bluuebunny/crossref_metadata_2025_split huggingface dataset:
Heritability of DNA methylation in threespine stickleback (Gasterosteus aculeatus)
Authors: Hu Juntao , Smith Sara J , Barry Tegan N , Jamniczky Heather A , Rogers Sean M , Barrett Rowan D H 
Published: February 2021

AbstractEpigenetic mechanisms underlying phenotypic change are hypothesized to contribute to population persistence and adaptation in the face of environmental change. To date, few studies have explored the heritability of intergenerationally stable methylation levels in natural populations, and little is known about the relative contribution of cis- and trans-regulatory changes to methylation variation. Here, we explore the heritability of DNA methylation, and conduct methylation quantitative trait loci (meQTLs) analysis to investigate the genetic architecture underlying methylation variation between marine and freshwater ecotypes of threespine stickleback (Gasterosteus aculeatus). We quantitatively measured genome-wide DNA methylation in fin tissue using reduced representation bisulfite sequencing of F1 and F2 crosses, and their marine and freshwater source populations. We identified cytosines (CpG sites) that exhibited stable methylation levels across generations. We found that additive genetic variance explained an average of 24–35% of the methylation variance, with a number of CpG sites possibly autonomous from genetic control. We also detected both cis- and trans-meQTLs, with only trans-meQTLs overlapping with previously identified genomic regions of high differentiation between marine and freshwater ecotypes. Finally, we identified the genetic architecture underlying two key CpG sites that were differentially methylated between ecotypes. These findings demonstrate a potential role for DNA methylation in facilitating adaptation to divergent environments and improve our understanding of the heritable basis of population epigenomic variation.
Altered Blood Cell Traits Underlie a Major Genetic Locus of Severe COVID-19
Authors: Zhou Jingqi , Sun Yitang , Huang Weishan , Ye Kaixiong 
Published: February 2021

Abstract

Background
The genetic locus 3p21.31 has been associated with severe coronavirus disease 2019 (COVID-19), but the underlying pathophysiological mechanism is unknown.

Methods
To identify intermediate traits associated with the 3p21.31 locus, we first performed a phenome-wide association study (PheWAS) with 923 phenotypes in 310 999 European individuals from the UK Biobank. For genes potentially regulated by the COVID-19 risk variant, we examined associations between their expression and the polygenic score (PGS) of 1263 complex traits in a meta-analysis of 31 684 blood samples. For the prioritized blood cell traits, we tested their associations with age and sex in the same UK Biobank sample.

Results
Our PheWAS highlighted multiple blood cell traits to be associated with the COVID-19 risk variant, including monocyte count and percentage (p = 1.07 × 10–8, 4.09 × 10–13), eosinophil count and percentage (p = 5.73 × 10–3, 2.20 × 10–3), and neutrophil percentage (p = 3.23 × 10–3). The PGS analysis revealed positive associations between the expression of candidate genes and genetically predicted counts of specific blood cells: CCR3 with eosinophil and basophil (p = 5.73 × 10–21, 5.08 × 10–19); CCR2 with monocytes (p = 2.40 × 10–10); and CCR1 with monocytes and neutrophil (p = 1.78 × 10–6, 7.17 × 10–5). Additionally, we found that almost all examined white blood cell traits are significantly different across age and sex groups.

Conclusions
Our findings suggest that altered blood cell traits, especially those of monocyte, eosinophil, and neutrophil, may represent the mechanistic links between the genetic locus 3p21.31 and severe COVID-19. They may also underlie the increased risk of severe COVID-19 in older adults and men.
Glacial isostatic adjustment of the Pacific Coast of North America: the influence of lateral Earth structure
Authors: Yousefi Maryam , Milne Glenn A , Latychev Konstantin 
Published: February 2021

SUMMARYThe Pacific Coast of Central North America is a geodynamically complex region which has been subject to various geophysical processes operating on different timescales. Glacial isostatic adjustment (GIA), the ongoing deformational response of the solid Earth to past deglaciation, is an important geodynamic process in this region. In this study, we apply earth models with 3-D structure to determine if the inclusion of lateral structure can explain the poor performance of 1-D models in this region. Three different approaches are used to construct 3-D models of the Earth structure. For the first approach, we adopt an optimal 1-D viscosity structure from previous work and add lateral variations based on four global seismic shear wave velocity anomalies and two global lithosphere thickness models. The results based on these models indicate that the addition of lateral structure significantly impacts modelled RSL changes, but the data-model fits are not improved. The global seismic models are limited in spatial resolution and so two other approaches were considered to produce higher resolution models of 3-D structure: inserting a regional seismic model into two of the global seismic models and, explicitly incorporating regional structure of the Cascadia subduction zone and vicinity, that is the subducting slab, the overlying mantle wedge and the plate boundary interface. The results associated with these higher resolution models do not reveal any clear improvement in satisfying the RSL observations, suggesting that our estimates of lateral structure are inaccurate and/or the data-model misfits are primarily due to limitations in the adopted ice-loading history. The different realizations of 3-D Earth structure gives useful insight to uncertainty associated with this aspect of the GIA model. Our results indicate that improving constraints on the deglacial history of the southwest sector of the Cordilleran ice sheet is an important step towards developing more accurate of GIA models for this region.
Widening the gap? Unintended consequences of health promotion measures for young people during COVID-19 lockdown
Authors: Alexander Stephanie A , Shareck Martine 
Published: February 2021

SummaryDuring the first wave of the COVID-19 pandemic, global measures preventing the spread of the new coronavirus required most of the population to lockdown at home. This sudden halt to collective life meant that non-essential services were closed and many health promoting activities (i.e. physical activity, school) were stopped in their tracks. To curb the negative health impacts of lockdown measures, activities adapting to this new reality were urgently developed. One form of activity promoted indoor physical activity to prevent the adverse physical and psychological effects of the lockdown. Another form of activity included the rapid development of online learning tools to keep children and youth engaged academically while not attending school. While these health promoting efforts were meant to benefit the general population, we argue that these interventions may have unintended consequences and inadvertently increase health inequalities affecting marginalized youth in particular, as they may not reap the same benefits, both social and physical, from the interventions promoting at-home physical activities or distance learning measures. We elaborate on several interventions and their possible unintended consequences for marginalized youth and suggest several strategies that may mitigate their impact.
Location flexibility in parcel delivery operations: framework and empirical analysis
Authors: Krushinsky Dmitry , Guo Xuezhen , Claassen G D H 
Published: February 2021

Abstract
In traditional parcel delivery operations, customers determine delivery locations and, hence, the performance of a transporter. We exploit this idea and show that customers can improve the efficiency of a transporter by giving the latter flexibility in choosing the delivery locations. Two possible policies to enable this flexibility are presented and evaluated. The first policy, conceptually similar to roaming vehicle routing, is related to the presence of alternative locations. The second policy is related to the possibility of aggregating/skipping some locations. We show that route optimization behind both policies can be modelled via the well-known generalized travelling salesman problem. Extensive computational experiments with real parcel delivery data are performed to evaluate the potential of the presented policies and to obtain insights for possible implementation in daily practice. The experiments show that under certain conditions, the two proposed policies can lead to 15 to 20% improvement in the route length and in extreme yet realistic cases up to 40 to 50%. Consequently, the concept of flexible delivery locations has potential for practice, especially in densely populated areas.
Impact of Vaccination on Haemophilus influenzae Type b Carriage in Healthy Children Less Than 5 Years of Age in an Urban Population in Nepal
Authors: Shrestha Sonu , Stockdale Lisa K , Gautam Madhav C , Gurung Meeru , Feng Shuo , Maskey Pratistha , Kerridge Simon , Kelly Sarah , Voysey Merryn , Pokhrel Bhishma , Rajbhandari Piyush , Thorson Stephen , Khadka Bibek , Shah Ganesh , Scherer Karin S , Kelly Dominic , Murdoch David R , Shrestha Shrijana , Pollard Andrew J 
Published: February 2021

Abstract

Background
Reduction in detection of asymptomatic carriage of Haemophilus influenzae type b (Hib) can be used to assess vaccine impact. In Nepal, routine vaccination against Hib in children at 6, 10, and 14 weeks of age was introduced in 2009. Before vaccine introduction, Hib carriage was estimated at 5.0% among children aged &lt;13 years in Nepal, with higher rates among children under 5. Large-scale evaluation of Hib carriage in children has not been investigated since the introduction of the pentavalent diphtheria-tetanus-pertussis/Hib/hepatitis B (DTP-Hib-HepB) vaccine in Nepal.

Methods
A total of 666 oropharyngeal swabs were collected between August and December 2018 from healthy children between 6 months and 5 years of age attending the vaccination clinic at Patan Hospital, Kathmandu, Nepal. Of these 666 swabs, 528 (79.3%) were tested for Hib by culture. Demographic and vaccination data were collected.

Results
Among 528 swabs tested for Hib, 100% came from fully vaccinated children. No swabs were positive for Hib (95% confidence interval, .0–.7). The absence of Hib in 2018 suggests vaccine-induced protection against Hib carriage 9 years after vaccine introduction.

Conclusions
Following 3 doses of pentavalent DTP-Hib-HepB vaccine, Hib carriage in children under the age of 5 years in Nepal is no longer common. Ongoing high coverage with Hib vaccine in early childhood is expected to maintain protection against Hib disease in Nepal.
Comparison of Culture, Antigen Test, and Polymerase Chain Reaction for Pneumococcal Detection in Cerebrospinal Fluid of Children
Authors: Hasanuzzaman Md , Saha Senjuti , Malaker Roly , Rahman Hafizur , Sajib Mohammad S I , Das Rajib C , Islam Maksuda , Hamer Davidson H , Darmstadt Gary L , Saha Samir K 
Published: February 2021

Abstract

Background
Sensitivity of culture for the detection of Streptococcus pneumoniae is limited by prior antibiotic exposure. Immunochromatographic test (ICT) is highly sensitive and specific for pneumococcal antigen detection in the cerebrospinal fluid (CSF) of meningitis cases. We determined the specificity and sensitivity of culture, ICT, and polymerase chain reaction (PCR) and the effect of antibiotic exposure on their performance.

Methods
CSF specimens from suspected meningitis cases admitted to Dhaka Shishu Hospital, Bangladesh, were tested using culture, ICT and PCR. Additionally, 165 specimens collected from 69 pneumococcal cases after antibiotic treatment were tested.

Results
Of 1883 specimens tested, culture detected 9, quantitative PCR (qPCR) detected 184, and ICT detected 207 pneumococcal cases (including all culture and qPCR positives). In comparison to ICT, sensitivity of culture was 4.4% and of qPCR was 90.6%; both were 100% specific. After antibiotic exposure, culture sensitivity plummeted rapidly; conventional PCR and qPCR sensitivity disappeared after day 6 and 20, respectively. ICT detected pneumococcal antigen for &gt;10 weeks.

Conclusions
While culture provides the most information about bacterial characteristics, in high antibiotic exposure settings, ICT exhibits maximum sensitivity. We recommend culture and ICT as mainstay for pneumococcal diagnosis and surveillance; qPCR can generate additional molecular data where possible.
COVID-19 and immunity: quo vadis?
Authors: Miyasaka Masayuki 
Published: February 2021

Abstract
Understanding the precise nature and durability of protective immunity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is essential in order to gain insight into the pathophysiology of coronavirus disease 2019 (COVID-19) and to develop novel treatment strategies to this disease. Here, I succinctly summarize what is currently known and unknown about the immune response during COVID-19 and discuss whether natural infections can lead to herd immunity.
Habits and Policy: The Social Construction of Foreign Policymaking Processes
Authors: Bertucci Mariano E 
Published: February 2021

AbstractThis article offers an alternative explanation for the processes by which foreign policy is made. It does so across three different countries, across different governments, across issues that had real “blood and treasure” at stake, across different domestic and international contexts, and while holding the target of policy, the United States, constant. Available theories argue that formal political institutions or norms determine who will influence the making of policy and how they will do so. However, Argentina, Brazil, and Chile—countries with strikingly similar formal rules for making foreign policy—have been following, for decades, fundamentally different foreign policymaking processes, and they have been doing so without resorting to any normative justifications. The article contrasts the theoretical expectations of rational choice institutionalism and norm-based arguments on foreign policymaking with a logic of habit not captured by the logics of consequences or appropriateness of rational choice institutionalism and norm-based explanations. The article makes two contributions. First, it furthers the theoretical development of the concept of habit in international relations and offers a means of studying habits empirically. Second, it challenges the assumption that the power of domestic actors in foreign policy is a function of formal institutions or prevailing norms.
Hagiography Unbound: A Theory of Making and Using Holy Media
Authors: Hollander Aaron T 
Published: February 2021

AbstractHagiography is a scholarly category that has been used primarily to group textual sources that represent the lives of Christian saints. This article contends that the utility of hagiography and hagiographical far exceeds this commonplace usage, in terms of both the ways they entail broadly enacted cultural dynamics and their applicability beyond conventional disciplinary expectations of what constitutes representations of saints (or even religious content). The article provides a retheorization along two analytic vectors: (1) framing hagiography in terms of a field of many interconnected media rather than identifying it with texts alone, and (2) studying it in terms of the psychosocial processes (imagination, representation, and appropriation) that generate and mobilize understandings of holiness in the world rather than limiting it to the products that instantiate but do not exhaust these processes.
Small molecule natural products in human nasal/oral microbiota
Authors: Barber Colin Charles , Zhang Wenjun 
Published: February 2021

Abstract
Small molecule natural products are a chemically diverse class of biomolecules that fulfill myriad biological functions, including autoregulation, communication with microbial neighbors and the host, interference competition, nutrient acquisition, and resistance to oxidative stress. Human commensal bacteria are increasingly recognized as a potential source of new natural products, which may provide insight into the molecular ecology of many different human body sites as well as novel scaffolds for therapeutic development. Here, we review the scientific literature on natural products derived from residents of the human nasal/oral cavity, discuss their discovery, biosynthesis, and ecological roles, and identify key questions in the study of these compounds.
Disruption of the Trichoderma reesei gul1 gene stimulates hyphal branching and reduces broth viscosity in cellulase production
Authors: Zhao Qinqin , Liu Qin , Wang Qi , Qin Yuqi , Zhong Yaohua , Gao Liwei , Liu Guodong , Qu Yinbo 
Published: February 2021

Abstract
Hyphal morphology is considered to have a close relationship with the production level of secreted proteins by filamentous fungi. In this study, the gul1 gene, which encodes a putative mRNA-binding protein, was disrupted in cellulase-producing fungus Trichoderma reesei. The hyphae of Δgul1 strain produced more lateral branches than the parent strain. Under the condition for cellulase production, disruption of gul1 resulted in smaller mycelial clumps and significantly lower viscosity of fermentation broth. In addition, cellulase production was improved by 22% relative to the parent strain. Transcriptome analysis revealed that a set of genes encoding cell wall remodeling enzymes as well as hydrophobins were differentially expressed in the Δgul1 strain. The results suggest that the regulatory role of gul1 in cell morphogenesis is likely conserved in filamentous fungi. To our knowledge, this is the first report on the engineering of gul1 in an industrially important fungus.
Comprehensive analysis of DNA mismatch repair-deficient gastric cancer in a Japanese hospital-based population
Authors: Ito Tetsuya , Suzuki Okihide , Kamae Nao , Tamaru Jun-ichi , Arai Tomio , Yamaguchi Tatsuro , Akagi Kiwamu , Eguchi Hidetaka , Okazaki Yasushi , Mochiki Erito , Ishida Hideyuki 
Published: February 2021

Abstract

Background
The attention on mismatch repair-deficient (dMMR) gastric cancer has increased in this era of anti-PD-1 blockade therapy; however, the prevalence and molecular genetics of patients with dMMR gastric cancer have not been completely investigated.

Methods
Immunohistochemistry of MMR proteins (MLH1, MSH2, MSH6 and PMS2) was performed on formalin-fixed paraffin-embedded sections prepared from resected primary gastric cancers of 513 consecutive patients. Genetic and/or epigenetic alterations of the MMR genes were also investigated.

Results
Loss of expression of one or more MMR proteins was observed in 58 patients (11.3%); 54 patients showed loss of MLH1/PMS2, 3 patients showed loss of MLH1/PMS2/MSH6 and 1 patient showed loss of PMS2 alone. Among these 58 patients, 55 showed hypermethylation of the promoter region of MLH1. Genetic testing revealed that the remaining three patients had Lynch syndrome (n = 1) or Lynch-like syndrome (n = 2). A total of 15 patients (25.9% of all patients with dMMR gastric cancer and 2.9% of all patients with gastric cancer), including 11 patients with stage I–III dMMR gastric cancer who had recurrence and 4 patients with stage IV dMMR gastric cancer, are potential candidates for the use of anti-PD-1 blockades.

Conclusions
This is the first study to investigate the frequency and molecular genetic mechanisms of dMMR gastric cancer comprehensively, focusing on the benefit of using PD-1 blockades. Our observations will be beneficial in the clinical practice of metastatic gastric cancer.
The effectiveness comparisons of eugenosedin-A, glibenclamide and pioglitazone on diabetes mellitus induced by STZ/NA and high-fat diet in SHR
Authors: Lin Hui-Li , Cheng Pei-Wen , Tu Yi-Chen , Yeh Bor-Chun , Wu Bin-Nan , Shen Kuo-Ping 
Published: February 2021

Abstract

Objectives
Eugenosedin-A (Eu-A), an adrenergic and serotonergic antagonist, is known to have anti-metabolic syndrome effects. In this study, we evaluated its protective effects against diabetes mellitus (DM) in spontaneous hypertensive rats (SHR) and compared it with two anti-diabetes medications, glibenclamide (Gli) and pioglitazone (Pio).

Methods
We divided 10-week-old SHRs into five groups: a control group fed a normal diet; an untreated DM group induced by injecting the SHRs with STZ/NA and feeding them a high-fat diet (HFD); and three treated groups (after giving STZ/NA and HFD) gavage given with Eu-A, Gli or Pio (5 mg/kg per day) for 4 weeks.

Key findings
The untreated DM group weighed less and had hyperglycaemia, hypoinsulinemia and hyperlipidemia. They were also found to have aberrant glucose-dependent insulin pathways, glucose metabolism and lipid synthesis proteins, while the controls did not. Eu-A, Gli and Pio ameliorated the above biochemical parameters in the treatment groups. Eu-A and Pio, but not Gli, improved hypertension and tachycardia.

Conclusions
Taken together, Eu-A ameliorated DM, hypertension and tachycardia by improving glucose, lipid homeostasis and anti-adrenergic, serotonergic activities. We concluded that Eu-A could be used in the development of an effective agent for controlling DM and its complications.
Primary brachial artery aneurysm with associated basilic vein aneurysm
Authors: Hamdulay Khaleel A , Laws Peter E , Ruiz Carmen M 
Published: February 2021

ABSTRACT
There are but a handful of reported brachial artery aneurysms, the majority of which are pseudoaneurysms or false aneurysms caused by trauma or fistula creation. True or primary brachial artery aneurysms are even more rare, and if they occur, they often do so in isolation. In this case report, we discuss the interesting finding of a large primary brachial aneurysm together with an adjacent aneurysmal basilic vein identified intra-operatively. This presentation was 21 years after the renal transplant and ligation of an arteriovenous fistula in that same arm. It is noteworthy that the fistula was in the forearm and far away from the site of the untouched brachial area.
Meckel’s diverticulitis in a COVID-19 adult
Authors: Marçal André , Marques Rita , Oliveira António , Pinto-de-Sousa João 
Published: February 2021

Abstract
Meckel’s diverticulitis is an unusual cause of acute abdomen condition in adults requiring prompt surgical treatment. We report a case of a 53-year-old male with coronavirus disease 19 (COVID-19), admitted to the emergency department with an acute abdominal pain. A computed tomography scan with intravenous contrast performed on the patient confirmed an inflamed short segment of the small bowel and the presence of a localized free peritoneal fluid. The definitive diagnosis was made intraoperatively, by means of an emergent ileal resection with primary anastomosis, which confirmed Meckel’s diverticulitis. Postoperative evolution was ordinary. The association of COVID-19 with the acute abdomen is found to be weak, therefore surgical consultation is advised to minimize delayed treatment.
Rare case of gigantic ulcerating phyllodes tumour in developed country with a review of the literature
Authors: Seow Yi Th’ng , Kunjuraman Bindu 
Published: February 2021

Abstract
Phyllodes tumour (PT) is a rare type of fibroepithelial breast tumour that can present in a wide spectrum of biological behaviours, accounting for &lt;1% of breast malignancies. Herein, we present a case of a rare gigantic ulcerating PT in a middle-aged woman from regional Western Australia, who presented with a rapidly growing right breast mass. Core biopsy showed spindle cell lesion with differentials being PT of at least borderline variety or metaplastic carcinoma. The ulcerations over the fungating tumour showed heavy growth of Staphylococcus aureus. The treating team subsequently proceeded to right total mastectomy with level 1 and 2 axillary clearance. This report emphasizes the rare presentation of PT, dilemma in investigations and the difficulties in managing non-compliant patient where treatment protocol needs to be modified.