bluuebunny/crossref_metadata_2025_split huggingface dataset:
Discovery of Photoexcited 2‐Chloro‐3,5‐Dinitrobenzoic Acid as a Chemical Deprenylase of i6A RNA
Authors: Sun Xin , Hui Tian‐He , Liu Li , Cheng Liang 
Published: May 2024

AbstractRNA modifications play crucial roles in regulating gene expression and cellular homeostasis. Modulating RNA modifications, particularly by targeting the enzymes responsible for their catalysis, has emerged as a promising therapeutic strategy. However, limitations, such as the lack of identified modifying enzymes and compensatory mechanisms, hinder targeted interventions. Chemical approaches independent of enzymatic activity offer an alternative strategy for RNA modification modulation. Here, we present the identification of 2‐chloro‐3,5‐dinitrobenzoic acid as a highly effective photochemical deprenylase of i6A RNA. This method demonstrates exceptional selectivity towards i6A, converting its substituent into a “N‐doped” ozonide, which upon hydrolysis releases natural adenine. We believe that this chemical approach will pave the way for a better understanding of RNA modification biology and the development of novel therapeutic modalities.
Clinical journey for patients with aortic regurgitation: A retrospective observational study from a multicenter database
Authors: Amoroso Nicholas S. , Sharma Rahul P. , Généreux Philippe , Pinto Duane S. , Dobbles Michael , Kwon Michelle , Thourani Vinod H. , Gillam Linda D. 
Published: May 2024

AbstractBackgroundData using real‐world assessments of aortic regurgitation (AR) severity to identify rates of Heart Valve Team evaluation and aortic valve replacement (AVR), as well as mortality among untreated patients, are lacking. The present study assessed these trends in care and outcomes for real‐world patients with documented AR.MethodsUsing a deidentified data set (January 2018–March 2023) representing 1,002,853 patients >18 years of age from 25 US institutions participating in the egnite Database (egnite, Inc.) with appropriate permissions, patients were classified by AR severity in echocardiographic reports. Rates of evaluation by the Heart Valve Team, AVR, and all‐cause mortality without AVR were examined using Kaplan–Meier estimates and compared using the log‐rank test.ResultsWithin the data set, 845,113 patients had AR severity documented. For moderate‐to‐severe or severe AR, respectively, 2‐year rates (95% confidence interval) of evaluation by the Heart Valve Team (43.5% [41.7%–45.3%] and 65.4% [63.3%–67.4%]) and AVR (19.4% [17.6%–21.1%] and 46.5% [44.2%–48.8%]) were low. Mortality at 2 years without AVR increased with greater AR severity, up to 20.7% for severe AR (p < 0.001). In exploratory analyses, 2‐year mortality for untreated patients with left ventricular end‐systolic dimension index > 25 mm/m2 was similar for moderate (34.3% [29.2%–39.1%]) and severe (37.2% [24.9%–47.5%]) AR.ConclusionsModerate or greater AR is associated with poor clinical outcomes among untreated patients at 2 years. Rates of Heart Valve Team evaluation and AVR were low for those with moderate or greater AR, suggesting that earlier referral to the Heart Valve Team could be beneficial.
Balloon predilation or direct valve implantation in TAVI for women: Insights from the DIRECTAVI study
Authors: Robert Pierre , Akodad Mariama , Lattuca Benoit , Gandet Thomas , Meunier Pierre Alain , Macia Jean‐Christophe , Schmutz Laurent , Steinecker Matthieu , Roubille Francois , Cayla Guillaume , Leclercq Florence 
Published: May 2024

AbstractBackgroundThe randomized DIRECTAVI trial demonstrated safety and feasibility of transcatheter aortic valve implantation (TAVI) without balloon aortic valvuloplasty (BAV) using SAPIEN 3 balloon‐expandable devices. However, the female population with smaller anatomy may have potential higher risk of residual gradient and/or mismatch.PurposeWe assessed the impact of BAV on the procedural success rate and clinical outcomes in the female population of the DIRECTAVI trial.MethodsBetween May 2016 and May 2018, 91 of the 250 patients included in the DIRECTAVI trial were women (38.6%), 45 of them (49.5%) were enrolled in the BAV group and 46 of them (50.5%) in the direct TAVI group. The primary endpoint was procedural success rate in women (Valve Academic Research Consortium‐2 criteria). The secondary endpoint included evaluation of PPM and 1‐month major adverse events according to the implantation stategy in women and comparison between men and women regarding major endpoints.ResultsThe primary endpoint occurred in 29 women (64.4%) in the BAV group and in 34 women (73.9%) in the direct TAVI group (mean difference 9.47%; 95% confidence interval: 6.5%–25.4%; p = 0.045 for non‐inferiority of the direct strategy). One‐month major adverse events were similar between the 2 women groups. Procedural success was lower in women vs men (p = 0.01) due to higher incidence of moderate mismatches in women (p = 0.001) but with no significant difference regarding the implantation strategy (p = 0.4).ConclusionDirect implantation of the balloon‐expandable SAPIEN 3 valve was non‐inferior to predilatation on procedural success in women. Incidence of moderate mismatch was higher in women but was not related to the implantation strategy.
Hypokalemic paralysis following intramuscular betamethasone injection: A case report and review of literature
Authors: Ebrahimi Pouya , Taheri Homa , Mousavinejad Seyed Ali , Nazari Pedram 
Published: May 2024

Key Clinical MessageAcute neuromuscular paralysis is a relatively common condition in emergency rooms (ERs). They can be caused by several reasons, including adverse drug reactions. Betamethasone is a glucocorticoid commonly used for various conditions, such as allergic conditions. One of the rare but known side effects of glucocorticoids is hypokalemia. Rare cases of hypokalemia following high‐ and low‐dose glucocorticoid injections have been reported. This study presents the history of a young, healthy male without significant past medical history who presented with an inability to stand and walk due to four‐limb paralysis (more prominent in the lower limbs) following an intramuscular injection of a 4 mg betamethasone, which was prescribed for the treatment of allergic rhinitis. The patient was stabilized with an intravascular injection of potassium chloride diluted in 1000 mL of normal saline and monitored for 24 h, ruling out any other endocrine condition. Hypokalemia and its severe form are defined as the serum level of lower than 3.5 and 2.5 mEq/Lit, respectively. One of the etiologies of drug‐induced hypokalemic paralysis is systemic glucocorticoid administration. In severe cases, it can cause quadriplegia and other neuromuscular, respiratory, and cardiac complications. Therefore, it is an urgent condition that should be managed carefully. Pregnant women who are receiving these medications are a specific group at risk of hypokalemic paralysis. There are several safer treatments for seasonal allergic rhinitis compared to systemic glucocorticoids, which should be considered by physicians. Moreover, paralysis in patients receiving these medications should be approached attentively since it might be caused by hypokalemia, which can be life threatening if not treated. It is advisable that the blood level of electrolytes, especially potassium, be checked for patients who present with paralysis or weakness after glucocorticoid injections.
Protecting‐Group‐Free Synthesis of ADP‐Ribose and Dinucleoside Di‐/Triphosphate Derivatives via P(V)‐P(V) Coupling Reaction
Authors: Hagino Rui , Kuwabara Ryo , Komura Naoko , Imamura Akihiro , Ishida Hideharu , Ando Hiromune , Tanaka Hide‐Nori 
Published: May 2024

AbstractBiomolecules containing adenosine di‐ or triphosphate (ADP or ATP) are crucial for diverse biological processes. Synthesis of these biomolecules and development of their chemical probes are important to elucidate their functions. Enabling reproducible and high‐yielding access to these ADP‐ and ATP‐containing molecules via conventional P(III)‐P(V) and P(V)‐P(V) coupling reactions is challenging owing to water content in highly polar phosphate‐containing substrates. Herein, we report an efficient and reliable method for protecting‐group‐free P(V)‐P(V) coupling reaction through in situ activation of phosphates using hydrolysis‐stable 2‐[N‐(2‐methylimidazoyl)]‐1,3‐dimethylimidazolinium chloride (2‐MeImIm‐Cl), providing the corresponding electrophilic P(V) intermediates for subsequent nucleophilic attack using their coupling partners. This P(V)‐P(V) coupling reaction proceeded even in a wet reaction medium and showed a broad substrate scope, accommodating protecting‐group‐free synthesis of ADP‐ribose and nicotinamide adenine diphosphate analogs, ATP‐containing biomolecules, and ADP‐ribosyl peptides.
Determination of benzophenone derivatives in wastewater by GC–MS/MS combined with in‐port derivatization
Authors: Tüzün Serenay Ceren , Karapinar Ilgi , Yücel Cemile , Ertaş Fatma Nil , Ertaş Hasan 
Published: May 2024

AbstractThe analysis of UV filters (UVFs) in water has become increasingly important due to their adverse effects on aquatic organisms and humans. This study describes a method for the determination of benzophenone derivatives UVF in wastewater samples. The selected UVFs are 2‐hydroxy‐4‐methoxybenzophenone (BP‐3), 2,4‐dihydroxybenzophenone (BP‐1), 4‐hydroxybenzophenone (4HB), 2,2′‐dihydroxy‐4‐methoxybenzophenone (DHMB) and lastly, 4,4′‐dihydroxybenzophenone (4DHB). The method includes solid‐phase extraction (SPE) of analytes from wastewater followed by on‐line derivatization with bis(trimethylsilyl)trifluoroacetamide (BSTFA) and analysis with GC‐MS/MS. Method validation studies resulted in good recoveries (86–112%), relative standard deviation RSD = 0.8 and 7.3%, the limits of detection LODs = 1.00–10.8 ng/L, and the limits of quantification LOQs = 3.00–32.3 ng/L. The method was successfully applied to domestic wastewater samples collected from influent and effluent of touristic hotels’ biological wastewater treatment plants. BP‐3 (24–1765 ng/L), BP‐1 (8–703 ng/L), 4HB (26–96 ng/L), and 4DHB (20–22 ng/L) were the common benzophenone derivatives in the influent wastewater while effluent contained mainly BP‐1 (8–32 ng/L), 4HB (12–57 ng/L) and 4DHB (20–102 ng/L). These results indicate that BP‐3 and BP‐1 are biodegraded in the treatment processes. However, 4HB and 4DHB are resistant to degradation and they are the main benzophenone metabolites discharged to receiving media.
TNF‐alpha promotes cilia elongation via mixed lineage kinases signaling in mouse fibroblasts and human RPE‐1 cells
Authors: Kumari Amrita , Caliz Amada D. , Yoo Hyung‐Jin , Kant Shashi , Vertii Anastassiia 
Published: May 2024

AbstractThe primary cilium is a characteristic feature of most non‐immune cells and functions as an environmental signal transduction sensor. The defects in primary cilium have profound effects on the developmental program, including the maturation of retinal epithelium. The ciliary length is tightly regulated during ciliogenesis, but the impact of inflammation on ciliary length remains elusive. The current study investigates the outcome of inflammatory stimuli for the primary cilium length in retinal epithelium cells and mouse embryonic fibroblasts. Here, we report that exposure to the pro‐inflammatory cytokine TNF‐alpha elongates cilia in a mixed‐lineage kinase (MLK)‐dependent manner. Pro‐inflammatory stimuli such as bacterial LPS and interferon‐gamma have similar effects on ciliary length. In contrast, febrile condition‐mimicking heat stress dramatically reduced the number of ciliated cells regardless of TNF‐alpha exposure but did not shorten TNF‐induced elongation, suggesting distinct but rapid effects of inflammatory stresses on ciliogenesis.
High‐dose chemotherapy and peripheral blood stem cell transplantation as salvage therapy in primary mediastinal nonseminomatous germ cell tumors: The Indiana University experience
Authors: Richardson Noah H. , Taza Fadi , Abonour Rafat , Althouse Sandra K. , Ashkar Ryan , Abu Zaid Mohammad , Hanna Nassar H. , Kesler Kenneth A. , Adra Nabil , Einhorn Lawrence H. 
Published: May 2024

AbstractBackgroundPatients with relapsed primary mediastinal nonseminomatous germ cell tumor have low cure rates with salvage chemotherapy or surgery. The authors report survival outcomes of patients who received high‐dose chemotherapy (HDCT) and peripheral blood stem cell transplantation (PBSCT) at Indiana University.MethodsThe prospectively maintained Indiana University germ cell tumor database identified 32 patients with primary mediastinal nonseminomatous germ cell tumor who progressed after first‐line cisplatin‐based combination chemotherapy and received HDCT and PBSCT between 2006 and 2021. Therapy included two consecutive courses of HDCT consisting of 700 mg/m2 carboplatin and 750 mg/m2 etoposide, each for 3 consecutive days, and each followed by PBSCT. A second course was not given if the patient experienced progressive disease or prohibitive toxicity. Progression‐free survival and overall survival were analyzed using the Kaplan–Meier method. Medians with 95% conﬁdence intervals were also calculated along with 2‐year probabilities.ResultsThe median age at HDCT was 30 years (range, 18–61 years). With a median follow‐up of 4.7 years (range, 1–14 years), the 2‐year progression‐free survival rate was 31% (95% confidence interval, 16%–47%), and the 2‐year overall survival rate was 35% (95% confidence interval, 19%–52%). At last follow‐up, nine patients (28%) remained without evidence of disease, including two platinum‐refractory patients and two patients who were receiving HDCT as third‐line therapy. There were three treatment‐related deaths.ConclusionsSalvage HDCT and PBSCT is an active combination in patients who have relapsed primary mediastinal nonseminomatous germ cell tumor with curative potential and prolonged survival, including in platinum‐refractory and third‐line settings. The authors recommend this approach for initial salvage chemotherapy in this patient population.
Treatment intensity affects immune reconstitution even after childhood cancer not treated with hematopoietic stem cell transplantation
Authors: Antikainen Ella , Grönroos Marika , Huurre Anu , Korhonen Laura , Peltola Ville , Lähteenmäki Päivi , Schuez‐Havupalo Linnea 
Published: May 2024

AbstractBackgroundOnly a few previous studies examine immune system recovery after completed cancer treatment.AimsThe aim of this study was to analyze immune reconstitution after childhood cancer therapy in a non‐hematopoietic stem cell transplantation setting.Methods and resultsWe analyzed children (N = 79) who received chemotherapy with/without irradiation for cancer diagnosed between 2014 and 2019 at Turku University Hospital, Finland. We retrospectively collected data on baseline parameters and post‐treatment immunological recovery, namely neutrophil and lymphocyte counts, IgG levels, CD19, CD4 and natural killer cell counts. Immunological parameters were followed until their normalization. Treatment intensity was stratified according to the Intensity of Treatment Rating Scale (ITR‐3). We analyzed the effects of treatment intensity on normalization of immunological parameters across the entire treatment range. Treatment intensity had a major effect on immune system recovery after completion of treatment. Most patients had normal immunological parameters 1–4 months post‐treatment both in high‐ and low‐intensity treatment groups, but patients classified in the high‐intensity group had low parameters more often than patients in the low‐intensity group.ConclusionOur data suggest a fast recovery of studied immunological parameters after the majority of current pediatric oncologic treatments. Treatment for high‐risk acute lymphoblastic leukemia, acute myeloid leukemia, medulloblastoma, and mature B‐cell lymphoma was associated with prolonged recovery times for a substantial proportion of cases. High treatment intensity was associated with prolonged immunological recovery.
Asking those who know their needs best: A framework for active engagement and involvement of childhood cancer survivors and parents in the process of psychosocial research—A workshop report
Authors: Weiler‐Wichtl Liesa J. , Schneider Carina , Gsell Hannah , Maletzky Anna‐Maria , Kienesberger Anita , Röhl Claas , Bocolli Albina , Gojo Johannes , Hansl Rita , Zettl Anna , Hopfgartner Maximilian , Leiss Ulrike 
Published: May 2024

AbstractBackgroundPatient and public involvement and engagement (PPIE) in healthcare research is crucial for effectively addressing patients' needs and setting appropriate research priorities. However, there is a lack of awareness and adequate methods for practicing PPIE, especially for vulnerable groups like childhood cancer survivors.AimsThis project aimed to develop and evaluate engagement methods to actively involve pediatric oncological patients, survivors, and their caregivers in developing relevant research questions and practical study designs.Methods and ResultsAn interdisciplinary working group recruited n = 16 childhood cancer survivors and their caregivers to work through the entire process of developing a research question and a practicable study design. A systematic literature review was conducted to gather adequate PPIE methods which were then applied and evaluated in a series of three workshop modules, each lasting 1.5 days. The applied methods were continuously evaluated, while a monitoring group oversaw the project and continuously developed and adapted additional methods. The participants rated the different methods with varying scores. Over the workshop series, the participants successfully developed a research question, devised an intervention, and designed a study to evaluate their project. They also reported increased expertise in PPIE and research knowledge compared to the baseline. The project resulted in a practical toolbox for future research, encompassing the final workshop structure, evaluated methods and materials, guiding principles, and general recommendations.ConclusionThese findings demonstrate that with a diverse set of effective methods and flexible support, actively involving patients, survivors, and caregivers can uncover patients' unmet disease‐related needs and generate practical solutions apt for scientific evaluation. The resulting toolbox, filled with evaluated and adaptable methods (workbook, Supplement 1 and 2), equips future scientists with the necessary resources to successfully perform PPIE in the development of health care research projects that effectively integrate patients' perspectives and address actual cancer‐related needs. This integration of PPIE practices has the potential to enhance the quality and relevance of health research and care, as well as to increase patient empowerment leading to sustainable improvements in patients' quality of life.
An optimal feedforward circuit with null audio susceptibility in feedback‐controlled buck converter
Authors: Daimary Isac , Jana Rajib , Narasimharaju Beeramangalla Lakshminarasaiah 
Published: May 2024

AbstractThe ability to manage abrupt disturbances in input supply voltage and sudden fluctuations in load represents a fundamental requirement for DC‐DC buck converters. While feedback control systems typically address such transients, certain applications necessitate even faster transient responses. This paper introduces an input voltage feedforward scheme (IVFS) integrated with voltage mode feedback controllers to enhance closed‐loop performance. Relevant transfer functions resulting from the inclusion of the feedforward circuit are derived, and an optimal condition for audio susceptibility nullification is identified. This scheme ensures an additional
attenuation in magnitude of audio susceptibility, in contrast to the buck converter without feedforward. In the time domain, the incorporation of IVFS results in a 20% reduction in percentage overshoot for a 12‐8‐12 step in supply voltage. Additionally, for a 12‐15‐12 step, the percentage overshoot and settling time are completely eliminated. Various active and passive parasitics are included in modeling of the buck converter to aid in designing the feedforward and feedback controller. A Type‐III controller is employed as a feedback controller to assess the closed‐loop performance. A hardware prototype is built to demonstrate the efficacy of the proposed feedforward scheme. The implementation of the entire circuit is straightforward due to its requirement of only a few discrete components, namely, analog multiplier, and error amplifier.
Downregulated SPESP1‐driven fibroblast senescence decreases wound healing in aged mice
Authors: Zhong Yun , Zhou Lei , Guo Yi , Wang Fan , He Fanping , Cheng Yufan , Meng Xin , Xie Hongfu , Zhang Yiya , Li Ji 
Published: May 2024

AbstractBackgroundHuman dermal fibroblasts (HDFs) are essential in the processes of skin ageing and wound healing. However, the underlying mechanism of HDFs in skin healing of the elderly has not been well defined. This study aims to elucidate the mechanisms of HDFs senescence and how senescent HDFs affect wound healing in aged skin.MethodsThe expression and function of sperm equatorial segment protein 1 (SPESP1) in skin ageing were evaluated via in vivo and in vitro experiments. To delve into the potential molecular mechanisms by which SPESP1 influences skin ageing, a combination of techniques was employed, including proteomics, RNA sequencing, immunoprecipitation, chromatin immunoprecipitation and liquid chromatography‐mass spectrometry analyses. Clearance of senescent cells by dasatinib plus quercetin (D+Q) was investigated to explore the role of SPESP1‐induced senescent HDFs in wound healing.ResultsHere, we define the critical role of SPESP1 in ameliorating HDFs senescence and retarding the skin ageing process. Mechanistic studies demonstrate that SPESP1 directly binds to methyl‐binding protein, leading to Decorin demethylation and subsequently upregulation of its expression. Moreover, SPESP1 knockdown delays wound healing in young mice and SPESP1 overexpression induces wound healing in old mice. Notably, pharmacogenetic clearance of senescent cells by D+Q improved wound healing in SPESP1 knockdown skin.ConclusionsTaken together, these findings reveal the critical role of SPESP1 in skin ageing and wound healing, expecting to facilitate the development of anti‐ageing strategies and improve wound healing in the elderly.
Exploring the link between comorbidities and Alzheimer's dementia in the Australian Imaging, Biomarker & Lifestyle (AIBL) study
Authors: Nguyen Catherine Quynh Nhu , Ma Liwei , Low Yi Ling Clare , Tan Edwin C. K. , Fowler Christopher , Masters Colin L. , Jin Liang , Pan Yijun ,   the AIBL research group
Published: May 2024

AbstractINTRODUCTIONMounting evidence suggests that certain comorbidities may influence the clinical evolution of Alzheimer's dementia (AD).METHODSWe conducted logistic regression analyses on the medical history and cognitive health diagnoses of participants in the Australian Imaging, Biomarker & Lifestyle study (n = 2443) to investigate cross‐sectional associations between various comorbidities and mild cognitive impairment (MCI)/AD.RESULTSA mixture of associations were observed. Higher comorbidity of anxiety and other neurological disorders was associated with higher odds of AD, while arthritis, cancer, gastric complaints, high cholesterol, joint replacement, visual defect, kidney and liver disease were associated with lower odds of AD.DISCUSSIONThis study underscores the links between specific comorbidities and MCI/AD. Further research is needed to elucidate the longitudinal comorbidity‐MCI/AD associations and underlying mechanisms of these associations.Highlights
Comorbidities that significantly increased AD odds included anxiety and other neurological disorders.
Arthritis, cancer, gastric complaints, high cholesterol, joint replacement, visual defect, kidney and liver disease were associated with lower odds of AD.
Alcohol consumption had the most significant confounding effect in the study.
Visual‐AD association was modified by age, sex, and APOE ε4 allele status.
Anxiety‐AD and depression‐AD associations were modified by sex.