bluuebunny/crossref_metadata_2025_split huggingface dataset:
Very low-depth whole-genome sequencing in complex trait association studies
Authors: Gilly Arthur , Southam Lorraine , Suveges Daniel , Kuchenbaecker Karoline , Moore Rachel , Melloni Giorgio E M , Hatzikotoulas Konstantinos , Farmaki Aliki-Eleni , Ritchie Graham , Schwartzentruber Jeremy , Danecek Petr , Kilian Britt , Pollard Martin O , Ge Xiangyu , Tsafantakis Emmanouil , Dedoussis George , Zeggini Eleftheria 
Published: December 2018

Abstract

Motivation
Very low-depth sequencing has been proposed as a cost-effective approach to capture low-frequency and rare variation in complex trait association studies. However, a full characterization of the genotype quality and association power for very low-depth sequencing designs is still lacking.

Results
We perform cohort-wide whole-genome sequencing (WGS) at low depth in 1239 individuals (990 at 1× depth and 249 at 4× depth) from an isolated population, and establish a robust pipeline for calling and imputing very low-depth WGS genotypes from standard bioinformatics tools. Using genotyping chip, whole-exome sequencing (75× depth) and high-depth (22×) WGS data in the same samples, we examine in detail the sensitivity of this approach, and show that imputed 1× WGS recapitulates 95.2% of variants found by imputed GWAS with an average minor allele concordance of 97% for common and low-frequency variants. In our study, 1× further allowed the discovery of 140 844 true low-frequency variants with 73% genotype concordance when compared to high-depth WGS data. Finally, using association results for 57 quantitative traits, we show that very low-depth WGS is an efficient alternative to imputed GWAS chip designs, allowing the discovery of up to twice as many true association signals than the classical imputed GWAS design.

Availability and implementation
The HELIC genotype and WGS datasets have been deposited to the European Genome-phenome Archive (https://www.ebi.ac.uk/ega/home): EGAD00010000518; EGAD00010000522; EGAD00010000610; EGAD00001001636, EGAD00001001637. The peakplotter software is available at https://github.com/wtsi-team144/peakplotter, the transformPhenotype app can be downloaded at https://github.com/wtsi-team144/transformPhenotype.

Supplementary information
Supplementary data are available at Bioinformatics online.
Disruption of ubiquitin specific protease 26 gene causes male subfertility associated with spermatogenesis defects in mice†
Authors: Tian Hong , Huo Yongwei , Zhang Jie , Ding Shangshu , Wang Zhiyong , Li Hecheng , Wang Lirong , Lu Ming , Liu Sen , Qiu Shudong , Zhang Qiuyang 
Published: December 2018

Abstract
Ubiquitin-specific protease 26 (USP26) is an X-linked gene exclusively expressed in the testis and codes for the USP26, a peptidase enzyme that belongs to the deubiquitinating enzyme family. Recent studies have indicated that mutations in USP26 affect spermatogenesis and are associated with male infertility in humans and mice. However, the exact role of USP26 in spermatogenesis and how it affects male reproduction remains unknown. In this study, we generated a conventional Usp26 knockout mouse model and found that deletion of Usp26 in male mice (Usp26−/Y) leads to significantly reduced pup numbers per litter and significantly increased intervals between two consecutive offspring. We also found that the serum follicle stimulating hormone and testosterone levels of adult Usp26−/Y mice were significantly decreased compared to those of Usp26+/Y mice. Histological examination results showed that Usp26−/Y mice had significantly increased percentage of abnormal seminiferous tubules at different ages. Flow cytometry results exhibited that Usp26−/Y mice had significantly reduced percentage of mature haploid cells in the testes compared to Usp26+/Y mice. Sperm counts in epididymis were also significantly declined in Usp26−/Y mice compared to those in Usp26+/Y mice. Immunohistochemistry and immunofluorescence staining and immunoprecipitation analysis results showed that USP26 and androgen receptor were co-localized in mouse testicular cells at different ages and they both had physiological interactions. All these results demonstrated that the loss of Usp26 affects spermatogenesis and hormone secretion and causes male subfertility. Our study also provides the evidence on the interactions between USP26 and androgen receptor in mouse testis, whereby pointing to a potential mechanism.
Theorizing Development of Parasocial Engagement
Authors: Tukachinsky Riva , Stever Gayle 
Published: December 2018

AbstractThe article proposes a theoretical model of the development of parasocial relationships (PSRs) building on Knapp’s model of relationship development. Through synthesis of research across disciplines, the model conceptualizes the relational goals and parasocial interactions (PSIs) specific to the PSR. The model identifies variables that predict engagement at that level, describes the stage’s outcomes/effects, and considers the utility of existing measures to assess these stages. The conceptualization of PSRs as a dynamic process rather than intensity of a monolithic experience offers new directions worthy of empirical examination.
Molecular Characterization of Two Mitogen-Activated Protein Kinases: p38 MAP Kinase and Ribosomal S6 Kinase From Bombyx mori (Lepidoptera: Bombycidae), and Insight Into Their Roles in Response to BmNPV Infection
Authors: Muhammad Azharuddin , Toufeeq Shahzad , Yu Hai-Zhong , Wang Jie , Zhang Shang-Zhi , Li Bing , Li Zhen , Yang Li-Ang , Hu Pei , Ma Yan , Xu Jia-Ping 
Published: December 2018

Abstract
Proteins p38 map kinase and ribosomal S6 kinase (S6K) as members of mitogen-activated protein kinases (MAPKs) play important roles against pathogens. In this study, Bmp38 and BmS6K were identified as differentially expressed proteins from iTRAQ database. Bmp38 and BmS6K were expressed, and recombinant proteins were purified. The bioinformatics analysis showed that both proteins have serine/threonine-protein kinases, catalytic domain (S_TKc) with 360 and 753 amino acids, respectively. The real-time quantitative polymerase chain reaction (RT-qPCR) results suggest that Bmp38 and BmS6K had high expression in the midgut and hemolymph. The comparative expression level of Bmp38 and BmS6K in BC9 was upregulated than in P50 in the midgut after Bombyx mori nucleopolyhedrovirus (BmNPV) infection. Western bolt results showed a positive correlation between RT-qPCR and iTRAQ data for Bmp38, but BmS6K data showed partial correlation with iTRAQ. Injection of anti-Bmp38 and anti-BmS6K serum suggested that Bmp38 may be involved against BmNPV infection, whereas BmS6K may require phosphorylation modification to inhibit BmNPV infection. Taken together, our results suggest that Bmp38 and BmS6k might play an important role in innate immunity of silkworm against BmNPV.
Optimal dose of PG600 when given to progestogen-synchronized ewes during anestrus as affected by day of the year and temperature1
Authors: Cross Lucy J , Cross Robin M , Stormshak Fredrick 
Published: December 2018

Abstract
The objective of this long-term study was to improve the out-of-season breeding rates for ewes by examining effectiveness of dose levels of PG600, a combination of 80-IU/mL pregnant mare serum gonadotropin and 40-IU/mL human chorionic gonadotropin. Each week, during the anestrous season from 1998 through 2016, mature ewes were inserted with 1 of 2 progestogen devices. After 9 to 13 d, at removal of the device, ewes were injected intramuscularly with a specific dose of PG600. A total of 1,402 ewes were treated in this study, with weekly treatment groups ranging from 3 to 12 ewes. Ewes were assigned randomly in equal numbers to 1 of 2 ram pens with one fertile ram in each pen. Rams were fitted with a marking harness. Between 36 and 48 h after removal of the device, rams were switched. Ewes were checked for crayon marks (indicative of estrus) at 36, 48, and 96 h after removal of synchronizing devices. Rams were removed after 1 wk. Pregnancy status was diagnosed at 90 d of gestation using radiography and verified at 120 d or at lambing. To explore the impact of dose level, daylight, and temperature on pregnancy rate, we formulated an ordered multinomial probit model. The model controls statistically for dose level, synchronization device type, device reuse, and natural variation in minimum daily temperature and day of the year (DOY). Predicted pregnancy rate and type of birth at 90 d of gestation were significantly affected by DOY and temperature as well as dose level. Both observed and predicted pregnancy rates were higher for PG600 dose levels between 2.00 and 3.50 mL than for those below 2.00 mL or above 3.99 mL. By giving optimal amounts of PG600 to anestrous ewes, producers will have a greater number of pregnant ewes at lambing during the out-of-season lambing time.
Genomic Study of Severe Fetal Anomalies and Discovery of GREB1L Mutations in Renal Agenesis
Authors: Boissel Sarah , Fallet-Bianco Catherine , Chitayat David , Kremer Valérie , Nassif Christina , Rypens Françoise , Delrue Marie-Ange , Soglio Dorothée Dal , Oligny Luc L. , Patey Natalie , Flori Elisabeth , Cloutier Mireille , Dyment David , Campeau Philippe , Karalis Aspasia , Nizard Sonia , Fraser William D. , Audibert François , Lemyre Emmanuelle , Rouleau Guy A. , Hamdan Fadi F. , Kibar Zoha , Michaud Jacques L. 
Published: December 2018

(Abstracted from Genet Med 2018;20(7):745–753)
Birth defects are a leading cause of mortality and mortality in infants and children. The etiology of birth defects is complex, and copy number variants (CNVs) detectable with chromosomal microarray currently represent the most commonly recognized cause of birth defects in fetuses and children.
The experiences and needs of Asian women experiencing menopausal symptoms: a meta-synthesis
Authors: Shorey Shefaly , Ng Esperanza D. 
Published: December 2018

Abstract

Objective:
The aim of the study was to explore the experiences and needs of Asian women who were experiencing or had experienced menopause and to determine possible differences in experiences due to acculturation by comparing Asian women living in Asia and those living in Western countries.

Methods:
Six electronic databases were systematically searched: PubMed, CINAHL, Embase, Scopus, PsycINFO, and ProQuest. The search resulted in 17 qualitative studies that met the inclusion and exclusion criteria. Quality appraisal was conducted using the Critical Appraisal Skills Programme Checklist. All 17 studies were analyzed using meta-summaries and, then, using meta-synthesis.

Results:
Five themes were identified from the 17 included studies (United States, n = 5; Asia, n = 12): (1) perceptions and attitudes toward menopause (n = 14), (2) physical and emotional experiences during menopause (n = 16), (3) changes in life and relationships (n = 11), (4) needs and coping strategies (n = 13), and (5) unique Asian experiences in Western societies (n = 5). Asian women generally had neutral or positive attitudes toward menopause, but their negative physical, emotional, and psychosocial experiences highlighted their unmet needs and unpreparedness for this phase of life. Diverse self-management strategies were adopted, but there was a high demand for more trustworthy informational resources. Asian women in Western societies were not highly acculturated and retained traditional practices.

Conclusions:
Although cultural influences serve as a protective factor against menopausal symptoms, the traditional and conservative nature of the Asian society poses as a help-seeking barrier. Therefore, to ensure the healthy well-being of postmenopausal women, the implementation of culturally appropriate mitigation and management strategies is necessary.
The effects of swimming training on arterial function, muscular strength, and cardiorespiratory capacity in postmenopausal women with stage 2 hypertension
Authors: Wong Alexei , Kwak Yi-Sub , Scott Steven D. , Pekas Elizabeth J. , Son Won-Mok , Kim Ji-Seok , Park Song-Young 
Published: December 2018

Abstract

Objective:
Aging is associated with progressive decreases in arterial health as well as muscular strength and cardiorespiratory capacity. It is crucial to prevent or reduce the negative effects of aging on vasculature, muscular, and cardiorespiratory function by implementing appropriate lifestyle interventions, such as exercise training. We examined the effects of a swimming (SWM) regimen on arterial stiffness (pulse wave velocity [PWV]), blood pressure (BP), wave reflection (augmentation index [AIx]), muscle strength, and aerobic capacity in sedentary, postmenopausal women with stage 2 hypertension.

Methods:
One hundred participants (∼74 years of age) were recruited from multiple general practice centers. Using a parallel experimental design, participants were randomly assigned to either SWM (n = 52) or nonexercising control group (n = 48) for 20 weeks. Participants in the SWM group trained 3 to 4 days/week. Participants’ carotid to radial PWV, BP, AIx, muscular strength, and cardiorespiratory capacity were measured at baseline and after 20 weeks of their assigned intervention.

Results:
There was a significant group × time interaction (P < 0.05) for carotid to radial PWV (Δ−1.2 m/s), AIx (Δ−4%), and systolic (Δ−9 mm Hg) and diastolic BP (Δ − 9 mm Hg), which significantly decreased (P < 0.05); and strength (Δ3 kg) and cardiorespiratory capacity (Δ4 mL/kg/min), which significantly increased (P < 0.05) following SWM compared to no changes in control.

Conclusions:
SWM led to reductions in arterial stiffness, wave reflection, and BP while increasing strength and aerobic capacity in postmenopausal women with stage 2 hypertension. SWM may be an effective intervention in the prevention and treatment of age-related vascular complications and declines in muscle strength and cardiorespiratory capacity.
Age at menarche and risk of all-cause and cardiovascular mortality: a systematic review and dose–response meta-analysis
Authors: Chen Xu , Liu Yu , Sun Xizhuo , Yin Zhaoxia , Li Honghui , Liu Xuejiao , Zhang Dongdong , Cheng Cheng , Liu Leilei , Liu Feiyan , Zhou Qionggui , Wang Chongjian , Li Linlin , Wang Bingyuan , Zhao Yang , Liu Dechen , Zhang Ming , Hu Dongsheng 
Published: December 2018

Abstract

Objective:
The evidence between age at menarche and mortality risk is controversial. We aimed to quantify the dose–response association of age at menarche and risk of all-cause and cardiovascular disease (CVD) mortality based on cohort studies.

Methods:
PubMed, EMBASE, Web of Science, and Scopus databases were searched up to March 15, 2018 for relevant articles. Random-effects models and restricted cubic splines were used for this meta-analysis.

Results:
Twelve cohort studies, with 79,363 deaths and 2,341,769 participants, met the inclusion criteria. With each 1-year increase in menarche age, the relative risk (RR) was reduced for all-cause mortality (RR: 0.977, 95% confidence interval [CI]: 0.970-0.984), CVD mortality (RR: 0.993, 95% CI: 0.975-1.011), ischemic heart disease (IHD) mortality (RR: 0.969, 95% CI: 0.947-0.993), and stroke mortality (RR: 0.983, 95% CI: 0.954-1.012). We found a nonlinear dose–response association (P
nonlinearity = 0.001) between age at menarche and all-cause mortality, with the lowest risk observed at menarche age 15 years (RR: 0.849 95% CI: 0.800-0.901), but no evidence of a nonlinear association between menarche age and CVD mortality (P
nonlinearity = 0.543), IHD mortality (P
nonlinearity = 0.310), or stroke mortality (P
nonlinearity = 0.824).

Conclusions:
Age at menarche is inversely associated with all-cause and IHD mortality.
What Is the Color of Your Lymph Node?
Authors: Ben Naftali Yeela , Brodsky Asia , Bar-Meir Eran D. 
Published: December 2018

Summary:
We describe a case of tattoo ink in an axillary lymph node, which was observed during an axillary dissection and mastectomy surgery. It is important to be aware of this phenomenon and correctly identify it at the time of surgery, as a misdiagnosis can have serious consequences.
Redefining the Anatomic Boundaries for Safe Dissection of the Skin Paddle in a Gracilis Myofasciocutaneous Free Flap: An Indocyanine Green Cadaveric Injection Study
Authors: Chidester Jeremy R. , Leland Hyuma A. , Navo Paul , Minneti Michael , Ghiassi Alidad , Stevanovic Milan 
Published: December 2018

Summary:
The gracilis free flap remains a versatile option in the reconstructive ladder. The flap itself can be harvested with or without a skin paddle. The gracilis myocutaneous free flap, however, is known for partial skin flap necrosis, especially in the distal one-third of the skin island. The gracilis myofasciocutaneous flap has been previously described as a technique to improve perfusion to the skin by harvesting surrounding deep fascia in a pedicled flap. However, limitations to this study required injection of multiple pedicles to demonstrate its perfusion. We demonstrate a novel technique using a cadaveric model that shows perfusion through injection via a single dominant pedicle (medial circumflex) with a large cutaneous paddle (average 770 cm2) with included deep fascia, using indocyanine green and near-infrared imaging. For comparison, we are also able to confirm the lack of perfusion to the distal cutaneous paddle when the fascia is not harvested, correlating with previous findings and ink injection studies. This novel technique is versatile, relatively inexpensive, and can demonstrate perfusion patterns via perforasomes that were otherwise not possible from previous techniques. Additionally, real-time imaging is possible, helping to elucidate the sequence of flow into the flap and potentially predict areas of flap necrosis.
Novel Treatment of a Malignant Peripheral Nerve Sheath Tumor of the Median Nerve
Authors: Liodaki Eirini , Robiller Sandra , Wenzel Eike , Mailaender Peter , Stang Felix 
Published: December 2018

Summary:
Malignant peripheral nerve sheath tumors are rare, associated with a poor prognosis and uncertainty regarding the appropriate management. We report a novel oncologic and reconstructive treatment of a young patient with a malignant peripheral nerve sheath tumor of the median nerve of the left hand. The patient underwent a wide local excision, an opponensplasty, a nerve reconstruction by nerve allografts followed by brachytherapy treatment. Two years later, the patient remains disease free with preserved function of her hand.
Virtual Surgical Planning Decreases Operative Time for Isolated Single Suture and Multi-suture Craniosynostosis Repair
Authors: Andrew Tom W. , Baylan Joseph , Mittermiller Paul A. , Cheng Homan , Johns Dana N. , Edwards Michael S. B. , Cheshier Sam H. , Grant Gerald A. , Lorenz H. Peter 
Published: December 2018

Background:
Cranial vault reconstruction is a complex procedure due to the need for precise 3-dimensional outcomes. Traditionally, the process involves manual bending of calvarial bone and plates. With the advent of virtual surgical planning (VSP), this procedure can be streamlined. Despite the advantages documented in the literature, there have been no case-control studies comparing VSP to traditional open cranial vault reconstruction.

Methods:
Data were retrospectively collected on patients who underwent craniosynostosis repair during a 7-year period. Information was collected on patient demographics, intraoperative and postoperative factors, and intraoperative surgical time. High-resolution computed tomography scans were used for preoperative planning with engineers when designing osteotomies, bone flaps, and final positioning guides.

Results:
A total of 66 patients underwent open craniosynostosis reconstruction between 2010 and 2017. There were 35 control (non-VSP) and 28 VSP cases. No difference in age, gender ratios, or number of prior operations was found. Blood loss was similar between the 2 groups. The VSP group had more screws and an increased length of postoperative hospital stay. The length of the operation was shorter in the VSP group for single suture and for multiple suture operations. Operative time decreased as the attending surgeon increased familiarity with the technique.

Conclusions:
VSP is a valuable tool for craniosynostosis repair. We found VSP decreases surgical time and allows for improved preoperative planning. Although there have been studies on VSP, this is the first large case-control study to be performed on its use in cranial vault remodeling.
Direct-Thrombin Inhibitor Utilization in Patients With Heparin-Induced Thrombocytopenia and Undergoing Catheter-Directed Thrombolysis
Authors: Badreldin Hisham A. , Albassam Ghada , Aldoughaim Maha , Alyami Majed 
Published: December 2018

Background:
Catheter-directed thrombolysis (CDT) is one of the emerging venous thromboembolism management modalities. There are fairly limited data regarding the use of direct-thrombin inhibitors (DTIs) in patients with heparin-induced thrombocytopenia and undergoing CDT.

Objectives:
The aim of this study was to provide a summary of the available evidence supporting the use of DTIs in patients undergoing CDT.

Methods and Results:
We included 6 case reports in our analysis after searching for peer-reviewed articles and case reports in multiple research engines. Four of the 6 cases used argatroban, and 2 cases used bivalirudin. Alteplase was used in all of the 6 cases. All cases used lower activated partial thromboplastin time target. The average initial dose of alteplase ranged from 0.5 to 3 mg/h. The average duration of CDT was 26 hours (SD, 13 hours). Five patients (83%) survived after the procedure, and no complications were reported.

Conclusions:
The use of DTIs might be safe and effective in selected patients with heparin-induced thrombocytopenia and undergoing CDT.
Healthcare Providers' Perceived Communication Barriers to Offering Palliative Care to Patients With Heart Failure
Authors: Schallmo Marianne K. , Dudley-Brown Sharon , Davidson Patricia M. 
Published: December 2018

Context
Heart failure is a chronic complex syndrome that is common and burdensome. International clinical practice guidelines recommend that healthcare providers communicate palliative care options with patients with heart failure.

Objectives
The aim of this study was to conduct an integrative review to evaluate how healthcare providers perceived communication barriers to offering information to individuals in the palliative phase of heart failure.

Methods
Four databases and the gray literature were searched from January 1987 to February 2017. Inclusion and exclusion criteria were applied. Studies were graded for strength and quality using a critical appraisal tool, and key themes were extracted and synthesized.

Results
Ten articles met the full inclusion criteria. Most studies were qualitative or nonexperimental studies of good quality. Authors of several studies found that healthcare providers lacked basic knowledge about palliative care or did not possess sufficient knowledge to effectively provide care. Poor knowledge of palliative care created a barrier between the provider and the patient. Inadequate education or inexperience in palliative care led to the resistance of health providers to implementing a palliative approach.

Conclusions
The results of this review emphasize a lack of knowledge as a barrier to delivering palliative care. Healthcare providers caring for individuals with heart failure need palliative care knowledge, skills, and competencies to ensure that this vulnerable population receives holistic patient-centered care.