bluuebunny/crossref_metadata_2025_split huggingface dataset:
Brain Development in Children With Early Onset Liver Disease
Authors: Earl Megan , Blackmore Charlotte , Day Jemma , Samyn Marianne , Dhawan Anil , McAlonan Grainne 
Published: June 2022

AimsBiliary Atresia (BA) is a progressive inflammatory liver disease and the most frequent indication for pediatric liver transplant. There is a strong association between BA in adulthood and reduced cognitive abilities, however, data on neurodevelopmental outcomes at an early age are scarce, with small participant numbers. Hence, the neurodevelopmental difficulties in BA are poorly understood in childhood even though the brain development and maturation occur in parallel with the time-course of BA. This study aimed to characterize the cognitive and behavioral phenotype within BA infants from the age of 14 months to 4 years and investigate the extent to which this group deviates from children of typical development.Methods42 infants with BA that were diagnosed and treated at Kings College Hospital were recruited into this study. These infants ranged from 14 months to 4 years (mean age = 3 Years, 1 month). Out of the 42 infants, 19 had received a liver transplant, 22 were stable on their native liver, and 1 was on the transplant waiting list. 36 Mullens Scale of Early Learning assessments and 42 Vineland Adaptive Behavior Scale Interviews were collected. 42 typically developing infants (TD) were also recruited into the study, matched for age and gender to the BA population. First, we compared the whole group with BA to TD; then we compared children with BA on their native liver to those with a transplant.ResultsAcross the cohort with BA, infants scored significantly lower on the Vineland Summary T-Score compared to age-matched TD control children (t(82) = −5.05, p < .001) and across all domains of the Vineland. They also scored significantly lower than TD children on the Mullens Development Assessment (t(66) = −6.52, p < .001), and this was also across all domains. BA children on their native liver scored lower on both instruments than children who had received a liver transplant, however, this difference did not reach significance.ConclusionIndividuals with Biliary Atresia, regardless of their transplant status, show lower levels of development across all aspects, suggesting a global delay. These findings suggest that all of these young children remain at significant risk for neurodevelopmental difficulties. These findings emphasize that special attention to neurodevelopment needs to be given as part of a holistic approach to care in a serious life-long illness. Work is ongoing to understand the trajectory of brain maturation in these children to ensure neurodevelopmental needs are addressed alongside physical health.
PREVENT: Assessing and Improving Knowledge of the Sodium Valproate Pregnancy Prevention Programme in Psychiatric Prescribing
Authors: Havens Laura 
Published: June 2022

AimsThe sodium valproate PREVENT programme was introduced by the Medicines and Healthcare products Regulatory Agency (MHRA) in March 2018, and is now a legal requirement due to valproate's risks in pregnancy. This project had two main aims: 1) To assess clinician knowledge of PREVENT, and identify deficiencies in current education. 2) To assess the barriers psychiatrists face in achieving compliance with PREVENT.MethodsKnowledge and awareness of PREVENT was assessed through an online survey sent to local consultants and specialty doctors in February 2021. The survey included ten questions, four were Likert style to assess attitudes, two assessed local arrangements and four were knowledge based. A free-text section allowed respondents to describe challenges faced implementing PREVENT. Results were analysed, an educational presentation given at local teaching and a poster was created and distributed - both targeting areas of weakest knowledge. A repeat survey was sent out in June 2021, and results collected to reassess.ResultsThe pre-teaching survey received twelve responses, the post teaching survey received eleven. In both, 75% of respondents represented general adult services, and 25% represented intellectual disability services.There was an improvement in confidence of knowledge with all respondents being either “somewhat” (55%) or “very confident” (45%) post-teaching compared to 75% being “somewhat” confident, 10% “unsure” and 17% “very confident” prior to intervention. Pre-teaching, 10% of respondents were unaware that a risk acknowledgement form must be signed annually, while post-teaching 100% correctly identified this should be annual.Respondents correctly identifying “highly effective” forms of contraception rose from 83% to 100% following teaching. Post-teaching there was an increase of 31% in the number of respondents correctly identifying the necessary documentation where a patient declines the PREVENT programme.Pre-teaching, half of respondents were unsure if their team had a reminder system for risk acknowledgement forms, and 42% reported having no system. Post-teaching, 27% of respondents reported now having a reminder system in place, and 27% had plans to implement one.ConclusionInitial results showed variable knowledge of the PREVENT programme, and a lack of awareness of the administrative requirements including risk acknowledgement forms. Results demonstrated an improvement in knowledge and organisation to help support compliance with the PREVENT programme. Respondents highlighted that knowledge of the PREVENT programme quickly deteriorates given how rarely it is used. Further work includes a full audit of compliance with PREVENT across the health board, as well as considering “refresher” sessions to prevent atrophy of knowledge.
The Contribution of Transference Focused Psychotherapy in Improving Psychiatry Trainees’ Attitude and Technical Confidence Towards Patients With Personality Disorders
Authors: Sinisi Arianna , Marchi Mattia , Prior David , Lee Tennyson 
Published: June 2022

AimsTransference-focused psychotherapy (TFP) is a manualized evidence-based treatment for severe personality disorders (PDs) based on a psychodynamic approach that focuses on object relations theory. It has been used as a teaching tool in different psychiatric settings. Psychiatry trainees are often the “first-responders” in multiple services, and they have to deal with patients with PDs in various settings. Yet there is a documented gap in psychiatry trainees’ education regarding the assessment and management of patients with PD pathology. The aim of our study was to evaluate whether a series of teaching sessions on TFP theory and techniques as applied to PD could improve the attitude and technical confidence of psychiatric trainees in the clinical encounter of a patient with a PD.MethodsTwo cohorts of psychiatry trainees in Tower Hamlet's East London Foundation Trust received four teaching sessions, each of one hour duration, on TFP theory and techniques. All the sessions were delivered online, using video teleconferencing software. 14 Trainees completed 2 questionnaires, pre- and post-teaching: the Attitude to Personality Disorder Questionnaire (APDQ) and the Clinical Confidence with Personality Disorder Questionnaire (CCPDQ). The APDQ asks the responder to score from 1–6 the frequency they experience certain feelings towards patients with PD. In the absence of a suitable instrument, we developed the CCPDQ consisting of a set of 13 questions rated on a 6-point Likert scale addressing key issues identified in TFP including establishing and maintaining the treatment frame and in implementing the 4 main techniques. We also conducted a 1-hour focus group post teaching which was videorecorded, transcribed, and analysed thematically.ResultsOn quantitative analysis, the Wilcoxon signed-rank test indicated statistically significant improvements in the total APDQ score (P = 0.003, r = 0.81) and in the CCPDQ questionnaires (P = 0.001, r = 0.88).The thematic analysis showed an overall positive effect of the TFP teaching on trainees’ attitude and confidence: they felt it improved their understanding of the nature of personality disorder, their awareness and management of countertransference, awareness of object relations and relation dyads at play in the encounter.ConclusionTraining junior doctors about TFP theory and techniques as applied to PD can significantly improve their attitude towards these patients and their technical confidence in the clinical encounter. Of note, our workshop is resource light and can easily be delivered by remote teaching. Based on these findings, teaching of TFP in the core psychiatric training curriculum should be considered.
ERG activity is regulated by endothelial FAK coupling with TRIM25/USP9x in vascular patterning
Authors: D'Amico Gabriela , Fernandez Isabelle , Gómez-Escudero Jesús , Kim Hyojin , Maniati Eleni , Azman Muhammad Syahmi , Mardakheh Faraz K. , Serrels Bryan , Serrels Alan , Parsons Maddy , Squire Anthony , Birdsey Graeme M. , Randi Anna M. , Bolado-Carrancio Alfonso , Gangeswaran Rathi , Reynolds Louise E. , Bodrug Natalia , Wang Yaohe , Wang Jun , Meier Pascal , Hodivala-Dilke Kairbaan M. 
Published: June 2022

ABSTRACT
Precise vascular patterning is crucial for normal growth and development. The ERG transcription factor drives Delta-like ligand 4 (DLL4)/Notch signalling and is thought to act as a pivotal regulator of endothelial cell (EC) dynamics and developmental angiogenesis. However, molecular regulation of ERG activity remains obscure. Using a series of EC-specific focal adhesion kinase (FAK)-knockout (KO) and point-mutant FAK-knock-in mice, we show that loss of ECFAK, its kinase activity or phosphorylation at FAK-Y397, but not FAK-Y861, reduces ERG and DLL4 expression levels together with concomitant aberrations in vascular patterning. Rapid immunoprecipitation mass spectrometry of endogenous proteins identified that endothelial nuclear-FAK interacts with the deubiquitinase USP9x and the ubiquitin ligase TRIM25. Further in silico analysis confirms that ERG interacts with USP9x and TRIM25. Moreover, ERG levels are reduced in FAKKO ECs via a ubiquitin-mediated post-translational modification programme involving USP9x and TRIM25. Re-expression of ERG in vivo and in vitro rescues the aberrant vessel-sprouting defects observed in the absence of ECFAK. Our findings identify ECFAK as a regulator of retinal vascular patterning by controlling ERG protein degradation via TRIM25/USP9x.
Metformin inactivates the cGAS-STING pathway through autophagy and suppresses senescence in nucleus pulposus cells
Authors: Ren Chenghao , Jin Jie , Li Chenchao , Xiang Jianwei , Wu Yaosen , Zhou Yifei , Sun Liaojun , Zhang Xiaolei , Tian Naifeng 
Published: June 2022

ABSTRACT
Intervertebral disc degeneration (IVDD) is a complex process involving many factors, among which excessive senescence of nucleus pulposus cells is considered to be the main factor. Our previous study found that metformin can inhibit senescence in nucleus pulposus cells; however, the mechanism of such an action was still largely unknown. In the current study, we found that metformin inactivates the cGAS-STING pathway during oxidative stress. Furthermore, knockdown of STING (also known as STING1) suppresses senescence, indicating that metformin might exert its effect through the cGAS-STING pathway. Damaged DNA is a major inducer of the activation of the cGAS-STING pathway. Mechanistically, our study showed that DNA damage was reduced during metformin treatment; however, suppression of autophagy by 3-methyladenine (3-MA) treatment compromised the effect of metformin on DNA damage. In vivo studies also showed that 3-MA might diminish the therapeutic effect of metformin on IVDD. Taken together, our results reveal that metformin may suppress senescence via inactivating the cGAS-STING pathway through autophagy, implying a new application for metformin in cGAS-STING pathway-related diseases.
Independently paced Ca2+ oscillations in progenitor and differentiated cells in an ex vivo epithelial organ
Authors: Kim Anna A. , Nguyen Amanda , Marchetti Marco , Du XinXin , Montell Denise J. , Pruitt Beth L. , O'Brien Lucy Erin 
Published: June 2022

ABSTRACT
Cytosolic Ca2+ is a highly dynamic, tightly regulated and broadly conserved cellular signal. Ca2+ dynamics have been studied widely in cellular monocultures, yet organs in vivo comprise heterogeneous populations of stem and differentiated cells. Here, we examine Ca2+ dynamics in the adult Drosophila intestine, a self-renewing epithelial organ in which stem cells continuously produce daughters that differentiate into either enteroendocrine cells or enterocytes. Live imaging of whole organs ex vivo reveals that stem-cell daughters adopt strikingly distinct patterns of Ca2+ oscillations after differentiation: enteroendocrine cells exhibit single-cell Ca2+ oscillations, whereas enterocytes exhibit rhythmic, long-range Ca2+ waves. These multicellular waves do not propagate through immature progenitors (stem cells and enteroblasts), of which the oscillation frequency is approximately half that of enteroendocrine cells. Organ-scale inhibition of gap junctions eliminates Ca2+ oscillations in all cell types – even, intriguingly, in progenitor and enteroendocrine cells that are surrounded only by enterocytes. Our findings establish that cells adopt fate-specific modes of Ca2+ dynamics as they terminally differentiate and reveal that the oscillatory dynamics of different cell types in a single, coherent epithelium are paced independently.
Prevalence of pulmonary tuberculosis in Al-Najaf governorate, Iraq
Authors: Al-Hadraawy Saleem Khteer , Alhadrawi Kais Khudhair , Aljanaby Israa Abduljabbar Jaloob , Aljanaby Ahmed Abduljabbar Jaloob , Zabibah Rahman S 
Published: June 2022

Background: pulmonary tuberculosis (PTB) is one of the most global dangerous infectious diseases worldwide, particularly in developing countries. Mycobacterium tuberculosis (Mtb) is the most infectious agent that caused PTB transferred by air droplets from one person to other. In the present epidemiological study, we aimed to record the total numbers and percentages of patients infected with PTB caused by Mtb during 12 months in AL-Najaf Governorate, Iraq. Methods: This study has been done in 2019 from January to the end of December in the north and south region of AL-Najaf Governorate, Iraq. Sputum of PTB-patients has been stained by Ziehl–Neelsen to Mtb diagnosis according to World Health Organization (WHO) recommendation. Results: We recorded 174 PTB-patients in AL-Najaf Governorate 2019; 89 male and 85 female; 101 and 73 in the north and south sections respectively. The age group 16-24 was the highest infected. Quarter two recorded the highest numbers of PTB-patients; 33 (60%) in the north section and 22 (40%) in the south section. Conclusion: There was low PTB incidence in AL-Najaf Governorate 2019 but the Youngers were the most susceptible to infection. Infection in the north section was higher than in the south section and there were no high differences between genders. Seasons have no high effect on the number of infections.
Prevalence of diabetes mellitus among newly detected sputum positive pulmonary tuberculosis patients and associated risk factors: A cross-sectional study
Authors: Hullalli Rashmi , Gudadinni M R , Motappa Rohith 
Published: June 2022

Background:Tuberculosis (TB) and diabetes mellitus (DM) co-morbidity is one of the rising public health problems. There is growing evidence that DM is an important risk factor for TB. This study was carried out to know the prevalence of DM among newly detected sputum positive pulmonary TB patients registered in District Tuberculosis Centre and to assess the risk factors of DM among TB patients.Methods:In a cross-sectional study, newly detected sputum positive pulmonary TB patients were screened for DM (those having symptoms of DM). Furthermore, they were diagnosed by detecting blood glucose levels (≥200 mg/dL). Mean, standard deviation (SD), Chi-squared and Fisher-Freeman-Halton exact tests were used to determine the significant associations. P-values less than 0.05 were considered to be statistically significant.Results:A total of 215 TB patients were included in this study. The prevalence of DM among TB patients was found to be 23.7% (2.8% known and 97.8% new cases). Significant associations were found between age (>46 years old), educational status, smoking habits, alcohol consumption, physical activity, presence of DM symptoms and family history of DM.Conclusions:Routine screening for DM is mandatory due to its increasing prevalence, which may help in early diagnosis and to reduce complications by proper management that in turn helps in the successful outcome of TB treatment.
Consumption of food supplements: is there a risk of muscle dysmorphia?
Authors: Kuzmar Isaac , Consuegra José Rafael , Calao María , Florez Andrea , Garcés Angie , Ibañez Nicolas , Harb Olga , Martínez Karen , Martínez Nelson , Castro Yiseth 
Published: June 2022

Background. Bigorexia is an eating disorder and obsessive-compulsive disorder where the subject has an incorrect perception of their body image with exercise addiction. This study aims to determine whether there is a relationship between body mass index (BMI), food supplement consumption, dietary adherence, gender and risk of muscle dysmorphia in the individual and to provide information to build recommendation systems to monitor the health and mental state of the population. Methods. A cross-sectional descriptive observational study was conducted in Barranquilla (Colombia) between February – May 2020. A face-to-face survey of 200 individuals of both sexes was used in which users evaluated different variables that helped to identify their risk of muscle dysmorphia. Results. Of the 200 participants, 105 men: N=48, 45.7% vs. women: N=57, 54.3%) consume nutritional supplements. There is no relationship in the total population with the risk of muscle dysmorphia with the consumption of nutritional supplements nor with the feeling of guilt for non-adherence to the diet, nor with age, gender, or BMI (p<0.05). In contrast, gender, age and BMI are related to nutritional supplement consumption, and gender is related to feelings of guilt for non-adherence to the diet. In the population that consumes nutritional supplements the risk of muscle dysmorphia is increased and the frequency varies by risk group: low risk: N=16, 15.2%; medium risk: N=46, 43.8%; high risk: N=28, 26.7%; and very high risk: N=15, 14.3%. The consumption of food supplements is higher in the female gender (57, 54.3% vs. 48, 45.7%), and moderate the feeling of guilt for not completing the diet, BMI and the risk of muscle dysmorphia. Conclusions. Women consume more food supplements, but gender does not determine the risk of muscle dysmorphia. Food supplement consumption influences the feeling of guilt for not completing the diet, BMI and the risk of muscle dysmorphia.
Investigating the effect of e-cigarette use on quitting smoking in adults aged 25 years or more using the PATH study
Authors: Lee Peter N. , Fry John S. 
Published: June 2022

Background: The evidence on harms and benefits of e-cigarettes partly concerns whether their use encourages smokers to quit. We addressed this using data from the nationally representative PATH study, with detailed accounting for potential confounding variables. Methods: We considered adults aged 25+. Our original analyses, reported in version 1 of this paper, used data for Waves 1 to 3, separate analyses considering Waves 1 to 2, 2 to 3 and 1 to 3. These related baseline ever e-cigarette use (or e-product use at Wave 2) to quitting at follow-up, adjusting for confounders derived from 55 candidates. Sensitivity analyses omitted ever other product users, linked quitting to current e-cigarette use, and used values of some predictors modified using follow-up data. Additional analyses used data for Waves 1 to 4, separately considering sustained, delayed and temporary quitting during Waves 1 to 3, 2 to 4 and 1 to 4. Sensitivity analyses considered 30-day quitting, restricted attention to smokers attempting to quit, and considered ever smokeless tobacco or snus use. Results: In the original analyses, unadjusted odds ratios (ORs) of quitting smoking for ever e-cigarette use were 1.29 (95% CI 1.01-1.66), 1.52 (1.26-1.83) and 1.47 (1.19-1.82) for the Wave 1 to 2, 2 to 3, and 1 to 3 analyses. These reduced after adjustment, to 1.23 (0.94-1.61), 1.51 (1.24-1.85) and 1.39 (1.11-1.74). Quitting rates remained elevated in users in all sensitivity analyses. The additional analyses found associations of e-cigarette use with sustained, delayed and temporary quitting, associations little affected by considering 30-day quitting, and only slightly reduced restricting attention to quit attempters. Ever use of smokeless tobacco or snus also predicted increased quitting. Conclusions: As does most evidence from clinical trials, other analyses of PATH, and other epidemiological studies, our results suggest using e-cigarettes helps adult smokers to quit.
Induction-phase treatment costs for cryptococcal meningitis in high HIV-burden African countries: New opportunities with lower costs
Authors: Larson Bruce , Shroufi Amir , Muthoga Charles , Oladele Rita , Rajasingham Radha , Jordan Alexander , Jarvis Joseph N. , Chiller Tom M. , Govender Nelesh P. 
Published: June 2022

Introduction: Access to and the cost of induction treatment for cryptococcal meningitis (CM) is rapidly changing. The newly-announced price for flucytosine ($0.75 per 500 mg pill) and possibly lower prices for liposomal amphotericin B (AmB-L) create opportunities to reduce CM treatment costs compared to the current standard treatment in low- and middle-income countries. Methods: We developed an Excel-based cost model to estimate health system treatment costs for CM over a two-week induction phase for multiple treatment combinations, newly feasible with improved access to flucytosine and AmB-L. CM treatment costs include medications, laboratory tests and other hospital-based costs (bed-day costs and healthcare worker time). We report results from applying the model using country-specific information for South Africa, Uganda, Nigeria, and Botswana. Results: A 14-day induction-phase of seven days of inpatient AmB-D with flucytosine, followed by seven days of high-dose fluconazole as an outpatient, will cost health systems less than a 14-day hospital stay with AmB-D and fluconazole. If daily AmB-L replaces AmB-D for those with baseline renal dysfunction, with a cost of $50 or less per 50 mg vial, incremental costs would still be less than the AmB-D with fluconazole regimen. Simple oral combinations (e.g., seven days of flucytosine with fluconazole as an inpatient) are practical when AmB-D is not available, and treatment costs would remain less than the current standard treatment. Conclusions: Improved access to and lower prices for flucytosine and AmB-L create opportunities for improving CM treatment regimens. An induction regimen of flucytosine and AmB-D for seven days is less costly than standard care in the settings studied here. As this regimen has also been shown to be more effective than current standard care, countries should prioritize scaling up flucytosine access. The cost of AmB-L based regimens is highly dependent on the price of AmB-L, which currently remains unclear.