bluuebunny/crossref_metadata_2025_split huggingface dataset:
Biallelic truncating variants in children with titinopathy represent a recognizable condition with distinctive muscular and cardiac characteristics: a report on five patients
Authors: Baban Anwar , Cicenia Marianna , Magliozzi Monia , Parlapiano Giovanni , Cirillo Marco , Pascolini Giulia , Fattori Fabiana , Gnazzo Maria , Bruno Pasqualina , De Luca Lorenzo , Di Chiara Luca , Francalanci Paola , Udd Bjarne , Secinaro Aurelio , Amodeo Antonio , Bertini Enrico Silvio , Savarese Marco , Drago Fabrizio , Novelli Antonio 
Published: July 2023

BackgroundMonoallelic and biallelic TTN truncating variants (TTNtv) may be responsible for a wide spectrum of musculoskeletal and cardiac disorders with different age at onset. Although the prevalence of heterozygous TTNtv is relatively high in the general population, cardiac phenotyping (mainly cardiomyopathies, CMPs) in biallelic titinopathy has rarely been described in children.MethodsWe reviewed the medical records of pediatric patients with biallelic TTNtv and cardiac involvement. Clinical exome sequencing excluded pathogenic/likely pathogenic variants in major CMP genes.ResultsFive pediatric patients (four male) with biallelic TTNtv were included. Major arthrogryposis multiplex was observed in four patients; no patient showed intellectual disability. At a cardiac level, congenital heart defects (atrial and ventricular septal defects, n = 3) and left ventricular non-compaction (n = 1) were reported. All patients had dilated cardiomyopathy (DCM) diagnosed at birth in one patient and at the age of 10, 13, 14, and 17 years in the other four patients. Heart rhythm monitoring showed tachyarrhythmias (premature ventricular contractions, n = 2; non-sustained ventricular tachycardia, n = 2) and nocturnal first-degree atrio-ventricular block (n = 2). Cardiac magnetic resonance (CMR) imaging was performed in all patients and revealed a peculiar late gadolinium enhancement distribution in three patients. HyperCKemia was present in two patients and end-stage heart failure in four. End-organ damage requiring heart transplantation (HT) was indicated in two patients, who were operated on successfully.ConclusionBiallelic TTNtv should be considered when evaluating children with severe and early-onset DCM, particularly if skeletal and muscular abnormalities are present, e.g., arthrogryposis multiplex and congenital progressive myopathy. End-stage heart failure is common and may require HT.
Application of enhanced methods of gravity data analysis for mapping the subsurface structure of the bahira basin in Morocco
Authors: Lghoul Meriem , Abd-Elhamid Hany F. , Zeleňáková Martina , Abdelrahman Kamal , Fnais Mohammed S. , Sbihi Karim 
Published: July 2023

Gravity-based imaging of the subsurface has increased worldwide recently. Improvements in the processing and analysis of gravity data have allowed us to locate the basement surface, map geologic basins, and define structural patterns. In this study, gravity data were analyzed to study the Bahira basin’s underlying geology. The Bahira basin is very important economically. The Ganntour plateau is distinctive due to the importance of the phosphate mining resources. Using gravity data, we mapped the subsurface and determined the underlying structural patterns that affect the study area. In this study, we used several techniques to edge detection including Total horizontal derivative (THDR), first vertical derivative (FVD), tilt derivative (TDR), and its horizontal derivative (THDR_TDR) methods. Accordingly, the geological history of the Bahira basin suggests that the main lineaments/faults trends are NE-SW, NW-SE, ENE-WSW, and WNW-ESE. The 3D Euler deconvolution showed the depth and location of lineaments/faults, and matched edge detection results. The eastern Bahira basin’s sedimentary layer is 2–8 km deeper according to the Euler technique. Two-dimensional forward modeling along three profiles in the Bahira basin revealed a horst-graben basement structure. The outcomes of this study improved the subsurface topographical variations of the Bahira Basin. The information collected so far can help future studies in the area.
SMARThealth PRegnancy And Mental Health study: protocol for a situational analysis of perinatal mental health in women living in rural India
Authors: Votruba Nicole , Praveen Devarsetty , Mellers Lucy , Rajan Eldho , Thout Sudhir Raj , Arora Varun , Malik Yogender , Kashyap Aditya , Majumdar Sreya , Hirst Jane , Maulik Pallab K. 
Published: July 2023

IntroductionThe situation for women experiencing mental health problems during pregnancy and postpartum in rural India is critical: a high burden of disease, a high estimated number of women are undiagnosed and untreated with mental health problems, a substantial gap in research on women's perinatal health, and severe stigma and discrimination. The SMARThealth Pregnancy study is a cluster randomised trial using a digital intervention to identify and manage anaemia, hypertension, and diabetes in the first year after birth in rural India. Within this study, the SMARThealth Pregnancy and Mental Health (PRAMH) study is a situational analysis to understand mental health problems during pregnancy and in the first year following birth in this population.Methods/designThis situational analysis aims to analyse and to assess the context of perinatal mental health, health services, barriers, facilitators, and gaps in Siddipet district of Telangana state in India, to develop an implementation framework for a future intervention. A tested, standardised situational analysis tool will be adapted and applied to perinatal mental health in rural India. A desktop and policy review will be conducted to identify and analyse relevant mental health and pregnancy care policies at the national and state levels. We will conduct in-depth interviews with policymakers, planners, mental health professionals and other experts in perinatal mental health (n = 10–15). We will also conduct focus group discussions with key stakeholders, including women with perinatal mental health problems, their families and carers, and community health workers (n = 24–40). A theory of change workshop with key stakeholders will be conducted which will also serve as a priority setting exercise, and will clarify challenges and opportunities, priorities, and objectives for a pilot intervention study. The analysis of qualitive data will be done using thematic analysis. Based on the data analysis and synthesis of the findings, an implementation framework will be developed to guide development, testing and scale up of a contextually relevant intervention for perinatal mental health.DiscussionThe situational analysis will help to establish relationships with all relevant stakeholders, clarify the context and hypotheses for the pilot intervention and implementation.
FcγR requirements and costimulatory capacity of Urelumab, Utomilumab, and Varlilumab
Authors: Leitner Judith , Egerer Ricarda , Waidhofer-Söllner Petra , Grabmeier-Pfistershammer Katharina , Steinberger Peter 
Published: July 2023

IntroductionTargeting costimulatory receptors of the tumor necrosis factor receptor (TNFR) superfamily with agonistic antibodies is a promising approach in cancer immuno therapy. It is known that their efficacy strongly depends on FcγR cross-linking.MethodsIn this study, we made use of a Jurkat-based reporter platform to analyze the influence of individual FcγRs on the costimulatory activity of the 41BB agonists, Urelumab and Utomilumab, and the CD27 agonist, Varlilumab.ResultsWe found that Urelumab (IgG4) can activate 41BB-NFκB signaling without FcγR cross-linking, but the presence of the FcγRs (CD32A, CD32B, CD64) augments the agonistic activity of Urelumab. The human IgG2 antibody Utomilumab exerts agonistic function only when crosslinked via CD32A and CD32B. The human IgG1 antibody Varlilumab showed strong agonistic activity with all FcγRs tested. In addition, we analyzed the costimulatory effects of Urelumab, Utomilumab, and Varlilumab in primary human peripheral blood mononuclear cells (PBMCs). Interestingly, we observed a very weak capacity of Varlilumab to enhance cytokine production and proliferation of CD4 and CD8 T cells. In the presence of Varlilumab the percentage of annexin V positive T cells was increased, indicating that this antibody mediated FcγR-dependent cytotoxic effects.ConclusionCollectively, our data underscore the importance to perform studies in reductionist systems as well as in primary PBMC samples to get a comprehensive understanding of the activity of costimulation agonists.
Resveratrol induces apoptosis by modulating the reciprocal crosstalk between p53 and Sirt-1 in the CRC tumor microenvironment
Authors: Brockmueller Aranka , Buhrmann Constanze , Shayan Parviz , Shakibaei Mehdi 
Published: July 2023

IntroductionP53 represents a key player in apoptosis-induction in cancers including colorectal cancer (CRC) that ranks third worldwide in cancer prevalence as well as mortality statistics. Although a pro-apoptotic effect of resveratrol has been repeatedly proven in CRC cells, its pathway mechanisms are not completely understood, as there are controversial statements in the literature regarding its activation or inhibition of the counteracting proteins Sirt-1 and p53.MethodsCRC cells as wild-type (HCT-116 WT) or p53-deficient (HCT-116 p53-/-) were cultured using multicellular tumor microenvironment (TME) cultures containing T-lymphocytes and fibroblasts to elucidate the role of p53/Sirt-1 modulation in resveratrol’s concentration-dependent, pro-apoptotic, and thus anti-cancer effects.ResultsResveratrol dose-dependently inhibited viability, proliferation, plasticity as well as migration, and induced apoptosis in HCT-116 WT more effectively than in HCT-116 p53-/- cells. Moreover, resveratrol stimulated Sirt-1 expression when administered at low concentrations (&lt;5µM) but suppressed it when added at high concentrations (&gt;10µM) to CRC-TME. In parallel, similar to the knockdown of Sirt-1 at the mRNA level, treatment with high-concentration resveratrol boosted the acetylation of p53, the expression of p21, Bax, cytochrome C, caspase-3, and ultimately induced apoptosis in CRC WT but not in CRC p53-/- cells. Notably, increasing concentrations of resveratrol were found to promote hyperacetylation of p53 and FOXO3a as post-translational substrates of Sirt-1, indicating a negative regulatory loop between Sirt-1 and p53.DiscussionThese results demonstrate for the first time, a negative reciprocal crosstalk between the regulatory circuits of p53 and Sirt-1, consequently, apoptosis induction by higher resveratrol concentrations in CRC-TME.
Hyperscanning fNIRS data analysis using multiregression dynamic models: an illustration in a violin duo
Authors: do Nascimento Diego Carvalho , Santos da Silva José Roberto , Ara Anderson , Sato João Ricardo , Costa Lilia 
Published: July 2023

IntroductionInterpersonal neural synchronization (INS) demands a greater understanding of a brain's influence on others. Therefore, brain synchronization is an even more complex system than intrasubject brain connectivity and must be investigated. There is a need to develop novel methods for statistical inference in this context.MethodsIn this study, motivated by the analysis of fNIRS hyperscanning data, which measure the activity of multiple brains simultaneously, we propose a two-step network estimation: Tabu search local method and global maximization in the selected subgroup [partial conditional directed acyclic graph (DAG) + multiregression dynamic model]. We illustrate this approach in a dataset of two individuals who are playing the violin together.ResultsThis study contributes new tools to the social neuroscience field, which may provide new perspectives about intersubject interactions. Our proposed approach estimates the best probabilistic network representation, in addition to providing access to the time-varying parameters, which may be helpful in understanding the brain-to-brain association of these two players.DiscussionThe illustration of the violin duo highlights the time-evolving changes in the brain activation of an individual influencing the other one through a data-driven analysis. We confirmed that one player was leading the other given the ROI causal relation toward the other player.
Case report: MELAS and T3271C mitochondrial mutation in an adult woman
Authors: Chen Dong-hua , Li Wei , Jiang Hai-shan , Yuan Chao 
Published: July 2023

IntroductionPatients with mitochondrial disorders always show neurological deficits. However, the diversity of clinical manifestations, genetic heterogeneity and threshold effect caused by maternal heredity make its diagnosis very challenging.Case presentationA 30-year-old female presented to our neurology department with a recurrence of symmetrical weakness proximally in the lower extremities. Seven years ago, the patient had a sudden onset of persistent weakness in bilateral proximal lower extremities, along with elevated creatinine kinase (CK) and CK-MB. Given the diagnosis of Guillain-Barre syndrome, she was treated with high-dose glucocorticoid (GC) therapy at the local hospital and recovered. After admission to our hospital, laboratory analysis revealed elevated CK and alpha-hydroxybutyrate dehydrogenase in serum. Electrocardiography showed sinus tachycardia and left high ventricular voltage. Electromyography (EMG) and evoked potential (EP) suggested peripheral neurogenic damage of the upper and lower extremities with myogenic wear. Chronic inflammatory demyelinating polyneuropathy (CIDP) was initially considered, but neurological symptoms were not significantly improved with glucocorticoid shock therapy. An elevated level of lactate was found. The short-tau inversion recovery (STIR) axial magnetic resonance image (MRI) revealed mild hyperintensities, indicating muscle edema. Meanwhile, muscle biopsies suggested pathological changes in mitochondrial disorders (MIDs) and neuronal damage. Further mitochondrial genome analysis revealed a heteroplasmic m3271 T&gt;C mutation in the mitochondrial tRNA-Leu gene (UUR). Collectively, the patient was finally diagnosed with mitochondrial disorder and apparently improved after the corresponding treatment to regulate energy metabolism.ConclusionsTo our knowledge, it's the first report about MELAS with 3271 mutation that have only shown peripheral nerve motion impairment. Proximal weakness is also common in CIDP. In the context of this patient's experience, mitochondrial genome analysis provides an auxiliary criterion for differential diagnosis between MIDs and CIDP. In the meantime, we discussed the clinical effect of GCs on MIDs.
A case of pure apraxia of speech after left hemisphere stroke: behavioral findings and neural correlates
Authors: Pracar Alexis L. , Ivanova Maria V. , Richardson Amber , Dronkers Nina F. 
Published: July 2023

IntroductionApraxia of speech (AOS) is a motor speech disorder impairing the coordination of complex articulatory movements needed to produce speech. AOS typically co-occurs with a non-fluent aphasia, or language disorder, making it challenging to determine the specific brain structures that cause AOS. Cases of pure AOS without aphasia are rare but offer the best window into the neural correlates that support articulatory planning. The goal of the current study was to explore patterns of apraxic speech errors and their underlying neural correlates in a case of pure AOS.MethodsA 67-year-old right-handed man presented with severe AOS resulting from a fronto-insular lesion caused by an ischemic stroke. The participant’s speech and language were evaluated at 1-, 3- and 12-months post-onset. High resolution structural MRI, including diffusion weighted imaging, was acquired at 12 months post-onset.ResultsAt the first assessment, the participant made minor errors on the Comprehensive Aphasia Test, demonstrating mild deficits in writing, auditory comprehension, and repetition. By the second assessment, he no longer had aphasia. On the Motor Speech Evaluation, the severity of his AOS was initially rated as 5 (out of 7) and improved to a score of 4 by the second visit, likely due to training by his SLP at the time to slow his speech. Structural MRI data showed a fronto-insular lesion encompassing the superior precentral gyrus of the insula and portions of the inferior and middle frontal gyri and precentral gyrus. Tractography derived from diffusion MRI showed partial damage to the frontal aslant tract and arcuate fasciculus along the white matter projections to the insula.DiscussionThis pure case of severe AOS without aphasia affords a unique window into the behavioral and neural mechanisms of this motor speech disorder. The current findings support previous observations that AOS and aphasia are dissociable and confirm a role for the precentral gyrus of the insula and BA44, as well as underlying white matter in supporting the coordination of complex articulatory movements. Additionally, other regions including the precentral gyrus, Broca’s area, and Area 55b are discussed regarding their potential role in successful speech production.
Regional homogeneity alterations of resting-state functional magnetic resonance imaging of chronic rhinosinusitis with olfactory dysfunction
Authors: Zhang Zhiqiang , Wu Ying , Luo Qing , Tu Junhao , Li Jiahao , Xiong Jiaxin , Lv Huiting , Ye Jing 
Published: July 2023

ObjectivesThe aim of this study was to assess the brain functional changes of patients with chronic rhinosinusitis with olfactory dysfunction (CRSwOD) using regional homogeneity (ReHo) of resting-state functional magnetic resonance imaging (MRI) scans, and to better explain the occurrence and development of olfactory decline in patients with chronic sinusitis provides a new idea for the study of more advanced olfactory therapy modalities.MethodsA total of 28 CRSwOD patients, 24 patients with CRS without olfactory dysfunction (CRSsOD), and 25 healthy controls (HCs) were recruited. All subjects underwent olfactory testing, clinical and brief psychological assessments, and MRI scans. A two-sided two-sample t test with AlphaSim correction (voxel-p &lt; 0.001, cluster size &gt;54 voxels) was used to detect differences between CRSwOD, CRSsOD, and HC groups.ResultsCompared with HCs, the ReHo values in traditional olfactory regions (e.g., parahippocampal gyrus (PHG), hippocampal, olfactory cortex) were increased, and ReHo values in the frontal gyrus, middle temporal gyrus, precuneus, and posterior cingulate gyrus were decreased in CRSwOD patients. The ReHo values in the precuneus and posterior cingulate gyrus of CRSwOD patients were negatively correlated with Questionnaire of Olfactory Disorders-Negative Statements (QOD-NS) scores. Compared with CRSsOD patients, the ReHo values in cerebellar regions were increased and those in the inferior temporal gyrus, precuneus, postcentral, and paracentral gyrus were decreased in CRSwOD patients. The receiver operating characteristic (ROC) curve showed that the mean ReHo values significantly differed between the CRSwOD and CRSsOD groups.ConclusionSynchronization of regional brain activity in the regions of the secondary olfactory cortex orbitofrontal cortex (OFC), temporal gyrus, precuneus, and cerebellum may be closely related to the development of olfactory dysfunction. Precuneus and posterior cingulate gyrus may be critical brain areas of action for emotional dysfunction in CRSwOD patients.
Associations between parenting strategies and BMI percentile among Latino children and youth with intellectual and developmental disabilities
Authors: Magaña Sandy , Errisuriz Vanessa L. , Yu Amy Pei-Lung , Heydaria Nazanin , Zeng Weiwen , Mirza Mansha , Vanegas Sandra , Brown Stephany , Parra-Medina Deborah , Suarez-Balcazar Yolanda 
Published: July 2023

IntroductionMaintaining healthy weight is a challenge for all children, and particularly for children with IDD compared to nondisabled children and for Latino children compared to non-Latino White children. Parenting practices related to food intake and physical activity have been found to be important in maintaining children's weight. In this study, we describe the prevalence of overweight and obesity status among Latino children with IDD and their maternal caregivers and determine the relationship between food and physical activity parenting practices and childhood obesity among Latino children with IDD.MethodsWe interviewed 94 Latino parent/child dyads and collected information about parenting practices, home environment, and parent and child height and weight using standardized measures. Parent body mass index (BMI) and child BMI percentile were calculated from height and weight.ResultsThe combined overweight/obesity status for children in our sample was high (60.3%) compared to national rates among nondisabled Latino children (56%) and non-Latino White children with autism (37%). Contrary to research on nondisabled children, we found that greater parental use of controlling dietary strategies was associated with lower BMI percentile in Latino children with IDD. These findings may be indicative of the fact that children with IDD tend to have unique dietary behaviors that warrant more disability and culturally sensitive strategies.DiscussionOur findings suggest that overweight and obesity is especially prevalent for Latino children with IDD and that more research is needed on family factors that promote health in Latino families of children with IDD.
Qing Hua Chang Yin alleviates chronic colitis of mice by protecting intestinal barrier function and improving colonic microflora
Authors: Han Yuying , Liu Liya , Chen Youqin , Zheng Huifang , Yao Mengying , Cao Liujing , Sferra Thomas J. , Ke Xiao , Peng Jun , Shen Aling 
Published: July 2023

Background: Qing Hua Chang Yin (QHCY) is a famous formula of traditional Chinese medicine (TCM) and has been proven to have protective effect on ulcerative colitis. However, its protective effect and potential therapeutic mechanisms in chronic colitis remain unclear. The purpose of this study is to explore the effects and underlying mechanisms of QHCY on dextran sulfate sodium (DSS)-induced chronic colitis mice model.Methods: The chronic colitis model was established by administration of 2% DSS for three consecutive cycles of 7 days with two intervals of 14 days for recovery by drinking water. The experiment lasted 49 days. The DSS + QHCY group received QHCY administration by oral gavage at doses of 1.6 g/kg/d, DSS + Mesalazine group was administrated Mesalazine by oral gavage at doses of 0.2 g/kg/d. The control and DSS group were given equal volume of distilled water. The body weight, stool consistency and blood in stool were monitored every 2 days. The disease activity index (DAI) was calculated. The colon length was measured after the mice were sacrificed. The histomorphology of colonic tissues was checked by the HE and PAS staining. Immunohistochemistry was performed to detect the expressions of pro-inflammatory cytokines (TNF-α, IL-1β and IL-6), tight junction proteins (ZO-1, occludin) and Mucin2 (MUC2). 16S rRNA sequencing analysis was conducted to study the diversity and abundance of gut microbiota changes.Results: QHCY treatment not only significantly attenuated DSS-induced the weight loss, DAI score increase, colon shortening and histological damage in mice, but also decreased the expression of pro-inflammatory cytokines in colonic tissues and increased the expression of ZO-1, occludin, and MUC2. Furthermore, QHCY enhanced the diversity of gut microbes and regulated the structure and composition of intestinal microflora in mice with chronic colitis.Conclusion: QHCY has a therapeutic effect on a murine model of chronic colitis. It can effectively reduce the clinical and pathological manifestations of colitis and prevent alterations in the gut microbiota.