bluuebunny/crossref_metadata_2025_split huggingface dataset:
Ommochrome pathway genes kynurenine 3-hydroxylase and cardinal participate in eye pigmentation in Plutella xylostella
Authors: Xu Xuejiao , Harvey-Samuel Tim , Yang Jie , Alphey Luke , You Minsheng 
Published: September 2020

Abstract
Background
Eye pigmentation genes have been utilized as visible markers for constructing genetic control prototypes in several insect vectors of human disease. Here, orthologs of two ommochrome pathway genes, kynurenine 3-hydroxylase (kmo) and cardinal, were investigated in Plutella xylostella, a globally distributed, economically important pest of Brassica crops.

Results
Both somatic mosaic and germline mutations were efficiently created using the CRISPR/Cas9 system, and null mutant strains of Pxkmo and Pxcardinal were obtained. A frame-shift mutation in Pxkmo caused yellow compound eyes at adult stage while an in-frame mutation lacking two amino acids resulted in a hypomorphic red eye phenotypes. In contrast, Pxcardinal-deficient moths with a frame-shift mutation exhibited yellow eye pigmentation in newly emerged adults which turned to red as the adults aged. Additionally, differences were observed in the coloration of larval ocelli, brains and testes in Pxkmo and Pxcardinal yellow-eye mutant lines.

Conclusions
Our work identifies the important roles of Pxkmo and Pxcardinal in P. xylostella eye pigmentation and provides tools for future genetic manipulation of this important crop pest.
Platelet adhesion and aggregate formation controlled by immobilised and soluble VWF
Authors: Schneider Matthias F. , Fallah Mohammad A. , Mess Christian , Obser Tobias , Schneppenheim Reinhard , Alexander-Katz Alfredo , Schneider Stefan W. , Huck Volker 
Published: September 2020

Abstract
Background
It has been demonstrated that von Willebrand factor (VWF) mediated platelet-endothelium and platelet-platelet interactions are shear dependent. The VWF’s mobility under dynamic conditions (e.g. flow) is pivotal to platelet adhesion and VWF-mediated aggregate formation in the cascade of VWF-platelet interactions in haemostasis.

Results
Combining microfluidic tools with fluorescence and reflection interference contrast microscopy (RICM), here we show, that specific deletions in the A-domains of the biopolymer VWF affect both, adhesion and aggregation properties independently. Intuitively, the deletion of the A1-domain led to a significant decrease in both adhesion and aggregate formation of platelets. Nevertheless, the deletion of the A2-domain revealed a completely different picture, with a significant increase in formation of rolling aggregates (gain of function). We predict that the A2-domain effectively ‘masks’ the potential between the platelet glycoprotein (GP) Ib and the VWF A1-domain. Furthermore, the deletion of the A3-domain led to no significant variation in either of the two functional characteristics.

Conclusions
These data demonstrate that the macroscopic functional properties i.e. adhesion and aggregate formation cannot simply be assigned to the properties of one particular domain, but have to be explained by cooperative phenomena. The absence or presence of molecular entities likewise affects the properties (thermodynamic phenomenology) of its neighbours, therefore altering the macromolecular function.
Genome-wide detection of signatures of selection in indicine and Brazilian locally adapted taurine cattle breeds using whole-genome re-sequencing data
Authors: Peripolli Elisa , Reimer Christian , Ha Ngoc-Thuy , Geibel Johannes , Machado Marco Antonio , Panetto João Cláudio do Carmo , do Egito Andréa Alves , Baldi Fernando , Simianer Henner , da Silva Marcos Vinícius Gualberto Barbosa 
Published: September 2020

AbstractBackgroundThe cattle introduced by European conquerors during the Brazilian colonization period were exposed to a process of natural selection in different types of biomes throughout the country, leading to the development of locally adapted cattle breeds. In this study, whole-genome re-sequencing data from indicine and Brazilian locally adapted taurine cattle breeds were used to detect genomic regions under selective pressure. Within-population and cross-population statistics were combined separately in a single score using the de-correlated composite of multiple signals (DCMS) method. Putative sweep regions were revealed by assessing the top 1% of the empirical distribution generated by the DCMS statistics.ResultsA total of 33,328,447 biallelic SNPs with an average read depth of 12.4X passed the hard filtering process and were used to access putative sweep regions. Admixture has occurred in some locally adapted taurine populations due to the introgression of exotic breeds. The genomic inbreeding coefficient based on runs of homozygosity (ROH) concurred with the populations’ historical background. Signatures of selection retrieved from the DCMS statistics provided a comprehensive set of putative candidate genes and revealed QTLs disclosing cattle production traits and adaptation to the challenging environments. Additionally, several candidate regions overlapped with previous regions under selection described in the literature for other cattle breeds.ConclusionThe current study reported putative sweep regions that can provide important insights to better understand the selective forces shaping the genome of the indicine and Brazilian locally adapted taurine cattle breeds. Such regions likely harbor traces of natural selection pressures by which these populations have been exposed and may elucidate footprints for adaptation to the challenging climatic conditions.
A nationwide assessment of lifestyle medicine counseling: knowledge, attitudes, and confidence of Israeli senior family medicine residents
Authors: Malatskey Lilach , Bar Zeev Yael , Polak Rani , Tzuk-Onn Adva , Frank Erica 
Published: September 2020

Abstract
Background
Non-communicable diseases are the leading causes of death, largely due to the last century’s often-unhealthy lifestyles. Family medicine (FM) and other physicians can improve patients’ lifestyle behaviors, yet FM residency programs in Israel and other countries do not uniformly deliver lifestyle medicine (LM) training. The readiness of FM residents to counsel on lifestyle issues is not known. The purpose of this study is to assess knowledge, attitudes, and confidence levels of senior Israeli FM residents regarding LM counseling, and to evaluate the influence of LM training and personal health behaviors on residents’ LM knowledge, attitudes, and confidence.

Methods
From May to June 2017, we surveyed all senior Israeli FM residents regarding their knowledge, attitudes, confidence, and personal health behaviors. We compared health behaviors, attitudes, and confidence in counselling between: 1) trained residents vs. untrained residents; 2) physically active residents vs. not physically active residents; 3) residents with a BMI < 25 vs. those with a BMI > 25; and 4) residents who eat a Mediterranean diet vs. those who do not.

Results
A total of 169 senior Israeli FM residents were surveyed, and 143 completed the survey, a response rate of 84.6%. Senior FM residents said they considered LM counseling to be an integral part of their role and an effective tool by which to improve a patient’s health. Yet, their knowledge of LM and their confidence in delivering LM counseling are low. Compared with untrained residents (n = 84), LM-trained residents (n = 55) had higher knowledge scores (30.9% vs. 13.1%, p = 0.016) and were more confident in their ability to impact their patients’ behaviors (53.7% vs. 34.5%, p = 0.004). Residents’ positive personal health behaviors correlated with a higher level of confidence to provide LM counseling.

Conclusions
FM physicians can play a key role in the management of patients with chronic diseases. Israeli FM residents consider counseling patients about a healthy lifestyle to be an integral part of their work, but do not feel well prepared to do so.
Dedicated LM training and resident’s personal health promotion may improve critically important levels of LM counseling and patient outcomes, and this training should therefore become a higher priority.
Efficacy, safety and drug survival of thioguanine as maintenance treatment for inflammatory bowel disease: a retrospective multi-centre study in the United Kingdom
Authors: Bayoumy Ahmed B. , van Liere Elsa L. S. A. , Simsek Melek , Warner Ben , Loganayagam Aathavan , Sanderson Jeremy D. , Anderson Simon , Nolan Jonathan , de Boer Nanne K. , Mulder Chris J. J. , Ansari Azhar 
Published: September 2020

Abstract
Background
Thioguanine (TG) is a thiopurine which has been used for patients with inflammatory bowel disease (IBD), who have failed azathioprine (AZA) or mercaptopurine (MP) due to adverse events or suboptimal response. Its widespread use has been hampered due to concerns about nodular regenerative hyperplasia (NRH) of the liver. The aim of this study was to investigate the long-term efficacy and safety of low-dose TG therapy in IBD patients failing AZA and MP.

Methods
A retrospective multicentre study was performed in IBD patients who failed prior treatment with conventional thiopurines with or without following immunomodulation (thiopurine-allopurinol, biologicals, methotrexate, tacrolimus) and were subsequently treated with TG as rescue monotherapy between 2003 and 2019 at three hospitals in the United Kingdom. Clinical response, adverse events, laboratory results, imaging and liver biopsies were retrospectively collected.

Results
A total of 193 patients (57% female and 64% Crohn’s disease) were included, with a median daily TG dose of 20 mg (range: 20–40 mg), a median treatment duration of 23 months (IQR 10–47) and a median follow-up of 36 months (IQR 22–53). The clinical response rate at 12 months was 65 and 54% remained on TG until the end of follow-up. Adverse events consisted primarily of elevated liver tests (6%), myelotoxicity (7%) and rash (5%). NRH was histologically diagnosed in two patients and two other patients (1%) developed non-cirrhotic portal hypertension. The median 6-TGN and TPMT levels were 953 pmol/8 × 108 RBC (IQR 145–1761) and 47 mu/L (IQR 34.5–96).

Conclusions
Long-term follow-up suggests that TG can be an effective and well-tolerated therapy in more than half of difficult-to-treat and multi-therapy failing IBD patients. Findings of this study indicate that TG can be used safely and the occurrence of hepatotoxicity was low. The incidence rate of NRH was within the background incidence.
Components of the transitional care model (TCM) to reduce readmission in geriatric patients: a systematic review
Authors: Morkisch Nadine , Upegui-Arango Luz D. , Cardona Maria I. , van den Heuvel Dirk , Rimmele Martina , Sieber Cornel Christian , Freiberger Ellen 
Published: September 2020

Abstract
Background
Demographic changes are taking place in most industrialized countries. Geriatric patients are defined by the European Union of Medical Specialists as aged over 65 years and suffering from frailty and multi-morbidity, whose complexity puts a major burden on these patients, their family caregivers and the public health care system. To counteract negative outcomes and to maintain consistency in care between hospital and community dwelling, the transitional of care has emerged over the last several decades. Our objectives were to identify and summarize the components of the Transitional Care Model implemented with geriatric patients (aged over 65 years, with multi-morbidity) for the reduction of all-cause readmission. Another objective was to recognize the Transitional Care Model components’ role and impact on readmission rate reduction on the transition of care from hospital to community dwelling (not nursing homes).

Methods
Randomized controlled trials (sample size ≥50 participants per group; intervention period ≥30 days), with geriatric patients were included. Electronic databases (MEDLINE, CINAHL, PsycINFO and The Cochrane Central Register of Controlled Trials) were searched from January 1994 to December 2019 published in English or German. A qualitative synthesis of the findings as well as a systematic assessment of the interventions intensities was performed.

Results
Three articles met the inclusion criteria. One of the included trials applied all of the nine Transitional Care Model components described by Hirschman and colleagues and obtained a high-intensity level of intervention in the intensities assessment. This and another trial reported reductions in the readmission rate (p < 0.05), but the third trial did not report significant differences between the groups in the longer follow-up period (up to 12 months).

Conclusions
Our findings suggest that high intensity multicomponent and multidisciplinary interventions are likely to be effective reducing readmission rates in geriatric patients, without increasing cost. Components such as type of staffing, assessing and managing symptoms, educating and promoting self-management, maintaining relationships and fostering coordination seem to have an important role in reducing the readmission rate. Research is needed to perform further investigations addressing geriatric patients well above 65 years old, to further understand the importance of individual components of the TCM in this population.
A novel TSC2 c.4511 T > C missense variant associated with tuberous sclerosis complex
Authors: He Shunzhi , Lv Na , Bao Hongchu , Wang Xiong , Li Jing 
Published: September 2020

Abstract
Background
Tuberous sclerosis complex (TSC) is an autosomal-dominant hereditary disease characterized by hamartomas of multiple organ systems, including the brain, skin, heart, kidney and lung. Genetically, TSC is caused by pathogenic variants in the TSC1 or TSC2 gene.

Case presentation
We reported a sporadic case of a 32-year-old Han Chinese male diagnosed with TSC, whose spouse had a history of two spontaneous miscarriages and an induced abortion of a 30-week fetus identified with cardiac rhabdomyoma by ultrasound. A novel heterozygous missense variant in the TSC2 gene (Exon35:c.4511 T > C:p.L1504P) was identified in the male patient and the aborted fetus by next-generation sequencing, but not in his wife or both his parents. According to the ACMG/AMP criteria, this variant was classified as a “likely pathogenic” variant.

Conclusion
The novel TSC2:c.4511 T > C variant identified was highly likely associated with TSC and could potentially lead to adverse reproductive outcomes. IVF-ET and pre-implantation genetic diagnosis for TSC are recommended for this patient in the future to prevent fetal TSC.
Aspergillosis infection over 20 years: a case report of probable vascular invasion in central nervous system
Authors: Zhang Yong , Wu Xu , Hu Yang-Pan 
Published: September 2020

AbstractBackgroundAspergillosis infection of central nervous system (CNS) is rare and fatal. Diagnosis of invasive aspergillosis remains difficult. Aspergillosis of CNS can be an acute, subacute, or chronic onset, and the longest course of the disease was currently reported to be 4 years. Here, we report a case with recurrent headache over 20 years.Case presentationA 54-year-old man was admitted to our neurological disease ward due to intermittent throbbing headache lasting for more than 20 years that had grown notably worse over the past week. The headache was localized to the side of his head blown by a cold wind. He also experienced nausea and vomiting when the headache became severe. The headache usually lasted for 3–4 h after he was blown by the cold wind, though he had no fever. The neurological examination was normal. Magnetic resonance imaging (MRI) of the brain was negative for parenchymal and meningeal lesions. However, the case had increased intracranial pressure (ICP), and elevated protein level in the cerebrospinal fluid (CSF).Aspergillus fumigatuswas found in CSF by nanopore targeted sequencing (NTS) and in blood by enzyme-linked immunosorbent assay (ELISA).Aspergillus fumigatus-specific antibody IgG was 104.62 AU/mL, aspergillus galactomannan (GM) antigen was 3.27 μg/L, D-dimer was 3.25 mg/L and fibrinogen degradation product was 11.50 mg/L, which were markedly higher than the normal levels. The patient was prescribed by voriconazole. After the treatment of 14 days, the ICP, CSF protein level,Aspergillus fumigatus-specific antibody IgG, GM antigen, D-dimer and fibrinogen degradation product returned normal.Aspergilluswas disappeared by NTS test of CSF. His headache has never occurred again after blowing by a cold wind.ConclusionsThis report reveals that aspergillosis infection of CNS can last for more than 20 years and the major symptom is only intermittent throbbing headache in an immunocompetent patient. Vascular invasion is probably the mechanism of headache in our case with CNS aspergillosis infection. Performing high-throughput gene sequencing technology in CSF is important when the pathogen is not determined for the patients with suspected CNS infection.
“I can guess the month … but beyond that, I can’t tell” an exploratory qualitative study of health care provider perspectives on gestational age estimation in Rajasthan, India
Authors: Scott K. , Gupta S. , Williams E. , Arthur M. , Somayajulu U. V. , Noguchi L. 
Published: September 2020

Abstract
Background
Accurately estimating gestational age is essential to the provision of time-sensitive maternal and neonatal interventions, including lifesaving measures for imminent preterm birth and trimester-specific health messaging.

Methods
We explored healthcare provider perspectives on gestational age estimation in the state of Rajasthan, India, including the methods they use (last menstrual period [LMP] dating, ultrasound, or fundal height measurement); barriers to making accurate estimates; how gestational age estimates are documented and used for clinical decision-making; and what could help improve the accuracy and use of these estimates. We interviewed 20 frontline healthcare providers and 10 key informants. Thematic network analysis guided our coding and synthesis of findings.

Results
Health care providers reported that they determined gestational age using some combination of LMP, fundal height, and ultrasound. Their description of their practices showed a lack of standard protocol, varying levels of confidence in their capacity to make accurate estimates, and differing strategies for managing inconsistencies between estimates derived from different methods. Many frontline healthcare providers valued gestational age estimation more to help women prepare for childbirth than as a tool for clinical decision making. Feedback on accuracy was rare. The providers sampled could not offer ultrasound directly, and instead could only refer women to ultrasound at higher level facilities, and usually only in the second or third trimesters because of late antenatal care-seeking. Low recall among pregnant women limited the accuracy of LMP. Fundal height was heavily relied upon, despite its lack of precision.

Conclusion
The accuracy of gestational age estimates is influenced by factors at four levels: 1. health system (protocols to guide frontline workers, interventions that make use of gestational age, work environment, and equipment); 2. healthcare provider (technical understanding of and capacity to apply the gestational age estimation methods, communication and rapport with clients, and value assessment of gestational age); 3. client (time of first antenatal care, migration status, language, education, cognitive approach to recalling dates, and experience with biomedical services); and, 4. the inherent limitations and ease of application of the methods themselves.
5α-reductase inhibitors impact prognosis of urothelial carcinoma
Authors: Wang Chien-Sheng , Li Ching-Chia , Juan Yung-Shun , Wu Wen-Jeng , Lee Hsiang-Ying 
Published: September 2020

Abstract
Background
5α-reductase inhibitors (5-ARIs) inhibit the pathway of converting the testosterone to dihydrotestosterone and are widely used in benign prostatic hyperplasia patients. Since androgen receptor activation may play a role in urothelial tumorigenesis, we conducted this retrospective cohort study to determine whether 5α-reductase inhibitors (5-ARIs) administration is associated with bladder cancer mortality, bladder cancer recurrence and upper tract urothelial carcinoma mortality, using the Taiwan National Health Insurance database.

Methods
The data of this retrospective cohort study were sourced from the Longitudinal Health Insurance Database of Taiwan, compiled by the Taiwan National Health Insurance database from 1996 to 2010. It consists of 18,530 men with bladder cancer, of whom 474 were 5-ARIs recipients and 4384 men with upper tract urothelial carcinoma, of whom 109 were 5-ARIs recipients. Propensity Score Matching on the age and geographic data was done at the ratio of 1:10. We analyzed the odds ratios (OR) and 95% confidence interval (CI) of the risk of bladder cancer death, bladder cancer recurrence rate and upper tract urothelial carcinoma related death by the 5-ARIs administration.

Results
Those who received 5-ARIs showed a lower risk of bladder cancer related death compared to nonusers in multivariable adjusted analysis (OR 0.835, 95% CI 0.71–0.98). However, there was no significant difference in the bladder cancer recurrence rate (OR 0.956, 95% CI 0.82–1.11) and upper tract urothelial carcinoma related mortality in multivariable adjusted analysis (OR 0.814, 95% CI 0.6–1.1).

Conclusions
Patients who receive 5-ARIs have lower bladder cancer related mortality compared to those who don’t. 5-ARIs may prove to be a viable strategy to improve bladder cancer outcomes.