bluuebunny/crossref_metadata_2025_split huggingface dataset:
Sperm histone H3 lysine 4 trimethylation is altered in a genetic mouse model of transgenerational epigenetic inheritance
Authors: Lismer Ariane , Siklenka Keith , Lafleur Christine , Dumeaux Vanessa , Kimmins Sarah 
Published: October 2020

AbstractAdvancing the molecular knowledge surrounding fertility and inheritance has become critical given the halving of sperm counts in the last 40 years, and the rise in complex disease which cannot be explained by genetics alone. The connection between both these trends may lie in alterations to the sperm epigenome and occur through environmental exposures. Changes to the sperm epigenome are also associated with health risks across generations such as metabolic disorders and cancer. Thus, it is imperative to identify the epigenetic modifications that escape reprogramming during spermatogenesis and embryogenesis. Here, we aimed to identify the chromatin signature(s) involved in transgenerational phenotypes in our genetic mouse model of epigenetic inheritance that overexpresses the histone demethylase KDM1A in their germ cells. We used sperm-specific chromatin immunoprecipitation followed by in depth sequencing (ChIP-seq), and computational analysis to identify whether differential enrichment of histone H3 lysine 4 trimethylation (H3K4me3), and histone H3 lysine 27 trimethylation (H3K27me3) serve as mechanisms for transgenerational epigenetic inheritance through the paternal germline. Our analysis on the sperm of KDM1A transgenic males revealed specific changes in H3K4me3 enrichment that predominantly occurred independently from bivalent H3K4me3/H3K27me3 regions. Many regions with altered H3K4me3 enrichment in sperm were identified on the paternal allele of the pre-implantation embryo. These findings suggest that sperm H3K4me3 functions in the transmission of non-genetic phenotypes transgenerationally.
Benzo[a]pyrene represses DNA repair through altered E2F1/E2F4 function marking an early event in DNA damage-induced cellular senescence
Authors: Allmann Sebastian , Mayer Laura , Olma Jessika , Kaina Bernd , Hofmann Thomas G , Tomicic Maja T , Christmann Markus 
Published: October 2020

AbstractTranscriptional regulation of DNA repair is of outmost importance for the restoration of DNA integrity upon genotoxic stress. Here we report that the potent environmental carcinogen benzo[a]pyrene (B[a]P) activates a cellular DNA damage response resulting in transcriptional repression of mismatch repair (MMR) genes (MSH2, MSH6, EXO1) and of RAD51, the central homologous recombination repair (HR) component, ultimately leading to downregulation of MMR and HR. B[a]P-induced gene repression is caused by abrogated E2F1 signalling. This occurs through proteasomal degradation of E2F1 in G2-arrested cells and downregulation of E2F1 mRNA expression in G1-arrested cells. Repression of E2F1-mediated transcription and silencing of repair genes is further mediated by the p21-dependent E2F4/DREAM complex. Notably, repression of DNA repair is also observed following exposure to the active B[a]P metabolite BPDE and upon ionizing radiation and occurs in response to a p53/p21-triggered, irreversible cell cycle arrest marking the onset of cellular senescence. Overall, our results suggest that repression of MMR and HR is an early event during genotoxic-stress induced senescence. We propose that persistent downregulation of DNA repair might play a role in the maintenance of the senescence phenotype, which is associated with an accumulation of unrepairable DNA lesions.
Association between thrombotic microangiopathy and activated alternative complement pathway in malignant nephrosclerosis
Authors: Zhang Ying , Yang Chaona , Zhou Xinjin , Hu Ruimin , Quan Songxia , Zhou Yali , Li Yuan , Xing Guolan 
Published: October 2020

Abstract

Background
Malignant nephrosclerosis, defined as renal microangiopathy in the setting of severe hypertension, remains a critical renal emergency leading to end-stage renal disease despite aggressive anti-hypertensive treatment. Recently, activation of the complement alternative pathway (AP) has been reported to play a prominent role in the pathogenesis of malignant nephrosclerosis. However, subsequent study failed to recapitulate the findings of genetic complement abnormalities in the disease. This study aimed to determine the presence of AP activation and genetic complement defects and establish their correlations to renal microangiopathy lesions, clinical features and prognosis in patients with malignant nephrosclerosis.

Methods
Fifty patients with malignant hypertension and concomitant thrombotic microangiopathy (TMA) proven by renal biopsy were investigated; 25 cases of kidney donors who received zero-hour allograft biopsies were used as normal controls. Various renal TMA lesions in patients with malignant nephrosclerosis were reviewed and evaluated using a semi-quantitative scoring system. Deposition of C5b-9, C3a, C5a, C4d and mannose-binding lectin was assessed by immunohistochemistry. Co-localization of C5b-9 and CD34 was detected by confocal microscopy. Complement factor B (FB), factor P (FP; properdin), factor D (FD), factor H (FH), C3a and C5a levels were quantified by enzyme-linked immonosorbent assay in plasma and urine samples of patients with malignant nephrosclerosis and controls. Genetic abnormalities of complement components were analysed by whole-exome sequencing.

Results
Renal biopsies of malignant nephrosclerosis showed identical histopathological and ultrastructural features to atypical haemolytic uraemic syndrome. C5b-9, C3a and C5a deposits were found along the walls of arteries/arterioles and glomerular capillaries and localized in the endothelial cells. Elevated plasma and urinary levels of FB, FP, FD, C3a and C5a as well as decreased FH levels were observed in patients with malignant nephrosclerosis compared with normal controls. The urinary levels of complement AP components, but not the plasma levels, were correlated with renal functions, prognosis and active TMA lesions except for arteriolar thrombi. Finally, mutations of the MCP, CFB, CFH and CFHR5 genes were identified in 8 of 20 patients with malignant nephrosclerosis.

Conclusions
Aberrant complement AP dysregulation was demonstrated and associated with the activity, severity and renal outcomes of malignant nephrosclerosis. This observation warrants screening for complement defects in patients with malignant nephrosclerosis for the potential use of complement regulators and also highlights the need for further investigation of the precise role of AP in the pathogenesis of the disease.
Massive Fluid Influx beneath the Colorado Plateau (USA) Related to Slab Removal and Diatreme Emplacement: Evidence from Oxygen Isotope Zoning in Eclogite Xenoliths
Authors: Hoover William F , Page F Zeb , Schulze Daniel J , Kitajima Kouki , Valley John W 
Published: October 2020

AbstractThe Colorado Plateau has undergone as much as 1·8 km of uplift over the past 80 Myr, but never underwent the pervasive deformation common in the neighboring tectonic provinces of the western USA. To understand the source, timing and distribution of mantle hydration, and its role in plateau uplift, garnets from four eclogite xenoliths of the Moses Rock diatreme (Navajo Volcanic Field, Utah, USA) were analyzed in situ for δ18O by secondary ion mass spectrometry. These garnets have the largest reported intra-crystalline oxygen isotope zoning to date in mantle-derived xenoliths with core-to-rim variations of as much as 3 ‰. All samples have core δ18O values greater than that of the pristine mantle (∼5·3 ‰, mantle garnet as derived from mantle zircon in earlier work) consistent with an altered upper oceanic crust protolith. Oxygen isotope ratios decrease from core to rim, recording interaction with a low-δ18O fluid at high temperature, probably derived from serpentinite in the foundering Farallon slab. All zoned samples converge at a δ18O value of ∼6 ‰, regardless of core composition, suggesting that fluid infiltration was widely distributed. Constraints on the timing of this fluid influx, relative to diatreme emplacement, can be gained from diffusion modeling of major element zoning in garnet. Modeling using best estimates of peak metamorphic conditions (620 °C, 3·7 GPa) yields durations of &lt;200 kyr, suggesting that fluid influx and diatreme emplacement were temporally linked. These eclogite xenoliths from the Colorado Plateau record extensive fluid influx, pointing to complex hydration–dehydration processes related to flat-slab subduction and foundering of the Farallon plate. Extensive hydration of the lithospheric mantle during this fluid influx may have contributed to buoyancy-driven uplift of the Colorado Plateau and melt-free emplacement of Navajo Volcanic Field diatremes.
Tilting Modules and Dominant Dimension with Respect to Injective Modules
Authors: Adachi Takahide , Tsukamoto Mayu 
Published: October 2020

Abstract
In this paper, we study a relationship between tilting modules with finite projective dimension and dominant dimension with respect to injective modules as a generalization of results of Crawley-Boevey–Sauter, Nguyen–Reiten–Todorov–Zhu and Pressland–Sauter. Moreover, we give characterizations of almost n-Auslander–Gorenstein algebras and almost n-Auslander algebras by the existence of tilting modules. As an application, we describe a sufficient condition for almost 1-Auslander algebras to be strongly quasi-hereditary by comparing such tilting modules and characteristic tilting modules.
RightPath: a model of community-based musculoskeletal care for children
Authors: Smith Nicola , Mercer Victoria , Firth Jill , Jandial Sharmila , Kinsey Katharine , Light Helen , Nye Alan , Rapley Tim , Foster Helen E 
Published: October 2020

Abstract

Objectives
Musculoskeletal (MSK) presentations are common (reported prevalence of one in eight children) and a frequent cause of consultations (6% of 7-year-olds in a cohort study from the UK). Many causes are self-limiting or raised as concerns about normal development (so-called normal variants). We aimed to describe a new model of care to identify children who might be managed in the community by paediatric physiotherapists and/or podiatrists rather than referral to hospital specialist services.

Methods
Using mixed methods, we tested the feasibility, acceptability and transferability of the model in two UK sites. Evaluation included patient flow, referral times, diagnosis and feedback (using questionnaires, focus groups and interviews).

Results
All general practitioner referrals for MSK presentations (in individuals &lt;16 years of age) were triaged by nurses or allied health professionals using a triage guide; ∼25% of all MSK referrals were triaged to be managed by community-based paediatric physiotherapists/podiatrists, and most (67%) had a diagnosis of normal variants. Families reported high satisfaction, with no complaints or requests for onward specialist referral. No children re-presented to the triage service or with serious MSK pathology to hospital specialist services in the subsequent 6 months after triage. Triagers reported paediatric experience to be important in triage decision-making and case-based learning to be the preferred training format.

Conclusion
The triage model is acceptable, feasible and transferable to enable appropriate care in the community for a proportion of children with MSK complaints. This is a multi-professional model of better working together between primary community and specialist providers.
Between Emotional Involvement and Professional Detachment: The Challenges of Nursing in Dutch Mental Institutions (1880–1980)
Authors: Oosterhuis Harry , Aan de Stegge Cecile 
Published: October 2020

Summary
This article is about the tension and changing balance between emotional involvement and professional detachment in the practice of nursing in Dutch mental institutions between the 1880s and 1990s. We address this issue in relation to institutional and material conditions, power differences between doctors, nurses and patients, different treatments, and the social marginalisation of hospitalised patients. On the basis of various sources (nursing textbooks, chronicles of skills learning by students, personal accounts, questionnaires and interviews), we describe how nurses were supposed to interact with patients and how they dealt with three sensitive issues: the need to use coercion in response to agitated patients, the sexual behaviour of patients and the risk of suicide in psychiatric institutions. We argue that nursing mental patients required a great deal of emotional work and that there was a shift from strict rules of behaviour imposed from above to more flexible self-regulation, guided by self-reflection.
Clinical application and mechanism of traditional Chinese medicine in treatment of lung cancer
Authors: Su Xiao-Lin , Wang Jiang-Wei , Che Hui , Wang Chang-Fu , Jiang Hai , Lei Xia , Zhao Wan , Kuang Hai-Xue , Wang Qiu-Hong 
Published: October 2020

Abstract
Lung cancer is a malignant tumor characterized by a rapid proliferation rate, less survivability, high mortality, and metastatic potential. This review focuses on updated research about the clinical application of traditional Chinese medicine (TCM) as an adjuvant therapy to lung cancer treatment and the mechanisms of TCM effect on lung cancer in vitro and in vivo. We summarized the recent 5 years of different research progress on clinical applications and antitumor mechanisms of TCM in the treatment of lung cancer. As a potent adjuvant therapy, TCM could enhance conventional treatments (chemotherapy, radiation therapy, and epidermal growth factor receptors [EGFRs] tyrosine kinase inhibitors [TKIs]) effects as well as provide synergistic effects, enhance chemotherapy drugs chemosensitivity, reverse drug resistance, reduce adverse reactions and toxicity, relieve patients’ pain and improve quality of life (QOL). After treating with TCM, lung cancer cells will induce apoptosis and/or autophagy, suppress metastasis, impact immune reaction, and therapeutic effect of EGFR-TKIs. Therefore, TCM is a promisingly potent adjuvant therapy in the treatment of lung cancer and its multiple mechanisms are worthy of an in-depth study.
Cross-sectional analysis tracking workforce density in surgery, anesthesia, and obstetrics as an indicator of progress toward improved global surgical access
Authors: Bouchard Megan E. , Justiniano Jeanine , Vervoort Dominique , Gore-Booth Julian , Emmanuel Adupa , Langer Monica 
Published: October 2020

Introdution:
Safe surgical care, including anesthesia, obstetrics, and trauma, is an essential component of a functional health system, yet is lacking in much of the world. One indicator of surgical access is the number of specialist surgeons, anesthesiologists, and obstetricians (SAO) per 100,000 population, but global progress reaching threshold SAO density (SAOD) is unknown. This study measured SAOD change/trajectory and highlighted components of workforce expansion.

Methods:
SAOD in 2019 was captured utilizing publicly available medical licensing data for a convenience sample of 21 countries. Projected 2030 SAOD were estimated by extrapolating annual changes since 2015. Ugandan medical students were surveyed regarding postgraduate plans and SAO training availability. Workforce contribution by nonphysician surgical and anesthetic providers was measured in Sierra Leone.

Results:
Three low-income countries (LICs), 4 lower middle-income countries (L-MICs), 7 upper middle-income countries (UMICs), and 7 high-income countries (HICs) were included. Overall SAOD increased since 2015. The average 2019 SAOD was 1.16±0.81 (LICs), 3.19±1.92 (L-MICs), 20.98±12.55 (UMICs), and 44.04±12.41 (HICs). The projected 2030 SAOD in LICs and L-MICs remains below 20. In Uganda, 144 specialist SAO training positions and practice preferences predict an inadequate future workforce. In Sierra Leone, nonphysician providers contributed a 6-fold increase in the surgical workforce, though remains inadequate.

Conclusions:
Despite incremental positive changes since 2015, the current SAOD trajectory is inadequate to realize 2030 access goals. Increased training and retention of specialists and nonphysician providers are necessary to address this critical deficit.
Five-year trend of colorectal cancer incidence in B.P. Koirala Memorial Cancer Hospital of Central Nepal: a cross-sectional study
Authors: Shrestha Gambhir , Khanal Suman , Mulmi Rashmi , Sapkota Ganga 
Published: October 2020

Background:
Colorectal cancer (CRC) is one of the most common cancers in the world including Nepal and has become a major public health issue. This study aims to describe the trend of CRC in a national tertiary cancer hospital in Nepal.

Materials and methods:
This was a cross-sectional study with secondary data analysis conducted at B.P. Koirala Memorial Hospital, Chitwan, Nepal. The data was obtained from the hospital cancer registry and included all new CRC cases registered during a period of 5 years from 2014 to 2018. Analysis was done with Statistical Package for Social Sciences version 20.

Results:
A total of 1129 new CRC cases were registered in the study period comprising 4.6% of total cancer cases. Out of which, 644 (57.0%) were males and 485 (43.0%) were females. The most common age group was 45–59 years. About 36% of CRC cases were of age under 45 years. Rectal cancer (50.0%) was the most common CRC with half of the total cases followed by colon (19.1%), and anal cancer (12.6%). There is an increase in the incidence of CRC with an average annual increase of 1.7% in under 45 years and 6.7% in 45 years and above.

Conclusions:
The incidence of CRC is increasing in Nepal with significant burden borne by younger age groups. Implementation of healthy lifestyle measures, awareness programs, along with routine screening should be implemented to control the burden of CRC in Nepal.
Social connections and hypertension in women and men: a population-based cross-sectional study of the Canadian Longitudinal Study on Aging
Authors: Hosseini Zeinab , Veenstra Gerry , Khan Nadia A. , Conklin Annalijn I. 
Published: October 2020

Background:
Associations between social ties and hypertension are poorly understood in women and men. We investigated the association between marital status, living arrangement, social network size and social participation and hypertension by sex/gender.

Methods:
Cross-sectional analysis of 28 238 middle-age and old-age adults (45–85 years) was conducted using the baseline Canadian Longitudinal Study on Aging Comprehensive cohort data. Blood pressure (BP) was measured using the automated BpTRU device and hypertension was defined as BP more than 140/90 mmHg, or more than 130/80 mmHg in participants with diabetes, self-reported history or receiving antihypertensive therapy.

Results:
Being nonpartnered, having limited social participation (≤2 social activities per month) or a small social network size was associated with higher odds of having hypertension in women. Odds of hypertension were higher among widowed women [odds ratio 1.33 (95% confidence interval (CI): 1.16, 1.51)] compared with married women. The largest difference in adjusted mean SBP in women was between widowed [3.06 mmHg (95% CI: 2.01, 4.11)], vs. married women. For men, lone-living (vs. coliving) was linked to a lower odds of hypertension [odds ratio 0.85 (95% CI: 0.75, 0.96)] When considering two social ties simultaneously, the adverse associations between nonpartnership (mainly for singles and divorced) and BP were mitigated with increased social participation, especially among women.

Conclusion:
Social ties appear to be more strongly associated with hypertension in middle and older aged women than men. Women who are nonpartnered or who engage in few social activities and men who are coliving represent at risk groups for having hypertension. Healthcare professionals may need to consider these social factors in addressing risk for hypertension and cardiovascular disease prevention.
Dignity
Authors: Mohammadi Fateme , Bijani Mostafa , Cheraghi Fatemeh , Kyle Hazel 
Published: October 2020

One of the most important areas of nursing care delivery is “dignity.” Because of the increase in hospitalized infants in neonatal intensive care units in recent years, this has led to an increased focus on “family care and maternal dignity.” Given the importance of understanding the phenomenon of maternal dignity in order to improve cooperation in the care of their infants and promote family-centered care, this study aims to describe the lived experience of hospitalized mothers of infants within the context of dignity. This is a descriptive phenomenological qualitative research study. Twenty mothers were invited to participate in this study using purposeful sampling. The data were generated through individual, semistructured interviews and field notes were developed during the interviews. Data were analyzed using the Colaizzi method.
Findings of the study were presented in 3 themes: “privacy,” “respecting individual identity,” and “authority,” and 7 additional subthemes. Mothers in this study needed to take care of their infants in an environment where their personal privacy is preserved, their individual identity is respected, and they have sufficient authority in obtaining medical decisions. It is essential that healthcare teams and policy makers of health organizations provide an appropriate supportive environment in terms of promoting mothers' dignity in different dimensions and subsequently improving family-centered care.
Hypercoagulability in Vestibular Schwannoma Surgery
Authors: Muelleman Thomas J. , Alonso Jose , Barnard Zachary R. , Maxwell Anne K. , Mahboubi Hossein , Stefan Michael , Lekovic Gregory P. , Slattery William H. , Brackmann Derald E. 
Published: October 2020

Objective:
Patients with vestibular schwannoma who harbor a genetic predisposition for venous thromboembolism require special consideration when determining optimal therapeutic management. The primary objective of the current study was to provide recommendations on treatment of hypercoagulable patients with vestibular schwannoma through a case series and review of the literature.

Patients:
Two patients who underwent resection of vestibular schwannomas.

Intervention(s):
Surgical resection and diagnostic testing.

Main Outcome Measure(s):
Postoperative venous thromboses.

Results:
One patient who underwent resection of vestibular schwannoma and suffered several postoperative thrombotic complications consistent with a clinical thrombophilia. One patient with known Factor V Leiden deficiency who underwent resection of vestibular schwannoma followed by postoperative chemoprophylaxis with a direct factor Xa inhibitor and experienced an uneventful postoperative course.

Conclusions:
In patients with a known propensity for venous thromboembolism, the skull base surgeon should consider nonsurgical management. If the patient undergoes surgical resection, we recommend careful effort to minimize trauma to the sigmoid sinus. In addition, the surgeon may consider retrosigmoid or middle fossa approaches. Best practice recommendations include the use of pneumatic compression devices, early ambulation, and consideration of postoperative prophylactic anticoagulation in patients with a known genetic predisposition.