bluuebunny/crossref_metadata_2025_split huggingface dataset:
Quantifying individual variability in exposure risk to mosquito bites in the Cascades region, Burkina Faso
Authors: Guglielmo Federica , Sanou Antoine , Churcher Thomas , Ferguson Heather M. , Ranson Hilary , Sherrard-Smith Ellie 
Published: January 2021

AbstractBackgroundThe Cascades region, Burkina Faso, has a high malaria burden despite reported high insecticide-treated mosquito net (ITN) use. Human and vector activities outside the hours when indoor interventions offer direct protection from infectious bites potentially increase exposure risk to bites from malaria-transmittingAnophelesmosquitoes. This work investigated the degree of variation in human behaviour both between individuals and through time (season) to quantify how it impacts exposure to malaria vectors.MethodsPatterns in human overnight activity (18:00–06:00) to quantify time spent using an ITN across 7 successive nights in two rural communities, Niakore (N = 24 participants) and Toma (71 participants), were observed in the dry and rainy seasons, between 2017 and 2018. Hourly human landingAnophelesmosquito catches were conducted in Niakore specifically, and Cascades region generally, between 2016 and 2017. Data were statistically combined to estimate seasonal variation in time spent outdoors andAnophelesbites received per person per night (bpppn).ResultsSubstantial variability in exposure to outdoorAnophelesbites was detected within and between communities across seasons. In October, whenAnophelesdensities are highest, an individual’s risk ofAnophelesbites ranged from 2.2 to 52.2 bites per person per night (bpppn) within the same week with variable risk dependent on hours spent indoors. Comparably higher outdoor human activity was observed in April and July but, due to lowerAnophelesdensities estimated, bpppn were 0.2–4.7 and 0.5–32.0, respectively. Males and people aged over 21 years were predicted to receive more bites in both sentinel villages.ConclusionThis work presents one of the first clear descriptions of the degree of heterogeneity in time spent outdoors between people and across the year. Appreciation of sociodemographic, cultural and entomological activities will help refine approaches to vector control.
Blending an implementation science framework with principles of proportionate universalism to support physical activity promotion in primary healthcare while addressing health inequities
Authors: Klepac Pogrmilovic Bojana , Linke Sarah , Craike Melinda 
Published: January 2021

AbstractGlobally, insufficient physical activity (PA) is one of the main risk factors for premature mortality. Although insufficient PA is prevalent in nearly every demographic, people with socio-economic disadvantage participate in lower levels of PA than those who are more affluent, and this contributes to widening health inequities. PA promotion interventions in primary healthcare are effective and cost effective, however they are not widely implemented in practice. Further, current approaches that adopt a ‘universal’ approach to PA promotion do not consider or address the additional barriers experienced by people who experience socioeconomic disadvantages. To address the research to policy and practice gap, and taking Australia as a case study, this commentary proposes a novel model which blends an implementation science framework with the principles of proportionate universalism. Proportionate universalism is a principle suggesting that health interventions and policies need to be universal, not targeted, but with intensity and scale proportionate to the level of social need and/or disadvantage. Within this model, we propose interrelated and multi-level evidence-based policies and strategies to support PA promotion in primary healthcare while addressing health inequities. The principles outlined in the new model which blends proportionate (Pro) universalism principles and Practical, Robust Implementation and Sustainability Model (PRISM), ‘ProPRISM’ can be applied to the implementation of PA promotion interventions in health care settings in other high-income countries. Future studies should test the model and provide evidence of its effectiveness in improving implementation and patient health outcomes and cost-effectiveness. There is potential to expand the proposed model to other health sectors (e.g., secondary and tertiary care) and to address other chronic disease risk factors such as unhealthy diet, smoking, and alcohol consumption. Therefore, this approach has the potential to transform the delivery of health care to a prevention-focused health service model, which could reduce the prevalence and burden of chronic disease and health care costs in high-income countries.
Acute colitis during chronic experimental traumatic brain injury in mice induces dysautonomia and persistent extraintestinal, systemic, and CNS inflammation with exacerbated neurological deficits
Authors: Hanscom Marie , Loane David J. , Aubretch Taryn , Leser Jenna , Molesworth Kara , Hedgekar Nivedita , Ritzel Rodney M. , Abulwerdi Gelareh , Shea-Donohue Terez , Faden Alan I. 
Published: January 2021

Abstract
Background
Disruptions of brain-gut axis have been implicated in the progression of a variety of gastrointestinal (GI) disorders and central nervous system (CNS) diseases and injuries, including traumatic brain injury (TBI). TBI is a chronic disease process characterized by persistent secondary injury processes which can be exacerbated by subsequent challenges. Enteric pathogen infection during chronic TBI worsened cortical lesion volume; however, the pathophysiological mechanisms underlying the damaging effects of enteric challenge during chronic TBI remain unknown. This preclinical study examined the effect of intestinal inflammation during chronic TBI on associated neurobehavioral and neuropathological outcomes, systemic inflammation, and dysautonomia.

Methods
Dextran sodium sulfate (DSS) was administered to adult male C57BL/6NCrl mice 28 days following craniotomy (Sham) or TBI for 7 days to induce intestinal inflammation, followed by a return to normal drinking water for an additional 7 to 28 days for recovery; uninjured animals (Naïve) served as an additional control group. Behavioral testing was carried out prior to, during, and following DSS administration to assess changes in motor and cognitive function, social behavior, and mood. Electrocardiography was performed to examine autonomic balance. Brains were collected for histological and molecular analyses of injury lesion, neurodegeneration, and neuroinflammation. Blood, colons, spleens, mesenteric lymph nodes (mLNs), and thymus were collected for morphometric analyses and/or immune characterization by flow cytometry.

Results
Intestinal inflammation 28 days after craniotomy or TBI persistently induced, or exacerbated, respectively, deficits in fine motor coordination, cognition, social behavior, and anxiety-like behavior. Behavioral changes were associated with an induction, or exacerbation, of hippocampal neuronal cell loss and microglial activation in Sham and TBI mice administered DSS, respectively. Acute DSS administration resulted in a sustained systemic immune response with increases in myeloid cells in blood and spleen, as well as myeloid cells and lymphocytes in mesenteric lymph nodes. Dysautonomia was also induced in Sham and TBI mice administered DSS, with increased sympathetic tone beginning during DSS administration and persisting through the first recovery week.

Conclusion
Intestinal inflammation during chronic experimental TBI causes a sustained systemic immune response and altered autonomic balance that are associated with microglial activation, increased neurodegeneration, and persistent neurological deficits.
An analytic perspective of a mixed methods study during humanitarian crises in South Sudan: translating facility- and community-based newborn guidelines into practice
Authors: Sami Samira , Amsalu Ribka , Dimiti Alexander , Jackson Debra , Kenneth Kemish , Kenyi Solomon , Meyers Janet , Mullany Luke C. , Scudder Elaine , Tomczyk Barbara , Kerber Kate 
Published: January 2021

Abstract
Background
In South Sudan, the civil war in 2016 led to mass displacement in Juba that rapidly spread to other regions of the country. Access to health care was limited because of attacks against health facilities and workers and pregnant women and newborns were among the most vulnerable. Translation of newborn guidelines into public health practice, particularly during periods of on-going violence, are not well studied during humanitarian emergencies. During 2016 to 2017, we assessed the delivery of a package of community- and facility-based newborn health interventions in displaced person camps to understand implementation outcomes. This case analysis describes the challenges encountered and mitigating strategies employed during the conduct of an original research study.

Discussion
Challenges unique to conducting research in South Sudan included violent attacks against humanitarian aid workers that required research partners to modify study plans on an ongoing basis to ensure staff and patient safety. South Sudan faced devastating cholera and measles outbreaks that shifted programmatic priorities. Costs associated with traveling study staff and transporting equipment kept rising due to hyperinflation and, after the July 2016 violence, the study team was unable to convene in Juba for some months to conduct refresher trainings or monitor data collection. Strategies used to address these challenges were: collaborating with non-research partners to identify operational solutions; maintaining a locally-based study team; maintaining flexible budgets and timelines; using mobile data collection to conduct timely data entry and remote quality checks; and utilizing a cascade approach for training field staff.

Conclusions
The case analysis provides lessons that are applicable to other humanitarian settings including the need for flexible research methods, budgets and timelines; innovative training and supervision; and a local research team with careful consideration of sociopolitical factors that impact their access and safety. Engagement of national and local stakeholders can ensure health services and data collection continue and findings translate to public health action, even in contexts facing severe and unpredictable insecurity.
The nuclear lamina is a hub for the nuclear function of Jacob
Authors: Samer Sebastian , Raman Rajeev , Laube Gregor , Kreutz Michael R. , Karpova Anna 
Published: January 2021

AbstractJacob is a synapto-nuclear messenger protein that couples NMDAR activity to CREB-dependent gene expression. In this study, we investigated the nuclear distribution of Jacob and report a prominent targeting to the nuclear envelope that requires NMDAR activity and nuclear import. Immunogold electron microscopy and proximity ligation assay combined with STED imaging revealed preferential association of Jacob with the inner nuclear membrane where it directly binds to LaminB1, an intermediate filament and core component of the inner nuclear membrane (INM). The association with the INM is transient; it involves a functional nuclear export signal in Jacob and a canonical CRM1-RanGTP-dependent export mechanism that defines the residing time of the protein at the INM. Taken together, the data suggest a stepwise redistribution of Jacob within the nucleus following nuclear import and prior to nuclear export.
The CXCL12gamma chemokine immobilized by heparan sulfate on stromal niche cells controls adhesion and mediates drug resistance in multiple myeloma
Authors: Ren Zemin , Lantermans Hildo , Kuil Annemieke , Kraan Willem , Arenzana-Seisdedos Fernando , Kersten Marie José , Spaargaren Marcel , Pals Steven T. 
Published: January 2021

Abstract
Background
The survival and proliferation of multiple myeloma (MM) cells in the bone marrow (BM) critically depend on interaction with stromal cells expressing the chemokine CXCL12. CXCL12 regulates the homing to the BM niche by mediating the transendothelial migration and adhesion/retention of the MM cells. The gamma isoform of CXCL12 (CXCL12γ) has been reported to be highly expressed in mouse BM and to show enhanced biological activity compared to the ‘common’ CXCL12α isoform, mediated by its unique extended C-terminal domain, which binds heparan sulfate proteoglycans (HSPGs) with an extraordinary high affinity.
Here, we investigated the expression of CXCL12γ in human BM and studied its functional role in the interaction of MM cells with BM stromal cells (BMSCs).

Methods
We assessed CXCL12γ mRNA and protein expression by human BMSCs using qPCR, flow cytometry, and immunohistochemistry. CRISPR-Cas9 was employed to delete CXCL12γ and the heparan sulfate (HS) co-polymerase EXT1 in BMSCs. To study the functional roles of BMSC-derived CXCL12γ and HSPGs in the interaction of MM cells with BMSCs cells, MM cell lines and primary MM cells were co-cultured with BMSCs.

Results
We observed that CXCL12γ is expressed in situ by reticular stromal cells in both normal and MM BM, as well as by primary BMSC isolates and BMSC lines. Importantly, upon secretion, CXCL12γ, unlike the CXCL12α isoform, was retained on the surface of BMSCs. This membrane retention of CXCL12γ is HSPG mediated, since it was completely annulated by CRISPR-Cas9-mediated deletion of the HS co-polymerase EXT1. CXCL12γ expressed by BMSCs and membrane-retained by HSPGs supported robust adhesion of MM cells to the BMSCs. Specific genetic deletion of either CXCL12γ or EXT1 significantly attenuated the ability of BMSCs to support MM cell adhesion and, in addition, impaired their capacity to protect MM cells from bortezomib-induced cell death.

Conclusions
We show that CXCL12γ is expressed by human BMSCs and upon secretion is retained on their cell surface by HSPGs. The membrane-bound CXCL12γ controls adhesion of MM cells to the stromal niche and mediates drug resistance. These findings designate CXCL12γ and associated HSPGs as partners in mediating MM–niche interaction and as potential therapeutic targets in MM.
Pre-hospital critical care management of severe hypoxemia in victims of Covid-19: a case series
Authors: Mæhlen Jens Otto , Mikalsen Roger , Heimdal Hans Julius , Rehn Marius , Hagemo Jostein S. , Ottestad William 
Published: January 2021

Abstract
Objective
Despite critical hypoxemia, Covid-19 patients may present without proportional signs of respiratory distress. We report three patients with critical respiratory failure due to Covid-19, in which all presented with severe hypoxemia refractory to supplemental oxygen therapy. We discuss possible strategies for ventilatory support in the emergency pre-hospital setting, and point out some pitfalls regarding the management of these patients. Guidelines for pre-hospital care of critically ill Covid-19 patients cannot be established based on the current evidence base, and we have to apply our understanding of respiratory physiology and mechanics in order to optimize respiratory support.

Methods
Three cases with similar clinical presentation were identified within the Norwegian national helicopter emergency medical service (HEMS) system. The HEMS units are manned by a consultant anaesthesiologist.
Patient’s next of kin and the Regional committee for medical and health research ethics approved the publication of this report.

Conclusion
Patients with Covid-19 and severe hypoxemia may pose a considerable challenge for the pre-hospital emergency medical services. Intubation may be associated with a high risk of complications in these patients and should be carried out with diligence when considered necessary. The following interventions are worth considering in Covid-19 patients with refractory hypoxemia before proceeding to intubation. First, administering oxygen via a tight fitting BVM with an oxygen flow rate that exceeds the patient’s ventilatory minute volume. Second, applying continuous positive airway pressure, while simultaneously maintaining a high FiO2. Finally, assuming the patient is cooperative, repositioning to prone position.
Risk factors for severity of thrombocytopenia in full term infants: a single center study
Authors: Saber Amira M. , Aziz Shereen P. , Almasry Al Zahraa E. , Mahmoud Ramadan A. 
Published: January 2021

Abstract
Background
Neonatal thrombocytopenia (NT) (platelet count < 150 × 109/L) is a common finding in the neonatal intensive care unit (NICU). The main aim of this study was to assess the prevalence, risk factors, and outcomes of severe NT in full term (FT) infants.

Methods
During the study period, all FT infants who met the inclusion criteria for NT on two occasions were included. Maternal data, such as maternal age, weight, gestational age, mode of delivery, and history of systemic diseases, including diabetes mellitus, pre-eclampsia, systemic lupus erythematosus, and immune thrombocytopenic purpura, were recorded. Furthermore, neonatal data, such as gender, neonatal weight, causes/duration of admission, types of respiratory support used, complete blood count measurements, and outcomes for neonates admitted to the NICU, were recorded.

Results
In total, 55 FT infants with NT met the inclusion criteria, and 29 (52.73%) cases had severe NT. The most common cause of NT was neonatal sepsis (20 cases, 36.35%), followed by a postoperative state (5 cases, 9.09%). Moreover, in cases of positive blood cultures, the most commonly isolated organism was Escherichia coli (6 cases, 10.90%), followed by Klebsiella (5 cases, 9.09%). Cases of severe NT needed more platelet transfusions (P = 0.001) and had higher rates of mortality (P = 0.001) when compared to cases of mild/moderate NT associated with signs of bleeding and pulmonary/intraventricular hemorrhage (IVH) (P = 0.001).

Conclusion
Severe NT compared to mild/moderate NT, associated with signs of bleeding and pulmonary/IVH, needed more platelet transfusions, and had increased mortality. Further research is needed to explain which of these complications related to severity of thrombocytopenia or were associated with original disease of the babies.
Advanced adenomas may be a red flag for hereditary cancer syndromes
Authors: Patel Swati G. , Hampel Heather , Smith Derek , Gao Dexiang , Cockburn Myles , Kastrinos Fay 
Published: January 2021

Abstract
Background
16–25% of colorectal cancers (CRCs) diagnosed under age 50 are associated with hereditary cancer syndromes. Advanced adenomas are considered precursors to CRC. Although polyp removal prevents cancer, polypectomy does not change underlying genetic risk. Patients with isolated advanced polyps do not currently qualify for genetic testing unless they have a personal or family history of cancer.

Aim
Describe the prevalence of hereditary cancer syndromes among patients with advanced colorectal polyps.

Methods
We performed a single center retrospective review from 2015 to 2019 of patients who underwent germline genetic testing with indication for testing listed as colorectal polyp. We excluded patients with a personal history of CRC and those with ≥10 cumulative polyps. We collected patient demographics, polyp characteristics, family history data and genetic testing results from the medical record. Discrete variables were reported as frequency and percentages and continuous variables reported as mean with range.

Results
A total of 42 patients underwent genetic testing due to a personal history of advanced adenoma. 17% of patients met current genetic testing criteria. All patients underwent multi-gene panel testing. Two patients (4.8%) had a germline pathogenic mutation (one in MLH1 and one in CHEK2). The patient with an MLH1 mutation met current criteria for genetic testing (PREMM5 score 5.8), however the patient with the CHEK2 mutation did not. Both mutation carriers had a personal history of synchronous or metachronous advanced adenomas. 38% had a variant of uncertain significance.

Conclusions
5% of patients with advanced adenomas in our retrospective series had a pathogenic germline mutation in a cancer predisposition gene. Though the patient with a pathogenic mutation in MLH1 met current clinical criteria for genetic testing, this was not recognized prior to referral; he was referred based on a personal history of advanced adenoma. Advanced polyps may be a red flag to identify patients who are at risk for hereditary cancer syndromes.
Conserved sequence motifs in human TMTC1, TMTC2, TMTC3, and TMTC4, new O-mannosyltransferases from the GT-C/PMT clan, are rationalized as ligand binding sites
Authors: Eisenhaber Birgit , Sinha Swati , Jadalanki Chaitanya K. , Shitov Vladimir A. , Tan Qiao Wen , Sirota Fernanda L. , Eisenhaber Frank 
Published: January 2021

Abstract
Background
The human proteins TMTC1, TMTC2, TMTC3 and TMTC4 have been experimentally shown to be components of a new O-mannosylation pathway. Their own mannosyl-transferase activity has been suspected but their actual enzymatic potential has not been demonstrated yet. So far, sequence analysis of TMTCs has been compromised by evolutionary sequence divergence within their membrane-embedded N-terminal region, sequence inaccuracies in the protein databases and the difficulty to interpret the large functional variety of known homologous proteins (mostly sugar transferases and some with known 3D structure).

Results
Evolutionary conserved molecular function among TMTCs is only possible with conserved membrane topology within their membrane-embedded N-terminal regions leading to the placement of homologous long intermittent loops at the same membrane side. Using this criterion, we demonstrate that all TMTCs have 11 transmembrane regions. The sequence segment homologous to Pfam model DUF1736 is actually just a loop between TM7 and TM8 that is located in the ER lumen and that contains a small hydrophobic, but not membrane-embedded helix. Not only do the membrane-embedded N-terminal regions of TMTCs share a common fold and 3D structural similarity with subgroups of GT-C sugar transferases. The conservation of residues critical for catalysis, for binding of a divalent metal ion and of the phosphate group of a lipid-linked sugar moiety throughout enzymatically and structurally well-studied GT-Cs and sequences of TMTCs indicates that TMTCs are actually sugar-transferring enzymes. We present credible 3D structural models of all four TMTCs (derived from their closest known homologues 5ezm/5f15) and find observed conserved sequence motifs rationalized as binding sites for a metal ion and for a dolichyl-phosphate-mannose moiety.

Conclusions
With the results from both careful sequence analysis and structural modelling, we can conclusively say that the TMTCs are enzymatically active sugar transferases belonging to the GT-C/PMT superfamily. The DUF1736 segment, the loop between TM7 and TM8, is critical for catalysis and lipid-linked sugar moiety binding. Together with the available indirect experimental data, we conclude that the TMTCs are not only part of an O-mannosylation pathway in the endoplasmic reticulum of upper eukaryotes but, actually, they are the sought mannosyl-transferases.