followed a consistent u-shaped curve over time with respect to age (i.e., higher among the 25–44 and 65 + age groups, and lower among 45-64-year-olds). Over the course of the study, the cessation rates in the 25–44 and 65 + age groups remained nearly unchanged around 4.5% and 5.6%, respectively. However, the rate in the 45–64 age group exhibited a substantial increase of 70%, from 2.5% to 2009 to 4.2% in 2017. The estimated cessation rates in all three age groups tended to converge to the weighted average cessation rate over time.

Conclusions
The Kalman filter approach offers a real-time estimation of cessation rates that can be helpful for monitoring smoking cessation behavior.
POMSNAME: an aide-mémoire to improve the assessment and documentation of palliative care – a longitudinal project
Authors: Dadich Ann , Gliniecka Martyna , Cull Michelle , Womsley Kerrie 
Published: October 2023

Abstract
Background
Evidence-based palliative care requires comprehensive assessment and documentation. However, palliative care is not always systemically documented – this can have implications for team communication and patient wellbeing. The aim of this project was to determine the effectiveness of an aide-mémoire – POMSNAME – to prompt the comprehensive assessment of the following domains by clinicians: pain, orientation and oral health, mobility, social situation, nausea and vomiting, appetite, medication, and elimination.

Methods
A placard depicting the aide-mémoire was distributed to community-based nurses who received training and support. The case notes of palliative care patients were evaluated one month before the intervention, and was repeated at one month, eight months, and fifty months following the intervention. The 235 case notes pertained to patients who received palliative care from a team of 13 registered nurses at one community health service.

Results
The documented assessment of palliative care patients improved across all nine domains. The most significant improvements pertained to patients’ social situation, orientation, and nausea, eight months after the aide-mémoire was introduced (170.1%, 116.9%, and 105.6%, respectively, all at p < .001). Although oral health and medication assessment declined one-month after the aide-mémoire was introduced (-41.7% and-2.1%, respectively), both subsequently improved, thereafter, at both 8 months and 50 months after the aide-mémoire was introduced.

Conclusions
The improvement of palliative care documentation across all nine domains demonstrates the potential of the POMSNAME aide-mémoire to prompt the comprehensive assessment of patients by clinicians with generalist expertise. Research is required to determine whether other domains warrant inclusion and how.