bluuebunny/crossref_metadata_2025_split huggingface dataset:
Usability and acceptability of a cognitive training intervention (SMART) for people with multiple sclerosis (MS): A prefeasibility formative evaluation
Authors: Frost Alexandra C. , Golijani-Moghaddam Nima , Burge Rupert , Dawson David L. , Evangelou Nikos , Roche Bryan , Turton James , Hawton Annie , Law Graham , Rowan Elise , das Nair Roshan 
Published: June 2022

Background: Multiple sclerosis (MS) is a chronic autoimmune, inflammatory neurological disease of the central nervous system (CNS), increasing in incidence and prevalence across both developed and developing countries. Cognitive difficulties are common in MS sufferers with 70% experiencing difficulties in higher-level brain functioning such as planning, attention, problem solving, and memory. Computerised cognitive training programmes may hold promise as a treatment option for improving cognitive function in people with MS, subject to exploring and addressing potential barriers to usability and acceptability. Methods: This study aimed to test the usability and acceptability of a computerised cognitive training intervention—Strengthening Mental Abilities Through Relational Training (SMART) —for people with MS, through a mostly qualitative prefeasibility design (n= 12). There were two phases of testing: (1) initial usability testing via a think-aloud protocol (n= 6) and (2) alpha-testing to assess experienced acceptability over a four-week period of engagement (n= 6). Data from the two phases were subjected to Framework Analysis, wherein we deductively applied the Health IT Usability Evaluation Model and Theoretical Framework of Acceptability to assess usability and acceptability, respectively. Results: Results show SMART to have satisfactory usability with participants reacting positively to the formatting, visuality, and process of the interface. Minor suggestions were made on how best to adapt SMART for people with MS, but the programme and facilitative support were generally perceived to be acceptable, with participants expressing positive feelings about taking part in the intervention, despite associated burdens. Conclusions: This prefeasibility study provides preliminary evidence of the usability and acceptability of SMART as a computerised cognitive training programme for people with MS. We conclude that we can now move forward with a feasibility trial of SMART, with the intention of proceeding to a definitive trial with cost-effectiveness analysis.
Prevenção e tratamento da osteonecrose dos maxilares relacionada ao uso de medicações: uma revisão integrativa
Authors: Cunha Rafaela Cavalcanti Dias da , Sousa Raulison Vieira de , Ribeiro Pedro José Targino , Pires Lívia Pereira Brocos 
Published: June 2022

Objetivo: Analisar as evidências de cuidados voltados para prevenção e tratamento da osteonecrose dos maxilares relacionada ao uso de medicações. Método: Revisão integrativa com busca e seleção nas seguintes bases eletrônicas de dados: MEDLINE via Pubmed, LILACS e IBECS via BVS. Os descritores foram extraídos de vocabulários controlados e combinados com os operadores OR e AND. Foram considerados para inclusão: estudos primários, publicados em português, inglês ou espanhol e no período de 2010 a 2021. A amostra totalizou 10 estudos e a análise ocorreu de forma descritiva. Resultados: A osteonecrose nos maxilares induzidas pelo uso de medicações é um evento adverso raro, grave e alvo crescente de novos estudos que evidenciam a necessidade de medidas para prevenção, controle da dor e promoção da qualidade de vida. As estratégias preventivas foram variadas e envolveram a avaliação odontológica antes do início do tratamento, a identificação e classificação do risco, o uso da radiografia, a suplementação diária de vitamina D, a aplicação tópica de flúor, o uso de enxaguantes a base de clorexidina e a aplicação de técnicas para fechamento de lesões existentes. Dentre as intervenções terapêuticas, destacaram-se os cuidados clínicos padrão e a gestão conservadora, assim como o tratamento com oxigênio hiperbárico, a teriparatida subcutânea e o uso de plasma rico em fatores de crescimento. Conclusão: Novas investigações são necessárias para evidenciar as principais estratégias odontológicas voltadas para gerenciamento da osteonecrose relacionada ao uso medicações. Ainda, para demonstrar a dimensão do problema e fomentar políticas públicas válidas, efetivas e baseadas em evidências.
Realizing High Photovoltaic Power Densities With Tracking-Integrated Concentrator Photovoltaics
Authors: Younes Kareem , Apostoleris Harry , Bin Saad Majed , Al Ghaferi Amal , Chiesa Matteo 
Published: June 2022

Concentrating photovoltaics (CPV) have long been held up as a solution to low power density in photovoltaics, but due to the requirement of sun tracking have been largely unable to realize high power densities in practically useful settings. The emerging concept of tracking-integrated CPV, in which the sun tracking apparatus is incorporated into the module itself, has the potential to finally achieve this goal by allowing CPV use in building integrated or rooftop settings. In this article, we will provide a status update on TI-CPV and an evaluation of its technical and economic potential with focus on diffuse light collection. We will seek to demonstrate how TI-CPV concepts that are now nearing commercialization are viable to offer, for the first time, the chance for CPV to actually deliver high power densities and high-efficiency utilization of the solar resource in practical settings such that it represents one of the best prospects for CPV to finally gain a foothold in large commercial markets. We identify TI-CPV designs with integrated mechanical tracking and diffuse light transmittance as the closest at resent to commercial feasibility, as the transmitted light offers a potential valuable secondary output. A semi-empirical performance model of such a system yields an annual electrical output of &gt;300 kWh/m2 and 59.4 million lux-hours optical output that are equivalent to 593.4 kWh/m2 if that light would otherwise be provided by LED lamps with 100 lumen/W luminous efficacy. This would indicate that full-system capex of up to $1,600/kW could be viable relative to conventional rooftop PV systems, providing a benchmark for future manufacturing and design improvements.
Reducing Lumbar Spine Vertebra Fracture Risk With an Adaptive Seat Track Load Limiter
Authors: Östling Martin , Lundgren Christer , Lubbe Nils , Pipkorn Bengt 
Published: June 2022

In future fully automated vehicles, sleeping or resting will be desirable during a drive. While a horizontal position currently appears infeasible, a relaxed seating position with a reclined seatback and an inclined seat pan which enables a safe, comfortable position for sleeping or resting is possible. However, the inclined seat pan increases the forces and moments acting on the lumbar spine of the occupant and thereby the risk of lumbar vertebra fractures in a frontal crash. An energy management system integrated into the longitudinal seat adjustment (a seat track load limiter: STLL) that can reduce this risk should be investigated. When evaluating the injury reduction potential of a new restraint system such as a STLL it is important to include variations in both occupant size and crash severity. Otherwise, there is a risk of sub-optimizing, that is, the restraint system is only working for a limited number of situations. The restraint systems addressing these variations are normally referred to as adaptive restraint systems. The first objective of the study is to develop an activation strategy (adaptive release time of the STLL) for different crash severities and occupant sizes, making full use of the available stroke distance without bottoming out the STLL. The second objective is to evaluate the potential of the adaptive STLL to reduce the risk of lumbar vertebra fractures by comparing it to 1) a fixed seat and 2) a passive version of the STLL. Simulated frontal impacts were performed with two male SAFER human body models (HBMs) as occupant surrogates: mid-sized (80 kg and 1.8 m) and large (130 kg and 1.9 m). Three crash pulse severity levels were evaluated: low (40 km/h), medium (50 km/h), and high (56 km/h) impact speeds. The fracture risk was evaluated for the five lumbar vertebrae (L1–L5) in three different seat conditions: 1) a seat fixed to the sled, 2) a passive STLL that moves when a given force is exceeded, and 3) an adaptive STLL which moves at a time that depends on the occupant mass and crash pulse severity. The risk for lumbar vertebra fracture increased with crash pulse severity, while HBM size had no effect on risk. For all conditions, the passive STLL reduced injury risks compared to the fixed seat, and the adaptive STLL reduced risk even further.
Transcriptomic Analysis of Dysregulated Genes of the nDNA-mtDNA Axis in a Mouse Model of Dilated Cardiomyopathy
Authors: Ziemann Mark , Wu Wei , Deng Xiu-Ling , Du Xiao-Jun 
Published: June 2022

Background: Mitochondrial dysfunction is implicated in the development of cardiomyopathy and heart failure. Transcription of mitochondrial DNA (mtDNA) encoded genes and subsequent protein synthesis are tightly regulated by nuclear DNA (nDNA) encoded proteins forming the nDNA-mtDNA axis. The scale of abnormalities in this axis in dilated cardiomyopathy (DCM) is unclear. We previously demonstrated, in a mouse DCM model with cardiac Mst1 overexpression, extensive downregulation of mitochondrial genes and mitochondrial dysfunction. Using the pre-acquired transcriptome sequencing database, we studied expression of gene sets of the nDNA-mtDNA axis.Methods: Using RNA-sequencing data from DCM hearts of mice at early and severe disease stages, transcriptome was performed for dysregulated nDNA-encoded gene sets that govern mtDNA transcription and in situ protein synthesis. To validate gene data, expression of a panel of proteins was determined by immunoblotting.Results: Relative to littermate controls, DCM hearts showed significant downregulation of all mtDNA encoded mRNAs, as well as mtDNA transcriptional activators. Downregulation was also evident for gene sets of mt-rRNA processing, aminoacyl-tRNA synthases, and mitoribosome subunits for in situ protein synthesis. Multiple downregulated genes belong to mitochondrial protein-importing machinery indicating compromised importing of proteins for mtDNA transcription and translation. Diverse changes were genes of mtRNA-binding proteins that govern maturation and stability of mtDNA-derived RNAs. Expression of mtDNA replicome genes was largely unchanged. These changes were similarly observed in mouse hearts at early and severe stages of DCM.Conclusion: Transcriptome revealed in our DCM model dysregulation of multiple gene sets of the nDNA-mtDNA axis, that is, expected to interfere with mtDNA transcription and in situ protein synthesis. Dysfunction of the nDNA-mtDNA axis might contribute to mitochondrial dysfunction and ultimately development of DCM.
Up-Regulation of TRIM32 Associated With the Poor Prognosis of Acute Myeloid Leukemia by Integrated Bioinformatics Analysis With External Validation
Authors: Xu Xiaoyan , Qi Jiaqian , Yang Jingyi , Pan Tingting , Han Haohao , Yang Meng , Han Yue 
Published: June 2022

BackgroundAcute myeloid leukemia (AML) is a malignant and molecularly heterogeneous disease. It is essential to clarify the molecular mechanisms of AML and develop targeted treatment strategies to improve patient prognosis.MethodsAML mRNA expression data and survival status were extracted from TCGA and GEO databases (GSE37642, GSE76009, GSE16432, GSE12417, GSE71014). Weighted gene co-expression network analysis (WGCNA) and differential gene expression analysis were performed. Functional enrichment analysis and protein-protein interaction (PPI) network were used to screen out hub genes. In addition, we validated the expression levels of hub genes as well as the prognostic value and externally validated TRIM32 with clinical data from our center. AML cell lines transfected with TRIM32 shRNA were also established to detect the proliferation in vitro.ResultsA total of 2192 AML patients from TCGA and GEO datasets were included in this study and 20 differentially co-expressed genes were screened by WGCNA and differential gene expression analysis methods. These genes were mainly enriched in phospholipid metabolic processes (biological processes, BP), secretory granule membranes (cellular components, CC), and protein serine/threonine kinase activity (molecular functions, MF). In addition, the protein-protein interaction (PPI) network contains 15 nodes and 15 edges and 10 hub genes (TLE1, GLI2, HDAC9, MICALL2, DOCK1, PDPN, RAB27B, SIX3, TRIM32 and TBX1) were identified. The expression of 10 central genes, except TLE1, was associated with survival status in AML patients (p&lt;0.05). High expression of TRIM32 was tightly associated with poor relapse-free survival (RFS) and overall survival (OS) in AML patients, which was verified in the bone marrow samples from our center. In vitro, knockdown of TRIM32 can inhibit the proliferation of AML cell lines.ConclusionTRIM32 was associated with the progression and prognosis of AML patients and could be a potential therapeutic target and biomarker for AML in the future.
Platelet Activation in High D-Dimer Plasma Plays a Role in Acquired Resistance to Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors in Patients with Mutant Lung Adenocarcinoma
Authors: Lee Meng-Jung , Weng Chih-Ming , Chao Wei , Fang Yueh-Fu , Chung Fu-Tsai , Lin Chien-Huang , Kuo Han-Pin 
Published: June 2022

ObjectivePlatelet activation and adhesion to cancer cells increase the release of multiple factors that contribute to EMT and chemoresistance. Elevated levels of D-dimer have been associated with poor clinical outcomes in lung cancer. Platelets in high D-dimer plasma may be activated and implicated in acquired resistance to EGFR TKI in advanced lung adenocarcinoma with mutant EGFR.Materials and MethodsClinical responsive rate (RR), progression-free survival (PFS), and overall survival (OS) were prospectively measured in treatment-naïve lung adenocarcinoma patients with activation mutation. Plasma or platelets from patients with high or low D-dimer level were obtained to investigate the cytotoxic effects of TKIs on mutant cancer cells, and the mechanistic pathways were also explored.ResultsPatients with high D-dimer had worse RR, PFS, and OS. High D-dimer plasma induced resistance to gefitinib, erlotinib, afatinib, or osimertinib in EGFR mutant lung cancer cells. Depletion of platelets in high D-dimer plasma reversed the resistance to TKI. Platelets of high D-dimer plasma had higher adherence capacity to cancer cells, and induced EGFR and Akt activation as well as EMT through Src activation. Inhibition of platelet adherence or activation of Src or Akt conquered the resistance to TKI. The acquired resistance to TKI by high D-dimer plasma was less attributed to secondary gene mutation.ConclusionIncreased platelet activation in the high D-dimer plasma may contribute to first-line acquired EGFR TKI resistance. Thus, therapeutic strategy against platelet activation in patients with high D-dimer levels may improve the efficacy of first-line treatment with EGFR TKI.
Targeting ALK in Neuroendocrine Tumors of the Lung
Authors: Akhoundova Dilara , Haberecker Martina , Fritsch Ralph , Höller Sylvia , Kiessling Michael K. , Rechsteiner Markus , Rüschoff Jan H. , Curioni-Fontecedro Alessandra 
Published: June 2022

BackgroundAnaplastic lymphoma kinase (ALK) rearrangements are known oncogenic drivers in non-small cell lung cancer (NSCLC). Few case reports described the occurrence of such rearrangements in large cell neuroendocrine carcinomas (LCNECs) of the lung without information on clinical responses to ALK tyrosine kinase inhibitors (TKIs) in these cases. Currently, neuroendocrine tumors of the lungs are not screened for ALK rearrangements.MethodsTo illustrate the clinical impact of molecular characterization in LCNECs, we report the disease course in three patients with ALK-rearranged metastatic LCNEC from our clinical routine, as well as their treatment response to ALK TKIs (index cases). To gain insight into the prevalence of ALK rearrangements in neuroendocrine tumors of the lung, we analyzed a retrospective cohort of 436 tumor biopsies including LCNEC (n = 61), small cell lung cancer (SCLC) (n = 206), typical (n = 91) and atypical (n = 69) carcinoids, and mixed histology (n = 9) for the presence of ALK rearrangements using a sequential diagnostic algorithm. ALK immunohistochemistry (IHC) was evaluable in 362 cases; fluorescence in situ hybridization (FISH) was evaluable in 28 out of the 35 IHC-positive cases, followed by next-generation sequencing (NGS) that was available in 12 cases.ResultsWithin the retrospective cohort, ALK IHC was positive in 35 out of 362 (9.7%) evaluable samples. FISH was positive in 3 out of the 28 (10.7%) evaluable cases: 2 with atypical carcinoids and 1 with LCNEC. Additionally, the 3 index cases showed positive ALK IHC, which was confirmed by NGS. Within the retrospective cohort, NGS confirmed the presence of an ALK genomic rearrangement in one FISH-positive atypical carcinoid where material was sufficient for sequencing. Two out of three patients with metastatic ALK-rearranged LCNEC received up-front treatment with the ALK TKI alectinib and showed rapid tumor response at all metastatic sites, including multiple brain metastases.ConclusionsALK rearrangements represent rare but targetable oncogenic driver alterations in LCNEC. Contrarily to NSCLC, the detection of ALK rearrangements in neuroendocrine tumors of the lung is challenging, since ALK IHC can lead to false-positive results and therefore needs confirmation by FISH or NGS. Up-front comprehensive molecular profiling with NGS should be performed in metastatic LCNEC in order not to miss actionable genomic alterations.
H3K27M Mutation Doesn’t Mean Worse Prognosis in Old Patients
Authors: Hu Xiao Mu , Nie Xiao yu , Xu Kai lun , Wang Yin , Tang Feng , Du Zun guo , Xiong Ji 
Published: June 2022

ObjectiveDiffuse midline glioma (DMG), H3K27 altered is a new entity that has become widely recognized. However, studies concerning DMG in adult patients remain rare. We did a retrospective study covering the largest amount of patients to date to analyze the clinicopathological characteristics of diffuse glioma in midline structures of the adult.MethodsWe reviewed 108 cases of adult DMG, collected their clinical data, and pathological results including H3K27 mutation. Summarized their features and the connection with overall survival in different age groups.ResultsAmong 108 cases, 79 tumors were located at the thalamus. 38 patients had H3K27M mutation, whose average age was 35.7 years. The median overall survival of H3K27M-mutant gliomas and the 70 H3K27M wild-type gliomas were both 17 months. For young patients (age ≤ 35), The median survival time of the H3K27M-mutant was 18 months, while that of the H3K27M wild-type was 37 months. For older patients (age&gt;35), the median survival time of the H3K27M-mutant was 16 months, while that of the H3K27M wild-type was 13 months. Other clinicopathological factors including sex, tumor location, the approach of surgery, histological grade, ATRX, and P53 were statistically irrelevant to prognosis.ConclusionThe DMG in adults mainly occurred in the thalamus. H3K27M mutations tend to happen more frequently in young adults, and this genetic alteration results in a worse outcome only in young patients (≤35). For old patients, age is the only independent prognostic factor. Patients who underwent different surgical operations including biopsy, subtotal resection, and total resection had similar prognoses.
Impact of SLCO1B1*5 on Flucloxacillin and Co-Amoxiclav–Related Liver Injury
Authors: Alshabeeb Mohammad , Alomar Fadhel A. , Khan Amjad 
Published: June 2022

Background: Idiosyncratic drug-induced liver injury (DILI) is a serious uncommon disease that may develop as a result of the intake of certain drugs such as the antimicrobials flucloxacillin and co-amoxiclav. The reported cases showed significant associations between DILI and various human leukocyte (HLA) markers. The solute carrier organic anion transporter 1B1 (SLCO1B1), a non-HLA candidate gene, was previously reported as a risk factor for liver injury induced by rifampin and methimazole. This study presumed that SLCO1B1 may play a general role in the DILI susceptibility and therefore investigated the association of rs4149056 (SLCO1B1*5, T521C) polymorphism with flucloxacillin- and co-amoxiclav–induced liver injury.Methodology: We recruited 155 and 165 DILI cases of white ancestral origin from various European countries but mainly from the United Kingdom owing to flucloxacillin and co-amoxiclav, respectively. Only adult patients (≥18 years) who were diagnosed with liver injury and who showed i) clinical jaundice or bilirubin &gt;2x the upper limit of normal (ULN), ii) alanine aminotransferase (ALT) &gt;5x ULN or iii) alkaline phosphatase (ALP) &gt;2x ULN and bilirubin &gt; ULN were selected. The population reference sample (POPRES), a European control group (n = 282), was used in comparison with the investigated cases. TaqMan SNP genotyping custom assay designed by Applied Biosystems was used to genotype both DILI cohorts for SLCO1B1 polymorphism (rs4149056). Allelic discrimination analysis was performed using a step one real-time PCR machine. Genotype differences between cases and controls were examined using Fisher’s exact test. GraphPad Prism version 5.0 was used to determine the p-value, odds ratio, and 95% confidence interval. Compliance of the control group with Hardy–Weinberg equilibrium was proven using a web-based calculator available at https://wpcalc.com/en/equilibrium-hardy-weinberg/.Results: A small number of cases failed genotyping in each cohort. Thus, only 149 flucloxacillin and 162 co-amoxiclav DILI cases were analyzed. Genotyping of both DILI cohorts did not show evidence of association with the variant rs4149056 (T521C) (OR = 0.71, 95% CI = 0.46–1.12; p = 0.17 for flucloxacillin cases and OR = 0.87, 95% CI = 0.56–1.33; p = 0.58 for co-amoxiclav), although slightly lower frequency (22.8%) of positive flucloxacillin cases was noticed than that of POPRES controls (29.4%).Conclusion: Carriage of the examined allele SLCO1B1*5 is not considered a risk factor for flucloxacillin DILI or co-amoxiclav DILI as presumed. Testing a different allele (SLCO1B1*1B) and another family member gene (SLCO1B3) may still be needed to provide a clearer role of SLCO1B drug transporters in DILI development–related to the chosen antimicrobials.