bluuebunny/crossref_metadata_2025 huggingface dataset:
Association of NAT2 genetic polymorphism with the efficacy of Neurotropin® for the enhancement of aggrecan gene expression in nucleus pulposus cells: a pilot study
Authors: Nakai Tomoko , Sakai Daisuke , Nakamura Yoshihiko , Horikita Natsumi , Matsushita Erika , Naiki Mitsuru , Watanabe Masahiko
Published: March 2021

Background

Intervertebral disc degeneration, one of the major causes of low-back pain, results from altered biosynthesis/turnover of extracellular matrix in the disc. Previously, we reported that the analgesic drug Neurotropin® (NTP) had an anabolic effect on glycosaminoglycan synthesis in cultured nucleus pulposus (NP) cells via the stimulation of chondroitin sulfate N-acetylgalactosaminyltransferase 1. However, its effect on the aggrecan core protein was not significantly detected, because of the data variance. A microarray analysis suggested that the effect of NTP on aggrecan was correlated with N-acetyltransferase 2 (NAT2), a drug-metabolizing enzyme. Specific NAT2 alleles are known to correlate with rapid, intermediate, and slow acetylation activities and side effects of various drugs. We investigated the association between the efficacy of NTP on aggrecan expression and the NAT2 genotype in cell donors.

Methods

NP cells were isolated from intervertebral disc tissues donated by 31 Japanese patients (28–68 years) who underwent discectomy. NTP was added to the primary cell cultures and its effect on the aggrecan mRNA was analyzed using real-time quantitative PCR. To assess acetylator status, genotyping was performed based on the inferred NAT2 haplotypes of five common single-nucleotide polymorphisms using allele-specific PCR.

Results

The phenotype frequencies of NAT2 in the patients were 0%, 42.0%, and 58.0% for slow, intermediate, and rapid acetylators, respectively. The proportions of responders to NTP treatment (aggrecan upregulation, ≥ 1.1-fold) in the intermediate and rapid acetylators were 76.9% and 38.9%, respectively. The odds ratio of the comparison of the intermediate acetylator status between responders and nonresponders was 5.2 (95% CI 1.06–26.0, P = 0.036), and regarding the 19 male patients, this was 14.0 (95% CI 1.54–127.2, P = 0.012). In the 12 females, the effect was not correlated with NAT2 phenotype but seemed to become weaker along with aging.

Conclusions

An intermediate acetylator status significantly favored the efficacy of NTP treatment to enhance aggrecan production in NP cells. In males, this tendency was detected with higher significance. This study provides suggestive data of the association between NAT2 variants and the efficacy of NTP treatment. Given the small sample size, results should be further confirmed.
A pan-cancer study of selenoprotein genes as promising targets for cancer therapy
Authors: Wu Wentao , Li Daning , Feng Xiaojie , Zhao Fanfan , Li Chengzhuo , Zheng Shuai , Lyu Jun
Published: March 2021

Background

The most important health benefit of selenium (Se) is in the prevention and control of cancer. Glutathione peroxidases (GPXs) and thioredoxin reductases (TXNRDs) are selenoenzymes that are thought to play a role in oxidative stress. The differential expression of genes of the TXNRD and GPX families is closely related to carcinogenesis and the occurrence of cancer. This study comprehensively analyzed the expression profiles of seven genes in the TXNRD and GPX families, in terms of their correlations with patient survival and immune-cell subtypes, tumor microenvironment, and drug sensitivity.

Results

The expression profiles of genes in the TXNRD and GPX families differ between different types of cancer, and also between and within individual cancer cases. The expression levels of the seven analyzed genes are related to the overall survival of patients. The TXNRD1 and TXNRD3 genes are mainly related to poor prognoses, while other genes are related to good or poor prognoses depending on the type of cancer. All of the genes were found to be correlated to varying degrees with immune-cell subtypes, level of mechanistic cell infiltration, and tumor cell stemness. The TXNRD1, GPX1, and GPX2 genes may exert dual effects in tumor mutagenesis and development, while the TXNRD1, GPX1, GPX2, and GPX3 genes were found to be related to drug sensitivity or the formation of drug resistance.

Conclusions

The results will greatly help in identifying the association between genes and tumorigenesis, especially in the immune response, tumor microenvironment, and drug resistance, and very important when attempting to identify new therapeutic targets.
“A piece of paper is not the same as having someone to talk to”: accessing post-diagnostic dementia care before and since COVID-19 and associated inequalities
Authors: Giebel Clarissa , Hanna Kerry , Tetlow Hilary , Ward Kym , Shenton Justine , Cannon Jacqueline , Butchard Sarah , Komuravelli Aravind , Gaughan Anna , Eley Ruth , Rogers Carol , Rajagopal Manoj , Limbert Stan , Callaghan Steve , Whittington Rosie , Shaw Lisa , Gabbay Mark
Published: March 2021

Background

Social support services such as day care centres are important in post-diagnostic dementia care to enable people living with dementia stay at home for longer. Little research has addressed potential inequalities in access, with no research on variations before and since COVID-19. The aim of this study was to explore inequalities in social support service usage before and since the pandemic.

Methods

Unpaid carers and people living with dementia were interviewed over the phone about their experiences of accessing social support services before and since the COVID-19 pandemic. Transcripts were analysed for key themes using inductive and deductive thematic analysis.

Results

Fifty participants (42 unpaid carers; eight people living with dementia) were interviewed, and five themes identified: (1) Service issues; (2) Access issues; (3) Relying on own initiative; (4) New inequalities due to COVID-19; and (5) Missing out on the benefits of support services. Participants reported transport, finances, and location as factors reducing their ability to access support service pre-COVID, with inequalities remaining and at times exacerbated since. Carers and people living with dementia also reported struggling with accessing basic necessities during COVID, including food and medicines.

Conclusions

Considering the benefits of accessing support services, resourced procedures and facilities are needed to maintain access to support services with more accessible remote support provision, enabling people from all backgrounds to access the care they need.
Evaluating cancer research impact: lessons and examples from existing reviews on approaches to research impact assessment
Authors: Hanna Catherine R. , Boyd Kathleen A. , Jones Robert J.
Published: March 2021

Background

Performing cancer research relies on substantial financial investment, and contributions in time and effort from patients. It is therefore important that this research has real life impacts which are properly evaluated. The optimal approach to cancer research impact evaluation is not clear. The aim of this study was to undertake a systematic review of review articles that describe approaches to impact assessment, and to identify examples of cancer research impact evaluation within these reviews.

Methods

In total, 11 publication databases and the grey literature were searched to identify review articles addressing the topic of approaches to research impact assessment. Information was extracted on methods for data collection and analysis, impact categories and frameworks used for the purposes of evaluation. Empirical examples of impact assessments of cancer research were identified from these literature reviews. Approaches used in these examples were appraised, with a reflection on which methods would be suited to cancer research  impact evaluation going forward.

Results

In total, 40 literature reviews were identified. Important methods to collect and analyse data for impact assessments were surveys, interviews and documentary analysis. Key categories of impact spanning the reviews were summarised, and a list of frameworks commonly used for impact assessment was generated. The Payback Framework was most often described. Fourteen examples of impact evaluation for cancer research were identified. They ranged from those assessing the impact of a national, charity-funded portfolio of cancer research to the clinical practice impact of a single trial. A set of recommendations for approaching cancer research impact assessment was generated.

Conclusions

Impact evaluation can demonstrate if and why conducting cancer research  is worthwhile. Using a mixed methods, multi-category assessment organised within a framework, will provide a robust evaluation, but the ability to perform this type of assessment may be constrained by time and resources. Whichever approach is used, easily measured, but inappropriate metrics should be avoided. Going forward, dissemination of the results of cancer research impact assessments will allow the cancer research community to learn how to conduct these evaluations.
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

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

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

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

Background

Making 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 body

The 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.

Conclusion

Despite 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

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

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

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

In 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

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

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

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
The cost-effectiveness of government actions to reduce sodium intake through salt substitutes in Vietnam
Authors: Taylor Colman , Hoek Annet C. , Deltetto Irene , Peacock Adrian , Ha Do Thi Phuong , Sieburg Michael , Hoang Dolly , Trieu Kathy , Cobb Laura K. , Jan Stephen , Webster Jacqui
Published: March 2021

Background

Dietary sodium reduction is recommended to reduce the burden of cardiovascular disease. In Vietnam food products including salt, fish sauce and bot canh contribute to ~ 70% of dietary sodium intake. Reduced sodium versions of these products can be produced by replacing some of the sodium chloride with potassium chloride. We aimed to assess the cost-effectiveness of three alternative approaches to introducing reduced sodium products onto the market with a view to lowering population sodium intake in Vietnam.

Methods

The three salt substitution strategies included voluntary, subsidised and regulatory approaches targeting salt, fish sauce and bot canh products. Costs were modelled using the WHO-CHOICE methodology. A Markov cohort model was developed to evaluate the cost-effectiveness of each strategy versus no intervention from the government perspective. The model linked each intervention strategy to assumed changes in levels of sodium intake and then to systolic blood pressure. Changes in SBP were linked to a probability of ischaemic heart disease or stroke. The model followed people over their lifetime to assess average costs and quality adjusted life years (QALYs) gained for each strategy.

Results

The voluntary salt substitution strategy was assumed to require no investment by government. Following ramp up (years 6+), the average annual costs for the subsidised and regulatory strategies were 21,808,968,902 ₫ (US$ 977,354) and 12,949,953,247 ₫ (US$ 580,410) respectively. Relative to no intervention, all three salt substitution strategies were found to be cost-effective. Cost savings were driven by reductions in strokes (32,595; 768,384; 2,366,480) and ischaemic heart disease (IHD) events (22,830; 537,157; 1,648,590) for the voluntary, subsidised & regulatory strategies, respectively. The voluntary strategy was least cost-effective (− 3445 ₫ US$ -0.15; 0.009 QALYs gained) followed by the subsidised strategy (− 43,189 ₫ US$ -1.86; 0.022 QALYs gained) and the regulatory strategy delivered the highest cost savings and health gains (− 243,530 ₫ US$ -10.49; 0.074 QALYs gained).

Conclusion

This research shows that all three modelled salt substitution strategies would be good value for money relative to no intervention in Vietnam. The subsidised alternative would require the highest level of government investment; however the implementation costs will be exceeded by healthcare savings assuming a reasonable time horizon is considered.
Foley catheter with noble metal alloy coating for preventing catheter-associated urinary tract infections: a large, multi-center clinical trial
Authors: Kai-Larsen Ylva , Grass Stefan , Mody Bhaumik , Upadhyay Swati , Trivedi Hargovind L. , Pal Dilip. K. , Babu Santosh , Bawari Bikash , Singh Shrawan. K.
Published: March 2021

Background

Catheter-associated urinary tract infections (CAUTI) are among the most frequent healthcare-associated infections in the world. They are associated with increased mortality, prolonged hospital stay and increased healthcare costs. The objective of this study was to evaluate the efficacy of the noble metal alloy (NMA) coated BIP Foley Catheter in preventing the incidence of symptomatic CAUTI in a large cohort of patients in India.

Methods

This multi-center, prospective study included 1000 adult patients admitted to six hospitals across India for urology, surgery and ICU requiring urethral catheterization and admission for ≥ 48 h. Patients were allocated to the NMA-coated BIP Foley Catheter group or a non-coated control catheter group, with a randomization ratio of 3:1. CAUTI surveillance was conducted at study entry, upon catheter removal, and 2 days after catheter removal. For statistical analysis, categorical data (e.g. gender) were compared using the chi-square or Fischer test, and numerical data were compared using the two-sample t-test. Associations were evaluated using logistic regression.

Results and conclusions

The incidence of symptomatic CAUTI was reduced by 69% in the BIP Foley Catheter group compared to the control group (6.5 vs 20.8 CAUTI/1000 catheter days), with an incidence rate ratio of 0.31 (95% confidence interval: 0.21–0.46; p < 0.001). A reduction in the cumulative CAUTI incidence was evident in the BIP Foley Catheter group within 3 days after catheterization; this reduction was maintained up to ~ 30 days, and the largest reductions were seen between 3 and 11 days. There were no serious adverse events related to either catheter, and the percentage of patients with ≥ 1 adverse event was significantly lower in the NMA-coated BIP Foley Catheter group than in the control group (21.6% vs. 48.4%; p = 0.001). In conclusion, the NMA-coated BIP Foley Catheter was effective in reducing CAUTI and was well tolerated, with a lower incidence of adverse events compared to the uncoated catheter.

Trial registration This study was registered prospectively (28 September 2015) in the Clinical Trials Registry of India (trial number CTRI/2015/09/006220; http://ctri.nic.in/Clinicaltrials/showallp.php?mid1=12631&EncHid=&userName=bactiguard).
Impact of previous exposure to systemic corticosteroids on unfavorable outcome in patients hospitalized for COVID-19
Authors:   and the Covid-Clinic-Toul investigators, Lafaurie Margaux , Martin-Blondel Guillaume , Delobel Pierre , Kamar Nassim , Charpentier Sandrine , Sommet Agnès , Moulis Guillaume
Published: March 2021

Background

The impact of prior exposure to systemic corticosteroids on COVID-19 severity in patients hospitalized for a SARS-CoV-2 pneumonia is not known. The present study was designed to answer to this question.

Methods

The population study was the Covid-Clinic-Toul cohort which records data about all hospitalized patients with a positive reverse transcriptase polymerase chain reaction for a SARS-CoV-2 infection at Toulouse University hospital, France. Exposure to systemic corticosteroids was assessed at hospital admission. A propensity score (PS) according to corticosteroid exposure was calculated including comorbidities, clinical, radiological and biological variables that impact COVID-19 severity. The primary outcome was composite, including admission to intensive care unit, need of mechanical ventilation and death occurring during the 14 days after hospital admission. Logistic regression models adjusted for the PS (overlap weighting) provided odds ratios (ORs) and their 95% confidence intervals (95% CIs).

Results

Overall, 253 patients were included in the study. Median age was 64 years, 140 patients (59.6%) were men and 218 (86.2%) had at least one comorbidity. Seventeen patients (6.7%) were exposed to corticosteroids before hospital admission. Chronic inflammatory disease (n = 8) was the most frequent indication. One hundred and twenty patients (47.4%) met the composite outcome. In the crude model, the OR of previous exposure to systemic corticosteroids was 1.64; 95% CI: 0.60–4.44. In the adjusted model, it was 1.09 (95% CI: 0.65–1.83).

Conclusion

Overall, this study provide some evidences for an absence of an increased risk of unfavorable outcome with previous exposure to corticosteroids in the general setting of patients hospitalized for COVID-19.
Data science approach to stock prices forecasting in Indonesia during Covid-19 using Long Short-Term Memory (LSTM)
Authors: Budiharto Widodo
Published: March 2021

Background

Stock market process is full of uncertainty; hence stock prices forecasting very important in finance and business. For stockbrokers, understanding trends and supported by prediction software for forecasting is very important for decision making. This paper proposes a data science model for stock prices forecasting in Indonesian exchange based on the statistical computing based on R language and Long Short-Term Memory (LSTM).

Findings

The first Covid-19 (Coronavirus disease-19) confirmed case in Indonesia is on 2 March 2020. After that, the composite stock price index has plunged 28% since the start of the year and the share prices of cigarette producers and banks in the midst of the corona pandemic reached their lowest value on March 24, 2020. We use the big data from Bank of Central Asia (BCA) and Bank of Mandiri from Indonesia obtained from Yahoo finance. In our experiments, we visualize the data using data science and predict and simulate the important prices called Open, High, Low and Closing (OHLC) with various parameters.

Conclusions

Based on the experiment, data science is very useful for visualization data and our proposed method using Long Short-Term Memory (LSTM) can be used as predictor in short term data with accuracy 94.57% comes from the short term (1 year) with high epoch in training phase rather than using 3 years training data.
Recent advances in electroconvulsive therapy and physical treatments for depression
Authors: Ferrier I. Nicol , Waite Jonathan , Sivasanker Vimal
Published: March 2021

This article gives an update for practitioners on recent developments in the use of electroconvulsive therapy (ECT) and related treatment modalities in the contemporary treatment of depression in the UK. Details are provided on new information on the efficacy and side-effects of ECT both in research studies and in the real world, together with recent research on ECT's mode of delivery. There is a focus on the safe administration of ECT in clinical practice. An update on the regulatory framework for ECT in the UK is provided, together with up-to-date information on the legal situation regarding its prescription. Finally, brief summaries of the current position for other neuromodulatory treatment modalities are given.
Container Closure and Delivery Considerations for Intravitreal Drug Administration
Authors: Parenky Ashwin C. , Wadhwa Saurabh , Chen Hunter H. , Bhalla Amardeep S. , Graham Kenneth S. , Shameem Mohammed
Published: March 2021

Intravitreal (IVT) administration of therapeutics is the standard of care for treatment of back-of-eye disorders. Although a common procedure performed by retinal specialists, IVT administration is associated with unique challenges related to drug product, device and the procedure, which may result in adverse events. Container closure configuration plays a crucial role in maintaining product stability, safety, and efficacy for the intended shelf-life. Careful design of primary container configuration is also important to accurately deliver small volumes (10-100 μL). Over- or under-dosing may lead to undesired adverse events or lack of efficacy resulting in unpredictable and variable clinical responses. IVT drug products have been traditionally presented in glass vials. However, pre-filled syringes offer a more convenient administration option by reducing the number of steps required for dose preparation there by potentially reducing the time demand on the healthcare providers. In addition to primary container selection, product development studies should focus on, among other things, primary container component characterization, material compatibility with the formulation, formulation stability, fill volume determination, extractables/leachables, and terminal sterilization. Ancillary components such as disposable syringes and needles must be carefully selected, and a detailed administration procedure that includes dosing instructions is required to ensure successful administration of the product. Despite significant efforts in improving the drug product and administration procedures, ocular safety concerns such as endophthalmitis, increased intraocular pressure, and presence of silicone floaters have been reported. A systematic review of available literature on container closure and devices for IVT administration can help guide successful product development.
Accessing Kardar-Parisi-Zhang universality sub-classes with exciton polaritons
(a)
Authors: Deligiannis Konstantinos , Squizzato Davide , Minguzzi Anna , Canet Léonie
Published: March 2021

Exciton-polariton condensates under driven-dissipative conditions are predicted to belong to the Kardar-Parisi-Zhang (KPZ) universality class, the dynamics of the condensate phase at long distance satisfying the same equation as for classical stochastic interface growth. We show that by engineering an external confinement for one-dimensional polaritons we can access two different universality sub-classes, which are associated to the flat or curved geometry for the interface. Our results for the condensate phase distribution and correlations match with great accuracy with the exact theoretical results for KPZ: the Tracy-Widom distributions (GOE and GUE) for the one-point statistics, and covariance of Airy processes (Airy1 and Airy2) for the two-point statistics. This study promotes the exciton-polariton system as a compelling platform to investigate KPZ universal properties.
Introduction: Thinking Comparison with the Politics of Storytelling
Authors: Rodríguez-Silva Ileana M. , Sears Laurie J.
Published: March 2021

This article highlights the overall aims of the special issue, which reconceptualizes island worlds as situated historical places, that is, islands and their networks as spaces that come to life through the multiple and contested meanings constantly attached to them, formed in the milieu of overlapping and competing European, US, and Southeast Asian empires and diasporas. By investigating the forms and politics of storytelling in the island South and Southeast Asia, along with parallel and intersecting formations in the Caribbean and diasporic Asian America, this article underlines the two scholarly interventions of the special issue in the study of world making: (1) it refashions the notion of comparison to move away from the project of “knowing”—habitually constituted through a top-down gaze aimed at assessment and measuring, which consequently leads to the formation of hierarchies, categories of containment, and reductionism—and to unearth forms of comparison emerging from local environments and local knowledge; and (2) in thinking of storytelling events or inscriptions as situated testimonies (i.e., identifying the politics of location of a telling), it centers affect and emotion as the means for unraveling and connecting different, contesting registers of experience.
Model Study toward Total Synthesis of Dimeric Pyranonaphthoquinones: Synthesis of Hemi-Actinorhodin
Authors: Ando Yoshio , Fukazawa Takumi , Ohmori Ken , Suzuki Keisuke
Published: March 2021

In connection with our synthetic study toward the dimeric pyranonaphthoquinone antibiotics, actinorhodin (1) and β-naphthocyclinone (3), we describe herein the synthesis of a monomer, hemi-actinorhodin (6) as a model target. Several implications were gained, including (1) stereoselective synthesis of the pyranonaphthoquinone, (2) viable construction of the naphthazarin core, and (3) the final deprotection conditions.