bluuebunny/crossref_metadata_2025_split huggingface dataset:
Inferring genetic relatedness in a large, multisite frontotemporal dementia series: Data from the ALLFTD consortium
Authors: Ramos Eliana Marisa , Wojta Kevin , Yang Zhongan , Brushaber Danielle , Foroud Tatiana M. , Forsberg Leah K. , Heuer Hilary W. , Lago Argentina Lario , Rademakers Rosa , Coppola Giovanni , Boeve Brad F. , Rosen Howard J. , Boxer Adam L. , Geschwind Daniel H. ,   ALLFTD consortium
Published: June 2023

AbstractBackgroundThe ARTFL‐LEFFTDS Longitudinal Frontotemporal Lobar Degeneration (ALLFTD) research consortium is actively enrolling participants across 23 North American centers to characterize sporadic and familial frontotemporal dementia (FTD) and prepare for disease‐modifying clinical trials. The ability to identify, otherwise unknown, relatives among these participants is critical to rigorously build family structures for downstream clinical and genetic research studies.MethodsGenome‐wide SNP genotyping data from ALLFTD participants was used to perform lineage analyses using PLINK. Briefly, QC was performed to remove individuals with low call rate and filter autosomal SNPs for missingness, allele frequency, and deviation from Hardy‐Weinberg equilibrium, before pruning SNPs for linkage disequilibrium. Identity‐by‐descent (IBD) estimates were then calculated for determining relatedness, followed by family‐network identification and pedigree reconstruction using PRIMUS.ResultsAbout 46% of ALLFTD participants that were genotyped and passed QC (n = 1,453) had reported a family history, while 50% (n = 721) did not and were considered sporadic. We identified a total of 460 participants that had at least one relative who was second degree or closer (PI_HAT>0.1875) based on IBD sharing, resulting in 150 family networks. This included 9 participants who self‐identified as sporadic, demonstrating the utility of direct genetic characterization to determine familiality in FTD. Most of the predicted families were associated with disease causing variants in the 3 major FTD‐causing genes: 66 families with known C9orf72 repeat expansion carriers, 35 with MAPT (including 11 families with the variant historically known as p.P301L) and 30 with GRN pathogenic variant carriers, as well as 2 families with carriers of both a C9orf72 expansion and a GRN pathogenic variant. We also identified 5 families with carriers of pathogenic variants in other familial dementia genes (2 TARDBP, 2 VCP and 1 PSEN1), as well as 12 families with yet unknown genetic etiology.ConclusionsThis dataset sets up a crucial resource to increase statistical accuracy and power in downstream association studies using the clinical, neuropsychological, neuroimaging and biomarker data currently being generated by the ALLFTD consortium. It will also facilitate genetic studies aimed at novel gene discovery, and identification of haplotypes and genetic modifiers associated with the 3 major FTD causal genes.
The state of the art exercise recommendations for older adults with cognitive impairments: A meta‐analysis of the meta‐analysis
Authors: Heyn Patricia C , Tagawa Alex , Sood Pallavi , Ng Ted K.S. , Ries Julie , Negm Ahmed 
Published: June 2023

AbstractBackgroundThere is accumulative evidence supporting the benefits of regular physical activity in improving cognition in older adults with cognitive impairments (OAwCIs). In the past decades, multiple meta‐analyses (MA) have been published, adding to the body of literature. However, there is limited information on the overall quality and synthesized results of these studies. Thus, initiating an umbrella review, our review synthesis team appraised the evidence generated from the meta‐analysis reviews that included randomized exercise trials for OAwCIs.MethodUpon completing the Prospero registration (ID:109720), we followed the PRISMA guidelines for reviews and performed a literature search up to January 1, 2022 to identify all published meta‐analyses which used randomized controlled trial (RCT) design. Once all potential studies were identified, three reviewers screened and reviewed studies to identify included studies, three reviewers collected and validated the data, and two reviewers assess risk of bias using the AMSTAR 2. After applying the study’s a priori inclusion and exclusion criteria, we quantitatively analyzed the effects of exercise on cognitive performance in OAwCIs.ResultOver 2000 studies were screened for inclusion, 21 MA studies met our inclusion criteria. Based on the AMSTAR 2, three studies were high quality, nine studies were moderate quality, and nine studies were low quality. The included MA evaluated 280 RCTs, which included 22,315 participants over the age of 65 years old diagnosed with mild cognitive impairment (MCI), dementia, or Alzheimer’s disease (AD). Combined exercise training paradigms averaged 188.48±40.72 minutes per week and lasted for 18.49±4.53 weeks. Exercise training significantly improved global cognitive function, with an effect size of 0.55 (95% CI = 0.36‐0.73)ConclusionSustained and prolonged exercise training (cardio endurance type) might provide an attractive and effective intervention for individuals with MCI and AD. This comprehensive umbrella review of meta‐analyses offers valuable and strong evidence‐based exercise recommendations for OAwCIs.
Gerichtete Evolution von Piperazinsäureeinbau durch eine Nichtribosomale Peptidsynthetase**
Authors: Stephan Philipp , Langley Chloe , Winkler Daniela , Basquin Jérôme , Caputi Lorenzo , O'Connor Sarah E. , Kries Hajo 
Published: June 2023

AbstractDas Engineering biosynthetischer Enzyme wird zunehmend eingesetzt, um strukturelle Analoga von Antibiotika zu synthetisieren. Von besonderem Interesse sind nichtribosomale Peptidsynthetasen (NRPS), die für die Produktion wichtiger antimikrobieller Peptide verantwortlich sind. Hier beschreiben wir, wie durch gerichtete Evolution einer Adenylierungsdomäne eines Pro‐spezifischen NRPS‐Moduls dessen Substratspezifität vollständig auf die Nicht‐Standard‐Aminosäure Piperazinsäure (Piz) geändert wurde, welche eine labile N−N‐Bindung enthält. Dieser Erfolg wurde durch UPLC‐MS/MS‐basiertes Screening kleiner, rational konzipierter Mutantenbibliotheken erzielt und kann vermutlich mit einer größeren Anzahl von Substraten und NRPS‐Modulen repliziert werden. Die evolvierte NRPS ist in der Lage, ein Piz‐beinhaltendes Gramicidin S‐Analogon zu produzieren. Damit geben wir der zu früh verworfenen Idee neuen Auftrieb, dass weithin zugängliche Methoden mit niedrigem Durchsatz die Spezifität von NRPS in einer biosynthetisch nützlichen Weise verändern können.
Synergic Electron and Defect Compensation Minimizes Voltage Loss in Lead‐Free Perovskite Solar Cells
Authors: Liu Gengling , Jiang Xianyuan , Feng Wenhuai , Yang Guo , Chen Xi , Ning Zhijun , Wu Wu‐Qiang 
Published: June 2023

AbstractSn perovskite solar cells have been regarded as one of the most promising alternatives to the Pb‐based counterparts due to their low toxicity and excellent optoelectronic properties. However, the Sn perovskites are notorious to feature heavy p‐doping characteristics and possess abundant vacancy defects, which result in under‐optimized interfacial energy level alignment and severe nonradiative recombination. Here, we reported a synergic “electron and defect compensation” strategy to simultaneously modulate the electronic structures and defect profiles of Sn perovskites via incorporating a traced amount (0.1 mol %) of heterovalent metal halide salts. Consequently, the doping level of modified Sn perovskites was altered from heavy p‐type to weak p‐type (i.e. up‐shifting the Fermi level by ∼0.12 eV) that determinately reducing the barrier of interfacial charge extraction and effectively suppressing the charge recombination loss throughout the bulk perovskite film and at relevant interfaces. Pioneeringly, the resultant device modified with electron and defect compensation realized a champion efficiency of 14.02 %, which is ∼46 % higher than that of control device (9.56 %). Notably, a record‐high photovoltage of 1.013 V was attained, corresponding to the lowest voltage deficit of 0.38 eV reported to date, and narrowing the gap with Pb‐based analogues (∼0.30 V).
Phosphine‐Triggered Structural Defects in Au44 Homologues Boost Electrocatalytic CO2 Reduction
Authors: Zhuang Shengli , Chen Dong , Ng Wai‐Pan , Liu Li‐Juan , Sun Meng‐Ying , Liu Dongyi , Nawaz Tehseen , Xia Qi , Wu Xia , Huang Yong‐Liang , Lee Seungkyu , Yang Jun , Yang Jun , He Jian 
Published: June 2023

AbstractThe systematic induction of structural defects at the atomic level is crucial to metal nanocluster research because it endows cluster‐based catalysts with highly reactive centers and allows for a comprehensive investigation of viable reaction pathways. Herein, by substituting neutral phosphine ligands for surface anionic thiolate ligands, we establish that one or two Au3 triangular units can be successfully introduced into the double‐stranded helical kernel of Au44(TBBT)28, where TBBT=4‐tert‐butylbenzenethiolate, resulting in the formation of two atomically precise defective Au44 nanoclusters. Along with the regular face‐centered‐cubic (fcc) nanocluster, the first series of mixed‐ligand cluster homologues is identified, with a unified formula of Au44(PPh3)n(TBBT)28−2n (n=0–2). The Au44(PPh3)(TBBT)26 nanocluster having major structural defects at the bottom of the fcc lattice demonstrates superior electrocatalytic performance in the CO2 reduction to CO. Density functional theory calculations indicate that the active site near the defects significantly lowers the free energy for the *COOH formation, the rate‐determining step in the whole catalytic process.
Prevalence of gastrointestinal symptoms among autistic individuals, with and without co‐occurring intellectual disability
Authors: Holingue Calliope , Pfeiffer Danika , Ludwig Natasha N. , Reetzke Rachel , Hong Ji Su , Kalb Luther G. , Landa Rebecca 
Published: June 2023

AbstractGastrointestinal symptoms (GI) are very common among individuals on the autism spectrum. Prior research reports mixed findings regarding whether individuals with autism and co‐occurring intellectual disability (ID) have elevated risk of gastrointestinal symptoms relative to individuals with autism alone. GI symptoms can be challenging to assess in individuals with autism spectrum disorder (ASD) and/or ID given challenges with language, communication, and interoception. Prior research has tended to only include individuals with documented presence or absence of GI symptoms or conditions, that is, to exclude observations in which there is uncertainty regarding presence of GI symptoms. Therefore, none of the prior autism studies reported the association between ID and the certainty regarding presence or absence of GI symptoms. The objective of this study was to examine differences in parental certainty and odds of reporting gastrointestinal signs and symptoms among children on the autism spectrum, with and without intellectual disability. Participants were 308 children (36% ID) with a clinical diagnosis of autism spectrum disorder (6–17 years). Parents endorsed whether their child had experienced or displayed a range of signs or symptoms related to GI problems in the past 3 months. Parents of autistic children with ID were less certain about the presence of more subjective symptoms, including abdominal pain, nausea, and bloating. Conversely, certainty regarding more objective signs (e.g., constipation, diarrhea, spitting up, etc.) was not significantly different. More accurate measures for GI signs/symptoms are needed for this population.
Comparison of tyrosine kinase inhibitors in the treatment of metastatic renal cell carcinoma with rhabdoid and sarcomatoid differentiations
Authors: Wang Kun , Duan Pengqiang , Chen Xusheng , Yang Qing , Feng Guowei , Diao Lei , Zhang Zhenting , Yao Xin 
Published: June 2023

AbstractObjectiveTo investigate the efficacy of tyrosine kinase inhibitors (TKIs) in the treatment of metastatic renal cell carcinoma (mRCC) with rhabdoid (mRCC‐R) and sarcomatoid (mRCC‐S) differentiations.Materials and MethodsIn this single‐institutional cohort study, we included patients with RCC with rhabdoid (RCC‐R) and sarcomatoid (RCC‐S) differentiation, who were treated with TKIs after metastasis at our institute from 2013 to 2021. Patient characteristics, treatments, and clinical outcomes were recorded and analyzed.ResultsWe identified 111 patients with RCC‐R or RCC‐S differentiations, of which 23 patients were included in the final analysis. Of the 23 patients, 10 (43.5%) were grouped as mRCC‐R and 13 (56.5%) as mRCC‐S. At a median follow‐up of 40 months, mRCC‐R and mRCC‐S progressed in 7 of 10 and 12 of 13 patients, respectively. In addition, four and eight patients died in the mRCC‐R and mRCC‐S groups, respectively. The median progression‐free survival (PFS) of the two groups was 19 months (mRCC‐R: 95% confidence interval [CI] 4.08–33.92) and 7 months (mRCC‐S: 95% CI 2.03–11.96), while the median overall survival (OS) was 32 months and 21 months, respectively. mRCC‐S had a worse prognosis than mRCC‐R. Based on the univariate Cox regression model, single metastasis or multiple metastasis of tumor, rhabdoid differentiation, and sarcomatoid differentiation were predictors of PFS but not OS.ConclusionThe efficacy of TKIs in the treatment of mRCC‐R and mRCC‐S may be different.
Radiological‐histopathological discordance in patients transplanted for HCC and its impact on post‐transplant outcomes
Authors: Mohamed Islam B. , Ismail Mohamed Saleh , El Sabagh Ahmed , Afifi Abdelwahab Ahmed M. , Polychronopoulou Efstathia , Kuo Yong‐Fang , Hassan Manal , Goss John A. , Kanwal Fasiha , Jalal Prasun K. 
Published: June 2023

AbstractBackground and AimsContrast‐enhanced cross‐sectional imaging is the cornerstone in the diagnosis, staging, and management of HCC, including eligibility for liver transplantation (LT). Radiological‐histopathological discordance may lead to improper staging and may impact patient outcomes. We aimed to assess the radiological‐histopathological discordance at the time of LT in HCC patients and its impact on the post‐LT outcomes.MethodsWe analyzed further the effect of 6‐month waiting policy on the discordance. Using United Network for Organ Sharing—Organ Procurement and Transplantation Network (UNOS‐OPTN) database, we examined the discordance between pre‐LT imaging and explant histopathology for all adult HCC patients who received liver transplants from deceased donors between April 2012 and December 2017. Kaplan–Meier methods and Cox regression analyses were used to evaluate the impact of discordance on 3‐year HCC recurrence and mortality.ResultsOf 6842 patients included in the study, 66.7% were within Milan criteria on both imaging and explant histopathology, and 33.3% were within the Milan based on imaging but extended beyond Milan on explant histopathology. Male gender, increasing numbers of tumors, bilobar distribution, larger tumor size, and increasing AFP are associated with increased discordance. Post‐LT HCC recurrence and death were significantly higher in patients who were discordant, with histopathology beyond Milan (adj HR 1.86, 95% CI 1.32–2.63 for mortality and 1.32, 95% CI 1.03–1.70 for recurrence). Graft allocation policy with 6‐month waiting time led to increased discordance (OR 1.19, CI 1.01–1.41), although it did not impact post‐LT outcome.ConclusionCurrent practice for staging of HCC based on radiological imaging features alone results in underestimation of HCC burden in one out of three patients with HCC. This discordance is associated with a higher risk of post‐LT HCC recurrence and mortality. These patients will need enhanced surveillance to optimize patient selection and aggressive LRT to reduce post‐LT recurrence and increase survival.
Mental health care utilization among men with castration‐resistant prostate cancer receiving abiraterone or enzalutamide
Authors: Tsao Phoebe A. , Burns Jennifer , Kumbier Kyle , Sparks Jordan B. , Entenman Shami , Bloor Lindsey E. , Bohnert Amy S. B. , Skolarus Ted A. , Caram Megan E. V. 
Published: June 2023

AbstractBackgroundAbiraterone and enzalutamide are castration‐resistant prostate cancer (CRPC) therapies with potentially distinct associations with mental health symptoms given their differing antiandrogen targets.MethodsWe used national Veterans Health Administration data to identify patients with CRPC who received first‐line abiraterone or enzalutamide from 2010 to 2017. Using Poisson regression, we compared outpatient mental health encounters per 100 patient‐months on drug between the abiraterone and enzalutamide cohorts adjusting for patient factors (e.g., age). We compared mental health encounters in the year before versus after starting therapy using the McNemar test.ResultsWe identified 2902 CRPC patients who received abiraterone (n = 1992) or enzalutamide (n = 910). We found no difference in outpatient mental health encounters between the two groups (adjusted incident rate ratio [aIRR] 1.04, 95% confidence interval [CI] 0.95–1.15). However, men with preexisting mental health diagnoses received 81.3% of the outpatient mental health encounters and had higher rates of these encounters with enzalutamide (aIRR 1.21, 95% CI 1.09–1.34). Among patients with ≥1 year of enrollment before and after starting abiraterone (n = 1139) or enzalutamide (n = 446), there was no difference in mental health care utilization before versus after starting treatment (17.0% of patients vs. 17.6%, p = 0.60, abiraterone; 16.4% vs. 18.4%, p = 0.26, enzalutamide).ConclusionWe found no overall differences in mental health care utilization between CRPC patients who received first‐line abiraterone versus enzalutamide. However, men with preexisting mental health diagnoses received the majority of mental health care and had more mental health visits with enzalutamide.
Efficacy and safety of irinotecan combined with raltitrexed or irinotecan monotherapy for salvage chemotherapy of esophageal squamous cell cancer: A prospective, open label, randomized phase II study
Authors: Dai Xichao , Tao Leilei , Wang Jinqiu , Wu Wenjuan , Bian Weigang , Dai Xichun , Chen Surong 
Published: June 2023

AbstractBackground: Esophageal squamous cell cancer (ESCC) accounts for approximately 90% of esophageal cancer cases in China. There are no standard regimens for second or third–line chemotherapy of metastatic squamous esophageal cancer. The objective of this study was to investigate the security and effectiveness of irinotecan combined with raltitrexed or irinotecan monotherapy for salvage chemotherapy of ESCC.Methods: One hundred and twenty–eight patients with metastatic ESCC confirmed by histopathology were enrolled into this study. These patients had failure of the first–line chemotherapy combination of fluorouracil or platinum or paclitaxel and had not undergone chemotherapy with irinotecan or raltitrexed previously. Patients were randomly divided into irinotecan combined with raltitrexed group (experiment group) and irinotecan monotherapy group (control group). Overall survival (OS) and progression–free survival (PFS) were the primary endpoint.Results: In the control group, the median PFS (mPFS) and median OS (mOS) of patients were 3.37 and 5.3 months. In the experiment group, mPFS and mOS were 3.91 and 7.0 months. There was statistical significance of PFS and OS between two groups (PFS P = 0.002, OS P = 0.01). In subgroup analysis, in the second–line treatment, the mPFS of control and experiment group, was 3.90 and 4.60 months, mOS was 6.95 and 8.5 months, which was statistically significant differences between the two groups. (PFS P = 0.001, OS P = 0.005), In the third–line and beyond treatment, mPFS of control and experiment group was 2.80 and 3.19 months, mOS were 4.5 and 4.8 months. But there was no significant difference of PFS or OS between the two groups (PFS P = 0.19, OS P = 0.31). There was no statistical significance of toxicity side effects between two groups.Conclusions: The PFS and OS of irinotecan plus raltitrexed may be better than that of irinotecan monotherapy, especially in second line treatment, which should be confirmed with a phase III study including much more patients.
Identification and validation of Birc5 as a novel activated cell cycle program biomarker associated with infiltration of immunosuppressive myeloid‐derived suppressor cells in hepatocellular carcinoma
Authors: Liu Yun , Chen Xi , Luo Wenwu , Zhao Yufei , Nashan Björn , Huang Lei , Yuan Xiaodong 
Published: June 2023

AbstractBackgroundPreclinical studies and clinical trials have demonstrated that tumor‐intrinsic activation of the cell cycle program impedes anticancer immunotherapy. Identification of cell cycle‐related biomarkers may provide novel therapeutic targets to augment the efficacy of immunotherapy in hepatocellular carcinoma (HCC).Method and ResultsBased on the genes related to cell cycle program, two clusters (Cluster 1 and Cluster 2) were detected in HCC patients via non‐negative matrix factorization algorithm. Multivariable‐adjusted Cox regression analysis indicated that the cell cycle gene‐based classification was a significant prognostic factor for predicting the clinical outcome of HCC patients. Cluster 1 showed shorter overall survival time and progression‐free interval time was associated with activated cell cycle program, higher infiltration of myeloid‐derived suppressor cells (MDSCs) and less sensitivity to immunotherapy. A three‐gene prognostic model, including BIRC5, C8G, and SPP1, was constructed to characterize the cell cycle‐based classification of HCC, which had strong robustness and a stable predictive performance. Notably, Birc5 was positively correlated with CD11b expression (a MDSC marker) in HCC tissue. Concordant high expression of Birc5 and intratumor infiltration level of MDSCs were correlated with worse prognosis of HCC patients. In vitro, hepatocellular Birc5 overexpression promoted immunosuppressive CD11b+CD33+HLA‐DR−MDSC expansion from human peripheral blood mononuclear cells. Genetically modified animal model of liver cancer revealed that Birc5 depletion upregulated the genes related to lymphocyte‐mediated immunity, natural killer cell‐mediated immunity, interferon‐gamma production, T‐cell activation, and T‐cell‐mediated cytotoxicity. These results suggest an immunosuppressive function of Birc5 in HCC.ConclusionBirc5 was a potential biomarker and inducer of intratumor infiltration of MDSCs, which led to T cell exclusion or dysfunction in tumor immune microenvironment, consequently resulting in reduced response to ICIs in HCC.