bluuebunny/crossref_metadata_2025_split huggingface dataset:
New RDEB intermediate variant with in-frame partial exon skipping in FN III-like domain of type VII collagen
Authors: Evtushenko N.A. , Kubanov A.A. , Martynova A.A. , Kondratyev N.V. , Beilin A.K. , Karamova A.E. , Monchakovskaya E.S. , Azimov К.A. , Nefedova M.A. , Bozhanova N.G. , Zaklyazminskaya E.V. , Gurskaya N.G. 
Published: September 2022

AbstractRecessive Dystrophic Epidermolysis Bullosa (RDEB) is a debilitating genodermatosis caused by pathogenic mutations in the COL7A1 gene, which induce absence or reduction in the number of anchoring fibrils. The severity of RDEB depends on the mutation type and localization, but many aspects of this dependence remain to be elucidated. Here, we report a novel variant of RDEB Intermediate in two unrelated patients. Their disease manifestation includes early skin and oral mucosa blistering and is associated with localized atrophic scarring. According to the exome and Sanger sequencing results, both investigated Probands are the carriers of complex heterozygosity in the COL7A1 gene with the same deletion in intron 19 of the COL7A1 gene. RT-PCR followed by sequence analysis revealed skipping of the part of exon19, as well as the rescue of the open reading frame (ORF) of COL7A1 in both Probands. We hypothesize that the mutation in the acceptor splice site leads to the activation of the cryptic donor splice site, resulting in the truncated but partially functional protein and the milder phenotype of intermediate RDEB. This rare type of mutation expands our understanding of RDEB etiology and invites further investigation.
Insights on neonatal mortality: differences between public and private health access at São Paulo city between 2012 and 2017
Authors: Beluzo Carlos Eduardo , Zaniboni Marcelo Zaccaro , Carvalho Tiago , Alves Luciana Correia 
Published: September 2022

AbstractUnder-five mortality is a survival measure that reflects the social, economic, and environmental conditions in which children live, including their health care, so they are reasonable measures to identify vulnerable populations. Infant Mortality, also a survival measure, refers to children dying before reaching the first year of life, and can also be disaggregated into events below 28 days, referred to as neonatal mortality, which currently concentrates the higher share of deaths. In 2020, more than 5 million under-five children died in the world, from which almost 50% occurred among newborns. The Sustainable Development Goals call for an end to preventable deaths of newborns and children under-five, but considering the current trends, many countries are not on track to achieve it. Neonatal mortality involves various biological, socioeconomic, and healthcare factors, and understanding its determinants can favor public policy funding planning and help with this problem. The increasing relevance of neonatal deaths aside from online platforms that make available health data in Brazil has enabled more precise analyses and led to a significant number of studies covering different factors, regions, and methods regarding this issue. Among the various determinants, access to private health services is an important one. In Brazil, mainly due to financial restrictions, a huge percentage of the population uses only public health services. In this context, the objective of this paper is to perform an evaluation of the NMR in the city of São Paulo - Brazil, in the period between 2012 and 2017, considering as a determinant for neonatal mortality rate if the delivery has occurred on private or on public health service sphere. Besides that, the determinant mother’s age is also included in the analysis, so it is also possible to evaluate associations between these two variables. A dataset having 8,110 neonatal deaths was analyzed and three graphics were created. The first one is used to assess information regarding the distribution of births by health service sphere and mother’s age. The second brings information on births and neonatal mortality rates combined and compared by year and by health service sphere. Finally, in the last one births and rates are also combined and compared by year, health service sphere, but now are desegregated by mother’s age group. From these results, some insights are raised and discussed, and some need further investigation to obtain more conclusive results, but the currents can already bring important knowledge about the problem.
Amygdala subdivisions exhibit aberrant whole-brain functional connectivity in relation to stress intolerance and psychotic symptoms in 22q11.2DS
Authors: Delavari Farnaz , Rafi Halima , Sandini Corrado , Murray Ryan , Latrech Caren , Van De Ville Dimitri , Eliez Stephan 
Published: September 2022

AbstractThe amygdala is a key region in emotional regulation, which is often impaired in psychosis. However, it is unclear if amygdala dysfunction directly contributes to psychosis, or whether it contributes to psychosis through symptoms of emotional dysregulation. We studied the functional connectivity of amygdala subdivisions in patients with 22q11.2DS, a known genetic model for psychosis susceptibility. We investigated how dysmaturation of each subdivision’s connectivity contributes to positive psychotic symptoms and impaired tolerance to stress in deletion carriers.Longitudinally-repeated MRI scans from 105 patients with 22q11.2DS (64 at high-risk for psychosis and 37 with impaired tolerance to stress) and 120 healthy controls between the ages of 5 to 30 years were included. We calculated seed-based whole-brain functional connectivity for amygdalar subdivisions and employed a longitudinal multivariate approach to evaluate the developmental trajectory of functional connectivity across groups.Patients with 22q11.2DS presented a multivariate pattern of decreased basolateral amygdala (BLA)-frontal connectivity alongside increased BLA-hippocampal connectivity. Moreover, associations between developmental drops in centro-medial amygdala (CMA)-frontal connectivity to both impaired tolerance to stress and positive psychotic symptoms in deletion carriers were detected. SFA hyperconnectivity to the striatum was revealed as a specific pattern arising in patients who develop mild to moderate positive psychotic symptoms.Overall, CMA-frontal dysconnectivity was found as a mutual neurobiological substrate in both impaired tolerance to stress and psychosis, suggesting a role in prodromal dysregulation of emotions in psychosis. While BLA dysconnectivity was presented as an early finding in patients with 22q11.2DS, contributing to impaired tolerance to stress.
Changes in Manual Therapy Techniques from the Perspective of Physical Therapists
Authors: Rojas Nelson A. , Jones Krista M. , Goetz Tami , Prashad Shikha 
Published: September 2022

AbstractObjectivePrior research has focused on comparing the effects of manual therapy techniques used in physical therapy in different conditions to determine which technique is more effective and less invasive for the patient. However, no focus has been placed on identifying and evaluating the changes in manual therapy techniques. This study aims to evaluate the changes in manual therapy techniques from the perspective of current and retired physical therapists who are or were licensed in Washington state.MethodsEighteen participants completed a modified Physical Therapy Profile Questionnaire (PTPQ) to explore their experience with manual therapy techniques and whether they implemented changes in their practice of these techniques.ResultsThe results suggest that changes in manual therapy techniques occur as physical therapists gain and develop more experience working with many clients and treating different conditions. Joint mobilization, taping, and muscle energy techniques were the most used and recommended manual therapy techniques by physical therapists in this sample. There was no significant correlation between the years of practice and the number of manual therapy techniques selected by participants (r = -0.044, p = 0.887).ConclusionsThis study suggests that changes and adjustments in manual therapy techniques have occurred throughout time as physical therapists gain practice in the field and can identify what manual technique will produce a better patient outcome in a specific patient.Impact StatementThis study examined how the use of manual therapy techniques has evolved in field of the physical therapy and the factors that contribute to these changes.
Cumulative Febrile, Respiratory, and Diarrheal Illness among Infants in Rural Guatemala and their Association with Neurodevelopmental and Growth Outcomes
Authors: Olson Daniel , Lamb Molly M. , Connery Amy K. , Colbert Alison M. , Calvimontes Mirella , Bauer Desiree , Paniagua-Avila M. Alejandra , Martínez María Alejandra , Arroyave Paola , Hernandez Sara , Colborn Kathryn L. , Roell Yannik , Waggoner Jesse J. , Natrajan Muktha S. , Anderson Evan J. , Bolaños Guillermo A. , El Sahly Hana M. , Munoz Flor M. , Asturias Edwin J. 
Published: September 2022

AbstractObjectiveWe aimed to evaluate the association between cumulative illness with neurodevelopment and growth outcomes in a birth cohort of Guatemalan infants.Study DesignFrom June 2017 to July 2018, infants 0-3 months of age living in a resource-limited region of rural southwest Guatemala were enrolled and completed weekly at-home surveillance for caregiver-reported cough, fever and vomiting/diarrhea. They also underwent anthropometric assessments and neurodevelopmental testing with the Mullen Scales of Early Learning (MSEL) at enrollment, six months, and one year.ResultsOut of 499 enrolled infants, 430 (86.2%) completed all study procedures and were included in the analysis. At 12-15 months of age, 140 (32.6%) infants had stunting (length-for-age Z [LAZ] score <-2 SD) and 72 (16.7%) had microcephaly (occipital-frontal circumference [OFC] <-2 SD of the mean). In multivariable analysis, greater cumulative weeks of reported cough illness (beta=-0.08/illness-week, p=0.06) and febrile illness (beta=-0.36/illness-week, p<0.001) were marginally or significantly associated with lower MSEL Early Learning Composite (ELC) Score at 12-15 months, respectively; there was no association with any illness (cough, fever, and/or vomiting/diarrhea; p=0.27) or with cumulative weeks of diarrheal/vomiting illness alone (p=0.66). No association was shown between cumulative weeks of illness and stunting or microcephaly at 12-15 months.ConclusionsThese findings highlight the negative cumulative consequences of frequent febrile and respiratory illness on neurodevelopment during infancy. Future studies should explore the inflammatory profile associated with these syndromic illnesses and their impact on neurodevelopment in the first years of life.
The future of computational pathology: expectations regarding the anticipated role of artificial intelligence in pathology by 2030
Authors: Berbís M Alvaro , McClintock David S. , Bychkov Andrey , Cheng Jerome Y , Delahunt Brett , Egevad Lars , Eloy Catarina , Farris Alton B , Fraggetta Filippo , García del Moral Raimundo , Hartman Douglas J. , Herrmann Markus D , Hollemans Eva , Iczkowski Kenneth A , Karsan Aly , Kriegsmann Mark , Lennerz Jochen K , Pantanowitz Liron , Salama Mohamed E. , Sinard John , Tuthill Mark , Van der Laak Jeroen , Williams Bethany , Casado-Sánchez César , Sánchez-Turrión Víctor , Luna Antonio , Aneiros-Fernández José , Shen Jeanne 
Published: September 2022

ABSTRACTBackgroundArtificial intelligence (AI) is rapidly fueling a fundamental transformation in the practice of pathology. However, AI’s clinical integration remains challenging, with no AI algorithms to date enjoying routine adoption within typical anatomic pathology (AP) laboratories. This survey gathered current expert perspectives and expectations regarding the role of AI in AP from those with first-hand computational pathology and AI experience.MethodsPerspectives were solicited using the Delphi method from 24 subject matter experts between December 2020 and February 2021 regarding the anticipated role of AI in pathology by the year 2030. The study consisted of three consecutive rounds: 1) an open-ended, free response questionnaire generating a list of survey items; 2) a Likert-scale survey scored by experts and analyzed for consensus; and 3) a repeat survey of items not reaching consensus to obtain further expert consensus.FindingsConsensus opinions were reached on 141 of 180 survey items (78.3%). Experts agreed that AI would be routinely and impactfully used within AP laboratory and pathologist clinical workflows by 2030. High consensus was reached on 100 items across nine categories encompassing the impact of AI on (1) pathology key performance indicators (KPIs) and (2) the pathology workforce and specific tasks performed by (3) pathologists and (4) AP lab technicians, as well as (5) specific AI applications and their likelihood of routine use by 2030, (6) AI’s role in integrated diagnostics, (7) pathology tasks likely to be fully automated using AI, and (8) regulatory/legal and (9) ethical aspects of AI integration in pathology.InterpretationThis is the first systematic consensus study detailing the expected short/mid-term impact of AI on pathology practice. These findings provide timely and relevant information regarding future care delivery in pathology and raise key practical, ethical, and legal challenges that must be addressed prior to AI’s successful clinical implementation.FundingThis research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors.
Real-world genetic screening with molecular ancestry supports comprehensive pan-ethnic carrier screening
Authors: Shewcraft Ryan A. , Higashi Mitchell K. , Zhang Yeting , Tyler Jonathan , Lau Lisa Y. , Webb Bryn D. , Lee Seungwoo , Ramasamudram-Chakravarthi Rajasekar , Cacchione Teresa A. , Copperman Alan B. , Birch Ashley , Francis Marra , Shi Lisong , Edelmann Lisa , Chen Rong , Li Li , Schadt Eric 
Published: September 2022

AbstractWe characterize the clinical utility and economic benefits of a comprehensive pan-ethnic carrier screening panel that spans 282 monogenic disease conditions in a large, diverse population of 397,540 reproductive health patients. For 142,049 of these patients, we were able to accurately estimate genetic ancestries across 7 major population groups. We examined individual carrier and at-risk carrier couple (ARCC) rates with respect to self-reported and genetic ancestries across ancestry-specific and pan-ethnic panels. Our results show that this comprehensive panel identified >10-times the ARCCs compared with a two-gene pan-ethnic panel and provided a substantial benefit over ancestry-specific screening panels across the major population groups. Finally, we generated a universal cost-of-care model across the monogenic disease conditions represented on the comprehensive pan-ethnic carrier screening panel to demonstrate potential healthcare savings in addition to the demonstrated clinical benefits that could be realized adopting this type of panel as standard of care for all.
Prevalence of multimorbidity in migrants, refugees, asylum seekers and displaced persons and association with mortality: A systematic review protocol
Authors: Abrahamsson A , Rozalen Gonzalez A , Nicholl BI , O’Donnell CA , Mair FS 
Published: September 2022

AbstractBackgroundMultimorbidity is the presence of two or more physical and/or mental long-term health conditions and is associated with aging, but also with socio-economic deprivation. Immigration status contributes to socio-economic deprivation, potentially increasing prevalence of multimorbidity. Prevalence of multimorbidity in different migrant populations, such as asylum seekers, refugees and displaced persons, and its effect on mortality is poorly understood and no systematic review on the topic exists to date.ObjectiveTo assess what is known about the prevalence of multimorbidity in refugees, asylum seekers, migrants and displaced persons and about the association, if any, between multimorbidity and mortality in these populations.DesignSystematic review of the literature. The following electronic medical databases will be searched: MEDLINE, Embase, Scopus, CINAHL and The Cochrane Library. A narrative synthesis of findings will be undertaken, and meta-analysis considered if appropriate. Title, abstract and full paper screening will be undertaken independently by two reviewers. Studies will be limited to English and Spanish language and publication date from 2000 onward. The Newcastle-Ottawa Scale for Cohort Studies will be used as a quality assessment tool. This protocol adheres to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Protocols (PRISMA) 2020 guidelines.ConclusionUnderstanding the prevalence of multimorbidity amongst refugees, migrants, asylum seekers and displaced persons, and its association with mortality will provide valuable insights to inform practice and policy responses to increasing global migration.
Metagenomic next-generation sequencing to characterize etiologies of non-malarial fever in a cohort living in a high malaria burden area of Uganda
Authors: Mwakibete Lusajo , Takahashi Saki , Ahyong Vida , Black Allison , Rek John , Ssewanyana Isaac , Kamya Moses , Dorsey Grant , Jagannathan Prasanna , Rodríguez-Barraquer Isabel , Tato Cristina M. , Greenhouse Bryan 
Published: September 2022

AbstractBackgroundCauses of non-malarial fevers in sub-Saharan Africa remain understudied. We hypothesized that metagenomic next-generation sequencing (mNGS), which allows for broad genomic-level detection of infectious agents in a biological sample, can systematically identify potential causes of non-malarial fevers.Methods and FindingsThe 212 participants in this study were of all ages and were enrolled in a longitudinal malaria cohort in eastern Uganda. Between December 2020 and August 2021, respiratory swabs and plasma samples were collected at 313 study visits where participants presented with fever and were negative for malaria by microscopy. Samples were analyzed using CZ ID, a web-based platform for microbial detection in mNGS data. Overall, viral pathogens were detected at 123 of 313 visits (39%). SARS-CoV-2 was detected at 11 visits, from which full viral genomes were recovered from nine. Other prevalent viruses included Influenza A (14 visits), RSV (12 visits), and three of the four strains of seasonal coronaviruses (6 visits). Notably, 11 influenza cases occurred between May and July 2021, coinciding with when the Delta variant of SARS-CoV-2 was circulating in this population. The primary limitation of this study is that we were unable to estimate the contribution of bacterial microbes to non-malarial fevers, due to the difficulty of distinguishing bacterial microbes that were pathogenic from those that were commensal or contaminants.ConclusionsThese results revealed the co-circulation of multiple viral pathogens likely associated with fever in the cohort during this time period. This study illustrates the utility of mNGS in elucidating the multiple causes of non-malarial febrile illness. A better understanding of the pathogen landscape in different settings and age groups could aid in informing diagnostics, case management, and public health surveillance systems.
Spatial determination of COVID-19 mortality
Authors: Arun GC 
Published: September 2022

AbstractCOVID-19 has affected at the global scale. However, its impacts are not evenly distributed. The article aims to explore the spatial determination of the COVID-19 related death. The data for the analysis has been accessed from the World Health Organization (WHO). Both descriptive and statistical analysis has been done to assess the COVID-19 related death and spatial explanation. The regression models suggested the explanatory power of spatial difference in the COVID-19 related death. However, further addition of various COVID-19 vaccine did not produce expected result.
Neurodoron® in patients with neurasthenia – A randomized, double-blind, placebo-controlled clinical trial
Authors: Hellhammer Juliane , Spitznagel-Schminke Luitgard , Semaca Cristina , Hufnagel Rebecca 
Published: September 2022

1AbstractIntroductionThe term neurasthenia has been introduced in the late 19th century. Stress was indicated as one of the main triggers. Many treatment options are available to reduce the associated symptoms. Complementary and alternative medicine (CAM) is widely used due to its long tradition and positive safety profile. This Phase IV placebo-controlled clinical trial was designed to demonstrate efficacy and safety of the CAM-product Neurodoron® in patients with neurasthenia.MethodsThis monocentre, randomized, double-blind, placebo-controlled, parallel-group clinical trial was conducted in a dedicated outpatient German trial site. Women and men aged 18 and above were randomized to receive either Neurodoron® or matching placebo if they reported typical symptoms of neurasthenia and a severe psychiatric disorder could be excluded. The primary objectives were a reduction in characteristic symptoms of nervous exhaustion and perceived stress as well as improvement in general health status after 6 weeks of treatment.Results204 patients underwent screening, 78 were randomized in each treatment group, and 77 patients each received treatment (intention-to-treat (ITT) population = 154 patients). For none of the primary efficacy variables, an advantage in favor of Neurodoron® could be demonstrated in the pre-specified analysis (p-values between 0.505 to 0.773, Student’s t-test). In a post-hoc analysis of intra-individual differences after 6 weeks treatment, a significant advantage of Neurodoron® vs. placebo was shown for characteristic symptoms of nervous exhaustion (irritability (p = 0.020); nervousness (p = 0.045), Student’s t-test). Adverse Event (AE) rates were similar between treatment groups, in both groups 6 AEs were assessed as causally related to treatment (severity mild or moderate). No AE resulted in discontinuation of treatment.ConclusionA significant improvement of neurasthenia was seen for the total study population at the end of the treatment period. Superiority of Neurodoron® vs. placebo could not be demonstrated with the pre-specified analysis. However, the post-hoc analysis suggests Neurodoron® as a beneficial option over placebo for the treatment of neurasthenia, especially given its confirmed markedly good safety.