bluuebunny/crossref_metadata_2025_split huggingface dataset:
Alveolar Repair Using Cancellous Bone and Beta Tricalcium Phosphate Seeded With Adipose-Derived Stem Cell
Authors: Putri Indri Lakhsmi , Fatchiyah  , Pramono Coen , Bachtiar Indra , Latief Fourier Dzar Eljabbar , Utomo Budi , Rachman Arif , Soesilawati Pratiwi , Hakim Lukman , Rantam Fedik Abdul , Perdanakusuma David Sontani 
Published: October 2022

Introduction Adipose-derived stem cells (ADSCs) have been subject of several studies due to their abundance, ease of preparation, and application in bone regeneration. We aim to compare effectiveness of alveolar reconstruction utilizing human cancellous freeze-dried graft (HCG) and beta tricalcium phosphate (BTP), both seeded with human ADSC (hADSC) and autologous bone graft (ABG). Material and Methods A 5 × 5 mm alveolar defect in 36 male Wistar rats were treated using: ABG (C), HCG–hADSC (H1), and BTP–hADSC (H2). At 1 and 8 weeks after surgery, runt-related transcription factor 2 (RUNX2), alkaline phosphatase (ALP), osterix (OSX), and bone morphogenetic protein 2 (BMP2; g/mL) were quantified using immunohistochemistry, while bone tissue volume (BV, mm3), bone tissue volume fraction (BF, percentage), and trabecular thickness of bone (TT, mm) were assessed using micro-computed tomography (CT). Results One week after surgery, H2 was higher in RUNX2, OSX, ALP, and BMP2 than C ( P < .05). Only RUNX2 and OSX were found to be higher in H1 than C, while ALP and BMP2 were higher in H2 than H1. Micro-CT revealed that H2 had a higher TT than C and C had a higher TT than H1 ( P < .05). Eight weeks after surgery, both H2 and H1 was higher in RUNX2, OSX, ALP, and BMP2 than C ( P < .05). RUNX2 and BMP2 were found to be higher in H1 than H2. Micro-CT revealed that H2 had higher BV and TT than C and H1 ( P < .05). Conclusions Exogenous hADSC strengthened the effectiveness of HCG and BTP to accelerate osteogenesis, osteoconduction, and osteoinduction. The latter was the most successful in bone formation, followed by HCG and ABG.
Investigation of the frequency of bortezomib neuropathy in patients with multiple myeloma diagnosis with normal and abnormal genetic characteristics
Authors: Kul Ayse N , Ipek Yildiz 
Published: October 2022

Introduction Bortezomib-induced peripheral neuropathy in patients with multiple myeloma is an undesirable and sometimes severe side effect. Our study aimed to examine whether there was a difference in bortezomib-induced peripheral neuropathy between multiple myeloma patients with normal and abnormal genetic characteristics. Methods This retrospective analysis is based on the assessment of bortezomib-induced peripheral neuropathy frequency in newly-diagnosed multiple myeloma patients with normal ( n = 68) and abnormal ( n = 45) genetic profiles. A total of 113 patients diagnosed with multiple myeloma according to the International Myeloma Working Group criteria, between 2016 and 2021, were included in this study. Results Neuropathy was detected in 42 (37.1%) patients. The most common genetic anomalies were 13q del (in 28.9%), t(4.14) (in 22.2%), and trisomy 7 (in 20.0%). When patients with and without bortezomib-induced peripheral neuropathy were compared, the only significant differences were observed for age ( p = 0.032) and genetic grouping ( p = 0.001); whereas other characteristics that could be associated with bortezomib-induced peripheral neuropathy were similarly distributed in both groups. Bortezomib-induced peripheral neuropathy was significantly more frequent in multiple myeloma patients with normal genetic characteristics ( p = 0.001). Conclusion As a result of our study, it was observed that the frequency of bortezomib neuropathy was significantly higher in patients with normal genetic features compared to those with abnormal genetic features. This result suggested that factors other than genetic factors should be investigated to clarify the etiology of bortezomib-associated neuropathy in patients with multiple myeloma.
Can We Expand the Pool of Youth Who Receive Telehealth Assessments for ADHD? Covariates of Service Utilization
Authors: Pritchard Alison E. , Northrup Rachel A. , Peterson Rachel , Lieb Rebecca , Wexler Danielle , Ng Rowena , Kalb Luke , Ludwig Natasha , Jacobson Lisa A. 
Published: October 2022

Background: During the COVID-19 pandemic, telehealth became widely utilized for healthcare, including psychological evaluations. However, whether telehealth has reduced or exacerbated healthcare disparities for children with Attention-Deficit/Hyperactivity Disorder (ADHD) remains unclear. Methods: Data (race, ethnicity, age, insurance type, ADHD presentation, comorbidities, and distance to clinic) for youth with ADHD ( Mage = 10.97, SDage = 3.42; 63.71% male; 51.62% White) were extracted from the medical record at an urban academic medical center. Three naturally occurring groups were compared: those evaluated in person prior to COVID-19 ( n =780), in person during COVID-19 ( n = 839), and via telehealth during COVID-19 ( n = 638). Results: Children seen via telehealth were significantly more likely to be older, White, have fewer comorbid conditions, and live farther from the clinic than those seen in person. Conclusions: The current study suggests that telehealth has not eliminated barriers to care for disadvantaged populations. Providers and institutions must take action to encourage telehealth use among these groups.
A proposed new taxonomy of cognitive phenotypes in multiple sclerosis: The International Classification of Cognitive Disorders in MS (IC-CoDiMS)
Authors: Hancock Laura M , Galioto Rachel , Samsonov Alexey , Busch Robyn M , Hermann Bruce , Matias-Guiu Jordi A 
Published: October 2022

Background: Characterization of cognitive impairment (CI) in multiple sclerosis into distinct phenotypes holds promise for individualized treatments and biomarker exploration. Objective: Apply a previously validated, neuropsychologically driven diagnostic algorithm to identify a taxonomy of the type of cognitive phenotypes in multiple sclerosis. Methods: An algorithm developed and validated in other neurological diseases was applied to a cohort of 1281 people with multiple sclerosis who underwent clinical neuropsychological evaluation across three multiple sclerosis centers. A domain was marked impaired if scores on two tests within the domain fell below one of the two thresholds of interest (compared to controls; −1.0 SD and −1.5 SD below the mean). Results were then tabulated for each participant to determine the type of impairments across the sample. Results: At −1 SD threshold, 48.7% were intact, 21.6% had single-domain, 14.3% bi-domain, and 15.4% multi-domain impairment. At −1.5 SD threshold, 72.9% were intact, 14.0% had single-domain, 8.2% bi-domain, and 5.0% multi-domain impairment. Processing speed was the most frequent single-domain impairment, followed by executive function and memory. Conclusions: These findings advance the taxonomy of cognitive phenotypes in multiple sclerosis and clarify the type and distribution of possible cognitive diagnoses, pave the way for further investigation of associated biomarkers, and provide clinically meaningful information to guide individualized treatment and rehabilitation.
Healthcare resource consumption prior to asthma-related death: a nationwide descriptive study
Authors: Guilleminault Laurent , Mounié Michael , Sommet Agnès , Camus Claire , Didier Alain , Reber Laurent L. , Costa Nadège , Conte Cécile 
Published: October 2022

Background: Although asthma mortality declined sharply until the mid-2000s, a stagnation in mortality has been observed over the past decade in different countries. Objective: The objective of this study is to describe healthcare resource consumption for patients who died from asthma in France. Method: This study was conducted using data from the French National Health Data System. Patients who died from asthma between 2013 and 2017 were identified by the ICD10 codes J45 and J46. Health care consumption data were collected. Patients were categorized into four categories according to age: ⩾75, (18–75), (12–18), (0–12). Daily doses of ICS were categorized according to GINA guidelines. Results: A total of 3829 patients were included. No ICS or an inadequate ICS dose was observed in 43.8%, 50.6%, 48.1%, and 54.0% of patients aged ⩾75, (18–74), (12–18), and (0–12) years, respectively. Dispensation of six or more SABA canisters was observed in 37.2%, 49.0%, and 70.3% of patients aged of ⩾75, (18–75), and (12–18) years, respectively. Omalizumab dispensation rate was very low [1.1% and 2.8% in patients aged ⩾75 and (18–75) years)]. The proportion of patients with a pulmonologist office visit was 13.8% and 14.6% in patients ⩾75 and (18–75) years, respectively. A lung function test was noted in only 18.6%, 28.3%, and 25.9% of patients ⩾75, (18–75) and (12–18) years, respectively. Conclusion: Half of the patients who died from asthma received inadequate ICS doses and only a small proportion had access to biological therapies. Less than 15% were referred to a specialist.
Effect of Joint Infection After Arthroscopic Single-Bundle ACL Reconstruction With Autologous Hamstring Tendon: A Retrospective Matched MRI Study
Authors: Chen Nayun , Wang Cheng , Li Dai , Jiang Yanfang , Ao Yingfang 
Published: October 2022

Background: Joint infection after anterior cruciate ligament (ACL) reconstruction is a rare but serious complication. Purpose: To assess the effect of joint infection on the graft, cartilage, and bone tunnel using magnetic resonance imaging (MRI) after arthroscopic single-bundle ACL reconstruction with autologous hamstring tendons. Study Design: Cohort study; Level of evidence, 3. Methods: This retrospective matched cohort study included 26 patients who underwent arthroscopic single-bundle ACL reconstruction with hamstring tendon graft at the authors’ institute between January 2002 and December 2017 and developed postoperative joint infection. These patients were matched 1:3 to patients who did not sustain joint infection after ACL reconstruction (control group). MRI scans were collected at the time of follow-up. The following parameters were evaluated: graft signal-to-noise quotient (SNQ); graft signal intensity at the bone-graft interface and within the knee joint; bone tunnel enlargement at the tunnel aperture, midsection, and exit of the tibial and femoral tunnels; and cartilage integrity. Results: The average follow-up time was 47.8 months in the infection group and 48.5 months in the control group. Compared with the control group, the infection group had a significantly higher SNQ (20.01 ± 12.08 vs 7.61 ± 6.70; P = .014) as well as a higher signal intensity at the bone-graft interface ( P = .037) and higher Howell grade ( P = .031). The mean enlargement at the femoral tunnel aperture was 31.20% ± 26.76% in the infection group and 19.22% ± 20.10% in the control group ( P = .037). The articular cartilage of the patellofemoral and lateral femorotibial joints showed more degenerative change in the infection group. Conclusion: Study findings indicated that graft ligamentization and incorporation graft maturity were inferior in patients who experienced a joint infection after ACL reconstruction compared with patients who did not.
General anesthesia versus conscious sedation during endovascular treatment in posterior circulation large vessel occlusion: A systematic review and meta-analysis
Authors: Terceño Mikel , Bashir Saima , Cienfuegos Juan , Murillo Alan , Vera-Monge Víctor Augusto , Pardo Laura , Reina Montserrat , Gubern-Mérida Carme , Puigoriol-Illamola Dolors , Carballo Laia , Costa Anna , Buxó Maria , Serena Joaquín , Silva Yolanda 
Published: October 2022

Purpose: The optimal anesthetic approach in the endovascular treatment (EVT) of patients with posterior circulation large vessel occlusion (PC-LVO) strokes is not clear. Little data has been published and no randomized clinical trials have been conducted so far. We aimed to perform an updated meta-analysis to compare clinical and procedural outcomes between conscious sedation (CS) and general anesthesia (GA). Methods: We reviewed the literature of the studies reporting CS and GA in patients with endovascularly-treated PC-LVO. The primary outcome was the functional outcome at 3 months measured using the modified Rankin Scale (mRS). A good functional outcome was defined as having a mRS 0–2. Secondary outcomes were mortality at 3 months, final successful recanalization (modified Thrombolysis in Cerebral Infarction (mTICI) scale from 2b to 3) and complete recanalization (mTICI of 3) and times from stroke onset to EVT completion. Random-effects models were completed to pool the outcomes and the I2 value was calculated to assess heterogeneity. Findings: Eight studies with a total of 1351 patients were included. The pooled results reveal that CS use was associated with higher rates of good outcome (OR 2.41, 95% CI 1.58–3.64, I2 = 49.67%) and with lower mortality at 3 months (OR 0.48, 95% CI 0.28–0.82, I2 =57.11%). No significant differences were observed in the final reperfusion rates, procedural duration, and time from stroke onset to EVT completion. Conclusion: In this meta-analysis, GA was associated with significantly lower rates of functional independence at 3 months in patients with PC-LVO strokes.
Different dosing regimens of Tenecteplase in acute ischemic stroke: A network meta-analysis of the clinical evidence
Authors: The Ei Zune , Lin Ne Naing , Matar Mazen , Teoh Hock Luen , Yeo Leonard Leong Litt 
Published: October 2022

Introduction: Acute ischemic stroke remains the major cause of death and disability and conclusive evidence of Tenecteplase in treating stroke is lacking. Objective: To conduct a meta-analysis to determine whether Tenecteplase produces better outcomes than Alteplase and a network meta-analysis comparing the different dosing regimens of Tenecteplase. Methods: Searches were made in MEDLINE, CENTRAL, and ClinicalTrials.gov. The outcome measures are recanalization, early neurological improvement, functional outcomes at 90 days (modified Rankin Scale 0–1 and 0–2), intracranial hemorrhage, symptomatic intracranial hemorrhage, and mortality within 90 days from treatment. Results: Fourteen studies are included in the meta-analyses and 18 studies in the network meta-analyses. In the meta-analysis, Tenecteplase 0.25 mg/kg has significant results in early neurological improvement (OR = 2.35, and 95% CI = 1.16–4.72) and excellent functional outcome (OR = 1.20, and 95% CI = 1.02–1.42). In the network meta-analysis, Tenecteplase 0.25 mg/kg produces significant results in early neurological improvement (OR = 1.52 [95% CI = 1.13–2.05], p-value = 0.01), functional outcomes (mRS 0–1 and 0–2) (OR = 1.19 [95% CI = 1.03–1.37], p-value = 0.02; OR = 1.21 [95% CI = 1.05–1.39], p-value = 0.01; respectively) and mortality (OR = 0.78 [95% CI = 0.64–0.96], p-value = 0.02) whereas Tenecteplase 0.40 mg/kg increases the chances of symptomatic intracranial hemorrhage (OR = 2.35 [95% CI = 1.19–4.64], p-value = 0.01). Conclusion: While not conclusive, our study lends evidence to 0.25 mg/kg Tenecteplase dose for ischemic stroke treatment. Further randomized trials need to be done to validate this finding. Registration: International prospective register of systematic reviews (PROSPERO) – CRD42022339774 URL: https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=339774
Aberrant function of pathogenic STAT3 mutant proteins is linked to altered stability of monomers and homodimers
Authors: Kasembeli Moses M. , Kaparos Efiyenia , Bharadwaj Uddalak , Allaw Ahmad , Khouri Alain , Acot Bianca , Tweardy David J. 
Published: October 2022

AbstractSTAT3 mutations, predominantly in the DNA-binding domain (DBD) and Src-homology 2 domain (SH2D), cause rare cases of immunodeficiency, malignancy, and autoimmunity. The exact mechanisms by which these mutations abrogate or enhance STAT3 function are not completely understood. Here, we examined how loss-of-function (LOF) and gain-of-function (GOF) STAT3 mutations within the DBD and SH2D affect monomer and homodimer protein stability as well as their effect on key STAT3 activation events, including recruitment to phosphotyrosine (pY) sites within peptide hormone receptors, tyrosine phosphorylation at Y705, dimerization, nuclear translocation, and DNA binding. The DBD LOF mutants showed reduced DNA binding when homodimerized, whereas the DBD GOF mutants showed increased DNA binding. DBD LOF and GOF mutants showed minimal changes in other STAT3 functions or in monomer or homodimer protein stability. However, SH2D LOF mutants demonstrated reduced conformational stability as either monomers or homodimers, leading to decreased pY-peptide recruitment, tyrosine phosphorylation, dimerization, nuclear localization, and DNA binding. In contrast, cancer-causing SH2D GOF mutants showed increased STAT3 homodimer stability, which increased their DNA binding. Of note, a small-molecule inhibitor of STAT3 that targets the tyrosine phosphopeptide–binding pocket within the STAT3 SH2D potently inhibited cell proliferation driven by STAT3 SH2D GOF mutants. These findings indicate that the stability of STAT3 protein monomer and homodimer is critical for the pathogenesis of diseases caused by SH2D LOF and GOF mutations and suggest that agents that modulate STAT3 monomer and/or homodimer protein stability may have therapeutic value in diseases caused by these mutations.
Integrated flow cytometry and sequencing to reconstruct evolutionary patterns from dysplasia to acute myeloid leukemia
Authors: Simoes Catia , Chillon Maria-Carmen , Martínez-Cuadrón David , Calasanz Maria-José , Vridiales María-Belén , Vazquez Iria , Hernández-Ruano Montserrat , Ariceta Beñat , Aguirre-Ruiz Paula , Burgos Leire , Alignani Diego , Sarvide Sarai , Villar Sara , Pierola Ana Alfonso , Prosper Felipe , Ayala Rosa , Martínez-López Joaquin , Bergua Burgues Juan Miguel , Vives Susana , Perez-Simon Jose A. , Garcia-Fortes Maria , Bernal del Castillo Teresa , Colorado Mercedes , Olave Mayte , Rodríguez-Gutiérrez Juan I. , Labrador Jorge , González Marcos , San-Miguel Jesús F. , Sanz Miguel Ángel , Montesinos Pau , Paiva Bruno 
Published: October 2022

Abstract
Clonal evolution in acute myeloid leukemia (AML) originates long before diagnosis and is a dynamic process that may affect survival. However, it remains uninvestigated during routine diagnostic workups. We hypothesized that the mutational status of bone marrow dysplastic cells and leukemic blasts, analyzed at the onset of AML using integrated multidimensional flow cytometry (MFC) immunophenotyping and fluorescence-activated cell sorting (FACS) with next-generation sequencing (NGS), could reconstruct leukemogenesis. Dysplastic cells were detected by MFC in 285 of 348 (82%) newly diagnosed patients with AML. Presence of dysplasia according to MFC and World Health Organization criteria had no prognostic value in older adults. NGS of dysplastic cells and blasts isolated at diagnosis identified 3 evolutionary patterns: stable (n = 12 of 21), branching (n = 4 of 21), and clonal evolution (n = 5 of 21). In patients achieving complete response (CR), integrated MFC and FACS with NGS showed persistent measurable residual disease (MRD) in phenotypically normal cell types, as well as the acquisition of genetic traits associated with treatment resistance. Furthermore, whole-exome sequencing of dysplastic and leukemic cells at diagnosis and of MRD uncovered different clonal involvement in dysplastic myelo-erythropoiesis, leukemic transformation, and chemoresistance. Altogether, we showed that it is possible to reconstruct leukemogenesis in ∼80% of patients with newly diagnosed AML, using techniques other than single-cell multiomics.
A novel candidate disease gene prioritization method using deep graph convolutional networks and semi-supervised learning
Authors: Azadifar Saeid , Ahmadi Ali 
Published: October 2022

Abstract
Background
Selecting and prioritizing candidate disease genes is necessary before conducting laboratory studies as identifying disease genes from a large number of candidate genes using laboratory methods, is a very costly and time-consuming task. There are many machine learning-based gene prioritization methods. These methods differ in various aspects including the feature vectors of genes, the used datasets with different structures, and the learning model. Creating a suitable feature vector for genes and an appropriate learning model on a variety of data with different and non-Euclidean structures, including graphs, as well as the lack of negative data are very important challenges of these methods. The use of graph neural networks has recently emerged in machine learning and other related fields, and they have demonstrated superior performance for a broad range of problems.

Methods
In this study, a new semi-supervised learning method based on graph convolutional networks is presented using the novel constructing feature vector for each gene. In the proposed method, first, we construct three feature vectors for each gene using terms from the Gene Ontology (GO) database. Then, we train a graph convolution network on these vectors using protein–protein interaction (PPI) network data to identify disease candidate genes. Our model discovers hidden layer representations encoding in both local graph structure as well as features of nodes. This method is characterized by the simultaneous consideration of topological information of the biological network (e.g., PPI) and other sources of evidence. Finally, a validation has been done to demonstrate the efficiency of our method.

Results
Several experiments are performed on 16 diseases to evaluate the proposed method's performance. The experiments demonstrate that our proposed method achieves the best results, in terms of precision, the area under the ROC curve (AUCs), and F1-score values, when compared with eight state-of-the-art network and machine learning-based disease gene prioritization methods.

Conclusion
This study shows that the proposed semi-supervised learning method appropriately classifies and ranks candidate disease genes using a graph convolutional network and an innovative method to create three feature vectors for genes based on the molecular function, cellular component, and biological process terms from GO data.