bluuebunny/crossref_metadata_2025_split huggingface dataset:
Sustainability of quality improvement teams in selected regional referral hospitals in Tanzania
Authors: Kacholi Godfrey , Mahomed Ozayr H 
Published: March 2020

Abstract

Objective
The aim of this study was to determine the sustainability of hospital quality improvement teams and to assess factors influencing their sustainability in the regional referral hospital in Tanzania.

Design
A cross-sectional study was conducted between April and August of 2018.

Setting and participants
The study was conducted in four selected regional referral hospitals in Tanzania. All members of the quality improvement teams available during the study period were recruited.

Intervention
Quality improvement teams and their activities.

Main outcome measure
The primary outcome was sustainability total scores. The secondary outcomes were process, staff and organizational sustainability scores. The sustainability of quality improvement teams was assessed by using the National Health Service Institute for Innovation and Improvement Sustainability Model self-assessment tool.

Results
The overall mean sustainability score was 59.08 (95% CI: 53.69–64.46). Tanga Regional Referral Hospital had the highest mean sustainability score of 66.15 (95% CI: 55.12–77.18). Mbeya Regional Referral Hospital obtained the lowest mean sustainability score of 52.49 (95% CI: 42.96–62.01). The process domain had the highest proportionate mean sustainability score of 22.46 (95% CI: 20.58–24.33) across four hospitals. The staff domain recorded the lowest proportionate sustainability score of 27.28 (95% CI: 24.76–29.80).

Conclusions
Perceived less involvement of senior leadership (hospital management teams) and clinical leadership (heads of clinical departments) and infrastructure limitation appeared to negatively affect the sustainability of the hospital quality improvement teams. Our study underscores the importance of establishing a permanent and fully resourced Quality Improvement Unit—with team members employed as full-time staff.
Human cerebral organoids as a new legal and ethical challenge†
Authors: Lavazza Andrea , Pizzetti Federico Gustavo 
Published: March 2020

ABSTRACT
Human cerebral organoids (HCOs) are miniature brains cultivated in a dish using pluripotent human cells that, thanks to advanced technologies, tend to reproduce the development path of the brain of an embryo in the mother’s uterus. Recent data from studies carried out in different laboratories have indicated that HCOs show complex electrical activity, are receptive to light stimuli, and can command a muscle connected to them. The presence of the main neuronal structures in them suggests that, despite currently lacking vascularization and sensory exchanges with the outside world, more developed HCOs could exhibit some rudimentary form of consciousness, specifically a minimal sentience with respect to the basic experiences of pain and pleasure. Faced with this possibility, which for many scientists is still a long way off, we have begun to reflect on how we could empirically investigate the presence of consciousness. If we were certain or had a reasonable belief that some types of HCOs are sentient, what kind of entity would we judge them to be? Would they have specific legal protection? Should they be attributed to a moral status? This article tries to give an initial answer to these two questions. On the one side, it seems that no special rights can be claimed for HCOs other than those relating to human biological material. On the other side, instead, a sentient HCO could aspire to having its moral status recognized. If this were the case, the law may have to adapt to this unprecedented situation.
Low risks for spiritual highs: Risk-taking behaviours and the protective benefits of spiritual health among Saskatchewan adolescents
Authors: Hatala Andrew , McGavock Jonathan , Michaelson Valerie , Pickett William 
Published: March 2020

Abstract

Objectives
Adolescent risk-taking behaviours, such as substance use and early sexual activity, can adversely impact physical health and psychosocial development. A connection to spiritual health may buffer against the negative health impacts of several risk-taking behaviours. The aim of this study was to determine if higher spiritual health was associated with lower risk-taking behaviours among school-attending adolescents in Saskatchewan, Canada.

Methods
A representative sample of 4,751 adolescents in the Canadian province of Saskatchewan completed the Health Behaviour of School-aged Children (HBSC) questionnaire during the 2014 to 2015 school year. The main risk-taking behavioural outcomes were self-reported: smoking; alcohol; and cannabis use; as well as sexual intercourse. The main exposures related to spiritual health included four factors: connectedness to (1) one’s self; (2) others; (3) nature; and (4) notions of the transcendent. Multivariable logistic regression analyses were used to test for associations between exposures and outcome measures.

Results
The sample was balanced across gender, primarily Caucasian (71%), and primarily ages 11 to 15 years (48%). Adolescents indicated a high prevalence of spiritual health. Across all adjusted models, the results demonstrated that adolescents who value the various components of spiritual health showed a decreased likelihood of engaging in cigarette smoking, alcohol and marijuana use, and sexual intercourse.

Conclusion
The findings indicate the potential for spiritual health to be considered as the basis for public- and community-health interventions, pending further evidence from experimental studies.
Understanding mechanisms of integrated behavioral therapy for co-occurring obesity and depression in primary care: a mediation analysis in the RAINBOW trial
Authors: Rosas Lisa G , Xiao Lan , Lv Nan , Lavori Phillip W , Venditti Elizabeth M , Snowden Mark B , Smyth Joshua M , Lewis Megan A , Williams Leanne M , Suppes Trisha , Goldstein-Piekarski Andrea N , Ma Jun 
Published: March 2020

Abstract
The RAINBOW trial demonstrated that an integrated collaborative care intervention was effective for improving weight and depression. This study examined mediation of the treatment effect by a priori specified lifestyle behaviors and cognitive functioning. Participants were randomized to a 12-month integrated intervention (n = 204) or usual care (n = 205). Body mass index (BMI) and 20-item Depression Symptom Check List (SCL-20) were co-primary outcomes (Y). To examine mediation, we assessed (a) the effect of the integrated intervention (X) on lifestyle behaviors (diet and physical activity) and cognitive functioning (problem-solving; M, X→M path a) and (b) the association of these behaviors with BMI and SCL-20 (M→Y path b). Mediation existed if paths a and b were significant or if path a and the product of coefficients test (paths a and b) were significant. Compared with usual care, the intervention led to significant improvements in leisure time physical activity (201.3 MET minutes/week [SD, 1,457.6]) and total calorie intake (337.4 kcal/day [818.3]) at 6 months but not 12 months (path a). These improvements were not significantly associated with improvements in BMI or SCL-20 (path b). However, avoidant problem-solving style score and increased fruit and vegetable intake significantly correlated with improvements in BMI at 6 and 12 months, respectively. Also, increased fruit and vegetable intake, higher dietary quality, and better problem-solving abilities significantly correlated with improvements in SCL-20 at 6 and 12 months. These findings did not support the hypothesized mediation, but suggest lifestyle behaviors and cognitive functioning to target in future intervention optimization.
Aberrant Prestimulus Oscillations in Developmental Dyslexia Support an Underlying Attention Shifting Deficit
Authors: Meyer Lars , Schaadt Gesa 
Published: March 2020

AbstractDevelopmental dyslexia (DD) impairs reading and writing acquisition in 5–10% of children, compromising schooling, academic success, and everyday adult life. DD associates with reduced phonological skills, evident from a reduced auditory mismatch negativity (MMN) in the electroencephalogram (EEG). It was argued that such phonological deficits are secondary to an underlying deficit in the shifting of attention to upcoming speech sounds. Here, we tested whether the aberrant MMN in individuals with DD is a function of EEG correlates of prestimulus attention shifting; based on prior findings, we focused prestimulus analyses on alpha-band oscillations. We administered an audio–visual oddball paradigm to school children with and without DD. Children with DD showed EEG markers of deficient attention switching (i.e., increased prestimulus alpha-band intertrial phase coherence [ITPC]) to precede and predict their reduced MMN—aberrantly increased ITPC predicted an aberrantly reduced MMN. In interaction, ITPC and MMN predicted reading abilities, such that poor readers showed both high ITPC and a reduced MMN, the reverse being true in good readers. Prestimulus ITPC may be an overlooked biomarker of deficient attention shifting in DD. The findings support the proposal that an attention shifting deficit underlies phonological deficits in DD, entailing new opportunities for targeted intervention.
Pyrazinamide enhances lipid peroxidation and antioxidant levels to induce liver injury in rat models through PI3k/Akt inhibition
Authors: Xu Yun , Jiang Yongfang , Li Yi 
Published: March 2020

AbstractPyrazinamide (PZA) is an anti-tuberculosis drug known to causes liver injury. phosphatidylinositol-3-kinase/protein kinase B (PI3K/Akt) signaling protects against liver injury by promoting cellular antioxidant defenses and reducing intracellular reactive oxygen species (ROS) and lipid peroxidation. The regulatory mechanisms and functions of PI3K/Akt signaling during the hepatotoxicity of PZA are however not fully understood. Rats were administered PZA or/and the PI3K activator (740Y-P) for 7 days. The levels of serum parameters were examined via standard enzymatic techniques and the pathological status of the liver was confirmed by H & E staining. The levels of lipid peroxidation and antioxidant production were determined using commercial kits. Liver apoptosis was assessed by TUNEL staining. The expression of apoptosis-related proteins and PI3K/Akt signaling were assessed by western blot analysis. PZA treatment significantly increased serum alanine transaminase, aspartate transaminase, gamma-glutamyl transpeptidase and tall bilirubin leading to liver damage in rats. PZA also facilitated lipid peroxidation and suppressed antioxidant defenses. PZA led to apoptotic induction in rat liver cells through the downregulation of Bcl-2 and the upregulation of Bax and caspase-3. PZA also dramatically inhibited PI3K/Akt signaling in rat liver cells. We further verified that PI3K/Akt signaling in response to 740Y-P could attenuate hepatic injury, lipid peroxidation and apoptosis in rat liver cells in response to PZA. We reveal that PZA-induced liver injury in rats occurs through PI3k/Akt signaling, the recovery of which prevents liver injury in rat models.
Per- and Polyfluoroalkyl Substances Differentially Inhibit Placental Trophoblast Migration and Invasion In Vitro
Authors: Szilagyi John T , Freedman Anastasia N , Kepper Stewart L , Keshava Arjun M , Bangma Jackie T , Fry Rebecca C 
Published: March 2020

AbstractPer- and polyfluoroalkyl substances (PFAS) are used as industrial surfactants and chemical coatings for household goods such as Teflon. Despite regulatory efforts to phase out legacy PFAS, they remain detectable in drinking water throughout the United States. This is due to the stability of legacy PFAS and the continued use of replacement compounds. In humans, PFAS have been detected in placenta and cord blood and are associated with low birth weight and preeclampsia risk. Preeclampsia is a leading cause of maternal mortality and is driven by insufficient endometrial trophoblast invasion, resulting in poor placental blood flow. PFAS alter invasion of other cell types, but their impact on trophoblasts is not understood. We therefore assessed the effects of PFAS on trophoblast migration, invasion, and gene expression in vitro. Trophoblast migration and invasion were assessed using a modified scratch assay in the absence or presence of Matrigel, respectively. Treatment with perfluorooctanoic sulfate (PFOS), perfluorooctanoic acid (PFOA), and GenX (1000 ng/ml) each decreased trophoblast migration over 24 h. However, only GenX (1000 ng/ml) significantly inhibited trophoblast invasion. Treatment with PFOS, PFOA, and GenX also decreased trophoblast expression of chemokines (eg, CCL2), chemokine receptors (eg, CCR4), and inflammatory enzymes (eg, ALOX15) involved in migration. Inhibition of chemokine receptors with pertussis toxin (10 ng/ml), a G-protein inhibitor, inhibited trophoblast migration similar to the PFAS. Taken together, PFAS decrease trophoblast migration, invasion, and inflammatory signaling. By understanding the mechanisms involved, it may be possible to identify the biological and exposure factors that contribute to preeclampsia.
Community coalescence: an eco-evolutionary perspective
Authors: Castledine Meaghan , Sierocinski Pawel , Padfield Daniel , Buckling Angus 
Published: March 2020

Community coalescence, the mixing of different communities, is widespread throughout microbial ecology. Coalescence can result in approximately equal contributions from the founding communities or dominance of one community over another. These different outcomes have ramifications for community structure and function in natural communities, and the use of microbial communities in biotechnology and medicine. However, we have little understanding of when a particular outcome might be expected. Here, we integrate existing theory and data to speculate on how a crucial characteristic of microbial communities—the type of species interaction that dominates the community—might affect the outcome of microbial community coalescence. Given the often comparable timescales of microbial ecology and microevolution, we explicitly consider ecological and evolutionary dynamics, and their interplay, in determining coalescence outcomes.This article is part of the theme issue ‘Conceptual challenges in microbial community ecology’.
Linking regional shifts in microbial genome adaptation with surface ocean biogeochemistry
Authors: Garcia Catherine A. , Hagstrom George I. , Larkin Alyse A. , Ustick Lucas J. , Levin Simon A. , Lomas Michael W. , Martiny Adam C. 
Published: March 2020

Linking ‘omics measurements with biogeochemical cycles is a widespread challenge in microbial community ecology. Here, we propose applying genomic adaptation as ‘biosensors’ for microbial investments to overcome nutrient stress. We then integrate this genomic information with a trait-based model to predict regional shifts in the elemental composition of marine plankton communities. We evaluated this approach using metagenomic and particulate organic matter samples from the Atlantic, Indian and Pacific Oceans. We find that our genome-based trait model significantly improves our prediction of particulate C : P (carbon : phosphorus) across ocean regions. Furthermore, we detect previously unrecognized ocean areas of iron, nitrogen and phosphorus stress. In many ecosystems, it can be very challenging to quantify microbial stress. Thus, a carefully calibrated genomic approach could become a widespread tool for understanding microbial responses to environmental changes and the biogeochemical outcomes.
This article is part of the theme issue ‘Conceptual challenges in microbial community ecology’.
Experimental manipulation of selfish genetic elements links genes to microbial community function
Authors: Quistad Steven D. , Doulcier Guilhem , Rainey Paul B. 
Published: March 2020

Microbial communities underpin the Earth's biological and geochemical processes, but their complexity hampers understanding. Motivated by the challenge of diversity and the need to forge ways of capturing dynamical behaviour connecting genes to function, biologically independent experimental communities comprising hundreds of microbial genera were established from garden compost and propagated on nitrogen-limited minimal medium with cellulose (paper) as sole carbon source. After 1 year of bi-weekly transfer, communities retained hundreds of genera. To connect genes to function, we used a simple experimental manipulation that involved the periodic collection of selfish genetic elements (SGEs) from separate communities, followed by pooling and redistribution across communities. The treatment was predicted to promote amplification and dissemination of SGEs and thus horizontal gene transfer. Confirmation came from comparative metagenomics, which showed the substantive movement of ecologically significant genes whose dynamic across space and time could be followed. Enrichment of genes implicated in nitrogen metabolism, and particularly ammonification, prompted biochemical assays that revealed a measurable impact on community function. Our simple experimental strategy offers a conceptually new approach for unravelling dynamical processes affecting microbial community function.This article is part of the theme issue ‘Conceptual challenges in microbial community ecology’.
Cohort Profile: Prematurity Immunology in HIV-infected Mothers and their infants Study (PIMS)
Authors: Malaba Thokozile R , Gray Clive M , Myer Landon , Newell Marie-Louise ,   for the PIMS Study Group
Published: March 2020

AbstractPurposePIMS, is a prospective cohort study in South Africa investigating the association between antiretroviral therapy (ART) use, preterm delivery (PTD)and small-for gestational age (SGA) live births. PIMS main hypotheses are that ART initiation in pregnancy and ART-induced hypertension are associated with PTD and SGA respectively and that reconstitution of cellular immune responses in women on ART from before pregnancy results in increases in PTD of appropriate-for-gestational age (AGA) infants.ParticipantsPregnant women (n=3972) aged ≥18 years regardless of HIV status recruited from 2015 to 2016 into the overall PIMS cohort (2517 HIV-uninfected, 1455 HIV-infected). A nested cohort contained 551 HIV-infected women who were ≤24 weeks’ GA on ultrasound: 261 initiated ART before pregnancy, 290 initiated during pregnancy.Findings to dateWomen in the overall cohort were followed antenatally through to delivery using routine clinical records; further women in the nested cohort were actively followed up until 12 months postpartum, with data were collected on maternal health (HIV care and ART use, clinical care and inter-current clinical history). Other procedures conducted on the nested cohort included physical examinations (anthropometry, blood pressure measurement), assessment of fetal growth (ultrasound), maternal and infant phlebotomy for storage of plasma, RNA and peripheral blood mononuclear cells, collection of delivery specimens (placenta and cord blood), and infant 12 month developmental assessment. Preliminary findings have contributed to our understanding of risk factors for adverse birth outcomes, and the relationship between pregnancy immunology, HIV/ART and adverse birth outcomes.Future plansUsing specimens collected from HIV-infected study participants throughout pregnancy and first year of life, the PIMS provides a valuable platform for answering a variety of research questions focused on temporal changes of immunology markers in women whose immune status is altered by HIV infection, and how ART initiated during pregnancy affects immune responses. The relationship between these immunological changes with adverse birth outcomes as well as possible longer-term impact of exposure to ART in fetal and early life will be explored. Additionally, further active and passive follow-up of mothers and their infants is planned at school-going age and beyond to chart growth, morbidity and development, as well as changes in family circumstances.
CAR T cell therapy in B-cell acute lymphoblastic leukaemia: Insights from mathematical models
Authors: León-Triana Odelaisy , Sabir Soukaina , Calvo Gabriel F. , Belmonte-Beitia Juan , Chulián Salvador , Martínez-Rubio Álvaro , Rosa María , Pérez-Martínez Antonio , Ramirez-Orellana Manuel , Pérez-García Víctor M. 
Published: March 2020

AbstractImmunotherapies use components of the patient immune system to selectively target cancer cells. The use of CAR T cells to treat B-cell malignancies – leukaemias and lymphomas– is one of the most successful examples, with many patients experiencing long-lasting complete responses to this therapy. This treatment works by extracting the patient’s T cells and adding them the CAR group, which enables them to recognize and target cells carrying the antigen CD19+, that is expressed in these haematological tumors.Here we put forward a mathematical model describing the time response of leukaemias to the injection of CAR T-cells. The model accounts for mature and progenitor B-cells, tumor cells, CAR T cells and side effects by incorporating the main biological processes involved. The model explains the early post-injection dynamics of the different compartments and the fact that the number of CAR T cells injected does not critically affect the treatment outcome. An explicit formula is found that provides the maximum CAR T cell expansion in-vivo and the severity of side effects. Our mathematical model captures other known features of the response to this immunotherapy. It also predicts that CD19+ tumor relapses could be the result of the competition between tumor and CAR T cells analogous to predator-prey dynamics. We discuss this fact on the light of available evidences and the possibility of controlling relapses by early re-challenging of the tumor with stored CAR T cells.
Geo-temporal distribution of 1,688 Chinese healthcare workers infected with COVID-19 in severe conditions – a secondary data analysis
Authors: Gao Wayne , Sanna Mattia , Wen Chi Pang 
Published: March 2020

IntroductionThe COVID-19 outbreak is posing an unprecedented challenge to healthcare workers. This study analyzes the geo-temporal effects on disease severity for the 1,688 Chinese healthcare workers infected with COVID-19.MethodUsing the descriptive results recently reported by the Chinese CDC, we compare the percentage of infected healthcare workers in severe conditions over time and across three areas in China, and the fatality rate of infected healthcare workers with all the infected individuals in China aged 22-59 years.ResultsAmong the infected Chinese healthcare workers whose symptoms onset appeared during the same ten-day period, the percentage of those in severe conditions decreased statistical significantly from 19.7% (Jan 11 – 20) to 14.4% (Jan 21 – 31) to 8.7% (Feb 1 – 11). Across the country, there was also a significant difference in the disease severity among patients symptoms onset during the same period, with Wuhan being the most severe (17%), followed by Hubei Province (10.4%), and the rest of China (7.0%). The case fatality rate for the 1,688 infected Chinese healthcare workers was significantly lower than that for the 29,798 infected patients aged 20-59 years—0.3% (5/1,688) vs. 0.65% (193/29,798), respectively.ConclusionThe disease severity improved considerably over a short period of time in China. The more severe conditions in Wuhan compared to the rest of the country may be attributable to the draconian lockdown. The clinical outcomes of infected Chinese healthcare workers may represent a more accurate estimation of the severity of COVID-19 for those who have access to quality healthcare.