bluuebunny/crossref_metadata_2025_split huggingface dataset:
Post–Acute Pancreatitis Pancreatic Exocrine Insufficiency
Authors: Paragomi Pedram , Phillips Anna Evans , Machicado Jorge D. , Lahooti Ali , Kamal Ayesha , Afghani Elham , Pothoulakis Ioannis , Reynolds Shari L. , Mays Melanie , Conwell Darwin L. , Lara Luis F. , Singh Vikesh K. , Papachristou Georgios I. 
Published: February 2021

Objectives
We describe the methodology of Post–Acute Pancreatitis Pancreatic Exocrine Insufficiency (PAPPEI), a prospective, observational, multicenter cohort study. The objectives of PAPPEI are to estimate the incidence rate of post–acute pancreatitis (AP) pancreatic exocrine insufficiency (PEI), define factors that determine the development of post-AP PEI, and evaluate the impact of post-AP PEI on nutritional status and quality of life.

Methods
Enrollment started in June 2017 in 3 expert academic centers in the United States. Data were collected during hospitalization (baseline) at 3 and 12 months after enrollment. Fecal elastase-1 was used to assess PEI. Study questionnaires are completed by patient interview and review of electronic medical records. Blood is obtained to evaluate vitamin deficiencies and nutritional markers.

Results
As of August 2020, 77 subjects have completed the baseline evaluation. The median age was 58 years (interquartile range, 39–67 years), 38% were male, and 90% were white. The etiology of AP was biliary in 39 subjects (51%), and 51 subjects (66%) had mild AP. Three- and 12-month follow-up data have been collected in 29 and 13 subjects, respectively.

Conclusion
The PAPPEI study aims to expand our understanding of post-AP PEI incidence, including its impact on nutritional status and quality of life.
Markers of Systemic Inflammation in Neuroendocrine Tumors
Authors: Chan David L. , Yao James C. , Carnaghi Carlo , Buzzoni Roberto , Herbst Fabian , Ridolfi Antonia , Strosberg Jonathan , Kulke Matthew H. , Pavel Marianne , Singh Simron 
Published: February 2021

Objective
The aim of the study was to assess the impact of systemic markers of inflammation on the outcomes in patients with neuroendocrine tumors (NETs) treated with everolimus or placebo (as measured by baseline neutrophil-to-lymphocyte ratio [NLR] and lymphocyte-to-monocyte ratio [LMR]).

Methods
Patient data (gastrointestinal, pancreatic, and lung NETs) from 2 large phase 3 studies, RADIANT-3 (n = 410) and RADIANT-4 (n = 302), were pooled and analyzed. The primary end point was centrally assessed progression-free survival (PFS) as estimated by the Kaplan-Meier method.

Results
In the pooled population, elevated LMR (median PFS, 11.1 months; 95% confidence interval, 9.3–13.7; hazard ratio, 0.69; P < 0.001) and reduced NLR (median PFS, 10.8 months; 95% confidence interval, 9.2–11.7; hazard ratio, 0.75; P = 0.0060) correlated with longer PFS among all patients. These markers were also found to be prognostic in the everolimus- and placebo-treated subgroups.

Conclusions
Data from this study suggest that LMR and NLR are robust prognostic markers for NETs and could potentially be used to identify patients who may receive or are receiving the most benefit from targeted therapies. As both are derived from a complete blood count, they can be routinely used in clinical practice, providing valuable information to clinicians and patients alike.
PVT1 Knockdown Inhibits Autophagy and Improves Gemcitabine Sensitivity by Regulating the MiR-143/HIF-1α/VMP1 Axis in Pancreatic Cancer
Authors: Liu Yun-Fei , Luo Dong , Li Xia , Li Zhi-Qiang , Yu Xiao , Zhu Hong-Wei 
Published: February 2021

Objectives
Elucidation of the regulatory mechanisms of gemcitabine sensitivity is needed to improve the therapeutic effects of this drug in pancreatic cancer.

Methods
PANC-1 cells were transfected with small hairpin RNA against PVT1 or microRNA (miR)-143 mimics or inhibitor. The gemcitabine sensitivity of pancreatic cancer was evaluated. Autophagosomes were analyzed with an immunofluorescence assay. Cell viability and proliferation were examined with MTT assays. Quantitative reverse transcription–polymerase chain reaction and Western blotting were used to analyze the expression of PVT1, miR-143, HIF-1α, VMP1, LC3I/II, p62, and Beclin-1. The interactions of PVT1/miR-143 and miR-143/HIF-1α were assessed by dual-luciferase reporter assays.

Results
PVT1 was upregulated while miR-143 was downregulated in pancreatic cancer. Both PVT1 knockdown and miR-143 overexpression suppressed autophagy and improved gemcitabine sensitivity in pancreatic cancer. PVT1 directly sponged miR-143 to regulate HIF-1α expression. MiR-143 inhibitor reversed the effect of PVT1 knockdown on autophagy and gemcitabine sensitivity.

Conclusions
PVT1 knockdown inhibited autophagy and improved gemcitabine sensitivity via the miR-143/HIF-1α/VMP1 axis in pancreatic cancer. Our investigation elucidated a novel regulatory mechanism of gemcitabine sensitivity and may contribute to improve the therapeutic effects of chemotherapy drugs on pancreatic cancer.
MiR-204-5p Performs a Protective Effect on Cerulein-Induced Rat Pancreatic Acinar Cell AR42J Cell Damage by Targeting Tyrosine 3-Monooxygenase/Tryptophan 5-Monooxygenase Activation Protein Gamma and Regulating PI3K/Hippo Pathways
Authors: Zhao Hongbo , Jiang Shaolian 
Published: February 2021

Objective
This research plans to address the function of miR-204-5p/tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein gamma (YWHAG) in cerulein-induced acute pancreatitis (AP).

Methods
Rat pancreatic acinar cell AR42J was stimulated by 100 nmol/L of cerulein to mimic the situation in AP. Gene Expression Omnibus database was used to select differentially expressed genes. StarBase database and Kyoto Encyclopedia of Genes and Genomes enrichment analysis were used to select the target genes of miR-204-5p, which were further affirmed by dual luciferase assay. The biological behaviors of AR42J cells were measured by cell proliferation and flow cytometry assays. Quantitative real-time polymerase chain reaction and western blot assays were executed to assess YWHAG expression. The secretion of C-C Motif Chemokine Ligand 2/Timp metallopeptidase inhibitor 1 in AR42J cells was evaluated by enzyme-linked immunosorbent assay. The protein expression of YAP1/p-YAP1/PI3K/p-PI3K was measured by western blot.

Results
miR-204-5p expression was profoundly reduced in cerulein-induced AP model. YWHAG was upregulated in cerulein-induced AP model and related to C-C Motif Chemokine Ligand 2/Timp1. In addition to the negative association between miR-204-5p and YWHAG, the alleviation impact of miR-204-5p mimic on cerulein-induced AR42J cell damage was blocked by YWHAG overexpression and PI3K/Hippo signaling pathways activation.

Conclusions
These observations indicated that the alleviation impact of miR-204-5p on cerulein-induced AR42J cell damage was mediated via YWHAG and PI3K/Hippo signaling pathways.
Attracting New Talent to the Governmental Public Health Workforce: Strategies for Improved Recruitment of Public Health Graduates
Authors: Locke Rachel , McGinty Meghan , Guerrero Ramirez Grace , Sellers Katie 
Published: February 2021

Context:
Governmental public health (GPH) agencies need a diverse, skilled, and motivated workforce to advance health and well-being, but they face a number of recruitment challenges. While there has been massive growth in public health degree programs and graduates, those with a degree in public health are underrepresented in the GPH workforce.

Objectives:
This study evaluates potential reasons undergraduate and graduate public health degree holders are underrepresented in the GPH workforce, assesses student awareness of and interest in GPH jobs, and identifies strategies for improved recruitment.

Design:
We conducted pilot focus groups to explore public health students' interest in working for GPH agencies, obstacles to employment, and how this career path could be better promoted.

Setting and participants:
Eight focus groups were conducted with a total of 33 participants at 3 universities and at the Annual Meeting of the American Public Health Association. Participants were enrolled full-time in or graduated within the last year from a public health bachelor's degree program or a public health master's degree program. Undergraduates had declared a public health major and were in their senior year; graduate students were in their second year and actively job seeking; or participants graduated within the past 12 months.

Main Outcome Measures:
The focus groups sought to capture students' perspectives of GPH agencies and how they believe recruitment can be improved.

Results:
Participants described attractive job attributes including fulfilling, meaningful work; a position at a mission-driven organization; and the opportunity to make an impact on their community. Governmental public health agencies were viewed as bureaucratic, lacking innovation, and underresourced. Participants reported difficulties accessing and finding relevant job postings.

Conclusions:
Key to effectively recruiting and retaining new graduates is understanding their perceptions about/experiences with GPH agencies. While GPH jobs have desired attributes, participants reported that health departments are not effectively recruiting them.
The Breast Response to Estrogenic Stimulation in Transwomen Classification
Authors: Alcon Andre , Wang Eric , Oliver-Allen Hunter , Srinivasa Dhivya , Kim Esther A. 
Published: February 2021

Background
Hormone therapy with exogenous estrogen and/or spironolactone is commonly used in transfemales to induce breast development. However, inherent differences in adult male and female anatomy create persistent deformities and inadequate gender congruency despite glandular breast development. This includes nipple characteristics, position of inframammary fold, and the distribution of breast tissue. Accordingly, the Tanner stages do not accurately reflect these persistent deformities because they relate to breast development in transwomen. Herein, we describe a classification system for breast development in transwomen treated with hormone therapy.

Methods
Ninety-nine transfemale patients who underwent breast augmentation from 2014 to 2018 were retrospectively reviewed and categorized using a novel scheme, the Breast Response to Estrogenic Stimulation in Transwomen (BREST) scale. Preoperative demographics, anatomic measurements, surgical technique, and postoperative results were also compared among BREST types.

Results
Most patients were rated as BREST type II (25%) or type IV (37%). The BREST scale exhibited moderate interrater reliability (κ = 0.58) between 3 plastic surgeons. Objective breast measurements such as sternal notch-to-nipple distance and nipple-to-inframammary fold distance correlated with the BREST scale. Multivariate logistical regression identified the nipple-to-inframammary fold distance and different between the bust and chest circumference as the strongest predictors of BREST type (odds ratio, 2.57 and 1.96, respectively). Body mass index was not a predictor of BREST type after controlling for confound variables on multivariate analysis.

Conclusions
The BREST scale uniquely captures the differences in breast phenotypes in transgender women according to hormone therapy response. Although some subjectivity exists with moderate interrater reliability, the BREST scale correlates with objective breast measurements. The BREST scale provides a transwoman-specific metric allowing for a common language in assessment of transgender breast development and optimal communication among providers, different specialties, and insurance companies.
Computational and neurocognitive approaches to the political brain: key insights and future avenues for political neuroscience
Authors: Zmigrod Leor , Tsakiris Manos 
Published: February 2021

Although the study of political behaviour has been traditionally restricted to the social sciences, new advances in political neuroscience and computational cognitive science highlight that the biological sciences can offer crucial insights into the roots of ideological thought and action. Echoing the dazzling diversity of human ideologies, this theme issue seeks to reflect the multiplicity of theoretical and methodological approaches to understanding the nature of the political brain. Cutting-edge research along three thematic strands is presented, including (i) computational approaches that zoom in on fine-grained mechanisms underlying political behaviour, (ii) neurocognitive perspectives that harness neuroimaging and psychophysiological techniques to study ideological processes, and (iii) behavioural studies and policy-minded analyses of such understandings across cultures and across ideological domains. Synthesizing these findings together, the issue elucidates core questions regarding the nature of uncertainty in political cognition, the mechanisms of social influence and the cognitive structure of ideological beliefs. This offers key directions for future biologically grounded research as well as a guiding map for citizens, psychologists and policymakers traversing the uneven landscape of modern polarization, misinformation, intolerance and dogmatism.
This article is part of the theme issue ‘The political brain: neurocognitive and computational mechanisms'.
Ideology, communication and polarization
Authors: Kashima Yoshihisa , Perfors Andrew , Ferdinand Vanessa , Pattenden Elle 
Published: February 2021

Ideologically committed minds form the basis of political polarization, but ideologically guided communication can further entrench and exacerbate polarization depending on the structures of ideologies and social network dynamics on which cognition and communication operate. Combining a well-established connectionist model of cognition and a well-validated computational model of social influence dynamics on social networks, we develop a new model of ideological cognition and communication on dynamic social networks and explore its implications for ideological political discourse. In particular, we explicitly model ideologically filtered interpretation of social information, ideological commitment to initial opinion, and communication on dynamically evolving social networks, and examine how these factors combine to generate ideologically divergent and polarized political discourse. The results show that ideological interpretation and commitment tend towards polarized discourse. Nonetheless, communication and social network dynamics accelerate and amplify polarization. Furthermore, when agents sever social ties with those that disagree with them (i.e. structure their social networks by homophily), even non-ideological agents may form an echo chamber and form a cluster of opinions that resemble an ideological group.This article is part of the theme issue ‘The political brain: neurocognitive and computational mechanisms’.
Profile of SARS-CoV-2-specific CD4 T cell response: Relationship with disease severity and impact of HIV-1 and activeMycobacterium tuberculosisco-infection
Authors: Riou Catherine , Bruyn Elsa du , Stek Cari , Daroowala Remy , Goliath Rene T. , Abrahams Fatima , Said-Hartley Qonita , Allwood Brian W. , Hsiao Marvin , Wilkinson Katalin A. , Arlehamn Cecilia S. Lindestam , Sette Alessandro , Wasserman Sean , Wilkinson Robert J. 
Published: February 2021

SUMMARYT cells are involved in control of COVID-19, but limited knowledge is available on the relationship between antigen-specific T cell response and disease severity. Here, we assessed the magnitude, function and phenotype of SARS-CoV-2-specific CD4 T cells in 95 hospitalized COVID-19 patients (38 of them being HIV-1 and/or tuberculosis (TB) co-infected) and 38 non-COVID-19 patients, using flow cytometry. We showed that SARS-CoV-2-specific CD4 T cell attributes, rather than magnitude, associates with disease severity, with severe disease being characterized by poor polyfunctional potential, reduced proliferation capacity and enhanced HLA-DR expression. Moreover, HIV-1 and TB co-infection skewed the SARS-CoV-2 T cell response. HIV-1 mediated CD4 T cell depletion associated with suboptimal T cell and humoral immune responses to SARS-CoV-2; and a decrease in the polyfunctional capacity of SARS-CoV-2-specific CD4 T cells was observed in COVID-19 patients with active TB. Our results also revealed that COVID-19 patients displayed reduced frequency of Mtb-specific CD4 T cells, with possible implications for TB disease progression. There results corroborate the important role of SARS-CoV-2-specific T cells in COVID-19 pathogenesis and support the concept of altered T cell functions in patients with severe disease.
Targeting the Coronavirus Nucleocapsid Protein through GSK-3 Inhibition
Authors: Liu Xiaolei , Verma Anurag , Garcia Gustavo , Ramage Holly , Myers Rebecca L. , Lucas Anastasia , Michaelson Jacob J. , Coryell William , Kumar Arvind , Charney Alexander W. , Kazanietz Marcelo G. , Rader Daniel J , Ritchie Marylyn D , Berrettini Wade H. , Schultz David C. , Cherry Sara , Damoiseaux Robert , Arumugaswami Vaithilingaraja , Klein Peter S. 
Published: February 2021

AbstractThe coronaviruses responsible for severe acute respiratory syndrome (SARS-CoV), COVID-19 (SARS-CoV-2), Middle East respiratory syndrome (MERS-CoV), and other coronavirus infections express a nucleocapsid protein (N) that is essential for viral replication, transcription, and virion assembly. Phosphorylation of N from SARS-CoV by glycogen synthase kinase 3 (GSK-3) is required for its function and inhibition of GSK-3 with lithium impairs N phosphorylation, viral transcription, and replication. Here we report that the SARS-CoV-2 N protein contains GSK-3 consensus sequences and that this motif is conserved in diverse coronaviruses, raising the possibility that SARS-CoV-2 may be sensitive to GSK-3 inhibitors including lithium. We conducted a retrospective analysis of lithium use in patients from three major health systems who were PCR tested for SARS-CoV-2. We found that patients taking lithium have a significantly reduced risk of COVID-19 (odds ratio = 0.51 [0.35 - 0.74], p = 0.005). We also show that the SARS-CoV-2 N protein is phosphorylated by GSK-3. Knockout of GSK3A and GSK3B demonstrates that GSK-3 is essential for N phosphorylation. Alternative GSK-3 inhibitors block N phosphorylation and impair replication in SARS-CoV-2 infected lung epithelial cells in a cell-type dependent manner. Targeting GSK-3 may therefore provide a new approach to treat COVID-19 and future coronavirus outbreaks.SignificanceCOVID-19 is taking a major toll on personal health, healthcare systems, and the global economy. With three betacoronavirus epidemics in less than 20 years, there is an urgent need for therapies to combat new and existing coronavirus outbreaks. Our analysis of clinical data from over 300,000 patients in three major health systems demonstrates a 50% reduced risk of COVID-19 in patients taking lithium, a direct inhibitor of glycogen synthase kinase-3 (GSK-3). We further show that GSK-3 is essential for phosphorylation of the SARS-CoV-2 nucleocapsid protein and that GSK-3 inhibition blocks SARS-CoV-2 infection in human lung epithelial cells. These findings suggest an antiviral strategy for COVID-19 and new coronaviruses that may arise in the future.
Accessible LAMP-Enabled Rapid Test (ALERT) for detecting SARS-CoV-2
Authors: Bektaş Ali , Covington Michael F. , Aidelberg Guy , Arce Anibal , Matute Tamara , Núñez Isaac , Walsh Julia , Boutboul David , Lindner Ariel B. , Federici Fernán , Jayaprakash Anitha 
Published: February 2021

AbstractThe COVID-19 pandemic has highlighted bottlenecks in large-scale, frequent testing of populations for infections. PCR-based diagnostic tests are expensive, reliant on expensive centralized labs, can take days to deliver results, and are prone to backlogs and supply shortages. Antigen tests, that bind and detect the surface proteins of a virus, are rapid and inexpensive but suffer from high false negative rates. To address this problem, we have created an inexpensive, simple, and robust 60-minute Do-It-Yourself (DIY) workflow to detect viral RNA from nasal swabs or saliva with high sensitivity (0.1 to 2 viral particles/µl) and specificity (>97% True Negative Rate) utilizing reverse transcription loop-mediated isothermal amplification (RT-LAMP).Our workflow, ALERT (Accessible LAMP-Enabled Rapid Test), incorporates the following features: 1) Increased shelf-life and ambient temperature storage by using wax layers to isolate enzymes from reaction, 2) Improved specificity by using sequence-specific QUASR reporters, 3) Increased sensitivity through use of a magnetic wand to enable pipette-free concentration of sample RNA and cell debris removal, 4) Quality control with a nasopharyngeal-specific mRNA target, and 5) Co-detection of other respiratory viruses, such as Influenza B, by duplexing QUASR-modified RT-LAMP primer sets.The flexible nature of the ALERT workflow allows easy, at-home and point-of-care testing for individuals and higher-throughput processing for centralized labs and hospitals. With minimal effort, SARS-CoV-2-specific primer sets can be swapped out for other targets to repurpose ALERT to detect other viruses, microorganisms or nucleic acid-based markers.
Essential hypertension is associated with changes in gut microbial metabolic pathways: A multi-site analysis of ambulatory blood pressure
Authors: Nakai Michael , Ribeiro Rosilene V , Stevens Bruce R. , Gill Paul , Muralitharan Rikeish R. , Yiallourou Stephanie , Muir Jane , Carrington Melinda , Head Geoffrey A. , Kaye David M. , Marques Francine Z. 
Published: February 2021

AbstractRecent evidence supports a role for the gut microbiota in hypertension, but whether ambulatory blood pressure (BP) is associated with gut microbiota and their metabolites remains unclear. We characterised the function of the gut microbiota, their metabolites and receptors in untreated human hypertensive participants in Australian metropolitan and regional areas. Ambulatory BP, faecal microbiome predicted from 16S rRNA gene sequencing, plasma and faecal metabolites called short-chain fatty acid (SCFAs), and expression of their receptors were analysed in 70 untreated and otherwise healthy participants from metropolitan and regional communities. Most normotensives were female (66%) compared to hypertensives (35%, P<0.01), but there was no difference in age between the groups (59.2±7.7 versus 60.3±6.6-years-old). Based on machine-learning multivariate covariance analyses of de-noised amplicon sequence variant prevalence data, we determined that there were no significant differences in predicted gut microbiome α- and β-diversity metrics between normotensives versus essential, white coat or masked hypertensives. However, select taxa were specific to these groups, notablyAcidaminococcus spp., Eubacterium fissicatena and Muribaculaceaewere higher, whileRuminococcusandEubacterium eligenswere lower in hypertensives. Importantly, normotensive and essential hypertensive cohorts could be differentiated based on gut microbiome gene pathways and metabolites. Specifically, hypertensive participants exhibited higher plasma acetate and butyrate, but their immune cells expressed reduced levels of SCFA-activated G-protein coupled re1ceptor 43 (GPR43). In conclusion, gut microbial diversity did not change in essential hypertension, but we observed a significant shift in microbial gene pathways. Hypertensive subjects had lower levels of GPR43, putatively blunting their response to BP-lowering metabolites.