bluuebunny/crossref_metadata_2025_split huggingface dataset:
Genetic variants associated with two major bovine milk fatty acids offer opportunities to breed for altered milk fat composition
Authors: Knutsen Tim Martin , Olsen Hanne Gro , Ketto Isaya Appelesy , Sundsaasen Kristil Kindem , Kohler Achim , Tafintseva Valeria , Svendsen Morten , Kent Matthew Peter , Lien Sigbjørn 
Published: May 2022

Abstract
Background
Although bovine milk is regarded as healthy and nutritious, its high content of saturated fatty acids (FA) may be harmful to cardiovascular health. Palmitic acid (C16:0) is the predominant saturated FA in milk with adverse health effects that could be countered by substituting it with higher levels of unsaturated FA, such as oleic acid (C18:1cis-9). In this work, we performed genome-wide association analyses for milk fatty acids predicted from FTIR spectroscopy data using 1811 Norwegian Red cattle genotyped and imputed to a high-density 777k single nucleotide polymorphism (SNP)-array. In a follow-up analysis, we used imputed whole-genome sequence data to detect genetic variants that are involved in FTIR-predicted levels of C16:0 and C18:1cis-9 and explore the transcript profile and protein level of candidate genes.

Results
Genome-wise significant associations were detected for C16:0 on Bos taurus (BTA) autosomes 11, 16 and 27, and for C18:1cis-9 on BTA5, 13 and 19. Closer examination of a significant locus on BTA11 identified the PAEP gene, which encodes the milk protein β-lactoglobulin, as a particularly attractive positional candidate gene. At this locus, we discovered a tightly linked cluster of genetic variants in coding and regulatory sequences that have opposing effects on the levels of C16:0 and C18:1cis-9. The favourable haplotype, linked to reduced levels of C16:0 and increased levels of C18:1cis-9 was also associated with a marked reduction in PAEP expression and β-lactoglobulin protein levels. β-lactoglobulin is the most abundant whey protein in milk and lower levels are associated with important dairy production parameters such as improved cheese yield.

Conclusions
The genetic variants detected in this study may be used in breeding to produce milk with an improved FA health-profile and enhanced cheese-making properties.
Paired guide RNA CRISPR-Cas9 screening for protein-coding genes and lncRNAs involved in transdifferentiation of human B-cells to macrophages
Authors: Arnan Carme , Ullrich Sebastian , Pulido-Quetglas Carlos , Nurtdinov Ramil , Esteban Alexandre , Blanco-Fernandez Joan , Aparicio-Prat Estel , Johnson Rory , Pérez-Lluch Sílvia , Guigó Roderic 
Published: May 2022

AbstractCRISPR-Cas9 screening libraries have arisen as a powerful tool to identify protein-coding (pc) and non-coding genes playing a role along different processes. In particular, the usage of a nuclease active Cas9 coupled to a single gRNA has proven to efficiently impair the expression of pc-genes by generating deleterious frameshifts. Here, we first demonstrate that targeting the same gene simultaneously with two guide RNAs (paired guide RNAs, pgRNAs) synergistically enhances the capacity of the CRISPR-Cas9 system to knock out pc-genes. We next design a library to target, in parallel, pc-genes and lncRNAs known to change expression during the transdifferentiation from pre-B cells to macrophages. We show that this system is able to identify known players in this process, and also predicts 26 potential novel ones, of which we select four (two pc-genes and two lncRNAs) for deeper characterization. Our results suggest that in the case of the candidate lncRNAs, their impact in transdifferentiation may be actually mediated by enhancer regions at the targeted loci, rather than by the lncRNA transcripts themselves. The CRISPR-Cas9 coupled to a pgRNAs system is, therefore, a suitable tool to simultaneously target pc-genes and lncRNAs for genomic perturbation assays.
Microarray analysis of potential biomarkers of brachial plexus avulsion caused neuropathic pain in male rat
Authors: Wang Le , Lao Jie 
Published: May 2022

AbstractThe present study aimed to investigate the expression of mRNA in the brachial plexus avulsion neuropathic pain model and analyze biological functions. Microarray mRNA assay and reverse transcriptase quantitative polymerase chain reaction (RT-PCR) were conducted. The whole blood was collected from two groups for Microarray mRNA analysis. The predicted mRNA targets were studied by gene ontology analysis and pathway analysis. We identified 3 targeted mRNAs, including PIK3CB, HRAS, and JUN. The results showed that PIK3CB, HRAS, and JUN gene expression was increased in the control group but decreased in the neuropathic pain group. These findings indicate that certain genes may be important biomarkers for the potential targets for the prevention and treatment of brachial plexus avulsion caused neuropathic pain.
Introducing Advanced Paramedics into the rural general practice team in Ireland – general practitioners attitudes
Authors: Feerick F. , Connor C. O. , Hayes P. , Kelly D. 
Published: May 2022

AbstractIntroductionAs Ireland's population increases and chronic disease becomes more prevalent, demand on limited general practice services will increase. Nursing roles within general practice are now considered to be standard, yet alternative allied health professional roles are under explored within an Irish context. Allied health personnel such as Advanced Paramedics (APs) may have the capability to provide support to general practice.AimTo explore General Practitioners’ (GPs) attitudes and opinions of integrating Advanced Paramedics (APs) into rural general practice in Ireland.MethodsA sequential explanatory mixed methodology was adopted. A questionnaire was designed and distributed to a purposeful sample of GPs attending a rural conference followed by semi-structured interviews. Data was recorded and transcribed verbatim and thematically analysed.ResultsIn totaln = 27 GPs responded to the survey andn = 13 GPs were interviewed. The majority of GPs were familiar with APs and were receptive to the concept of closely collaborating with APs within a variety of settings including out-of-hours services, home visits, nursing homes and even roles within the general practice surgery.ConclusionGeneral Practitioner and Advanced Paramedic clinical practice dovetail within many facets of primary care and emergency care. GPs recognise that current rural models are unsustainable and realise the potential of integrating APs into the general practice team to help support and sustain the future of rural general practice services in Ireland. These interviews provided an exclusive, detailed insight into the world of general practice in Ireland that has not been previously documented in this way.
Development and validation of a risk score to predict the frequent emergency house calls among older people who receive regular home visits
Authors: Sun Yu , Iwagami Masao , Sakata Nobuo , Ito Tomoko , Inokuchi Ryota , Uda Kazuaki , Hamada Shota , Ishimaru Miho , Komiyama Jun , Kuroda Naoaki , Yoshie Satoru , Ishizaki Tatsuro , Iijima Katsuya , Tamiya Nanako 
Published: May 2022

AbstractBackgroundThe demand for home healthcare is increasing in Japan, and a 24-hour on-call system could be a burden for primary care physicians. Identifying high-risk patients who need frequent emergency house calls could help physicians prepare and allocate medical resources. The aim of the present study was to develop a risk score to predict the frequent emergency house calls in patients who receive regular home visits.MethodsWe conducted a retrospective cohort study with linked medical and long-term care claims data from two Japanese cities. Participants were ≥ 65 years of age and had newly started regular home visits between July 2014 and March 2018 in Tsukuba city and between July 2012 and March 2017 in Kashiwa city. We followed up with patients a year after they began the regular home visits or until the month following the end of the regular home visits if this was completed within 1 year. We calculated the average number of emergency house calls per month by dividing the total number of emergency house calls by the number of months that each person received regular home visits (1–13 months). The primary outcome was the “frequent” emergency house calls, defined as its use once per month or more, on average, during the observation period. We used the least absolute shrinkage and selection operator (LASSO) logistic regression with 10-fold cross-validation to build the model from 19 candidate variables. The predictive performance was assessed with the area under the curve (AUC).ResultsAmong 4888 eligible patients, frequent emergency house calls were observed in 13.0% of participants (634/4888). The risk score included three variables with the following point assignments: home oxygen therapy (3 points); long-term care need level 4–5 (1 point); cancer (4 points). While the AUC of a model that included all candidate variables was 0.734, the AUC of the 3-risk score model was 0.707, suggesting good discrimination.ConclusionsThis easy-to-use risk score would be useful for assessing high-risk patients and would allow the burden on primary care physicians to be reduced through measures such as clustering high-risk patients in well-equipped medical facilities.
Factors associated with prolonged hospital stay of imported malaria cases in Chengdu, China: a retrospective study
Authors: Huang Liang , Jin Hong , Zhang Hong , Liu Yang , Shi Xinxing , Kang Xintong , Zeng Yilan , Wang Lin 
Published: May 2022

Abstract
Background
Although China has entered the post-malaria-elimination era, imported cases remain a public health concern in China.

Methods
We retrospectively analyzed data from cases of imported malaria from January 2017 to December 2020 in Chengdu Public Health Clinical Center. We assessed potential clinical, epidemiological, geographical, and seasonal effects on duration of hospital stay. Cox proportional hazards model was used to identify predictive factors for prolonged hospital stay. Multivariate logistic regression was used to assess the potential risk factors associated with severe cases.

Results
The highest number of imported cases of malaria were from the Democratic Republic of the Congo (23%, 34/150) and most patients (74%, 26/34) were infected by Plasmodium falciparum. The Edwards test indicated no significant seasonality in imported cases of malaria (χ2 = 2.51, p = 0.28). Bacterial infection (adjusted hazard ratio [aHR] for discharge = 0.58, p = 0.01) and thrombocytopenia (aHR = 0.66, p = 0.02) were risk factors for prolonged hospital stay. The C-reactive protein (OR = 1.02, p = 0.01) and procalcitonin (OR = 1.03, p = 0.01) were risk factors for severe cases.

Conclusions
Bacterial infection and thrombocytopenia are risk factors for prolonged hospital stay among imported malaria cases. The C-reactive protein and procalcitonin level were risk factors for severe cases.
A cross-sectional study on the perceived barriers to physical activity and their associations with domain-specific physical activity and sedentary behaviour
Authors: Koh Yen Sin , Asharani P. V. , Devi Fiona , Roystonn Kumarasan , Wang Peizhi , Vaingankar Janhavi Ajit , Abdin Edimansyah , Sum Chee Fang , Lee Eng Sing , Müller-Riemenschneider Falk , Chong Siow Ann , Subramaniam Mythily 
Published: May 2022

Abstract
Background
Physical inactivity and sedentary behaviour have detrimental consequences to the individual and the economy. Our study examined the prevalence of perceived barriers to physical activity in Singapore’s adult population and their associations with physical activity and sedentary behaviour.

Methods
This cross-sectional analysis utilised data from a nationwide survey in Singapore. Participants (n = 2867) were recruited from February 2019 to March 2020. The independent variables were internal (e.g. fatigue, age) and external (e.g. weather, cost) perceived barriers to physical activity. The outcomes were domain-specific physical activity (work, transport and leisure) and sedentary behaviour, all of which were assessed using the Global Physical Activity Questionnaire. The associations were examined using zero-inflated negative binomial regressions for physical activity and linear regression for sedentary behaviour.

Results
The median (Interquartile range) for work-related, transport-related and leisure-related physical activity were 0 (0 – 1440), 600 (160 – 1120) and 360 (0 – 1080) MET (metabolic equivalent)-minutes per week. The median sedentary behaviour (IQR) was 360 (240 – 540) minutes per day. The top three barriers were lack of time (65.3%), fatigue (64.7%) and pollution (56.1%). After adjustment, the level of transport-related physical activity was lower for respondents who cited lacking pavement or parks as a barrier, but higher for those who indicated cost and safety concerns. Respondents who reported pollution as a barrier were more likely to engage in transport-related physical activity. The level of leisure-related physical activity was lower for respondents indicating weather, lack of time and age as barriers, but higher for those reporting safety concerns. The odds of engaging in leisure-related physical activity was lower for those citing age, cost and fatigue as barriers, but higher for those indicating the weather. Sedentary behaviour was positively associated with work and limited accessibility to exercise facilities, but negatively with safety concerns.

Conclusion
Individuals can be motivated to overcome internal barriers (fatigue, lack of time, cost and age) through social support and emphasis on exercise benefits. External barriers (weather and lack of pavements or parks) can be reduced by raising awareness of existing infrastructure. Sedentary behaviour can be improved by implementing workplace measures, such as reducing the time spent sitting.
Predictors of incident diabetes in two populations: framingham heart study and hispanic community health study / study of latinos
Authors: Kaplan Robert C. , Song Rebecca J. , Lin Juan , Xanthakis Vanessa , Hua Simin , Chernofsky Ariel , Evenson Kelly R. , Walker Maura E. , Cuthbertson Carmen , Murabito Joanne M. , Cordero Christina , Daviglus Martha , Perreira Krista M. , Gellman Marc , Sotres-Alvarez Daniela , Vasan Ramachandran S. , Xue Xiaonan , Spartano Nicole L. , Mossavar-Rahmani Yasmin 
Published: May 2022

Abstract
Background
Non-genetic factors contribute to differences in diabetes risk across race/ethnic and socioeconomic groups, which raises the question of whether effects of predictors of diabetes are similar across populations. We studied diabetes incidence in the primarily non-Hispanic White Framingham Heart Study (FHS, N = 4066) and the urban, largely immigrant Hispanic Community Health Study/Study of Latinos (HCHS/SOL, N = 6891) Please check if the affiliations are captured and presented correctly.

Methods
Clinical, behavioral, and socioeconomic characteristics were collected at in-person examinations followed by seven-day accelerometry. Among individuals without diabetes, Cox proportional hazards regression models (both age- and sex-adjusted, and then multivariable-adjusted for all candidate predictors) identified predictors of incident diabetes over a decade of follow-up, defined using clinical history or laboratory assessments.

Results
Four independent predictors were shared between FHS and HCHS/SOL. In each cohort, the multivariable-adjusted hazard of diabetes increased by approximately 50% for every ten-year increment of age and every five-unit increment of body mass index (BMI), and was 50–70% higher among hypertensive than among non-hypertensive individuals (all P < 0.01). Compared with full-time employment status, the multivariable-adjusted hazard ratio (HR) and 95% confidence interval (CI) for part-time employment was 0.61 (0.37,1.00) in FHS and 0.62 (0.41,0.95) in HCHS/SOL. Moderate-to-vigorous physical activity (MVPA) was an additional predictor in common observed in age- and sex-adjusted models, which did not persist after adjustment for other covariates (compared with MVPA ≤ 5 min/day, HR for MVPA level ≥ 30 min/day was 0.48 [0.31,0.74] in FHS and 0.74 [0.56,0.97] in HCHS/SOL). Additional predictors found in sex- and age-adjusted analyses among the FHS participants included male gender and lower education, but these predictors were not found to be independent of others in multivariable adjusted models, nor were they associated with diabetes risk among HCHS/SOL adults.

Conclusions
The same four independent predictors – age, body mass index, hypertension and employment status – were associated with diabetes risk across two disparate US populations. While the reason for elevated diabetes risk in full-time workers is unclear, the findings suggest that diabetes may be part of the work-related burden of disease. Our findings also support prior evidence that differences by gender and socioeconomic position in diabetes risk are not universally present across populations.
An individual nomogram can reliably predict tumor spread through air spaces in non-small-cell lung cancer
Authors: Wang Shuai , Shou Huankai , Wen Haoyu , Wang Xingxing , Wang Haixing , Lu Chunlai , Gu Jie , Xu Fengkai , Zhu Qiaoliang , Wang Lin , Ge Di 
Published: May 2022

Abstract
Background
Tumor spread through air spaces (STAS) has been shown to adversely affect the prognosis of lung cancer. The correlation between clinicopathological and genetic features and STAS remains unclear.

Method
We retrospectively reviewed 3075 NSCLC patients between2017-2019. We evaluated the relationship between STAS and patients’ clinicopathological and molecular features. The chi-square test was performed to compare categorical variables. Univariate analysis and multivariate logistic regression analysis were performed to investigate the association of clinical factors with STAS. A nomogram was formulated to predict the presence of STAS.

Results
STAS was identified in 617 of 3075 patients (20.07%). STAS was significantly related to sex (p < 0.001), smoking (p < 0.001), CEA (p < 0.001), differentiation (p < 0.001), histopathological type (p < 0.001), lymphatic vessel invasion (p < 0.001), pleural invasion (p < 0.001), T stage (p < 0.001), N stage (p < 0.001), M stage (p < 0.001), and TNM stage (p < 0.001). STAS was frequently found in tumors with wild-type EGFR (p < 0.001), KRAS mutations (p < 0.001), ALK rearrangements (p < 0.001) or ROS1 rearrangements (p < 0.001). For programmed death-1 (PD-1)/programmed death ligand-1 (PD-L1), STAS was associated with PD-L1 expression level in tumor cells (p < 0.001) or stromal cells (p < 0.001), while PD-1 only in stromal cells (p < 0.001). Multivariable analyses demonstrated significant correlations between STAS and CEA level (p < 0.001), pathological grade (p < 0.001), lymphatic vessel invasion (p < 0.001), pleural invasion (p = 0.001), and TNM stage (p = 0.002). A nomogram was formulated based on the results of the multivariable analysis.

Conclusions
Tumor STAS was associated with several invasive clinicopathological features. A nomogram was established to predict the presence of STAS in patients with NSCLC.
Comparison of survival between patients receiving general outpatient palliative care and patients receiving other palliative care - analysis of data of a statutory health insurance data
Authors: Moon Kilson , Rehner Laura , Hoffmann Wolfgang , van den Berg Neeltje 
Published: May 2022

Abstract
Background
The care of palliative patients takes place as non-specialized and specialized care, in outpatient and inpatient settings. However, palliative care is largely provided as General Outpatient Palliative Care (GOPC). This study aimed to investigate whether the survival curves of GOPC patients differed from those of the more intensive palliative care modalities and whether GOPC palliative care was appropriate in terms of timing.

Methods
The study is based on claims data from a large statutory health insurance. The analysis included 4177 patients who received palliative care starting in 2015 and who were fully insured 1 year before and 1 year after palliative care or until death. The probability of survival was observed for 12 months. Patients were classified into group A, which consisted of patients who received palliative care only with GOPC, and group B including patients who received inpatient or specialized outpatient palliative care. Group A was further divided into two subgroups. Patients who received GOPC on only 1 day were assigned to subgroup A1, and patients who received GOPC on two or more days were assigned to subgroup A2. The survival analysis was carried out using Kaplan-Meier curves. The median survival times were compared with the log-rank test.

Results
The survival curves differed between groups A and B, except in the first quartile of the survival distribution. The median survival was significantly longer in group A (137 days, n = 2763) than in group B (47 days, n = 1424, p < 0.0001) and shorter in group A1 (35 days, n = 986) than in group A2 (217 days, n = 1767, p < 0.0001). The survival rate during the 12-month follow-up was higher in group A (42%) than in group B (11%) and lower in group A1 (38%) than in group A2 (44%).

Conclusions
The results of the analysis revealed that patients who received the first palliative care shortly before death suspected insufficient care, especially patients who received GOPC for only 1 day and no further palliative care until death or 12-month follow-up. Palliative care should start as early as necessary and be continuous until the end of life.
Locally advanced rectal cancer receiving total neoadjuvant therapy combined with nivolumab: a case report and literature review
Authors: Mori Ryota , Uemura Mamoru , Sekido Yuki , Hata Tsuyoshi , Ogino Takayuki , Takahashi Hidekazu , Miyoshi Norikatsu , Mizushima Tsunekazu , Doki Yuichiro , Eguchi Hidetoshi 
Published: May 2022

Abstract
Background
The standard treatment for locally advanced rectal cancer (LARC) is preoperative chemoradiotherapy (CRT) followed by surgery and adjuvant chemotherapy. However, it has been suggested that intensification of neoadjuvant treatment with polychemotherapy in addition to CRT instead of as an adjuvant chemotherapy is better tolerated and associated with a higher pathological complete response (pCR) rate. This concept is known as total neoadjuvant therapy (TNT).
Recently, the addition of immunotherapy to preoperative CRT has been reported to be useful in LARC patients with mismatch-repair-deficiency and high levels of microsatellite instability (MSI-H), but there are no reports showing the therapeutic effect of nivolumab in combination with TNT.

Case presentation
A 23-year-old man had frequent diarrhea. Preoperative examination revealed two adenocarcinomas in the rectum. His maternal grandmother had a rectal cancer patient who developed the disease at age 70s. The larger tumor was located at the peritoneal reflection, and its anterior border close to the prostate (<1 mm); there were eight enlarged pararectal lymph nodes. Considering the size and depth of the tumor, it was judged that radical resection with sufficient margins would be difficult. Therefore, it was decided that TNT would be performed. At first, CAPOX (capecitabine and L-OHP) was administered, followed by preoperative CRT (RT:50.4 Gy and capecitabine). During this period, genetic testing diagnosed this patient as MSI-H, so additional nivolumab was administered after CRT. Colonoscopy revealed that the larger tumor was no longer detectable, so robot-assisted intersphincteric resection and bilateral lateral lymph node dissection was performed. The diagnosis of pCR was made for the larger tumor and partial response was achieved for the smaller tumor, and no lymph node metastasis was found. Major complications were not observed and the patient was discharged on the 14th day after surgery. He was followed up without adjuvant chemotherapy and is alive and recurrence-free after 9 months.

Conclusion
A case of LARC with MSI-H was treated with TNT with nivolumab, resulting in pCR and complete radical resection. This result suggests that nivolumab in addition to TNT can be an option as a preoperative strategy for LARC with MSI-H.