bluuebunny/crossref_metadata_2025_split huggingface dataset:
Chromatin state dynamics confers specific therapeutic strategies in enhancer subtypes of colorectal cancer
Authors: Orouji Elias , Raman Ayush T , Singh Anand K , Sorokin Alexey , Arslan Emre , Ghosh Archit K , Schulz Jonathan , Terranova Christopher , Jiang Shan , Tang Ming , Maitituoheti Mayinuer , Callahan Scot C , Barrodia Praveen , Tomczak Katarzyna , Jiang Yingda , Jiang Zhiqin , Davis Jennifer S , Ghosh Sukhen , Lee Hey Min , Reyes-Uribe Laura , Chang Kyle , Liu Yusha , Chen Huiqin , Azhdarinia Ali , Morris Jeffrey , Vilar Eduardo , Carmon Kendra S , Kopetz Scott E , Rai Kunal 
Published: June 2021

ObjectiveEnhancer aberrations are beginning to emerge as a key epigenetic feature of colorectal cancers (CRC), however, a comprehensive knowledge of chromatin state patterns in tumour progression, heterogeneity of these patterns and imparted therapeutic opportunities remain poorly described.DesignWe performed comprehensive epigenomic characterisation by mapping 222 chromatin profiles from 69 samples (33 colorectal adenocarcinomas, 4 adenomas, 21 matched normal tissues and 11 colon cancer cell lines) for six histone modification marks: H3K4me3 for Pol II-bound and CpG-rich promoters, H3K4me1 for poised enhancers, H3K27ac for enhancers and transcriptionally active promoters, H3K79me2 for transcribed regions, H3K27me3 for polycomb repressed regions and H3K9me3 for heterochromatin.ResultsWe demonstrate that H3K27ac-marked active enhancer state could distinguish between different stages of CRC progression. By epigenomic editing, we present evidence that gains of tumour-specific enhancers for crucial oncogenes, such asASCL2andFZD10,was required for excessive proliferation. Consistently, combination of MEK plus bromodomain inhibition was found to have synergistic effects in CRC patient-derived xenograft models. Probing intertumour heterogeneity, we identified four distinct enhancer subtypes (EPIgenome-based Classification, EpiC), three of which correlate well with previously defined transcriptomic subtypes (consensus molecular subtypes, CMSs). Importantly, CMS2 can be divided into two EpiC subgroups with significant survival differences. Leveraging such correlation, we devised a combinatorial therapeutic strategy of enhancer-blocking bromodomain inhibitors with pathway-specific inhibitors (PARPi, EGFRi, TGFβi, mTORi and SRCi) for EpiC groups.ConclusionOur data suggest that the dynamics of active enhancer underlies CRC progression and the patient-specific enhancer patterns can be leveraged for precision combination therapy.
Homozygous mutation in MCM7 causes autosomal recessive primary microcephaly and intellectual disability
Authors: Ravindran Ethiraj , Gutierrez de Velazco Cynthia , Ghazanfar Ali , Kraemer Nadine , Zaqout Sami , Waheed Abdul , Hanif Mohsan , Mughal Sadia , Prigione Alessandro , Li Na , Fang Xiang , Hu Hao , Kaindl Angela M 
Published: June 2021

BackgroundMinichromosomal maintenance (MCM) complex components 2, 4, 5 and 6 have been linked to human disease with phenotypes including microcephaly and intellectual disability. The MCM complex has DNA helicase activity and is thereby important for the initiation and elongation of the replication fork and highly expressed in proliferating neural stem cells.MethodsWhole-exome sequencing was applied to identify the genetic cause underlying the neurodevelopmental disease of the index family. The expression pattern of Mcm7 was characterised by performing quantitative real-time PCR, in situ hybridisation and immunostaining. To prove the disease-causative nature of identified MCM7, a proof-of-principle experiment was performed.ResultsWe reported that the homozygous missense variant c.793G>A/p.A265T (g.7:99695841C>T, NM_005916.4) in MCM7 was associated with autosomal recessive primary microcephaly (MCPH), severe intellectual disability and behavioural abnormalities in a consanguineous pedigree with three affected individuals. We found concordance between the spatiotemporal expression pattern of Mcm7 in mice and a proliferative state: Mcm7 expression was higher in early mouse developmental stages and in proliferative zones of the brain. Accordingly, Mcm7/MCM7 levels were detectable particularly in undifferentiated mouse embryonal stem cells and human induced pluripotent stem cells compared with differentiated neurons. We further demonstrate that the downregulation of Mcm7 in mouse neuroblastoma cells reduces cell viability and proliferation, and, as a proof-of-concept, that this is counterbalanced by the overexpression of wild-type but not mutant MCM7.ConclusionWe report mutations of MCM7 as a novel cause of autosomal recessive MCPH and intellectual disability and highlight the crucial function of MCM7 in nervous system development.
Reheating in small-field inflation on the brane: the swampland criteria and observational constraints in light of the PLANCK 2018 results
Authors: Osses Constanza , Videla Nelson , Panotopoulos Grigoris 
Published: June 2021

AbstractWe study cosmological inflation and its dynamics in the framework of the Randall–Sundrum II brane model. In particular, we analyze in detail four representative small-field inflationary potentials, namely Natural inflation, Hilltop inflation, Higgs-like inflation, and Exponential SUSY inflation, each characterized by two mass scales. We constrain the parameters for which a viable inflationary Universe emerges using the latest PLANCK results. Furthermore, we investigate whether or not those models in brane cosmology are consistent with the recently proposed Swampland Criteria, and give predictions for the duration of reheating as well as for the reheating temperature after inflation. Our results show that (i) the distance conjecture is satisfied, (ii) the de Sitter conjecture and its refined version may be avoided, and (iii) the allowed range for the five-dimensional Planck mass, $$M_5$$

M
5

, is found to be $$10^5\,\text {TeV}\lesssim M_5\lesssim 10^{12}\,\text {TeV}$$

10
5

TeV
≲

M
5

≲

10
12

TeV

. Our main findings indicate that non-thermal leptogenesis cannot work within the framework of RS-II brane cosmology, at least for the inflationary potentials considered here.
Prevalence of Food Insecurity and Its Associated Factors among Adult People with Human Immunodeficiency Virus in Ethiopia: A Systematic Review and Meta-Analysis
Authors: Hidru Hagos Degefa , Gebremedhine Haftay , Gebretsadik Alem , Teame Hirut , Negash Hadush , Mengesha Meresa Berwo 
Published: June 2021

Background. Food insecurity is the shortage of both the quantity and quality of food and a negative impact on the overall nutritional and health status of people with human immunodeficiency virus (HIV). Ethiopia is intensely affected by food insecurity which is about 87.4% of adult people living with human immuno deficiency virus (HIV) are still facing shortage to have access to safe, sufficient, and nutritious food for themselves and their family. However, there is no concrete scientific evidence established at the national level in Ethiopia. Hence, this review gave special emphasis on adult people with human immunodeficiency virus (HIV) to estimate the pooled prevalence of food insecurity and its associated factor at the national level in Ethiopia. Methods. Studies were retrieved from selected electronic data bases, including PubMed/Medlin, Cochrane library, Sciences Direct, Google, and Google Scholar. Random-effects model meta-analysis was used to estimate the pooled prevalence of food insecurity and its associated factors at 95% confidence interval with odds ratio (OR) using statistical

R

-software version 3.6.1. Moreover, quality appraisal of the included studies, publication bias was checked using the funnel symmetry test, and heterogeneity was checked using forest plot and inverse variance square (

I

2

). The searches were restricted to articles published in the English language only, and Medical Subject Headings (MeSH terms) was used to help expand the search in advanced PubMed search. Result. A total of 650 articles were identified through the initial search of which 20 studies were included in the final review yielding a total sample size of 7,797 adult people with human immunodeficiency virus (HIV). The pooled prevalence of food insecurity was 52% (95% CI, 40%, 63%). Cluster of

differentiation

4

CD
4

count
<
350

cell
/
m

m

3

[

AOR
=
1.29

(95% CI, 1.08, 1.54)], develop opportunistic infection [

AOR
=
4.09

(95% CI, 2.47, 6.78)], rural residence [

AOR
=
1.59

(95% CI, 1.09, 2.34)], and World Health Organization (WHO) clinical stages III and IV [

AOR
=
1.98

(95% CI, 1.23, 3.19)] was among the significantly associated factors. Conclusion. In this review, there was a high prevalence of food insecurity among adult people with human immunodeficiency virus. Therefore, the responsible stockholders should strengthen the system and procedure for early diagnosis of opportunistic infection, under nutrition, screening of underlying problems.
How Big is the Ballpark? Assessing Variation in Grant Aid Awards within Net Price Calculator Student Profiles
Authors: Anthony Aaron M. , Page Lindsay C. 
Published: June 2021

Abstract
Net Price Calculators (NPCs) are online tools designed to increase transparency in college pricing by presenting students with individualized estimates of net prices to attend a given postsecondary institution. The federal template NPC predicts identical aid awards for similarly-profiled students attending the same institution. Using the 2012 National Postsecondary Student Aid Survey, we use regression analysis to assess variation in actual financial aid awards among students predicted by the federal template NPC to receive identical awards. We find estimated aid, derived from the federal template NPC, accounts for 70 percent of the variation in actual grant aid received by students. We then consider modifications to the federal template NPC that include an additional upper income bracket option and indicators of both high school grade point average and Free Application for Federal Student Aid filing time. These modifications explain an additional 16 percentage points, or more than half, of the unexplained variation in actual grant aid awards across all institutional sectors. These findings are especially relevant as legislators consider policy efforts to bring greater transparency to college cost and pricing, including creating a universal NPC in which prospective students can enter information once to receive net price estimates at any institution.
Data Construction and Spatiotemporal Trend Attribution of Runoff over the African Continent (1981–2016)
Authors: Karamage Fidele , Liu Yongwei , Liu Yuanbo 
Published: June 2021

AbstractThe availability of streamflow records in Africa has been declining since the 1980s due to malfunctioning gauging stations and data collection failures. Africa also has insufficient hydrological information owing to the allocation of few resources to research efforts. Unreliable runoff datasets and large uncertainties in runoff trends due to climate change patterns and human activities are major challenges to water resource management in Africa. Therefore, this study aimed to improve runoff estimates and to assess runoff trend responses to climate change and human activities in Africa during 1981–2016. Using statistical methods, monthly gridded runoff datasets were generated for the period of 1981–2016 from a modified runoff curve number method calibrated with river discharge data from 535 gauging stations. According to the cross-validation results, the constructed runoff datasets comprised the Nash and Sutcliffe coefficients ranging from 0.5 to 1, coefficients of determination ranging from 0.5 to 1 and percent biases between ±25% for a large number of stations up to 73%, 80% and 91% of the 535 gauged catchments used as references. Analysis of runoff trend responses to climate change and human activities revealed that land cover change contributed more (72%) to the observed net runoff change (0.30%•a−1) than continental climate changes (28%). These contributions were results of cropland expansion rate of 0.46%•a−1 and a precipitation increase of 0.07%•a−1. The performance and simplicity of the statistical methods used in this study could be useful for improving runoff estimations in other regions with limited streamflow data data. The results of the current study could be important to natural resource managers and decision makers in terms of raising awareness of climate change adaptation strategies and agricultural land-use policies in Africa.
An Analytical Spectral Model for Infragravity Waves over Topography in Intermediate and Shallow Water under Nonbreaking Conditions
Authors: Liao Zhiling , Li Shaowu , Liu Ye , Zou Qingping 
Published: June 2021

AbstractThe theoretical model for group-forced infragravity (IG) waves in shallow water is not well established for nonbreaking conditions. In the present study, analytical solutions of the group-forced IG waves at O(β1) (β1 = hx/(Δkh), hx = bottom slope, Δk = group wavenumber, h = depth) in intermediate water and at in shallow water are derived separately. In case of off-resonance [β1μ−1 = O(β1), where is the resonant departure parameter, cg = group speed] in intermediate water, additional IG waves in quadrature with the wave group forcing (hereinafter, the nonequilibrium response or component) are induced at O(β1) relative to the equilibrium bound IG wave solution of Longuet–Higgins and Stewart (1962) in phase with the wave group. The present theory indicates that the nonequilibrium response is mainly attributed to the spatial variation of the equilibrium bound IG wave amplitude instead of group-forcing. In case of near-resonance [β1μ−1 = O(1)] in shallow water; however, both the equilibrium and nonequilibrium components are at the leading order. Based on the nearly-resonant solution, the shallow water limit of the local shoaling rate of bound IG waves over a plane sloping beach is derived to be ~h−1 for the first time. The theoretical predictions compare favorably with the laboratory experiment by Van Noorloos (2003) and the present numerical model results generated using SWASH. Based on the proposed solution, the group-forced IG waves over a symmetric shoal are investigated. In case of off-resonance, the solution predicts a roughly symmetric reversible spatial evolution of the IG wave amplitude, while in cases of near to full resonance the IG wave is significantly amplified over the shoal with asymmetric irreversible spatial evolution.
Improving the Estimation of Temperature and Salinity by Assimilation of Observed Sound Speed Profiles
Authors: Zhang Jiali , Zhang Liang , Zhang Anmin , Zhang Lianxin , Li Dong , Zhang Xuefeng 
Published: June 2021

AbstractSound Speed Profile (SSP) affecting underwater acoustics is closely related to the temperature and the salinity fields. It is of great value to obtain the temperature and the salinity information through the high-precision sound speed profiles. In this paper, a data assimilation scheme by introducing sound speed profiles as a new constraint is proposed within the framework of 3DVAR data assimilation (referenced as SSP-constraint 3DVAR (SSPC-3DVAR) ), which aims at improving the analysis accuracy of initial fields of the temperature and salinity in coastal sea areas. In order to validate the performance of the new assimilation scheme, ideal experiments are firstly carried out to show the advantages of the new proposed SSPC-3DVAR. Then the temperature, the salinity, and the SSP observations from field experiments in a coastal area are assimilated into the Princeton Ocean Model to validate the performance of short-time forecasts, adopting the SSPC-3DVAR scheme. Results show that it is efficient to improve the estimate accuracy by as much as 14.6% (11.1%) for the temperature (salinity), compared with the standard 3DVAR. It demonstrates that the proposed SSPC-3DVAR approach works better in practice than the standard 3DVAR and will primarily benefit from variously and widely distributed observations in the future.
Reducing Constipation-Related Admissions: The Effectiveness of Antegrade Continence Enema Procedures in Children
Authors: Esparaz Joseph R. , Waters Alicia M. , Mathis Michelle S. , Mortellaro Vincent E. 
Published: June 2021

Introduction Constipation in pediatrics remains a common problem. Antegrade continence enema (ACE) procedures have been shown to decrease the distress of daily therapy. Patients are able to administer more aggressive washouts in the outpatient setting. Therefore, we hypothesize that patients following an ACE procedure would have reduced admissions for constipation. Methods Patients who underwent an ACE procedure at a large children’s hospital from 2015 to 2018 were included. Demographics, diagnosis, procedure, and preoperative/postoperative hospital admissions were analyzed. Results Forty-eight patients were included in the study. Over half were diagnosed with idiopathic constipation. Majority of patients underwent an appendicostomy (88%, n = 42). Preoperatively, 26 patients were admitted for a combined total of 63 times for constipation. Postoperatively, 4 patients were admitted for a total of 5 visits ( P = .021). Twenty-eight patients required a nonscheduled appendicostomy tube replacement. Conclusion This study demonstrates ACE procedures can improve constipation-related symptoms in children and are associated with decrease hospital admissions.
Surgical Resection After Talimogene Laherparepvec for Melanoma: Persistent Fuorodeoxyglucose Avidity on Positron Emission Tomography Despite No Viable Disease
Authors: MacArthur Taleen A. , Fahy Aodhnait S. , Jakub James W. 
Published: June 2021

Background Talimogene laherparepvec (TVEC) is an injectable attenuated oncolytic herpes simplex virus (HSV-1) used in the treatment of loco regionally metastatic melanoma. Lesions managed by TVEC are generally considered unresectable at time of initiation of intralesional therapy; however, a subset of patients go on to have surgical resection of loco regionally controlled disease. We sought to review our experience with surgical excision of treated lesions to offer an insight into the radiologic correlate, treatment effect, and pathological findings of intralesional TVEC therapy. Methods This is a retrospective descriptive case series of patients who underwent TVEC injection at Mayo Clinic, Rochester, MN, between October 2016 and July 2020. Institutional Institutional Review Board approval was obtained. Results Twenty-one patients underwent intralesional TVEC, met inclusion criteria, and were included in this series. Seven went on to surgical excision of the injected lesions after an initial course of TVEC. Of those 7 patients, 4 had residual melanoma in the specimen on final pathology, while 3 had a complete pathologic response. All 3 patients who had no residual disease on pathology continued to have fluorodeoxyglucose (FDG) avidity on preoperative positron emission tomography scan of the excised lesions. Discussion Despite ongoing FDG avidity on PET scan, patients who have well-controlled disease and stability over time of the injected lesions may benefit from surgical excision following a course of TVEC. This may render the patient clinically disease free and/or allow them a reprieve from TVEC treatment.
A Contemporary Analysis of the Effect of Trauma Center Verification Level on Mortality in Severe Injury
Authors: Plurad David S. , Geesman Glenn , Sheets Nicholas W. , Chawla-Kondal Bhani , Ayutyanont Napatakamon , Mahmoud Ahmed 
Published: June 2021

Background Literature demonstrates increased mortality for the severely injured at a Level II vs. Level I center. Our objective is to reevaluate the impact of trauma center verification level on mortality for patients with an Injury Severity Score (ISS) > 15 utilizing more contemporary data. We hypothesize that there would be no mortality discrepancy. Study Design Utilizing the ACS Trauma Quality Program Participant Use File admission year 2017, we identified severely injured (ISS >15) adult (age >15 years) patients treated at an ACS-verified Level I or Level II center. We excluded patients who underwent interfacility transfer. Logistic regression was performed to determine adjusted associations with mortality. Results There were 63 518 patients included, where 43 680 (68.8%) were treated at a Level I center and 19 838 (31.2%) at a Level II. Male gender (70.1%) and blunt injuries (92.0%) predominated. Level I admissions had a higher mean ISS [23.8 (±8.5) vs. 22.9 (±7.8), <.001], while Level II patients were older [mean age (y) 52.3 (±21.6) vs. 48.6 (±21.0), <.001] with multiple comorbidities (37.7% vs. 34.9%, <.001). Adjusted mortality between Level I and II centers was similar (12.0% vs. 11.8%, .570). Conclusions Despite previous findings, mortality outcomes are similar for severely injured patients treated at a Level I vs. Level II center. We theorize that this relates to mandated Level II resourcing as defined by an updated American College of Surgeons verification process.
Subacute Enteritis Two Months After COVID-19 Pneumonia With Mucosal Bleeding, Perforation, and Internal Fistulas
Authors: Abbassi Babak , Deb Anasua , Costilla Vanessa , Bankhead-Kendall Brittany 
Published: June 2021

Chronic sequelae of COVID-19 remain undetermined. We report a case of postinfection sequelae in a patient presenting with subacute obstruction 2 months after COVID-19 infection. A 34-year-old man with a prior prolonged hospital stay due to COVID-19 complicated by upper gastrointestinal (GI) bleed presented with subacute obstruction and failure to thrive. Upper GI push enteroscopy revealed residual ulcers and multiple proximal jejuno-jejunal fistulae. Midline laparotomy revealed strictures with dense intra-abdominal adhesions, a large jejuno-jejunal fistula, and evidence of prior jejunal perforation following severe COVID-19 infection. The patient recovered after small bowel resection with anastomoses and was discharged home. Histopathological examination of resected specimen confirmed transmural infarction with evidence of prior hemorrhage, diffuse ulcers, and multifocal inflammation. This is the first report of a chronic GI sequelae resulting from COVID-19. As the pandemic evolves, medical professionals must be vigilant to consider alternative GI diagnoses in the COVID-19 survivors.
Transcranial Magnetic Stimulation in Succinic Semialdehyde Dehydrogenase Deficiency: A Measure of Maturational Trajectory of Cortical Excitability
Authors: Tsuboyama Melissa , Liu Jingjing , Kaye Harper , DiBacco Melissa , Pearl Phillip L , Rotenberg Alexander 
Published: June 2021

Background: Succinic semialdehyde dehydrogenase deficiency (SSADHD) is a disorder of GABA degradation with use-dependent downregulation of postsynaptic GABAA/B receptors. We aim to measure the resulting cortical excitation: inhibition ratio using transcranial magnetic stimulation. Methods: In this single-center observational study, 18 subjects with SSADHD and 8 healthy controls underwent transcranial magnetic stimulation. Resting motor threshold, cortical silent period, and long-interval intracortical inhibition were measured in both groups. Resting motor threshold in focal epilepsy patients from an institutional transcranial magnetic stimulation database were also included. Results: SSADHD subjects had higher resting motor threshold than healthy controls but lower relative to focal epilepsy patients. Resting motor threshold decreased with age in all groups. Cortical silent period was longer in SSADHD subjects than in healthy controls. No difference was detected in long-interval intracortical inhibition between the 2 groups. Conclusion: Findings suggest abnormal corticospinal tract physiology in SSADHD, but with preserved developmental trajectory for corticospinal tract maturation. Defining features of these transcranial magnetic stimulation metrics in SSADHD will be better elucidated through this ongoing longitudinal study.