bluuebunny/crossref_metadata_2025_split huggingface dataset:
Addressing Patient Safety Hazards Using Critical Incident Reporting in Hospitals: A Systematic Review
Authors: Goekcimen Ken , Schwendimann René , Pfeiffer Yvonne , Mohr Giulia , Jaeger Christoph , Mueller Simon 
Published: August 2022

Introduction
Critical incident reporting systems (CIRS) are in use worldwide. They are designed to improve patient care by detecting and analyzing critical and adverse patient events and by taking corrective actions to prevent reoccurrence. Critical incident reporting systems have recently been criticized for their lack of effectiveness in achieving actual patient safety improvements. However, no overview yet exists of the reported incidents’ characteristics, their communication within institutions, or actions taken either to correct them or to prevent their recurrence. Our main goals were to systematically describe the reported CIRS events and to assess the actions taken and their learning effects. In this systematic review of studies based on CIRS data, we analyzed the main types of critical incidents (CIs), the severity of their consequences, their contributing factors, and any reported corrective actions.

Methods
Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, we queried MEDLINE, Embase, CINAHL, and Scopus for publications on hospital-based CIRS. We classified the consequences of the incidents according to the National Coordinating Council for Medication Error Reporting and Prevention index, the contributing factors according to the Yorkshire Contributory Factors Framework and the Human Factors Classification Framework, and all corrective actions taken according to an action hierarchy model on intervention strengths.

Results
We reviewed 41 studies, which covered 479,483 CI reports from 212 hospitals in 17 countries. The most frequent type of incident was medication related (28.8%); the most frequent contributing factor was labeled “active failure” within health care provision (26.1%). Of all professions, nurses submitted the largest percentage (83.7%) of CI reports. Actions taken to prevent future CIs were described in 15 studies (36.6%). Overall, the analyzed studies varied considerably regarding methodology and focus.

Conclusions
This review of studies from hospital-based CIRS provides an overview of reported CIs’ contributing factors, characteristics, and consequences, as well as of the actions taken to prevent their recurrence. Because only 1 in 3 studies reported on corrective actions within the healthcare facilities, more emphasis on such actions and learnings from CIRS is required. However, incomplete or fragmented reporting and communication cycles may additionally limit the potential value of CIRS. To make a CIRS a useful tool for improving patient safety, the focus must be put on its strength of providing new qualitative insights in unknown hazards and also on the development of tools to facilitate nomenclature and management CIRS events, including corrective actions in a more standardized manner.
Risk factors for pneumococcal carriage in adults living with HIV on antiretroviral therapy in the infant pneumococcal vaccine era in Malawi
Authors: Thindwa Deus , Mwalukomo Thandie S. , Msefula Jacquline , Jambo Kondwani C. , Brown Comfort , Kamng’ona Arox , Mwansambo Charles , Ojal John , Flasche Stefan , French Neil , Heyderman Robert S. , Swarthout Todd D. 
Published: August 2022

Objective:
Adults living with HIV (ALWHIV) on antiretroviral therapy (ART) are at high risk of pneumococcal carriage and disease. To help evaluate carriage risk in African ALWHIV at least 4 years after infant pneumococcal conjugate vaccination introduction in 2011, we assessed association between pneumococcal carriage and potential risk factors.

Methods:
Nasopharyngeal swabs were collected from adults aged 18–40 years attending an ART clinic during rolling, cross-sectional surveys in Blantyre, Malawi between 2015 and 2019. We fitted generalized additive models to estimate the risk of sex, social economic status (SES), living with a child less than 5 years, and ART duration on carriage.

Results:
Of 2067 adults, median age was 33 years (range 28–37), 1427 (69.0%) were women, 1087 (61.4%) were in low–middle socioeconomic-status (SES), 910 (44.0%) were living with a child less than 5 years, and median ART duration was 3 years (range 0.004–17). We estimated 38.2 and 60.6% reductions in overall and vaccine-serotype carriage prevalence. Overall carriage was associated with low SES, living with a child less than 5 years and shorter duration on ART. By contrast, vaccine-type carriage was associated with living without a child less than 5 years and male sex.

Conclusion:
Despite temporal reductions in overall and vaccine-serotype carriage, there is evidence of incomplete vaccine-serotype indirect protection. A targeted-vaccination campaign should be considered for ALWHIV, along with other public health measures to further reduce vaccine-serotype carriage and therefore disease.
With the Increasing Health Awareness: Clinical and Computed Tomography Findings in Primary Pulmonary Mucosa-Associated Lymphoid Tissue Lymphoma Lymphoma
Authors: Xie Xiaodong , Dong Min , Zhang Lei , Ding Deqin , Huang Xing , Shen Wenrong , Zhou Zhengyang 
Published: August 2022

Objective
The objective of this study is to investigate the clinical manifestations, computed tomography (CT) findings, and prognosis of primary pulmonary mucosa-associated lymphoid tissue lymphoma (MALToma) with the improved health awareness nowadays.

Methods
Clinical data and CT images of patients with pathologically confirmed MALToma from October 2012 to October 2021 were retrospectively analyzed.

Results
Eighteen MALToma patients were included in the study (8 men and 10 women; mean age, 56.17 years; range, 33–73 years). Six men had a long-term history of smoking (>20 years). One patient had an autoimmune disease (Sjögren syndrome). Eight patients (44.44%) were asymptomatic, and 10 (55.56%) had mild chest or systemic symptoms. Most lesions (88.89%) were subpleural or located along the bronchovascular tree. According to the CT characteristics, the lesions were divided into 4 groups: nodular type (n = 8; 44.44%, including 5 solid nodules and 3 ground-glass nodules), mass type (n = 4, 22.22%), patch or consolidate type (n = 5, 27.78%), and mixed type (n = 1, 5.56%). Air bronchogram (11/18, 61.11%) and angiogram sign (8/16, 50%) were the most frequent CT findings and may help differential diagnosis. The patients were misdiagnosed with lung cancer (n = 11, 61.11%), inflammatory or chronic inflammatory disease (n = 4, 22.22%), bronchiectasis accompanied by infection (n = 1, 5.56%), diffuse interstitial lung disease (n = 1, 5.56%), and granuloma or tuberculosis (n = 1, 5.56%). The prognosis of all patients was favorable; 1 patient was lost to follow-up.

Conclusions
Nowadays, patients with MALToma are usually asymptomatic or paucisymptomatic. Nodular lesions, including ground-glass nodules, are the most common presentation. Mucosa-associated lymphoid tissue lymphoma is most likely misdiagnosed as lung cancer. Lesions located in the subpleural areas or along the bronchovascular tree and presenting with an air bronchogram or angiogram sign could indicate a MALToma diagnosis.
PLATELET FUNCTION IN TRAUMA: IS CURRENT TECHNOLOGY IN FUNCTION TESTING MISSING THE MARK IN INJURED PATIENTS?
Authors: Schriner Jacob B. , George Mitchell J. , Cardenas Jessica C. , Olson Scott D. , Mankiewicz Kimberly A. , Cox Charles S. , Gill Brijesh S. , Wade Charles E. 
Published: August 2022

ABSTRACT
Platelets are subcellular anucleate components of blood primarily responsible for initiating and maintaining hemostasis. After injury to a blood vessel, platelets can be activated via several pathways, resulting in changed shape, adherence to the injury site, aggregation to form a plug, degranulation to initiate activation in other nearby platelets, and acceleration of thrombin formation to convert fibrinogen to fibrin before contracting to strengthen the clot. Platelet function assays use agonists to induce and measure one or more of these processes to identify alterations in platelet function that increase the likelihood of bleeding or thrombotic events. In severe trauma, these assays have revealed that platelet dysfunction is strongly associated with poor clinical outcomes. However, to date, the mechanism(s) causing clinically significant platelet dysfunction remain poorly understood. We review the pros, cons, and evidence for use of many of the popular assays in trauma, discuss limitations of their use in this patient population, and present approaches that can be taken to develop improved functional assays capable of elucidating mechanisms of trauma-induced platelet dysfunction. Platelet dysfunction in trauma has been associated with need for transfusions and mortality; however, most of the current platelet function assays were not designed for evaluating trauma patients, and there are limited data regarding their use in this population. New or improved functional assays will help define the mechanisms by which platelet dysfunction occurs, as well as help optimize future treatment.
Study Protocol for a Research and Development Project: Optimizing a Unified Parent Training Intervention to Prevent Child Mental Health Problems and Neglect
Authors: Tømmerås Truls , Backer-Grøndahl Agathe , Arnesen Anne , Apeland Anett , Laland Hanne , Askeland Elisabeth , Kjøbli John , Idsøe Thormod , Grønlie Anette Arnesen , Begõna Gomez Maria , Aakre Karlsson Line Ragna , Dyrkoren Elise , Torsvik Sissel , Høstmælingen Andreas , Amlund-Hagen Kristine , Forgatch Marion , Fisher Phillip Andrew 
Published: August 2022

AbstractThis protocol describes a research and development (R&D) project aimed at optimizing a targeted, preventive, efficacious, and tailored intervention called Supportive Parents – Coping Kids (SPARCK). Combining recent developments in basic and intervention research, the goal of this project is to develop, test and optimize a unified parent training intervention targeting children who display externalizing and internalizing symptoms and parents who are at risk of exhibiting maladaptive or neglectful parenting behaviors. We plan to utilize various design-based research methodologies to investigate what works for whom in which context, points which are essential to the innovation process, by employing a mixed methods research design and an iterative optimization process of testing and refinement. Furthermore, we introduce a cocreation process for SPARCK to involve relevant stakeholders working in Norwegian frontline services for children and their families to ensure that the intervention adheres to the needs and constraints encountered by these stakeholders and thereby promote the scalability and sustainable implementation of SPARCK. In this paper, we present the theoretical and methodological background of this approach to R&D in the field of mental health prevention as well as the operationalization of innovative methodology in the current project. This R&D approach aims to produce new knowledge concerning individual change mechanisms in parent training interventions and stakeholder feedback pertaining to intervention components and implementation strategies, all of which are imperative for the iterative SPARCK design process.
A conserved HOTAIRM1-HOXA1 regulatory axis coordinates early neuronal differentiation
Authors: Segal Dana , Coulombe Samy , Sim Jasper , Dostie Josée 
Published: August 2022

AbstractHOTAIRM1 is unlike most long non-coding RNAs in that its sequence is highly conserved across mammals. Such evolutionary conservation points to it having a role in key cellular processes. We previously reported that HOTAIRM1 is required to curb premature activation of downstream HOXA genes in a cell model recapitulating their sequential induction during development. We found that it regulates 3’ HOXA gene expression by a mechanism involving epigenetic and three-dimensional chromatin changes. Here we show that HOTAIRM1 is required for proper progression through the early stages of neuronal differentiation. We found that it associates with the HOXA1 transcription factor and participates in its downstream transcriptional program. Particularly, HOTAIRM1 affects the NANOG/POU5F1/SOX2 core pluripotency network maintaining an undifferentiated cell state. HOXA1 depletion similarly perturbed expression of these pluripotent factors, suggesting that HOTAIRM1 is a modulator of this transcription factor pathway. Also, given that binding of HOTAIRM1 to HOXA1 was observed in different cell types and species, our results point to this ribonucleoprotein complex as an integral part of a conserved HOTAIRM1-HOXA1 regulatory axis controlling the transition from a pluripotent to a differentiated neuronal state.
Mathematical Modeling Of Systems Biology
Authors: Gupta Aaditya Prasad 
Published: August 2022

ABSTRACTA modeling is a mathematical tool, like a microscope, which allows consequences to logically follow from a set of assumptions by which a real world problem can be described by a mathematical formulation. It has become indispensable tools for integrating and interpreting heterogeneous biological data, validating hypothesis and identifying potential diagnostic markers. The modern molecular biology that is characterized by experiments that reveal the behaviours of entire molecular systems is called systems biology. A fundamental step in synthetic biology and systems biology is to derive appropriate mathematical model for the purposes of analysis and design. This manuscript has been engaged in the use of mathematical modeling in the Gene Regulatory System (GRN). Different mathematical models that are inspired in gene regulatory network such as Central dogma, Hill function, Gillespie algorithm, Oscillating gene network and Deterministic vs Stochastic modelings are discussed along with their codes that are programmed in Python using different modules. Here, we underlined that the model should describes the continuous nature of the biochemical processes and reflect the non-linearity. It is also found that the stochastic model is far better than deterministic model to calculate future event exactly with low chance of error.
Epistasis lowers the genetic barrier to SARS-CoV-2 neutralizing antibody escape
Authors: Witte Leander , Baharani Viren , Schmidt Fabian , Wang Zijun , Cho Alice , Raspe Raphael , Guzman-Cardozo Maria C. , Muecksch Frauke , Gaebler Christian , Caskey Marina , Nussenzweig Michel C. , Hatziioannou Theodora , Bieniasz Paul D. 
Published: August 2022

AbstractConsecutive waves of SARS-CoV-2 infection have been driven in part by the repeated emergence of variants with mutations that confer resistance to neutralizing antibodies Nevertheless, prolonged or repeated antigen exposure generates diverse memory B-cells that can produce affinity matured receptor binding domain (RBD)-specific antibodies that likely contribute to ongoing protection against severe disease. To determine how SARS-CoV-2 omicron variants might escape these broadly neutralizing antibodies, we subjected chimeric viruses encoding spike proteins from ancestral, BA.1 or BA.2 variants to selection pressure by a collection of 40 broadly neutralizing antibodies from individuals with various SARS-CoV-2 antigen exposures. Notably, pre-existing substitutions in the BA.1 and BA.2 spikes facilitated acquisition of resistance to many broadly neutralizing antibodies. Specifically, selection experiments identified numerous RBD substitutions that did not confer resistance to broadly neutralizing antibodies in the context of the ancestral Wuhan-Hu-1 spike sequence, but did so in the context of BA.1 and BA.2. A subset of these substitutions corresponds to those that have appeared in several BA.2 daughter lineages that have recently emerged, such as BA.5. By including as few as 2 or 3 of these additional changes in the context of BA.5, we generated spike proteins that were resistant to nearly all of the 40 broadly neutralizing antibodies and were poorly neutralized by plasma from most individuals. The emergence of omicron variants has therefore not only allowed SARS-CoV-2 escape from previously elicited neutralizing antibodies but also lowered the genetic barrier to the acquisition of resistance to the subset of antibodies that remained effective against early omicron variants.
The short chain fatty acid propionic acid activates the Rcs stress response system partially through inhibition of D-alanine racemase
Authors: Harshaw Nathaniel S. , Meyer Mitchell D. , Stella Nicholas A. , Lehner Kara M. , Kowalski Regis P. , Shanks Robert M.Q. 
Published: August 2022

AbstractThe Enterobacterial Rcs stress response system reacts to envelope stresses through a complex two-component phosphorelay system to regulate a variety of environmental response genes such as capsular polysaccharide and flagella biosynthesis. However, beyond Escherichia coli, the stresses that activate Rcs are not well understood. In this study, we used a Rcs system dependent luminescent transcriptional reporter to screen a library of over 240 antimicrobial compounds for those that activated the Rcs system in Serratia marcescens, a Yersiniaceae family bacterium. Using an isogenic rcsB mutant to establish specificity, both new and expected activators were identified including the short chain fatty acid propionic acid found at millimolar levels in the human gut. Propionic acid did not reduce bacterial intracellular pH as hypothesized for its antibacterial mechanism. Rather than reduction of intracellular pH, data suggests that the Rcs-activating mechanism of propionic acid is, in part, due to inactivation of the enzyme alanine racemase. This enzyme is responsible for D-alanine biosynthesis, an amino-acid required for generating bacterial cell walls. These results suggest host gut short chain fatty acids can influence bacterial behavior through activation of the Rcs stress response system.
A feasibility study of perioperative vitamin D supplementation in patients undergoing colorectal cancer resection
Authors: Vaughan-Shaw P.G. , Buijs L.F. , Blackmur J.P. , Ewing A. , Theodoratou E. , Ooi Li-Yin. , Din F.V.N. , Farrington S.M. , Dunlop M.G. 
Published: August 2022

ABSTRACTBACKGROUNDPost-operative vitamin D supplementation improves CRC survival outcomes in randomised trials. The aim of this study was to test the feasibility, safety and efficacy of vitamin D in the pre- and perioperative period in patients undergoing CRC surgery.METHODSPatients were given 3200IU oral cholecalciferol per day perioperatively. Serial serum 25OHD was measured by liquid chromatography tandem mass spectrometry and compared to untreated CRC controls. 25OHD/CRP levels were compared using adjusted generalized linear mixed-effects models.RESULTS122 patients underwent serial perioperative sampling, including 41 patients given high-dose perioperative supplementation. 25OHD was higher in patients given high-dose supplementation compared to controls at all peri-operative timepoints (P<0.001) and supplementation attenuated the post-operative drop in 25OHD (46% vs 24% drop). Rate of vitamin D insufficiency was significantly less in those on supplementation (14% vs. 56%, P=0.003), with multivariate modelling indicating a ∼60nmol/l higher 25OHD compared to control patients (P=1.22E-15). Supplementation was associated with lower peri-operative CRP (P=0.035).DISCUSSIONSHigh dose pre-operative vitamin D supplementation is associated with higher perioperative 25OHD levels, lower rates of vitamin D insufficiency and reduced early postoperative CRP. These findings provide compelling rationale for early initiation of vitamin D supplementation after a diagnosis of CRC.
Prevalence of non-communicable diseases risk factors and their determinants in Malawi: Evidence from 2017 WHO STEPwise Survey
Authors: Ng’ambi Wingston Felix , Mwase Takondwa , Chinkhumba Jobiba , Udedi Michael , Chigaru Farai , Banda Jonathan Chiwanda , Nkhoma Dominic , Mfutso-Bengo Joseph 
Published: August 2022

ABSTRACTIntroductionBy 2030, the non-communicable diseases (NCDs) are expected to overtake communicable, maternal, neonatal, and nutritional (CMNN) diseases combined as the leading cause of mortality in sub-Saharan Africa (SSA). With the increasing trend in NCDs, the NCD risk factors (NCDRF) need to be understood at local level in order to guide NCD risk mitigation efforts. Therefore, we provide a detailed analysis of some modifiable NCDRF and their determinants in Malawi using the 2017 Stepwise survey (STEPS).MethodsThis is a secondary analysis of the Malawi 2017 STEPS. Data was analysed using frequencies, proportions, odds ratios (OR) and their associated 95% confidence intervals (95%CI). We fitted multiple logistic regression of the NCD risk factors on the explanatory variables using likelihood ratio test. The level of statistical significance was set at P< 0.05.ResultsOf the 4187 persons, 9% were current smokers, 1% were taking alcohol, 16% had high salt intake, 64% had insufficient fruit intake, 21% had low physical activity, 25% had high blood sugar, and 11% had high blood pressure. Smoking odds increased with age but decreased with level of education. Females had lower odds of engaging in harmful alcohol use than males (AOR=0.04, 95%CI: 0.01-0.17, P<0.001). Females had lower odds of high salt uptake than the males (AOR=0.70, 95%CI: 0.58-0.84, P=0.0001). Persons in non-paid jobs had higher odds of salt uptake than those employed (AOR=1.70, 95%CI: 1.03-2.79, P=0.04). Females were 22% more likely to have insufficient fruit uptake compared to males (AOR=1.22, 95%CI: 1.06-1.41, P=0.007).ConclusionThe high prevalence of physical inactivity, high salt consumption, insufficient fruit intake, raised blood glucose and high relatively blood pressure calls for a sound public health approach. The Malawi Ministry of Health should devise multi-sectoral approaches that minimize exposure to modifiable NCD risk factors at population and individual levels.
Murine infection by Mycobacterium marinum is a reliable model for Bone and Soft-Tissue Damage
Authors: Kumar Mahendra , Ambati Ramaraju , Urade Prachi J , Lotke Anil , Krishnasastry Musti 
Published: August 2022

AbstractExtra-pulmonary tuberculosis (EPTB) constitutes 15-20% of the entire TB cases worldwide, and immune-suppressive conditions like HIV-AIDS further aggravate the disease often without symptoms and lack of proper diagnostic method delays the treatment. A thorough understanding of the EPTB infection and the pathogenesis is necessary and requires a reliable in-vivo animal model that mimics pathology similar to human infection. The M. marinum mice infection model presented here offers visible and quantifiable pathological features. Moreover, sections of the infected tails exhibited infiltration of the immune cells, a prominent feature frequently observed. Interestingly, the micro-CT imaging of the infected mice’s tails displayed bone erosion to the extent of the coccygeal vertebral loss. Furthermore, infection of the mice with drug-resistant such as Isoniazid (IRP) and Ethambutol (EmbRP) of M. marinum populations exhibited pathological features akin to wild-type M. marinum infection. At the same time, for EmbRP, the severity is significantly reduced, suggesting the nature of the selected population and its ability to retain or fix the virulent determinant(s) during bacterial growth. These findings advocate the use of the developed model to understand the EPTB precisely bone and spine TB, and it can be further utilized to develop novel therapeutics and diagnostics.