bluuebunny/crossref_metadata_2025_split huggingface dataset:
Fetal inflammation induces acute immune tolerance in the neonatal rat hippocampus
Authors: Singh Garima , Segura Bradley J. , Georgieff Michael K. , Gisslen Tate 
Published: March 2021

Abstract
Background
Infants born preterm due to chorioamnionitis are frequently affected by a fetal inflammatory response syndrome (FIRS) and then by subsequent postnatal infections. FIRS and postnatal systemic inflammatory events independently contribute to poor neurocognitive outcomes of preterm infants. Developmental integrity of the hippocampus is crucial for intact neurocognitive outcomes in preterms and hippocampally dependent behaviors are particularly vulnerable to preterm systemic inflammation. How FIRS modulates the hippocampal immune response to acute postnatal inflammatory events is not well understood.

Methods
Prenatal LPS exposed (FIRS) and control neonatal rats received i.p. LPS or saline at postnatal day (P) 5. On P7, immune response was evaluated in the hippocampus of four treatment groups by measuring gene expression of inflammatory mediators and cytosolic and nuclear NFκB pathway proteins. Microglial activation was determined by CD11b+ and Iba1+ immunohistochemistry (IHC) and inflammatory gene expression of isolated microglia. Astrocyte reactivity was measured using Gfap+ IHC.

Results
Postnatal LPS resulted in a robust hippocampal inflammatory response. In contrast, FIRS induced by prenatal LPS attenuated the response to postnatal LPS exposure, evidenced by decreased gene expression of inflammatory mediators, decreased nuclear NFκB p65 protein, and fewer activated CD11b+ and Iba1+ microglia. Isolated microglia demonstrated inflammatory gene upregulation to postnatal LPS without evidence of immune tolerance by prenatal LPS.

Conclusion
Prenatal LPS exposure induced immune tolerance to subsequent postnatal LPS exposure in the hippocampus. Microglia demonstrate a robust inflammatory response to postnatal LPS, but only a partial immune tolerance response.
Assessment of dengue and COVID-19 antibody rapid diagnostic tests cross-reactivity in Indonesia
Authors: Santoso Marsha S. , Masyeni Sri , Haryanto Sotianingsih , Yohan Benediktus , Hibberd Martin L. , Sasmono R. Tedjo 
Published: March 2021

Abstract
Background
The coronavirus disease 2019 (COVID-19) pandemic remains ongoing around the world, including in areas where dengue is endemic. Dengue and COVID-19, to some extent, have similar clinical and laboratory features, which can lead to misdiagnosis, delayed treatment and patient’s isolation. The use of rapid diagnostic tests (RDT) is easy and convenient for fast diagnosis, however there may be issues with cross-reactivity with antibodies for other pathogens.

Methods
We assessed the possibility of cross-reactivity between SARS-CoV-2 and dengue antibodies by: (1) testing five brands of COVID-19 IgG / IgM RDTs on 60 RT-PCR-confirmed dengue samples; (2) testing 95 RT-PCR-confirmed COVID-19 samples on dengue RDT; and (3) testing samples positive for COVID-19 IgG and/or IgM on dengue RDT.

Results
We observed a high specificity across all five brands of COVID-19 RDTs, ranging from 98.3 to 100%. Out of the confirmed COVID-19 samples, one patient tested positive for dengue IgM only, another tested positive for dengue IgG only. One patient tested positive for dengue IgG, IgM, and NS1, suggesting a co-infection. In COVID-19 IgG and/or IgM samples, 6.3% of COVID-19 IgG-positive samples also tested positive for dengue IgG, while 21.1% of COVID-19 IgM-positive samples also tested positive for dengue IgG.

Conclusion
Despite the high specificity of the COVID-19 RDT, we observed cross-reactions and false-positive results between dengue and COVID-19. Dengue and COVID-19 co-infection was also found. Health practitioners in dengue endemic areas should be careful when using antibody RDT for the diagnosis of dengue during the COVID-19 pandemic to avoid misdiagnosis.
Major depression with musical obsession treated with vortioxetine: a case report
Authors: Yoshimura Reiji , Okamoto Naomichi , Konishi Yuki , Ikenouchi Atsuko 
Published: March 2021

Abstract
Background
Musical obsession has been reported as the “stuck song syndrome” and can be accompanied by obsessive compulsive disorder (OCD). Musical obsession is the phenomenon where a particular set of known musical notes are perceived repeatedly. We present a case of major depression with musical obsession. In this case, vortioxetine improved both depressive symptoms and musical obsession.

Case presentation
A female, 34-year-old, high school teacher presented with a depressed mood, anergia, difficulty in concentration, poor motivation, restlessness, anxiety, insomnia, and loss of appetite. She was diagnosed with major depression by her family physician and prescribed escitalopram (20 mg/day). Her depressive state partially responded to escitalopram. When she had been depressed, she also experienced musical obsessions as repetitive commercial tunes or instrumental notes inside her head that were not under conscious voluntary control and lasting several hours, causing a high level of distress in her daily life. After switching from escitalopram to vortioxetine (20 mg/day), her depressive symptoms and musical obsession symptoms were ameliorated.

Conclusions
This case report endorses the utility of vortioxetine for major depression with musical obsession, and further studies should be conducted to establish the optimal treatment.
Primary mucinous ovarian tumors vs. ovarian metastases from gastrointestinal tract, pancreas and biliary tree: a review of current problematics
Authors: Dundr Pavel , Singh Naveena , Nožičková Barbora , Němejcová Kristýna , Bártů Michaela , Stružinská Ivana 
Published: March 2021

AbstractBackgroundMaking the distinction between primary mucinous and metastatic ovarian tumors is often difficult, especially in tumors with a primary source from the gastrointestinal tract, pancreas and biliary tree. The aim of the following paper is to provide an overview of the problematics, with a focus on the possibilities of the differential diagnosis at the macroscopic, microscopic and immunohistochemical level.Main bodyThe three main aspects of mucinous ovarian tumors are described in detail, including the comparison of the available diagnostic algorithms based on the evaluation of mostly macroscopic features, characterization of the spectrum of microscopic features, and a detailed analysis of the immunophenotype comparing 20 antibodies with the assessment of their statistical significance for differential diagnosis purposes. Specific features, including Krukenberg tumor and pseudomyxoma peritonei, are also discussed.ConclusionDespite the growing knowledge of the macroscopic and microscopic features of ovarian mucinous tumors and the availability of a wide range of immunohistochemical antibodies useful in this setting, there still remains a group of tumors which cannot be precisely classified without close clinical-pathological cooperation.
The decision sampling framework: a methodological approach to investigate evidence use in policy and programmatic innovation
Authors: Mackie Thomas I. , Schaefer Ana J. , Hyde Justeen K. , Leslie Laurel K. , Bosk Emily A. , Fishman Brittany , Sheldrick R. Christopher 
Published: March 2021

Abstract
Background
Calls have been made for greater application of the decision sciences to investigate and improve use of research evidence in mental health policy and practice. This article proposes a novel method, “decision sampling,” to improve the study of decision-making and research evidence use in policy and programmatic innovation. An illustrative case study applies the decision sampling framework to investigate the decisions made by mid-level administrators when developing system-wide interventions to identify and treat the trauma of children entering foster care.

Methods
Decision sampling grounds qualitative inquiry in decision analysis to elicit information about the decision-making process. Our case study engaged mid-level managers in public sector agencies (n = 32) from 12 states, anchoring responses on a recent index decision regarding universal trauma screening for children entering foster care. Qualitative semi-structured interviews inquired on questions aligned with key components of decision analysis, systematically collecting information on the index decisions, choices considered, information synthesized, expertise accessed, and ultimately the values expressed when selecting among available alternatives.

Results
Findings resulted in identification of a case-specific decision set, gaps in available evidence across the decision set, and an understanding of the values that guided decision-making. Specifically, respondents described 14 inter-related decision points summarized in five domains for adoption of universal trauma screening protocols, including (1) reach of the screening protocol, (2) content of the screening tool, (3) threshold for referral, (4) resources for screening startup and sustainment, and (5) system capacity to respond to identified needs. Respondents engaged a continuum of information that ranged from anecdote to research evidence, synthesizing multiple types of knowledge with their expertise. Policy, clinical, and delivery system experts were consulted to help address gaps in available information, prioritize specific information, and assess “fit to context.” The role of values was revealed as participants evaluated potential trade-offs and selected among policy alternatives.

Conclusions
The decision sampling framework is a novel methodological approach to investigate the decision-making process and ultimately aims to inform the development of future dissemination and implementation strategies by identifying the evidence gaps and values expressed by the decision-makers, themselves.
Evidence for use of damage control surgery and damage control interventions in civilian trauma patients: a systematic review
Authors:   for the Indications for Trauma Damage Control Surgery International Study Group, Roberts Derek J. , Bobrovitz Niklas , Zygun David A. , Kirkpatrick Andrew W. , Ball Chad G. , Faris Peter D. , Stelfox Henry T. 
Published: March 2021

Abstract
Background
Although damage control (DC) surgery is widely assumed to reduce mortality in critically injured patients, survivors often suffer substantial morbidity, suggesting that it should only be used when indicated. The purpose of this systematic review was to determine which indications for DC have evidence that they are reliable and/or valid (and therefore in which clinical situations evidence supports use of DC or that DC improves outcomes).

Methods
We searched 11 databases (1950–April 1, 2019) for studies that enrolled exclusively civilian trauma patients and reported data on the reliability (consistency of surgical decisions in a given clinical scenario) or content (surgeons would perform DC in that clinical scenario or the indication predicted use of DC in practice), construct (were associated with poor outcomes), or criterion (were associated with improved outcomes when DC was conducted instead of definitive surgery) validity for suggested indications for DC surgery or DC interventions.

Results
Among 34,979 citations identified, we included 36 cohort studies and three cross-sectional surveys in the systematic review. Of the 59 unique indications for DC identified, 10 had evidence of content validity [e.g., a major abdominal vascular injury or a packed red blood cell (PRBC) volume exceeding the critical administration threshold], nine had evidence of construct validity (e.g., unstable patients with combined abdominal vascular and pancreas gunshot injuries or an iliac vessel injury and intraoperative acidosis), and six had evidence of criterion validity (e.g., penetrating trauma patients requiring > 10 U PRBCs with an abdominal vascular and multiple abdominal visceral injuries or intraoperative hypothermia, acidosis, or coagulopathy). No studies evaluated the reliability of indications.

Conclusions
Few indications for DC surgery or DC interventions have evidence supporting that they are reliable and/or valid. DC should be used with respect for the uncertainty regarding its effectiveness, and only in circumstances where definitive surgery cannot be entertained.
Smoking and alcohol, health-related quality of life and psychiatric comorbidities in Leber’s Hereditary Optic Neuropathy mutation carriers: a prospective cohort study
Authors: Rabenstein Andrea , Catarino Claudia B. , Rampeltshammer Verena , Schindler David , Gallenmüller Constanze , Priglinger Claudia , Pogarell Oliver , Rüther Tobias , Klopstock Thomas 
Published: March 2021

Abstract
Background
Leber’s hereditary optic neuropathy (LHON) is a rare mitochondrial disorder, characterized by acute or subacute bilateral vision loss, frequently leading to significant chronic disability, mainly in young people. The causal LHON mutations of the mitochondrial DNA have incomplete penetrance, with the highest risk of disease manifestation for male mutation carriers in the second and third decades of life. Here we evaluated smoking, alcohol drinking habits, health-related quality of life (QOL) and psychiatric comorbidities in a cohort of LHON patients and asymptomatic mutation carriers from a tertiary referral centre.

Methods
Cross-sectional analysis of the ongoing Munich LHON prospective cohort study. Participants included all LHON patients and asymptomatic LHON mutation carriers older than 16 years at baseline, who were recruited between February 2014 and June 2015 and consented to participate. General, neurological and ophthalmological investigations were performed, including validated questionnaires on smoking, alcohol drinking habits, depressive symptoms and health-related QOL.

Results
Seventy-one participants were included, 34 LHON patients (82% male) and 37 asymptomatic mutation carriers (19% male). Median age at baseline was 36 years (range 18–75 years). For LHON patients, median age at visual loss onset was 27 years (9 to 72 years). Smoking is more frequent in LHON patients than asymptomatic LHON mutation carriers, and significantly more frequent in both groups than in the general population. Sixty percent of LHON patients, who smoked at disease onset, stopped or significantly reduced smoking after visual loss onset, yet 40% of LHON patients continued to smoke at study baseline. Excessive alcohol consumption is more frequent in male LHON patients than in LHON asymptomatic and more frequent than in the male general population. Further, female asymptomatic LHON mutation carriers are at risk for depression and worse mental QOL scores.

Conclusions
Given the high prevalence of smoking and excessive drinking in LHON mutation carriers, implementing effective measures to reduce these risk factors may have a significant impact in reducing LHON disease conversion risk. The underrecognized prevalence of mental health issues in this population of LHON mutation carriers highlights the need for awareness and more timely diagnosis, which may lead to improved outcomes.
Biotechnological Activities and Applications of Bacterial Pigments Violacein and Prodigiosin
Authors: Choi Seong Yeol , Lim Sungbin , Yoon Kyoung-hye , Lee Jin I. , Mitchell Robert J. 
Published: March 2021

AbstractIn this review, we discuss violacein and prodigiosin, two chromogenic bacterial secondary metabolites that have diverse biological activities. Although both compounds were “discovered” more than seven decades ago, interest into their biological applications has grown in the last two decades, particularly driven by their antimicrobial and anticancer properties. These topics will be discussed in the first half of this review. The latter half delves into the current efforts of groups to produce these two compounds. This includes in both their native bacterial hosts and heterogeneously in other bacterial hosts, including discussing some of the caveats related to the yields reported in the literature, and some of the synthetic biology techniques employed in this pursuit.
THF co-solvent pretreatment prevents lignin redeposition from interfering with enzymes yielding prolonged cellulase activity
Authors: Patri Abhishek S. , Mohan Ramya , Pu Yunqiao , Yoo Chang G. , Ragauskas Arthur J. , Kumar Rajeev , Kisailus David , Cai Charles M. , Wyman Charles E. 
Published: March 2021

Abstract
Background
Conventional aqueous dilute sulfuric acid (DSA) pretreatment of lignocellulosic biomass facilitates hemicellulose solubilization and can improve subsequent enzymatic digestibility of cellulose to fermentable glucose. However, much of the lignin after DSA pretreatment either remains intact within the cell wall or readily redeposits back onto the biomass surface. This redeposited lignin has been shown to reduce enzyme activity and contribute to rapid enzyme deactivation, thus, necessitating significantly higher enzyme loadings than deemed economical for biofuel production from biomass.

Results
In this study, we demonstrate how detrimental lignin redeposition on biomass surface after pretreatment can be prevented by employing Co-solvent Enhanced Lignocellulosic Fractionation (CELF) pretreatment that uses THF–water co-solvents with dilute sulfuric acid to solubilize lignin and overcome limitations of DSA pretreatment. We first find that enzymatic hydrolysis of CELF-pretreated switchgrass can sustain a high enzyme activity over incubation periods as long as 5 weeks with enzyme doses as low as 2 mg protein/g glucan to achieve 90% yield to glucose. A modified Ninhydrin-based protein assay revealed that the free-enzyme concentration in the hydrolysate liquor, related to enzyme activity, remained unchanged over long hydrolysis times. DSA-pretreated switchgrass, by contrast, had a 40% drop in free enzymes in solution during incubation, providing evidence of enzyme deactivation. Furthermore, measurements of enzyme adsorption per gram of lignin suggested that CELF prevented lignin redeposition onto the biomass surface, and the little lignin left in the solids was mostly integral to the original lignin–carbohydrate complex (LCC). Scanning electron micrographs and NMR characterization of lignin supported this observation.

Conclusions
Enzymatic hydrolysis of solids from CELF pretreatment of switchgrass at low enzyme loadings was sustained for considerably longer times and reached higher conversions than for DSA solids. Analysis of solids following pretreatment and enzymatic hydrolysis showed that prolonged cellulase activity could be attributed to the limited lignin redeposition on the biomass surface making more enzymes available for hydrolysis of more accessible glucan.
Diagnostic significance of serum PP4R1 and its predictive value for the development of chronic complications in patients with type 2 diabetes mellitus
Authors: Li Wenjing , Peng Lanbo , Yang Chao , Chen Guangmin 
Published: March 2021

Abstract
Background
Protein phosphatase 4 regulatory subunit 1 (PP4R1) is one of the regulatory subunits of PP4. It has been determined to be involved in the regulation of TNF-α-induced hepatic insulin resistance and gluconeogenesis. Considering the important role of PP4R1 in hepatic insulin resistance, the current study explored the expression and diagnostic value of PP4R1 in type 2 diabetes mellitus (T2DM) patients and further investigated its predictive value for the development of chronic complications.

Method
Hundred and five patients with T2DM and 97 healthy controls were collected. qRT-PCR was used for the measurement of serum PP4R1 mRNA level in both T2DM and control groups. The diagnostic value of PP4R1 in T2DM patients was evaluated using receiver operating characteristic (ROC) curve. Kaplan-Meier methods and Cox regression analysis were used to evaluate the predictive value of PP4R1 for the development of chronic complications in T2DM patients.

Results
PP4R1 was determined to be elevated in the serum of T2DM patients compared with healthy controls. Serum PP4R1 had the potential to distinguish T2DM patients from healthy controls with a sensitivity of 81.9% and specificity of 82.5%. Patients with high PP4R1 expression experienced more chronic complications events. The multivariate Cox analysis results suggested that serum PP4R1 expression was an independent factor for the occurrence of chronic complications for T2DM patients.

Conclusion
PP4R1 is elevated in the serum of T2DM patients, had the potential to distinguish T2DM patients from healthy controls. PP4R1 serves as a promising biomarker for predicting the risk of future chronic complications in T2DM patients.
Effects of non-invasive brain stimulation in children and young people with psychiatric disorders: a protocol for a systematic review
Authors: Lewis Yael D. , Gallop Lucy , Campbell Iain C. , Schmidt Ulrike 
Published: March 2021

Abstract
Background
Most psychiatric disorders have their onset in childhood or adolescence, and if not fully treated have the potential for causing life-long psycho-social and physical sequelae. Effective psychotherapeutic and medication treatments exist, but a significant proportion of children and young people do not make a full recovery. Thus, novel, safe, brain-based alternatives or adjuncts to conventional treatments are needed. Repetitive transcranial magnetic stimulation (rTMS) and transcranial direct current stimulation (tDCS) are non-invasive brain stimulation (NIBS) techniques which have shown clinical benefits in adult psychiatric conditions. However, in children and young people their efficacy is not well established. The objective of this study will be to systematically evaluate the evidence on clinical effects of NIBS in children and young people with psychiatric disorders, assessing disorder-specific symptoms, mood and neurocognitive functions.

Methods
We designed and registered a study protocol for a systematic review. We will include randomised and non-randomised controlled trials and observational studies (e.g. cohort, case-control, case series) assessing the effects of NIBS in children and young people (aged ≤ 24 years old) for psychiatric disorders. The primary outcome will be reduction of disorder-specific symptoms. Secondary outcomes will include effects on mood and cognition. A comprehensive search from database inception onwards will be conducted in MEDLINE, EMBASE and PsycINFO. Grey literature will be identified through searching multiple clinical trial registries. Two reviewers will independently screen all citations, full-text articles and abstract data. The methodological quality of the studies will be appraised using appropriate tools. We will provide a narrative synthesis of the evidence and according to heterogeneity will conduct an appropriate meta-analysis. Additional analyses will be conducted to explore the potential sources of heterogeneity.

Discussion
This systematic review will provide a broad and comprehensive evaluation of the evidence on clinical effects of NIBS in children and young people with psychiatric disorders. Our findings will be reported according to the PRISMA guidelines and will be of interest to multiple audiences (including patients, researchers, healthcare professionals and policy-makers). Results will be published in a peer-reviewed journal.

Systematic review registration
PROSPERO CRD42019158957