bluuebunny/crossref_metadata_2025 huggingface dataset:
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

Globally, 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

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

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

Jacob 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

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

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

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

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

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.
Clip placement to prevent delayed bleeding after colonic endoscopic mucosal resection (CLIPPER): study protocol for a randomized controlled trial
Authors:   on behalf of the Dutch EMR Study Group, Turan Ayla S. , Moons Leon M. G. , Schreuder Ramon-Michel , Schoon Erik J. , Terhaar sive Droste Jochim S. , Schrauwen Ruud W. M. , Straathof Jan Willem , Bastiaansen Barbara A. J. , Schwartz Matthijs P. , Hazen Wouter L. , Alkhalaf Alaa , Allajar Daud , Hadithi Muhammed , van der Spek Bas W. , Heine Dimitri G. D. N. , Tan Adriaan C. I. T. L. , de Graaf Wilmar , Boonstra Jurjen J. , Voogd Fia J. , Roomer Robert , de Ridder Rogier J. J. , Kievit Wietske , Siersema Peter D. , Didden Paul , van Geenen Erwin J. M.
Published: January 2021

Background

Endoscopic mucosal resection (EMR) for large colorectal polyps is in most cases the preferred treatment to prevent progression to colorectal carcinoma. The most common complication after EMR is delayed bleeding, occurring in 7% overall and in approximately 10% of polyps ≥ 2 cm in the proximal colon. Previous research has suggested that prophylactic clipping of the mucosal defect after EMR may reduce the incidence of delayed bleeding in polyps with a high bleeding risk.

Methods

The CLIPPER trial is a multicenter, parallel-group, single blinded, randomized controlled superiority study. A total of 356 patients undergoing EMR for large (≥ 2 cm) non-pedunculated polyps in the proximal colon will be included and randomized to the clip group or the control group. Prophylactic clipping will be performed in the intervention group to close the resection defect after the EMR with a distance of < 1 cm between the clips. Primary outcome is delayed bleeding within 30 days after EMR. Secondary outcomes are recurrent or residual polyps and clip artifacts during surveillance colonoscopy after 6 months, as well as cost-effectiveness of prophylactic clipping and severity of delayed bleeding.

Discussion

The CLIPPER trial is a pragmatic study performed in the Netherlands and is powered to determine the real-time efficacy and cost-effectiveness of prophylactic clipping after EMR of proximal colon polyps ≥ 2 cm in the Netherlands. This study will also generate new data on the achievability of complete closure and the effects of clip placement on scar surveillance after EMR, in order to further promote the debate on the role of prophylactic clipping in everyday clinical practice.

Trial registration

ClinicalTrials.gov NCT03309683. Registered on 13 October 2017. Start recruitment: 05 March 2018. Planned completion of recruitment: 31 August 2021.
Managing clinical trials during COVID-19: experience from a clinical research facility
Authors: Shiely Frances , Foley Jean , Stone Amy , Cobbe Emma , Browne Shaunagh , Murphy Ellen , Kelsey Maeve , Walsh-Crowley Joanne , Eustace Joseph A.
Published: January 2021

There is a dearth of literature on best practices for managing clinical trials, and little is understood on the role of the clinical trial manager. The COVID-19 pandemic has brought this into focus, and the continuance of clinical trials worldwide has been catapulted into a state of uncertainty as countries enter lockdown to manage the spread of the virus. Participant retention is an ongoing issue in clinical trials, and the concern is that in the current pandemic environment, attrition will be an issue which could potentially jeopardise trial completion. The current situation has necessitated timely problem solving by the trial manager to ensure trials remain open, and most importantly, that participant safety, paramount in clinical trials, is monitored. The purpose of our study is to highlight key issues arising in the management of clinical trials during a pandemic from first-hand experience in a clinical research facility managing both academic and commercial clinical trials. We offer some practical guidance on solution implementation.
Cellular and humoral peritoneal immunity to Mesocestoides vogae metacestode infection in mice
Authors: Mačak Kubašková Terézia , Mudroňová Dagmar , Vargová Miroslava , Reiterová Katarína , Hrčková Gabriela
Published: January 2021

Background

Here,Mesocestoides (M.) vogaeinfection in mice is proposed as a suitable experimental model for studying the immunity in the peritoneal cavity of mice.

Methods

To investigate the kinetics of immune parameters inM. vogae-infected mice, we detected, using flow cytometry, the expression of selected lymphoid and myeloid markers within the peritoneal cell population at day 0, 3, 6, 10, 14, 19, 25, 30 and 35 post-infection. Then, using ELISA, we analyzed the cytokine IFN-γ, TGF-β, IL-4 and IL-10 responses and the levels of anti-M. vogaeIgG and IgM antibodies in the peritoneal lavage fluid. Cells isolated from the peritoneal cavity were subjected to further molecular analysis. To assess cell activation, peritoneal cells were exposed to LPS, and culture supernatants were collected and assayed for the level of cytokines and production of nitrite. Ly6C+ and Ly6G+ cells were isolated using MACS from the peritoneal cells at day 35 post-infection. Both MACS-isolated subsets were co-cultured with preactivated T cells to measure their suppressive capacity. Next, the role of parasite excretory-secretory antigens in induction of CD11b+ myeloid cells with the suppressive phenotype and the production of IL-10 was examined.

Results

In the peritoneal cavity an initial increase of CD11b+Gr-1+F4/80highMHC IIhighcells, NK, NKT cells and CD8+ cytotoxic T cells was observed in the first week of infection. At day 14 post-infection, an increase in the number of myeloid CD11b+Gr-1+ cells was detected, and most of this cell population expressed low levels of F4/80 and MHC II in later stages of infection, suggesting the impairment of antigen-presenting cell functions, probably through the excretory-secretory molecules. Moreover, we confirmed that peritoneal Gr1+ cells (Ly6C+ and Ly6G+ population) are phenotypically and functionally consistent with myeloid-derived suppressor cells. Metacestode infection elicited high levels of IL-10 and upregulated STAT-3 in peritoneal cells. A higher level of IgM suggests that this isotype may be predominant and is involved in the host protection.

Conclusions

Mesocestoides vogaetetrathyridia induced the recruitment of immunosuppressive cell subsets, which may play a key role in the downregulation of immune response in long-term parasitic diseases, and excretory-secretory antigens seem to be the main regulatory factor.

Graphical Abstract
The Dfam community resource of transposable element families, sequence models, and genome annotations
Authors: Storer Jessica , Hubley Robert , Rosen Jeb , Wheeler Travis J. , Smit Arian F.
Published: January 2021

Dfam is an open access database of repetitive DNA families, sequence models, and genome annotations. The 3.0–3.3 releases of Dfam (https://dfam.org) represent an evolution from a proof-of-principle collection of transposable element families in model organisms into a community resource for a broad range of species, and for both curated and uncurated datasets. In addition, releases since Dfam 3.0 provide auxiliary consensus sequence models, transposable element protein alignments, and a formalized classification system to support the growing diversity of organisms represented in the resource. The latest release includes 266,740 new de novo generated transposable element families from 336 species contributed by the EBI. This expansion demonstrates the utility of many of Dfam’s new features and provides insight into the long term challenges ahead for improving de novo generated transposable element datasets.
Association of variably methylated tumour DNA regions with overall survival for invasive lobular breast cancer
Authors: Suman Medha , Dugué Pierre-Antoine , Wong Ee Ming , Joo JiHoon Eric , Hopper John L. , Nguyen-Dumont Tu , Giles Graham G. , Milne Roger L. , McLean Catriona , Southey Melissa C.
Published: January 2021

Background

Tumour DNA methylation profiling has shown potential to refine disease subtyping and improve the diagnosis and prognosis prediction of breast cancer. However, limited data exist regarding invasive lobular breast cancer (ILBC). Here, we investigated the genome-wide variability of DNA methylation levels across ILBC tumours and assessed the association between methylation levels at the variably methylated regions and overall survival in women with ILBC.

Methods

Tumour-enriched DNA was prepared by macrodissecting formalin-fixed paraffin embedded (FFPE) tumour tissue from 130 ILBCs diagnosed in the participants of the Melbourne Collaborative Cohort Study (MCCS). Genome-wide tumour DNA methylation was measured using the HumanMethylation 450K (HM450K) BeadChip array. Variably methylated regions (VMRs) were identified using the DMRcate package in R. Cox proportional hazards regression models were used to assess the association between methylation levels at the ten most significant VMRs and overall survival. Gene set enrichment analyses were undertaken using the web-based tool Metaspace. Replication of the VMR and survival analysis findings was examined using data retrieved from The Cancer Genome Atlas (TCGA) for 168 ILBC cases. We also examined the correlation between methylation and gene expression for the ten VMRs of interest using TCGA data.

Results

We identified 2771 VMRs (P < 10−8) in ILBC tumours. The ten most variably methylated clusters were predominantly located in the promoter region of the genes: ISM1, APC, TMEM101, ASCL2, NKX6, HIST3H2A/HIST3H2BB, HCG4P3, HES5, CELF2 and EFCAB4B. Higher methylation level at several of these VMRs showed an association with reduced overall survival in the MCCS. In TCGA, all associations were in the same direction, however stronger than in the MCCS. The pooled analysis of the MCCS and TCGA data showed that methylation at four of the ten genes was associated with reduced overall survival, independently of age and tumour stage; APC: Hazard Ratio (95% Confidence interval) per one-unit M-value increase: 1.18 (1.02–1.36), TMEM101: 1.23 (1.02–1.48), HCG4P3: 1.37 (1.05–1.79) and CELF2: 1.21 (1.02–1.43). A negative correlation was observed between methylation and gene expression for CELF2 (R = − 0.25, P = 0.001), but not for TMEM101 and APC.

Conclusions

Our study identified regions showing greatest variability across the ILBC tumour genome and found methylation at several genes to potentially serve as a biomarker of survival for women with ILBC.
Gender score development in the Berlin Aging Study II: a retrospective approach
Authors: Nauman Ahmad Tauseef , Behlouli Hassan , Alexander Nicholas , Kendel Friederike , Drewelies Johanna , Mantantzis Konstantinos , Berger Nora , Wagner Gert G. , Gerstorf Denis , Demuth Ilja , Pilote Louise , Regitz-Zagrosek Vera
Published: January 2021

In addition to biological sex, gender, defined as the sociocultural dimension of being a woman or a man, plays a central role in health. However, there are so far few approaches to quantify gender in a retrospective manner in existing study datasets. We therefore aimed to develop a methodology that can be retrospectively applied to assess gender in existing cohorts. We used baseline data from the Berlin Aging Study II (BASE-II), obtained in 2009–2014 from 1869 participants aged 60 years and older. We identified 13 gender-related variables and used them to construct a gender score by using primary component and logistic regression analyses. Of these, nine variables contributed to a gender score: chronic stress, marital status, risk-taking behaviour, personality attributes: agreeableness, neuroticism, extraversion, loneliness, conscientiousness, and level of education. Females and males differed significantly in the distribution of the gender score, but a significant overlap was also found. Thus, we were able to develop a gender score in a retrospective manner from already collected data that characterized participants in addition to biological sex. This approach will allow researchers to introduce the notion of gender retrospectively into a large number of studies.
New evidence for a hydroxylation pathway for anaerobic alkane degradation supported by analyses of functional genes and signature metabolites in oil reservoirs
Authors: Shou Li-Bin , Liu Yi-Fan , Zhou Jing , Liu Zhong-Lin , Zhou Lei , Liu Jin-Feng , Yang Shi-Zhong , Gu Ji-Dong , Mu Bo-Zhong
Published: January 2021

Microbial degradation of recalcitrant alkanes under anaerobic conditions results in the accumulation of heavy oil fraction in oil reservoirs. Hydroxylation of alkanes is an important activation mechanism under anaerobic conditions, but the diversity and distribution of the responsible microorganisms in the subsurface environment are still unclear. The lack of functional gene polymerase chain reaction (PCR) primers and commercially available intermediate degradation chemical compounds are the major obstacles for this research. In this investigation, PCR primers for the ahyA gene (encoding alkane hydroxylase) were designed, evaluated, and improved based on the nucleotide sequences available. Using microbial genomic DNA extracted from oil-contaminated soil and production water samples of oil reservoirs, ahyA gene nucleotide sequences were amplified and retrieved successfully from production water sample Z3-25 of Shengli oilfield. Additionally, the signature biomarker of 2-acetylalkanoic acid was detected in both Shengli and Jiangsu oilfields. These results demonstrate that anaerobic hydroxylation is an active mechanism used by microorganisms to degrade alkanes in oxygen-depleted oil reservoirs. This finding expands the current knowledge of biochemical reactions about alkane degradation in subsurface ecosystems. In addition, the PCR primers designed and tested in this study serve as an effective molecular tool for detecting the microorganisms responsible for anaerobic hydroxylation of alkanes in this and other ecosystems.
Comparative transcriptome analysis revealed differential gene expression in multiple signaling pathways at flowering in polyploid Brassica rapa
Authors: Braynen Janeen , Yang Yan , Yuan Jiachen , Xie Zhengqing , Cao Gangqiang , Wei Xiaochun , Shi Gongyao , Zhang Xiaowei , Wei Fang , Tian Baoming
Published: January 2021

Background

Polyploidy is widespread in angiosperms and has a significant impact on plant evolution, diversity, and breeding program. However, the changes in the flower development regulatory mechanism in autotetraploid plants remains relatively limited. In this study, RNA-seq analysis was used to investigate changes in signaling pathways at flowering in autotetraploid Brassica rapa.

Results

The study findings showed that the key genes such as CO, CRY2, and FT which promotes floral formation were down-regulated, whereas floral transition genes FPF1 and FD were up-regulated in autotetraploid B. rapa. The data also demonstrated that the positive regulators GA1 and ELA1 in the gibberellin’s biosynthesis pathway were negatively regulated by polyploidy in B. rapa. Furthermore, transcriptional factors (TFs) associated with flower development were significantly differentially expressed including the up-regulated CIB1 and AGL18, and the down-regulated AGL15 genes, and by working together such genes affected the expression of the down-stream flowering regulator FLOWERING LOCUS T in polyploid B. rapa. Compared with that in diploids autotetrapoid plants consist of differential expression within the signaling transduction pathway, with 13 TIFY gens up-regulated and 17 genes related to auxin pathway down-regulated.

Conclusion

Therefore, polyploidy is more likely to integrate multiple signaling pathways to influence flowering in B. rapa after polyploidization. In general, the present results shed new light on our global understanding of flowering regulation in polyploid plants during breeding program.
Bias correction for direct spectral estimation from irregularly sampled data including sampling schemes with correlation
Authors: Damaschke Nils , Kühn Volker , Nobach Holger
Published: January 2021

The prediction and correction of systematic errors in direct spectral estimation from irregularly sampled data taken from a stochastic process is investigated. Different sampling schemes are investigated, which lead to such an irregular sampling of the observed process. Both kinds of sampling schemes are considered, stochastic sampling with non-equidistant sampling intervals from a continuous distribution and, on the other hand, nominally equidistant sampling with missing individual samples yielding a discrete distribution of sampling intervals. For both distributions of sampling intervals, continuous and discrete, different sampling rules are investigated. On the one hand, purely random and independent sampling times are considered. This is given only in those cases, where the occurrence of one sample at a certain time has no influence on other samples in the sequence. This excludes any preferred delay intervals or external selection processes, which introduce correlations between the sampling instances. On the other hand, sampling schemes with interdependency and thus correlation between the individual sampling instances are investigated. This is given whenever the occurrence of one sample in any way influences further sampling instances, e.g., any recovery times after one instance, any preferences of sampling intervals including, e.g., sampling jitter or any external source with correlation influencing the validity of samples. A bias-free estimation of the spectral content of the observed random process from such irregularly sampled data is the goal of this investigation.
Energy-efficient hierarchical routing in wireless sensor networks based on fog computing
Authors: Abidoye Ademola Philip , Kabaso Boniface
Published: January 2021

Wireless sensor networks (WSNs) have been recognized as one of the most essential technologies of the twenty-first century. The applications of WSNs are rapidly increasing in almost every sector because they can be deployed in areas where cable and power supply are difficult to use. In the literature, different methods have been proposed to minimize the energy consumption of sensor nodes to prolong WSNs utilization. In this article, we propose an efficient routing protocol for data transmission in WSNs; it is called energy-efficient hierarchical routing protocol for wireless sensor networks based on fog computing. Fog computing is integrated into the proposed scheme due to its capability to optimize the limited power source of WSNs and its ability to scale up to the requirements of the Internet of things applications. In addition, we propose an improved ant colony optimization algorithm that can be used to construct an optimal path for efficient data transmission for sensor nodes. The performance of the proposed scheme is evaluated in comparison with P-SEP, EDCF, and RABACO schemes. The results of the simulations show that the proposed approach can minimize sensor nodes’ energy consumption, data packet losses, and extends the network lifetime. We are aware that in WSNs, the certainty of the sensed data collected by a sensor node can vary due to many reasons such as environmental factors, drained energy, and hardware failures.
Rough fuzzy model based feature discretization in intelligent data preprocess
Authors: Chen Qiong , Huang Mengxing
Published: January 2021

Feature discretization is an important preprocessing technology for massive data in industrial control. It improves the efficiency of edge-cloud computing by transforming continuous features into discrete ones, so as to meet the requirements of high-quality cloud services. Compared with other discretization methods, the discretization based on rough set has achieved good results in many applications because it can make full use of the known knowledge base without any prior information. However, the equivalence class of rough set is an ordinary set, which is difficult to describe the fuzzy components in the data, and the accuracy is low in some complex data types in big data environment. Therefore, we propose a rough fuzzy model based discretization algorithm (RFMD). Firstly, we use fuzzyc-means clustering to get the membership of each sample to each category. Then, we fuzzify the equivalence class of rough set by the obtained membership, and establish the fitness function of genetic algorithm based on rough fuzzy model to select the optimal discrete breakpoints on the continuous features. Finally, we compare the proposed method with the discretization algorithm based on rough set, the discretization algorithm based on information entropy, and the discretization algorithm based on chi-square test on remote sensing datasets. The experimental results verify the effectiveness of our method.
Contradictions in the promotion of publishing academic and scientific journal articles, and the inability to cope with the new coronavirus (COVID-19)
Authors: Jalali Rostam , Hosseinian-Far Amin , Mohammadi Masoud
Published: January 2021

Background

Translating research into practice is a central priority within the National Institutes of Health (NIH) Roadmap. The underlying aim of the NIH Roadmap is to accelerate the movement of scientific findings into practical health care provisions through translational research.

Main text

Despite the advances in health sciences, emerging infectious diseases have become more frequent in recent decades. Furthermore, emerging and reemerging pathogens have led to several global public health challenges. A question, and to an extent a concern, arises from this: Why our health care system is experiencing several challenges in encountering the coronavirus outbreak, despite the ever-growing advances in sciences, and the exponential rise in the number of published articles in the first quartile journals and even the ones among the top 1%?

Conclusion

Two responses could be potentially provided to the above question: First, there seems to be a significant gap between our theoretical knowledge and practice. And second that many scholars and scientists publish papers only to have a longer list of publications, and therefore publishing is viewed as a personal objective, rather than for improving communities’ public health.
Economic analysis of integrated vegetable–poultry production systems in the Babati District of Tanzania
Authors: Habiyaremye Naphtal , Ochieng Justus , Heckelei Thomas
Published: January 2021

Background

Integrated vegetable–poultry production system has recently attracted attention both from the scientific and policy making communities for its potential contribution to food security as well as the opportunities it offers in improving the livelihoods of smallholder farmers in Tanzania. Despite the efforts made, its benefits and costs in heterogeneous and real-world settings are not fully understood. Despite the promising design of the vegetable–poultry production system, rather little is known of its profitability and its contribution to better living conditions of rural households in different real-world settings. The same applies regarding the knowledge on factors influencing the decision to adopt such an integrated system.

Methods

Using cross-sectional data collected from 250 households in Babati district of Tanzania, we employ a gross margin analysis and a logit model to evaluate the profitability and to investigate the factors influencing the decision to integrate vegetable and poultry production systems.

Results

We find that the integrated vegetable–poultry production system is more profitable than vegetable farming alone and the profitability increases as the poultry flock size increases. An integrating household should keep 18 birds to get significant higher profit than non-integrator. Furthermore, gender and education level of the household head, awareness of integration benefits, land owned, household size, off-farm income, and total income received by the household influence the decision to integrate vegetable and poultry.

Conclusion

The study strongly promotes the integration of vegetable–poultry production system and highlights the influence of gender and awareness of integration benefits on the decision to integrate vegetable and poultry. Hence, the policy implication is to empower women and provide capacity building through training and extension services such as provision of affordable and improved vegetable seeds and poultry breeds.
Experimental Investigation of the Mechanical Behaviour of Wall–Beam–Strut Joints for Prefabricated Underground Construction
Authors: Liu Tingjin , Lu Jiandong , Wang Di , Liu Hongyuan
Published: January 2021

Prefabricated construction is becoming increasingly prevalent, however, it is rarely applied in underground constructions, except for tunnel linings, due to the difficulties that arise in jointing various prefabricated components in underground conditions. To solve the vertical location problem of embedded mechanical couplers during the construction of wall–beam–strut joints for a prefabricated metro station, a new connection using welded steel plates is proposed. In this paper, four full-scale specimens of wall–beam–strut joints connected using welded steel plates and mechanical couplers were experimentally tested under monotonic and low-reversed cyclic loading conditions. The testing results were analysed in terms of the ultimate bearing capacity, failure mode, hysteresis, skeleton curve, stiffness degradation, energy dissipation and strain of the reinforcement bars. Notably, the two kinds of joints had similar ultimate bearing capacities and failure modes, but the crack distributions on the tops of the waler beams were different. For the specimens with the welded steel plate connection, tensile horizontal cracks first appeared on the top surface of the beam, where the welded steel plate was located, and then coalesced gradually; however, this cracking pattern was not observed during the experimental test of the specimens connected with the mechanical couplers. Furthermore, it was determined that the energy dissipation and ductility of the welded steel plate connection were better than those of the mechanical coupler connected joint, because the steel plate could redistribute the internal force in the joint and increase the stiffness. It was concluded that the proposed welded steel plate connection could be more favourable than the mechanical coupler connection in the construction of a prefabricated metro station in Guangzhou. Moreover, the results obtained from these experiments could provide guidelines for the corresponding connections employed in underground-prefabricated structures.