bluuebunny/crossref_metadata_2025_split huggingface dataset:
Identification and functional characterization of de novo variant in the SYNGAP1 gene causing intellectual disability
Authors: Li Boxuan , Wang Yu , Hou Dong , Song Zhen , Zhang Lihua , Li Na , Yang Ruifang , Sun Ping 
Published: October 2023

Background: Intellectual disability (ID) is defined by cognitive and social adaptation defects. Variants in the SYNGAP1 gene, which encodes the brain-specific cytoplasmic protein SYNGAP1, are commonly associated with ID. The aim of this study was to identify novel SYNGAP1 gene variants in Chinese individuals with ID and evaluate the pathogenicity of the detected variants.Methods: Whole exome sequencing (WES) was performed on 113 patients diagnosed with ID. In the study, two de novo variants in SYNGAP1 were identified. Sanger sequencing was used to confirm these variants. Minigene assays were used to verify whether the de novo intronic variant in SYNGAP1 influenced the normal splicing of mRNA.Results: Two de novo heterozygous pathogenic variants in SYNGAP1, c.333del and c.664-2A&gt;G, were identified in two ID patients separately. The c.333del variant has been reported previously as a de novo finding in a child with ID, while the c.664-2A&gt;G variant was novel de novo intronic variant, which has not been reported in the literature. Functional studies showed that c.664-2A&gt;G could cause aberrant splicing, resulting in exon 7 skipping and a 16bp deletion within exon 7.Conclusion: We identified two de novo pathogenic heterozygous variants in SYNGAP1 in two patients with ID, among which the c.664-2A&gt;G variant was a novel de novo pathogenic variant. Our findings further enrich the variant spectrum of the SYNGAP1 gene and provide a research basis for the genetic diagnosis of ID.
13C tracer analysis reveals the landscape of metabolic checkpoints in human CD8+ T cell differentiation and exhaustion
Authors: Kirchmair Alexander , Nemati Niloofar , Lamberti Giorgia , Trefny Marcel , Krogsdam Anne , Siller Anita , Hörtnagl Paul , Schumacher Petra , Sopper Sieghart , Sandbichler Adolf , Zippelius Alfred , Ghesquière Bart , Trajanoski Zlatko 
Published: October 2023

IntroductionNaïve T cells remain in an actively maintained state of quiescence until activation by antigenic signals, upon which they start to proliferate and generate effector cells to initiate a functional immune response. Metabolic reprogramming is essential to meet the biosynthetic demands of the differentiation process, and failure to do so can promote the development of hypofunctional exhausted T cells.MethodsHere we used 13C metabolomics and transcriptomics to study the metabolism of CD8+ T cells in their complete course of differentiation from naïve over stem-like memory to effector cells and in exhaustion-inducing conditions. ResultsThe quiescence of naïve T cells was evident in a profound suppression of glucose oxidation and a decreased expression of ENO1, downstream of which no glycolytic flux was detectable. Moreover, TCA cycle activity was low in naïve T cells and associated with a downregulation of SDH subunits. Upon stimulation and exit from quiescence, the initiation of cell growth and proliferation was accompanied by differential expression of metabolic enzymes and metabolic reprogramming towards aerobic glycolysis with high rates of nutrient uptake, respiration and lactate production. High flux in anabolic pathways imposed a strain on NADH homeostasis, which coincided with engagement of the proline cycle for mitochondrial redox shuttling. With acquisition of effector functions, cells increasingly relied on glycolysis as opposed to oxidative phosphorylation, which was, however, not linked to changes in mitochondrial abundance. In exhaustion, decreased effector function concurred with a reduction in mitochondrial metabolism, glycolysis and amino acid import, and an upregulation of quiescence-associated genes, TXNIP and KLF2, and the T cell suppressive metabolites succinate and itaconate. DiscussionOverall, these results identify multiple metabolic features that regulate quiescence, proliferation and effector function, but also exhaustion of CD8+ T cells during differentiation. Thus, targeting these metabolic checkpoints may be a promising therapeutic strategy for both prevention of exhaustion and promotion of stemness of anti-tumor T cells.
Using the modified Delphi technique to develop a framework for interprofessional education during international electives in health professions training institutions in Sub-Saharan Africa
Authors: Nawagi Faith , Munabi Ian Guyton , Vyt Andre , Kiguli Sarah , Rabin Tracy , Waggie Firdouza , Mubuuke Aloysius Gonzaga 
Published: October 2023

BackgroundInternational electives provide a learning platform where interprofessional education and collaborative practice (IPECP) skills can be cultivated. However, hardly any frameworks to guide the implementation of interprofessional education (IPE) during international electives, especially in the context of low-income settings have been published. To address this gap, this study used the modified Delphi approach to develop an IPE framework guide for international electives to be used by health professions training institutions in Sub-Saharan Africa.MethodsA rapid literature review and a study among students and faculty in four African health professional training institutions were done to inform the process. This was followed by the modified Delphi technique that used three Delphi rounds with a panel of eight experts to build consensus on the final framework for IPE during international electives. The level of consensus was set at ≥70% on each of the statements in all rounds.ResultsOut of the 52 statements in round 1 (n = 37, 71%) reached consensus while (n = 15, 29%) of the statements did not reach consensus and were discussed in round 2. Round 2 led to 42 statements to be utilized for round 3. In round 3, all statements (42) reached a consensus and an IPE framework to guide the implementation of international electives was developed. The framework consists of three sections. Section one highlights the various IPECP competencies to be gained by learners in the areas of teamwork, interprofessional communication, roles and responsibilities of interprofessional collaborative practice, values and ethics of interprofessional collaboration, and reflection and evaluation of oneself and the team. Section two gives guidance on the structuring of the IPE international electives in health professional training institutions. This includes subsections on operational/institutional needs, acculturation considerations, teaching strategies, assessment strategies, mode of delivery, and public health considerations. Section three consists of the various practical guides and approaches that health professional training institutions could use according to what works best in their setting.ConclusionThe modified Delphi technique was an adequate approach to aid the development of an IPE framework to guide implementation during international electives in various health professional training institutions.
Improved first-pass effect in acute stroke thrombectomy using Solitaire-X compared to Solitaire-FR
Authors: Biederko Ron , Honig Asaf , Shabad Ksenia , Zlotnik Yair , Ben-Arie Gal , Alguayn Farouq , Shelef Ilan , Horev Anat 
Published: October 2023

BackgroundIn acute ischemic stroke (AIS), successful endovascular thrombectomy (EVT) of large vessel occlusion (LVO) necessitates the most suited device. Solitaire-X has longer and larger diameter pusher wires than Solitaire-FR.As the role of a larger pusher-wire diameter is uncertain, we aim to compare procedural, clinical, and radiological outcomes for AIS patients undergoing EVT using either type of Solitaire device. Procedures were performed using the Solumbra technique, which combines a large-bore aspiration catheter with a stentriever. The primary outcome was to compare rates of successful first-pass recanalization (defined as TICI 2b/3 score). The secondary objectives were procedural (rates of successful recanalization), clinical (post-procedural NIHSS and days of hospitalization), and radiological (post-procedural ASPECT score and hemorrhagic transformation) outcome measures.DesignConsecutive AIS patients undergoing EVT for LVO were recruited into a prospective multicenter database at our academic center. We have used Solitaire-FR until October 2020 and Solitaire-X ever since. We retrospectively analyzed our prospective consecutive registry. Included in our analysis are patients undergoing EVT using Solitaire only; patients with tandem lesions or underlying stenosis requiring emergent stenting during the procedure were excluded. The cohort of patients treated with Solitaire-X was compared with a cohort consisting of the most recent consecutive cases undergoing EVT with the Solitaire-FR.ResultsA total of 182 (71.9 ± 14, 61% male patients) AIS patients were included in the analysis with both groups (n = 91 each) sharing similar demographic characteristics, premorbid conditions, and stroke characteristics (time from symptom-onset, NIHSS, ASPECTS, occlusion site, and rates of intravenous-tPA treatment). The Solitaire-X group had a higher rate of first-pass recanalization (65.9% vs. 50.5%, p = 0.049). On 24-h post-procedural head-CT, the Solitaire-X group had higher ASPECT scores (6.51 ± 2.9 vs. 5.49 ± 3.4, p = 0.042) and lower post-procedural average bleeding volumes (0.67 ± 2.1 vs. 1.20 ± 3.4 mL, p = 0.041). The Solitaire-X group had shorter duration of hospitalization (16.6 ± 13.1 days vs. 25.1 ± 23.2, p = 0.033). On multivariate analysis, using Solitaire-X was the sole independent predictor of first-pass recanalization (OR 2.17, 95% CI 1.12–4.26, p = 0.023).ConclusionIn our study, the use of the Stentriever-X with a larger pusher-wire diameter was associated with a higher likelihood of first-pass effect and improved procedural, clinical, and radiological outcomes in AIS patients.
Differences in resting state functional connectivity relative to multiple sclerosis and impaired information processing speed
Authors: Carter Sean L. , Patel Ronak , Fisk John D. , Figley Chase R. , Marrie Ruth Ann , Mazerolle Erin L. , Uddin Md Nasir , Wong Kaihim , Graff Lesley A. , Bolton James M. , Marriott James J. , Bernstein Charles N. , Kornelsen Jennifer 
Published: October 2023

BackgroundFifty-one percent of individuals with multiple sclerosis (MS) develop cognitive impairment (CI) in information processing speed (IPS). Although IPS scores are associated with health and well-being, neural changes that underlie IPS impairments in MS are not understood. Resting state fMRI can provide insight into brain function changes underlying impairment in persons with MS.ObjectivesWe aimed to assess functional connectivity (FC) differences in (i) persons with MS compared to healthy controls (HC), (ii) persons with both MS and CI (MS-CI) compared to HC, (iii) persons with MS that are cognitively preserved (MS-CP) compared to HC, (iv) MS-CI compared to MS-CP, and (v) in relation to cognition within the MS group.MethodsWe included 107 participants with MS (age 49.5 ± 12.9, 82% women), and 94 controls (age 37.9 ± 15.4, 66% women). Each participant was administered the Symbol Digit Modalities Test (SDMT) and underwent a resting state fMRI scan. The MS-CI group was created by applying a z-score cut-off of ≤−1.5 to locally normalized SDMT scores. The MS-CP group was created by applying a z-score of ≥0. Control groups (HCMS-CI and HCMS-CP) were based on the nearest age-matched HC participants. A whole-brain ROI-to-ROI analysis was performed followed by specific contrasts and a regression analysis.ResultsIndividuals with MS showed FC differences compared to HC that involved the cerebellum, visual and language-associated brain regions, and the thalamus, hippocampus, and basal ganglia. The MS-CI showed FC differences compared to HCMS-CI that involved the cerebellum, visual and language-associated areas, thalamus, and caudate. SDMT scores were correlated with FC between the cerebellum and lateral occipital cortex in MS. No differences were observed between the MS-CP and HCMS-CP or MS-CI and MS-CP groups.ConclusionOur findings emphasize FC changes of cerebellar, visual, and language-associated areas in persons with MS. These differences were apparent for (i) all MS participants compared to HC, (ii) MS-CI subgroup and their matched controls, and (iii) the association between FC and SDMT scores within the MS group. Our findings strongly suggest that future work that examines the associations between FC and IPS impairments in MS should focus on the involvement of these regions.
The association between hypertensive angiopathy and cerebral amyloid angiopathy in primary intracerebral hemorrhage
Authors: Zhu Yuyi , Liu Lu , Zhong Luyao , Cheng Yajun , Zhang Shihong , Wu Bo , Wang Deren , Xu Mangmang 
Published: October 2023

ObjectiveTo determine the association between the burden of cerebral small vessel disease (CSVD) due to hypertensive angiopathy (HA) and cerebral amyloid angiopathy (CAA) on MRI in patients with primary intracerebral hemorrhage (ICH).MethodsPatients with primary ICH admitted to our center from March 2012 to November 2021 were consecutively enrolled. We used multivariate binary and ordinal regression analyses to assess the association between HA-CSVD burden and CAA-CSVD burden. Lobar cerebral microbleeds (CMBs) were categorized into three level of severity: 0–1, 2–4, and ≥ 5 lobar CMBs. A high CAA-CSVD score was defined as a CAA-CSVD score of ≥3.ResultsOverall, 222 participants (mean age 59.88 ± 13.56) were included into analysis. Age and ICH etiology differed among different lobar CMB severity and between the presence and absence of high CAA-CSVD score (all p &lt; 0.05). Positive associations between HA-related markers and both lobar CMB severity and high CAA-CSVD score (p &lt; 0.05 for the presence of lacune, deep CMBs ≥5, the presence of WMH, and HA-CSVD score) were observed in univariate analysis. These associations remained significant after adjusting for age, sex, ICH etiology, and potential vascular risk factors. The distribution of CAA-CSVD score was significantly different between patients with and without CMBs ≥5 (adjusted OR 2.351, 95% CI 1.242–4.455, p = 0.009) after correcting for age, sex, ICH etiology, and vascular risk factors.ConclusionOur study provides evidence of an association between HA-CSVD and CAA-CSVD in patients with primary ICH, which needs to be verified in future studies.
Premature drug reduction after subthalamic nucleus deep brain stimulation leading to worse depression in patients with Parkinson's disease
Authors: Diao Yu , Hu Tianqi , Xie Hutao , Fan Houyou , Meng Fangang , Yang Anchao , Bai Yutong , Zhang Jianguo 
Published: October 2023

BackgroundReduction of medication in Parkinson's disease (PD) following subthalamic nucleus deep brain stimulation (STN-DBS) has been recognized, but the optimal timing for medication adjustments remains unclear, posing challenges in postoperative patient management.ObjectiveThis study aimed to provide evidence for the timing of medication reduction post-DBS using propensity score matching (PSM).MethodsIn this study, initial programming and observation sessions were conducted over 1 week for patients 4–6 weeks postoperatively. Patients were subsequently categorized into medication reduction or non-reduction groups based on their dyskinesia evaluation using the 4.2-item score from the MDS-UPDRS-IV. PSM was employed to maintain baseline comparability. Short-term motor and neuropsychiatric symptom assessments for both groups were conducted 3–6 months postoperatively.ResultsA total of 123 PD patients were included. Baseline balance in motor and non-motor scores was achieved between the two groups based on PSM. Short-term efficacy revealed a significant reduction in depression scores within the non-reduction group compared to baseline (P &lt; 0.001) and a significant reduction compared to the reduction group (P = 0.037). No significant differences were observed in UPDRS-III and HAMA scores between the two groups. Within-group analysis showed improvements in motor symptoms, depression, anxiety, and subdomains in the non-reduction group, while the reduction group exhibited improvements only in motor symptoms.ConclusionThis study provides evidence for the timing of medication reduction following DBS. Our findings suggest that early maintenance of medication stability is more favorable for improving neuropsychiatric symptoms.
Impact of sarcopenia and sarcopenic obesity on survival in patients with primary liver cancer: a systematic review and meta-analysis
Authors: Li Xuanmei , Huang Xue , Lei Lifu , Tong Shiwen 
Published: October 2023

BackgroundSarcopenia and sarcopenic obesity are associated with an increased possibility of adverse clinical outcomes; however, the effects of sarcopenia and sarcopenic obesity on patients with primary liver cancer remain controversial. Therefore, the present study aimed to determine the impact of sarcopenia and sarcopenic obesity on survival in patients with primary liver cancer.MethodsWe searched studies published in English in PubMed, Embase, Web of Science, and Cochrane Library databases up to 13 November 2022. Cohort studies that reported the association among sarcopenia, sarcopenic obesity, and patient survival were included.ResultsA total of 64 cohort studies with data on 11,970 patients with primary liver cancer were included in the meta-analysis. Sarcopenia was associated with poor overall survival in patients with primary liver cancer [adjusted hazard ratio (HR) 2.11, 95% confidence interval (CI): 1.89–2.36, P &lt; 0.0001], with similar findings for sarcopenic obesity (adjusted HR: 2.87, 95% CI: 2.23–3.70, P &lt; 0.0001). Sarcopenia was also associated with poor overall survival across the subgroups analyzed by ethnicity, type of liver cancer, treatment modalities, method used to define sarcopenia, and etiology of liver cancer. We also found a negative correlation among sarcopenia, sarcopenic obesity, and recurrence-free/disease-free survival (adjusted HR: 1.73, 95% CI: 1.50–1.99, P &lt; 0.001; adjusted HR: 2.28, 95% CI: 1.54–3.35, P &lt; 0.001, respectively).ConclusionSarcopenia and sarcopenic obesity were significantly associated with poor overall survival and recurrence-free/disease-free survival in patients with primary liver cancer.Systematic review registrationhttps://www.crd.york.ac.uk/prospero/display_record.php?RecordID=378433, PROSPERO [42022378433].
Symptomatic presentation influences outcomes in pediatric restrictive cardiomyopathy
Authors: Lorenzo Melissa , Lynch Aine , Ashkanase Jenna , Fazari Linda , George Kristen , Arathoon Katelyn , Minn Sunghoon , Nicolson Dawn , Jeewa Aamir , Jean-St-Michel Emilie 
Published: October 2023

IntroductionChildren with restrictive cardiomyopathy (RCM) traditionally have a poor prognosis, with most patients either dying or requiring heart transplantation within 2 years of diagnosis. The development of symptoms in RCM suggests advanced disease. However, as screening practices evolve and lead to diagnosis of early disease, identifying appropriate timing of transplant listing becomes increasingly important. In this context we compared outcomes of children with RCM presenting with clinical symptoms to those asymptomatic at initial presentation.MethodsThis retrospective cohort study included 25 patients with RCM presenting to a quaternary care center between 2001 and 2018. Times to transplantation, death, and a composite outcome of adverse cardiac events (CPR, cardioversion, inotropic support, mechanical ventilation, mechanical support, or heart transplant) were compared between those symptomatic and asymptomatic at presentation.ResultsAt 2 years following diagnosis, patients asymptomatic at presentation had a significantly better transplant-free survival at 57% compared to 17% for symptomatic patients (p = 0.03). Those asymptomatic at diagnosis also had significantly improved cardiac event-free survival at 71% compared to symptomatic patients at 25% (p = 0.01). In multivariable analysis, cardiac symptoms at presentation remained an independent risk factor for heart-transplant or death [hazard ratio 5.17 (1.28–20.85), p = 0.02].ConclusionPatients with RCM who are symptomatic at time of diagnosis have significantly worse transplant-free survival and cardiac event-free survival. Given current practice variability in timing of transplant listing, the presence of any cardiac symptoms is an important negative prognostic marker and should prompt urgent transplant listing.
The effectiveness of an immersive virtual reality and telemedicine-based cognitive intervention on prospective memory in Parkinson’s disease patients with mild cognitive impairment and healthy aged individuals: design and preliminary baseline results of a placebo-controlled study
Authors: De Simone Maria Stefania , Costa Alberto , Tieri Gaetano , Taglieri Sara , Cona Giorgia , Fiorenzato Eleonora , Carlesimo Giovanni Augusto , Caltagirone Carlo , Zabberoni Silvia 
Published: October 2023

IntroductionProspective memory (PM) impairments have been extensively documented in individuals with Parkinson’s disease associated with mild cognitive impairment (PD-MCI) and in those with healthy aging. Considering how PM failure decreases individuals’ quality of life and functional independence in the activities of daily living, training to enhance this ability could be a prior target of intervention.ObjectiveHere, we aimed to present the study protocol and preliminary results of a novel immersive virtual reality (IVR) and telemedicine-based (TM) cognitive intervention focused on executive abilities (i.e., planning, shifting, and updating) to improve PM functioning in PD-MCI patients and healthy elderly individuals.MethodsOutcome measures, collected before, immediately after and 2 months after the intervention, included: (1) pre-post training changes in objective cognitive functioning, evaluated with tests assessing executive functions and PM; (2) pre-post training changes in subjective perception of memory functioning, psychiatric symptoms, autonomy in daily living and quality of life, evaluated using the appropriate scales; (3) usability, feasibility and users’ compliance with the proposed IVR and telemedicine program. The efficacy of this intervention compared to an active control condition is currently being evaluated in a randomized, double-blind controlled trial, which will be conducted on 30 eligible PD-MCI patients and 30 older adults.ResultsPreliminary results concerning between-group comparisons of demographic and neuropsychological screening data show a good balance among the intervention groups considered in this study. The results also suggest good levels of usability, feasibility and acceptability, thus supporting the notion that our intervention can be used to promote cognitive functioning, even in people with cognitive decline.ConclusionConsidering the relatively low costs and easy accessibility to this program, it could prove valuable in primary prevention initiatives and early cognitive rehabilitation for dementia risk reduction.