bluuebunny/crossref_metadata_2025_split huggingface dataset:
COVID‐19‐induced immune thrombocytopenia management approach: A case report and literature review
Authors: Alahwal Hatem Mahmoud , Alsharif Mansour Hani , Alsharif Mada Hani , Almohammadi Abdullah Talal , Al‐Marzouki Adel Fahad , Barefah Ahmed Saleh , Bahashwan Salem Mohammad , Radhwi Osman Omer , Damanhouri Ghazi Abdullah 
Published: June 2024

Key Clinical MessageVincristine therapy can be effective in refractory Immune thrombocytopenia (ITP) following COVID‐19 vaccination. Our case report highlights the need for further research to establish standard management guidelines for COVID‐19‐vaccine‐associated ITP.AbstractAdult immune thrombocytopenia (ITP) can occur as a rare complication following several viral infections or a rare adverse event or complication of vaccination. In this paper, we report a case of a 39‐year‐old male patient with severe refractory ITP that began 4‐weeks after receiving his third (booster) dose of the COVID‐19 vaccine (BNT162b2, Pfizer‐BioNTech). He was given oral dexamethasone 40 mg daily for 4 days followed by prednisone at 1 mg/kg (85 mg daily) for 10 days. In the following weeks, we attempted several other lines of therapy to treat his ITP, including anti‐RhD immunoglobulin, which, unfortunately, caused moderate hemolysis requiring packed red blood cell transfusion, intravenous immunoglobulin (given at a subtherapeutic dose of 0.4 g/kg for only 1 day since it was not available), rituximab, and eltrombopag. The patient, unfortunately, showed no response to any of these treatments. This was an indicator to initiate salvage therapy with vincristine 2 mg weekly for 3 weeks. The patient's platelet count started to increase remarkably during the third week of vincristine and normalized after 4 weeks. We review the findings, clinical characteristics, and management approaches that were reported in the literature regarding COVID‐19‐vaccine‐induced ITP. More in‐depth research is needed to delineate standard guidelines for the management of such cases. This report underscores the importance of resorting to vincristine and eltrombopag as great options for severe and refractory ITP related to the COVID‐19 vaccine.
Comparative study of the thermo‐catalytic reforming of agricultural and forest residue and advanced characterization of final products in a cold climate
Authors: Dhakal Bijay , Kurian Vinoj , Bhattacharjee Neelanjan , Gupta Rajender , Olfert Jason , Kostiuk Larry , Hornung Andreas , Kumar Amit 
Published: June 2024

AbstractGlobal agricultural and forest residues hold promise for renewable fuel production through thermo‐catalytic reforming (TCR). Limited data exists on TCR outcomes for regions known for cold conditions like Canada. This study used a 2 kg h−1 TCR unit for the intermediate pyrolysis/reforming of agricultural (wheat straw pellet, WSP) and forest (softwood pellet, SWP) residues. Maximum bio‐oil yields were 8.43% for wheat straw pellets and 7.99% for softwood pellets at 400 and 500°C reactor and reformer temperatures. Feedstock, bio‐oil, and biochar properties were analyzed through proximate and ultimate analysis. At 550°C reactor and 700°C reforming temperatures, 70.73% of the wheat straw pellet‐based gas yield contained 36.11 vol.% H2 and 11.08 vol.% CH4, giving a higher heating value (HHV) of 12.54 MJ kg−1. A high concentration of CH4 (22.02 vol.%) in the softwood pellet‐based gas gave an HHV of 17.94 MJ kg−1. The low viscosity (3.9 mPa · s−1) and total acid number (7.3 mg KOH g−1) wheat straw pellet‐based bio‐oil had an O/C molar ratio of 0.09 and an HHV of 35.80 MJ kg−1. The 400/600°C reactor/reformer temperatures gave the lowest area percentage of mono‐aromatic (16 vol.%) and polycyclic aromatic (11.20 vol.%) compounds in the softwood pellet bio‐oil. The O/C molar ratio (0.5–0.6) in softwood pellet biochar elevated the higher heating value from 32.37 to 34.57 MJ kg−1. The study results guide optimal TCR unit operation in cold climates like Canada with local feedstocks, emphasizing its notable hydrogen production over bio‐oil and biochar.
MEK inhibitors and DA‐Raf, a dominant‐negative antagonist of the Ras–ERK pathway, prevent the migration and invasion of KRAS‐mutant cancer cells
Authors: Matsuda Aoi , Masuzawa Ryuichi , Takahashi Kazuya , Takano Kazunori , Endo Takeshi 
Published: June 2024

AbstractThe Ras‐induced ERK pathway (Raf–MEK–ERK signaling cascade) regulates a variety of cellular responses including cell proliferation, survival, and migration. Activating mutations in RAS genes, particularly in the KRAS gene, constitutively activate the ERK pathway, resulting in tumorigenesis, cancer cell invasion, and metastasis. DA‐Raf1 (DA‐Raf) is a splicing isoform of A‐Raf and contains the Ras‐binding domain but lacks the kinase domain. Consequently, DA‐Raf antagonizes the Ras–ERK pathway in a dominant‐negative manner and can serve as a tumor suppressor that targets mutant Ras protein‐induced tumorigenesis. We show here that MEK inhibitors and DA‐Raf interfere with the in vitro collective cell migration and invasion of human KRAS‐mutant carcinoma cell lines, the lung adenocarcinoma A549, colorectal carcinoma HCT116, and pancreatic carcinoma MIA PaCa‐2 cells. DA‐Raf expression was silenced in these cancer cell lines. All these cell lines had high collective migration abilities and invasion properties in Matrigel, compared with nontumor cells. Their migration and invasion abilities were impaired by suppressing the ERK pathway with the MEK inhibitors U0126 and trametinib, an approved anticancer drug. Expression of DA‐Raf in MIA PaCa‐2 cells reduced the ERK activity and hindered the migration and invasion abilities. Therefore, DA‐Raf may function as an invasion suppressor protein in the KRAS‐mutant cancer cells by blocking the Ras–ERK pathway when DA‐Raf expression is induced in invasive cancer cells.
Cytologic features of differentiated high‐grade thyroid carcinoma: A multi‐institutional study of 40 cases
Authors: Torous Vanda F. , Jitpasutham Tikamporn , Baloch Zubair , Cantley Richard L. , Kerr Darcy A. , Liu Xiaoying , Maleki Zahra , Merkin Ross , Nosé Vania , Pantanowitz Liron , Resta Isabella Tondi , Rossi Esther D. , Faquin William C. 
Published: June 2024

AbstractBackgroundDifferentiated high‐grade thyroid carcinoma (DHGTC) is recently recognized by the World Health Organization (WHO) as a subgroup of thyroid carcinomas with high‐grade features while retaining the architectural and/or cytologic features of well‐differentiated follicular–cell‐derived tumors. The cytomorphology of DHGTC is not well documented despite potential implications for patient triage and management.MethodsThe pathology archives of six institutions were searched for cases diagnosed on resection as “high‐grade thyroid carcinoma” using WHO criteria. The fine‐needle aspiration (FNA) cohort represents a 10‐year period (2013–2023); all were reviewed to confirm DHGTC classification. The corresponding FNAs were assessed for 32 cytomorphologic features.ResultsForty cases of DHGTC with prior FNA were identified. The mean patient age was 64.2 years. The average lesion size was 4.9 cm, and the majority demonstrated a TI‐RADS score of 4 or 5 (95.2%). Three main high‐grade subsets of DHGTC based on corresponding histology included papillary thyroid carcinoma (65%), follicular carcinoma (22.5%), and oncocytic carcinoma (12.5%). Over 97% of FNA cases were classified as Bethesda category IV or above. Approximately 25% of DHGTC showed cytologic features that included marked cytologic atypia, increased anisonucleosis, large oval nuclei, mitotic activity, or necrosis (p < .05); 68% of DHGTC cases were associated with high‐risk molecular alterations. TERT mutations occurred in 41%, of which 89% of these were associated with a second mutation, usually RAS or BRAF p.V600E.ConclusionsCytology has a low sensitivity for DHGTC, although a subset of DHGTCs have cytologic features raising the possibility of a high‐grade thyroid carcinoma. Other findings include high‐risk molecular changes and clinicopathologic features such as older patient age and larger lesion size.
Protodefluorinated Selectfluor® Aggregatively Activates Selectfluor® for Efficient Radical C(sp3)−H Fluorination Reactions
Authors: Yakubov Shahboz , Dauth Bastian , Stockerl Willibald J. , da Silva Wagner , Gschwind Ruth M. , Barham Joshua P. 
Published: June 2024

AbstractEfficient fluorination reactions are key in the late‐stage functionalization of complex molecules in medicinal chemistry, in upgrading chemical feedstocks, and in materials science. Radical C(sp3)−H fluorinations using Selectfluor® – one of the most popular fluorination agents – allow to directly engage unactivated precursors under mild photochemical or thermal catalytic conditions. However, H−TEDA(BF4)2 to date is overlooked and discarded as waste, despite comprising 95% of the molecular weight of Selectfluor®. We demonstrate that the addition of H−TEDA(BF4)2 at the start of fluorination reactions markedly promotes their rates and accesses higher overall yields of fluorinated products (~3.3 × higher on average across the cases studied) than unpromoted reactions. Several case studies showcase generality of the promotor, for photochemical, photocatalytic and thermal radical fluorination reactions. Detailed mechanistic investigations reveal the key importance of aggregation changes in Selectfluor® and H−TEDA(BF4)2 to fill gaps of understanding in how radical C(sp3)−H fluorination reactions work. This study exemplifies an overlooked reaction waste product being upcycled for a useful application.
Artificial intelligence approaches for phenotyping heart failure in U.S. Veterans Health Administration electronic health record
Authors: Shao Yijun , Zhang Sijian , Raman Venkatesh K. , Patel Samir S. , Cheng Yan , Parulkar Anshul , Lam Phillip H. , Moore Hans , Sheriff Helen M. , Fonarow Gregg C. , Heidenreich Paul A. , Wu Wen‐Chih , Ahmed Ali , Zeng‐Treitler Qing 
Published: June 2024

AbstractAimsHeart failure (HF) is a clinical syndrome with no definitive diagnostic tests. HF registries are often based on manual reviews of medical records of hospitalized HF patients identified using International Classification of Diseases (ICD) codes. However, most HF patients are not hospitalized, and manual review of big electronic health record (EHR) data is not practical. The US Department of Veterans Affairs (VA) has the largest integrated healthcare system in the nation, and an estimated 1.5 million patients have ICD codes for HF (HF ICD‐code universe) in their VA EHR. The objective of our study was to develop artificial intelligence (AI) models to phenotype HF in these patients.Methods and resultsThe model development cohort (n = 20 000: training, 16 000; validation 2000; testing, 2000) included 10 000 patients with HF and 10 000 without HF who were matched by age, sex, race, inpatient/outpatient status, hospital, and encounter date (within 60 days). HF status was ascertained by manual chart reviews in VA's External Peer Review Program for HF (EPRP‐HF) and non‐HF status was ascertained by the absence of ICD codes for HF in VA EHR. Two clinicians annotated 1000 random snippets with HF‐related keywords and labelled 436 as HF, which was then used to train and test a natural language processing (NLP) model to classify HF (positive predictive value or PPV, 0.81; sensitivity, 0.77). A machine learning (ML) model using linear support vector machine architecture was trained and tested to classify HF using EPRP‐HF as cases (PPV, 0.86; sensitivity, 0.86). From the ‘HF ICD‐code universe’, we randomly selected 200 patients (gold standard cohort) and two clinicians manually adjudicated HF (gold standard HF) in 145 of those patients by chart reviews. We calculated NLP, ML, and NLP + ML scores and used weighted F scores to derive their optimal threshold values for HF classification, which resulted in PPVs of 0.83, 0.77, and 0.85 and sensitivities of 0.86, 0.88, and 0.83, respectively. HF patients classified by the NLP + ML model were characteristically and prognostically similar to those with gold standard HF. All three models performed better than ICD code approaches: one principal hospital discharge diagnosis code for HF (PPV, 0.97; sensitivity, 0.21) or two primary outpatient encounter diagnosis codes for HF (PPV, 0.88; sensitivity, 0.54).ConclusionsThese findings suggest that NLP and ML models are efficient AI tools to phenotype HF in big EHR data to create contemporary HF registries for clinical studies of effectiveness, quality improvement, and hypothesis generation.
Phenotype and outcomes according to loop diuretic use in pulmonary arterial hypertension
Authors: Savonitto Giulio , Barbisan Davide , Ameri Pietro , Lombardi Carlo Maria , Monti Simonetta , Driussi Mauro , Gentile Piero , Howard Luke , Toma Matteo , Pagnesi Matteo , Collini Valentino , Bauleo Carolina , Adamo Marianna , D'Angelo Luciana , Nalli Chiara , Giannoni Alberto , Vecchiato Veronica , Di Poi Emma , Airo Edoardo , Metra Marco , Garascia Andrea , Sinagra Gianfranco , Lo Giudice Francesco , Stolfo Davide 
Published: June 2024

AbstractAimsThe use of loop diuretics in pulmonary arterial hypertension (PAH) is less frequent compared with heart failure. The clinical and prognostic characteristics of PAH patients according to loop diuretic use remain unexplored. In this study, we retrospectively analysed the characteristics and survival of PAH patients requiring different doses of loop diuretics.Methods and resultsPatients diagnosed with PAH between 2001 and 2022 at seven European centres for the management of PAH. According to the median equivalent dose of furosemide in the overall cohort, patients were divided into two subgroups: no/low‐dose loop diuretic and high‐dose loop diuretic. Primary outcome was 5 year all‐cause mortality. Among the 397 patients included, 227 (57%) were treated with loop diuretics. Median daily furosemide equivalent dose was 25 mg, and accordingly patients were divided in no/low dose (i.e. ≤25 mg, n = 257, 65%) vs. high dose (i.e. >25 mg, n = 140, 35%). Patients in the high‐dose group were older, more likely to have comorbidities, and had a more severe disease according to the ESC/ERS risk category. Crude 5 year survival was significantly shorter in patients in the high‐dose group, but after adjustment for age, sex, and risk category, high loop diuretic dose was not significantly associated with the primary outcome.ConclusionsUse of high dose of loop diuretics in PAH is associated with a higher burden of comorbidities, more severe disease, and worse survival. However, in PAH, the need of high loop diuretic dose is a marker of disease severity and not an independent prognostic factor.
Validity of a motor–cognitive dual‐task agility test in elite youth football players
Authors: Friebe David , Sieland Johanna , Both Hendrik , Giesche Florian , Haser Christian , Hülsdünker Thorben , Pfab Florian , Vogt Lutz , Banzer Winfried 
Published: June 2024

AbstractAgility, as the ability to react rapidly to unforeseen events, is an essential component of football performance. However, existing agility diagnostics often do not reflect the complex motor–cognitive interaction required on the field. Therefore, this study evaluates the criterion and ecological validity of a newly developed motor–cognitive dual‐task agility approach in elite youth football players and compare it to a traditional reactive agility test. Twenty‐one male youth elite football players (age:17.4 ±0 .6; BMI:23.2 ± 1.8) performed two agility tests (reactive agility, reactive agility with integrated multiple‐object‐tracking (Dual‐Task Agility)) on the SKILLCOURT system. Performance was correlated to motor (sprint, jump), cognitive (executive functions, attention, reaction speed) and football specific tests (Loughborough soccer passing test (LSPT)) as well as indirect game metrics (coaches' rating, playing time). Reactive agility performance showed moderate correlations to attention and choice reaction times (r = 0.48−0.63), as well as to the LSPT (r = 0.51). The dual‐task agility test revealed moderate relationships with attention and reaction speed (r = 0.47−0.58), executive functions (r = 0.45−0.63), as well as the game metrics (r = 0.51−0.61). Finally, the dual‐task agility test significantly differentiated players based on their coaches' rating and playing time using a median split (p < 0.05; d = 0.8–1.28). Motor–cognitive agility performance in elite youth football players seems to be primarily determined by cognitive functions. The integration of multiple object tracking into reactive agility testing seems to be an ecologically valid approach for performance diagnostics in youth football.
Development of a novel dosing paradigm to model diazepam rescue therapy in preclinical seizure and epilepsy models
Authors: Guignet Michelle , White H. Steve , Misra Sunita N. , Carrazana Enrique , Rabinowicz Adrian L. 
Published: June 2024

AbstractDiazepam is a cornerstone immediate‐use antiseizure rescue therapy that may extend the duration between seizure clusters in people living with epilepsy. However, our mechanistic understanding of intermittent rescue therapy on disease progression is limited by the lack of suitable preclinical models. Specifically, the pharmacokinetics of diazepam varies widely between humans and laboratory animals. Here, we developed a novel repeat rescue therapy dosing paradigm in rats to maintain prolonged therapeutic concentrations seen in humans. Rats received three diazepam doses separated by 1 h (0.75, 1.5, or 3 mg/kg, intraperitoneal); plasma and brains were collected at 10 min and 1, 3, or 6 h following the last dose. Plasma and brain concentrations followed a dose‐dependent increase with peak concentrations following the repeat 3 mg/kg paradigm (180 ng/mL) being equivalent to plasma levels observed in human studies with diazepam nasal spray. Increased brain‐to‐plasma ratios in this paradigm indicate that diazepam accumulation in the brain may be long‐acting at the site of action. Overall, our repeat diazepam dosing paradigm mimics drug concentrations and accumulation seen in humans, offering a preclinical tool to study the impact of benzodiazepine rescue therapy on seizure‐cluster biology in rodent models of epilepsy.Plain language summaryThere is more to learn about how diazepam works in the brains of people who use it only when they have two or more seizures in 24 h (this is called a seizure cluster). Ethical studies in animals can be used to learn more about medicines in the body. In this study, we showed that three doses of diazepam in rats give about the same amount of the drug as one dose for a person. We can now test rats with epilepsy to see how the drug might work in people who take it when needed for seizure clusters.
Cardiovascular risk factor assessment in late‐onset seizures: A study protocol to assess the value of structured intervention
Authors: Larsson David , Åsberg Signild , Sundström Johan , Frid Petrea , Zelano Johan 
Published: June 2024

AbstractObjectiveA growing body of evidence suggests patients with late‐onset seizures are at an increased risk of stroke, but the potential for reducing cardiovascular morbidity through risk factor screening and management is unknown. We aim to determine whether individuals with new‐onset unprovoked seizures after middle age should undergo vascular risk assessment. The long follow‐up needed to assess stroke risk and the known benefit of vascular risk factor modification make a standard RCT logistically and ethically challenging. Instead, we propose and have developed a protocol for a cluster project assessing the effect of vascular risk factor screening in an intervention trial as well as a cohort study.MethodsParticipating neurology clinics will implement standard cardiovascular risk factor assessment into the routine evaluation for individuals aged ≥50 years attending their first specialized consultation after an unprovoked seizure, excluding those with progressive brain disease. The project has two interlinked components: a prospective single group trial, in which risk factor assessment is performed and subsequent management is followed for one year; and a register‐based cohort study examining the long‐term effects of the intervention on a system level by comparing patients attending initial consultations in the 2 years after start of the study, with patients seen in the four preceding years at the same clinics.AnalysisThe primary outcome of the intervention trial is the proportion of patients receiving subsequent pharmacological treatment. The primary outcome of the cohort study is the incidence of acute stroke in the Swedish Stroke Register.Ethics and DisseminationSwedish Ethical Review Authority approval (which is valid for 2 years only) will be sought when funding is obtained. The results will be disseminated through peer‐reviewed scientific publications.Registration DetailsThe study will be registered at clinicaltrials.gov.Plain Language SummaryA first seizure in a middle‐aged or older person indicates a higher risk of stroke. It is not known whether investigating and treating blood pressure, blood cholesterol, or similar risk factors after a first seizure is an effective way to prevent stroke. A traditional clinical study would need too many patients and it would be unethical not to treat the control group. We have designed a study in which participating neurology departments change their practice to test and treat vascular risk factors. Patients are then compared to historic controls using registered data.
Magnetic micro‐fluidics in 3D microchannel at the micro‐scale: Unlocking nano‐porous electrode potential for lithium‐ion micro‐batteries
Authors: Ashraf Adeel , Manzoor Tareq , Iqbal Shaukat , Anwar Tauseef , Farooq‐i‐Azam Muhammad , Khan Zeashan , Manzoor Habib Ullah 
Published: June 2024

AbstractEnhancing the nanosized‐electrolyte's characteristics in Lithium‐driven micro‐batteries (LIMBs) is indispensable to improve the overall efficiency, security, and lifespan of these energy devices, designing nano‐sized electrolyte with a wide electrochemical stability window while keeping them compatible with electrode materials is one of the improvement goals. Battery technologies must go through this optimization process in order to be used practically. A sensing mechanism to keep an eye on the health of Li‐ion energy devices through the magnetization. Magnetic micro‐fluidic patterns that change could be a sign of battery deterioration or other problems with performance. Li‐ion battery health is one application of magnetic sensing that you can do with magnetic sensing. Battery health variations and other performance problems can be found using magnetic mass transport patterns. Present study examines the effects of magnetic field on Eyring–Powel mass transport in nano‐porous channels over a stretching sheet. The principal equations exhibiting the phenomenon are transformed into non‐linear differential equation by second‐order approximation by using a similarity transformation. Furthermore, a semi‐analytic technique named optimal homotopy asymptotic method (OHAM) is used to solve the transformed Eyring–Powell model. The numerical results demonstrated the impact of variations in velocity, skin‐friction coefficient and Sherwood number for the proposed scheme.