bluuebunny/crossref_metadata_2025_split huggingface dataset:
The impacts of undetected nonadherence in phase II, III and post‐marketing clinical trials: An overview
Authors: Le Flohic Elise , Vrijens Bernard , Hiligsmann Mickaël 
Published: May 2024

AbstractAimsThis research aims to provide an overview of the consequences of undiagnosed nonadherence (noninitiation, suboptimal implementation, nonpersistence) in randomized clinical trials (RCTs).MethodsThis research was conducted by combining a literature review and qualitative semistructured interviews with key opinion leaders. Based on this groundwork, the consequences of undiagnosed nonadherence in RCTs were summarized and reported in a figure. This study focused on phases II, III and post‐marketing in ambulatory settings across a variety of therapeutic areas and indications.ResultsVarious consequences of nonadherence in RCTs were investigated. In phase II, drug efficacy may be underestimated, variability in the outcomes may be high and a distorted picture of side effects could be reported, resulting in an uncertain impression of the investigational product's profile and complicating decision‐making. The sponsor may need to increase the sample size of the upcoming phase III study to improve its power, representing additional costs, or even terminate the study. In phase III, similar phenomena may be observed, making demonstration of efficacy to the regulatory bodies more difficult. Lastly, after commercialization, a distortion in pharmacometrics may occur: the drug may underperform, prescriptions may be refilled less often than expected or extra expenses may be incurred by the payers. This can result in post‐marketing dose reduction, new competitors coming into the market and, eventually, product withdrawal.ConclusionsThis research highlighted the many potential adverse consequences of undiagnosed nonadherence in RCTs, including additional costs. Collecting accurate data appeared to be crucial for decision‐making throughout the drug development process.
Montelukast improves disease outcome in SOD1G93A female mice by counteracting oligodendrocyte dysfunction and aberrant glial reactivity
Authors: Raffaele Stefano , Nguyen Nhung , Milanese Marco , Mannella Francesca C. , Boccazzi Marta , Frumento Giulia , Bonanno Giambattista , Abbracchio Maria P. , Bonifacino Tiziana , Fumagalli Marta 
Published: May 2024

AbstractBackground and PurposeAmyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder characterized by progressive motor neuron (MN) loss and consequent muscle atrophy, for which no effective therapies are available. Recent findings reveal that disease progression is fuelled by early aberrant neuroinflammation and the loss of oligodendrocytes with neuroprotective and remyelinating properties. On this basis, pharmacological interventions capable of restoring a pro‐regenerative local milieu and re‐establish proper oligodendrocyte functions may be beneficial.Experimental ApproachHere, we evaluated the in vivo therapeutic effects of montelukast (MTK), an antagonist of the oligodendroglial G protein‐coupled receptor 17 (GPR17) and of cysteinyl‐leukotriene receptor 1 (CysLT1R) receptors on microglia and astrocytes, in the SOD1G93A ALS mouse model. We chronically treated SOD1G93A mice with MTK, starting from the early symptomatic disease stage. Disease progression was assessed by behavioural and immunohistochemical approaches.Key ResultsOral MTK treatment significantly extended survival probability, delayed body weight loss and ameliorated motor functionalityonly in female SOD1G93A mice. Noteworthy, MTK significantly restored oligodendrocyte maturation and induced significant changes in the reactive phenotype and morphological features of microglia/macrophages and astrocytes in the spinal cord of female SOD1G93A mice, suggesting enhanced pro‐regenerative functions. Importantly, concomitant MN preservation has been detected after MTK administration. No beneficial effects were observed in male mice, highlighting a sex‐based difference in the protective activity of MTK.Conclusions and ImplicationsOur results provide the first preclinical evidence indicating that repurposing of MTK, a safe and marketed anti‐asthmatic drug, may be a promising sex‐specific strategy for personalized ALS treatment.
Incidence and predictors of posttraumatic epilepsy and cognitive impairment in patients with traumatic brain injury: A retrospective cohort study in Malaysia
Authors: Ngadimon Irma Wati , Mohan Devi , Shaikh Mohd. Farooq , Khoo Ching Soong , Tan Hui Jan , Chamhuri Nor Syazwani , Cheong Wing Loong , Aledo‐Serrano Angel , Yong Li Ling , Lee Yu Mey , Fadzil Farizal , Thanabalan Jegan 
Published: May 2024

AbstractObjectivePosttraumatic epilepsy (PTE) significantly impacts morbidity and mortality, yet local PTE data remain scarce. In addition, there is a lack of evidence on cognitive comorbidity in individuals with PTE in the literature. We sought to identify potential PTE predictors and evaluate cognitive comorbidity in patients with PTE.MethodsA 2‐year retrospective cohort study was employed, in which adults with a history of admission for traumatic brain injury (TBI) in 2019 and 2020 were contacted. Three hundred one individuals agreed to participate, with a median follow‐up time of 30.75 months. The development of epilepsy was ascertained using a validated tool and confirmed by our neurologists during visits. Clinical psychologists assessed the patients’ cognitive performance.ResultsThe 2‐year cumulative incidence of PTE was 9.3% (95% confidence interval [CI] 5.9–12.7). The significant predictors of PTE were identified as a previous history of brain injury [hazard ratio [HR] 4.025, p = .021], and intraparenchymal hemorrhage (HR: 2.291, p = .036), after adjusting for other confounders. TBI patients with PTE performed significantly worse on the total ACE‐III cognitive test (73.5 vs 87.0, p = .018), CTMT (27.5 vs 33.0, p = .044), and PSI (74.0 vs 86.0, p = .006) than TBI patients without PTE. A significantly higher percentage of individuals in the PTE group had cognitive impairment, compared to the non‐PTE group based on ACE‐III (53.6% vs 46.4%, p = .001) and PSI (70% vs 31.7%, p = .005) scores at 2 years post‐TBI follow‐up.SignificanceThis study emphasizes the link between TBI and PTE and the chance of developing cognitive impairment in the future. Clinicians can target interventions to prevent PTE by identifying specific predictors, which helps them make care decisions and develop therapies to improve patients’ quality of life.
Regulatory competition and cross‐fertilization in bank performance in the US banking markets
Authors: Tirtiroglu Dogan , Tanyeri‐Günsür Basak , Tirtiroglu Ercan 
Published: May 2024

AbstractThis paper examines empirically cross‐fertilization in the productivity growth of banks between a state and its neighbouring and non‐neighbouring states (i) before (i.e. 1971–1977) the interstate multibank holding company (IMBHC) deregulations and (ii) during (i.e. 1982–1995) the IMBHC deregulations, which, through cross‐border bank M&As mainly among neighbouring states, could inject new blood, awaken the market for corporate control and enhance cross‐fertilization in bank performance among neighbouring states. Further, the 1978–1981 period offers a natural experiment to examine Baumol's Contestable Markets Hypothesis (CMH). The legislature of Maine made the first IMBHC deregulatory move in 1978. There was no reciprocity until New York and Alaska made their moves in 1982. Under CMH, Maine's move should inject a competitive spirit and alter bank performance for better across all—neighbouring or non‐neighbouring – banking markets during this period. Theoretically, Kane's regulatory equilibrium framework provides guidance to address these matters and Tiebout's people vote with their feet framework extends and supplements this guidance. Empirically, FDIC's annual banking data, aggregated at the state level, constitute the main input in computing the productivity growth indices for each of the 48 contiguous sample states between 1971 and 1995. Estimations of a novel spatially driven fixed effects model that uses these indices produce empirical results. The empirical model exploits the proximity of one sample state to its neighbouring states while also embracing a set of randomly chosen non‐neighbouring states as a control sample. Results show that cross‐fertilization in bank performance, observed among neighbouring states before the introduction of the IMBHC deregulations during 1971–1977, gets stronger in response to the dynamically evolving IMBHC deregulations during 1982–1995 and that improvements in banks' productivity growth during 1978–1981 support Baumol's CMH. Overall, our results demonstrate the importance and influence of cross‐fertilization, as a matter of proximity of subjects, on banks' performance and suggest promise for future research that embraces the spatial dimension of banking markets and data.
Geographic Progression of Infant Respiratory Syncytial Virus Associated Bronchiolitis Across the United States Before and Since the Onset of COVID‐19: Results From Four Health Systems, 2015–2023
Authors: Blatt Adam Z. , Suh Mina , Walter Emmanuel B. , Wood Charles T. , Espinosa Claudia , Enriquez‐Bruce Maria E. , Domachowske Joseph , Daniels Danielle , Budhecha Sonia , Elliott Amanda , Wolf Zachary , Waddell Emory B. , Movva Naimisha , Reichert Heidi , Fryzek Jon P. , Nelson Christopher B. 
Published: May 2024

ABSTRACTBackgroundRespiratory syncytial virus (RSV) is a substantial cause of infant morbidity and mortality due to seasonal peaks of bronchiolitis across the United States. Clinical and viral surveillance plays a pivotal role in helping hospital systems prepare for expected surges in RSV bronchiolitis. Existing surveillance efforts have shown a geographic pattern of RSV positivity across the United States, with cases typically starting in the southeast and spreading north and west. Public health measures implemented due to the COVID‐19 pandemic disrupted viral transmission across the nation and altered the expected seasonality of RSV. The impact of these changes on the geographic progression of infant RSV bronchiolitis across the United States has not been described.MethodsHere, we used clinical and viral surveillance data from four health care systems located in different regions of the United States to describe the geographic progression of infant RSV bronchiolitis across the country from 2015 to 2023.ResultsPrior to widespread circulation of SARS‐CoV‐2, infant RSV bronchiolitis followed an established geographic pattern associated with seasonal epidemics originating in Florida and spreading north (North Carolina and New York) and later westward (Nevada). Although public health and social measures implemented during the COVID‐19 pandemic disrupted the seasonality of RSV disease, infant RSV bronchiolitis epidemics progressed across the nation in a pattern identical to the prepandemic era.ConclusionsOur findings highlight the importance of ongoing clinical and viral surveillance to optimally track the onset of RSV epidemics and allow health care systems to prepare for expected RSV bronchiolitis surges.
Cryoablation of atrial fibrillation in “very severe” obese patients (BMI ≥ 40): Indications, feasibility, procedural safety and efficacy, and clinical outcome (the ICE‐Obese Extreme)
Authors: Urbanek Lukas , Schmidt Boris , Bordignon Stefano , Schaack David , Ebrahimi Ramin , Tohoku Shota , Hirokami Jun , Efe Tolga Han , Plank Karin , Schulte‐Hahn Britta , Nowak Bernd , Chun Julian K. R. , Chen Shaojie 
Published: May 2024

AbstractBackgroundManagement of atrial fibrillation (AF) in very severe obese patients is challenging. Cryoballoon ablation (CBA) represents an effective rhythm control strategy. However, data in this patient group were limited.MethodsHighly symptomatic AF patients with body mass index (BMI) ≥ 40 kg/m2 who had failed antiarrhythmic drug therapy and electrocardioversion and failure to achieve targeted body‐weight‐reduction underwent CBA.ResultsData of 72 very severe obese AF patients (Group A) and 129 AF patients with normal BMI (Group B, BMI < 25 kg/m2) were consecutively collected. Group A had significantly younger age (60.6 ± 10.4 vs. 69.2 ± 11.2 years), higher BMI (44.3 ± 4.3 vs. 22.5 ± 1.6 kg/m2). Procedural pulmonary vein isolation (PVI) was successful in all patients (2 touch‐up ablation in Group A). Compared to Group B, Group A had similar procedural (61.3 ± 22.6 vs. 57.5 ± 19 min), similar fluoroscopy time (10.1 ± 5.5 vs. 9.2 ± 4.8 min) but significantly higher radiation dose (2852 ± 2095 vs. 884 ± 732 µGym2). We observed similar rates of real‐time‐isolation (78.6% vs. 78.5%), single‐shot‐isolation (86.5% vs. 88.8%), but significantly longer time‐to‐sustained‐isolation (53.5 ± 33 vs. 43.2 ± 25 s). There was significantly higher rate of puncture‐site‐complication (6.9% vs. 1.6%) in Group A. One‐year clinical success in paroxysmal AF was (Group A: 69.4% vs. Group B: 80.2%; p < .001), in persistent AF was (Group A: 58.1% vs. Group B: 62.8%; p = .889). In Re‐Do procedures Group A had a numerically lower PVI durability (75.0% vs. 83.6%, p = .089).ConclusionFor very severe obese AF patients, CBA appears feasible, leads to relatively good clinical outcome.
CRISPR/Cas9 Ribo nucleoprotein complex‐mediated editing of the OBP13 gene affected the response of male Bactrocera dorsalis (Diptera: Tephritidae) to methyl eugenol
Authors: Sujatha Parvathy Madhusoodanan , Karuppannasamy Ashok , Chalapathi Pradeep , Dhawane Yogi , Narasimhappa Nagesha Somakalahalli , Narayanappa Anu Cholenahalli , Munikrishnappa Vinay Kumar Thirumalahatti , Chikmagalur Nagaraja Bhargava , Thalooru Shashikala , Kesavan Subhaharan , Maligeppagol Manamohan , Ramasamy Asokan 
Published: May 2024

AbstractThe oriental fruit fly (Bactrocera dorsalis) is an exceptionally hazardous pest that can cause up to 100% loss. Male annihilation using male attractant methyl eugenol (ME) is the most adopted control measure of this insect. The molecular process underlying this perception of insects remains unexplored. In this study, we focus on gene functionality of odorant‐binding protein 13 (OBP13) in ME perception by knockout using CRISPR/Cas9 mediated embryonic editing through microinjection. The electrophysiological study of mutant flies through electroantennogram has shown highly depressed ME perception and further the genetic‐level mutational confirmation stating that OBP13 is a major OBP involved in ME perception. The molecular docking of OBP13 with ME revealed the predicted key interactions involved, thus providing more scope in targeting gene editing and in engineering ME substitutes.
New insights into the reproduction and migration of the porbeagle shark Lamna nasus (Bonnaterre 1788) in the Southwest Atlantic Ocean
Authors: Colonello Jorge H. , Cortés Federico , Burla Juan , Storni Benjamin , Laurentxena Mercedes , Allega Lucrecia 
Published: May 2024

AbstractThe objective of this study was to estimate the reproductive parameters of porbeagle shark in the Southwest Atlantic Ocean and thus characterize the adult fraction of this population. Therefore, 1012 specimens were measured by scientific observers on board the commercial trawl fleet operating south of 50° S. The size range of the specimens was from 77 to 292 cm fork length (LF). The mean size at maturity was estimated to be 153 cm LF for males and 172 cm LF for females. Porbeagle shark catches were recorded throughout the year, with the highest frequency occurring between November and June. The presence of pregnant females was observed from December to July, along with an increase in the average size of embryos in each litter. The information presented in this study improves the knowledge of the reproductive biology and allows to propose a migratory pattern of adult porbeagle females in the Southwest Atlantic Ocean. The likely seasonal increase in vulnerability of this shark to austral trawl fishery, despite all conservation management measures established in Argentina, underscores the importance of promoting its proper management and conservation given the need to improve understanding of porbeagle population dynamics in the Southern Hemisphere.
An orchestrated ethylene–gibberellin signaling cascade contributes to mesocotyl elongation and emergence of rice direct seeding
Authors: Lyu Yusong , Dong Xinli , Niu Shipeng , Cao Ruijie , Shao Gaoneng , Sheng Zhonghua , Jiao Guiai , Xie Lihong , Hu Shikai , Tang Shaoqing , Wei Xiangjin , Hu Peisong 
Published: May 2024

ABSTRACTA mechanized direct seeding of rice with less labor and water usage, has been widely adopted. However, this approach requires varieties that exhibit uniform seedling emergence. Mesocotyl elongation (ME) offers the main drive of fast emergence of rice seedlings from soils; nevertheless, its genetic basis remains unknown. Here, we identify a major rice quantitative trait locus Mesocotyl Elongation1 (qME1), an allele of the Green Revolution gene Semi‐Dwarf1 (SD1), encoding GA20‐oxidase for gibberellin (GA) biosynthesis. ME1 expression is strongly induced by soil depth and ethylene. When rice grains are direct‐seeded in soils, the ethylene core signaling factor OsEIL1 directly promotes ME1 transcription, accelerating bioactive GA biosynthesis. The GAs further degrade the DELLA protein SLENDER RICE 1 (SLR1), alleviating its inhibition of rice PHYTOCHROME‐INTERACTING FACTOR‐LIKE13 (OsPIL13) to activate the downstream expansion gene OsEXPA4 and ultimately promote rice seedling ME and emergence. The ancient traits of long mesocotyl and strong emergence ability in wild rice and landrace were gradually lost in company with the Green Revolution dwarf breeding process, and an elite ME1‐R allele (D349H) is found in some modern Geng varieties (long mesocotyl lengths) in northern China, which can be used in the direct seeding and dwarf breeding of Geng varieties. Furthermore, the ectopic and high expression of ME1 driven by mesocotyl‐specific promoters resulted in rice plants that could be direct‐seeded without obvious plant architecture or yield penalties. Collectively, we reveal the molecular mechanism of rice ME, and provide useful information for breeding new Green Revolution varieties with long mesocotyl suitable for direct‐seeding practice.
Reconstructing an ancient fish: Three‐dimensional skeletal restoration of the head of Mawsonia (Sarcopterygii, Actinistia) using CT scan, and an adjusted model for body size estimation in fossil coelacanths
Authors: Toriño Pablo , Dutel Hugo , Soto Matías , Norbis Walter , Ezquerra Víctor , Perea Daniel 
Published: May 2024

AbstractMawsonia constitutes one of the most conspicuous fossil coelacanth taxa, due to its unique anatomy and possible maximum body size. It typifies Mesozoic coelacanth morphology, before the putative disappearance of the group in the fossil record. In this work, the three‐dimensional cranial anatomy and body size estimations of this genus are re‐evaluated from a recently described specimen from Upper Jurassic deposits of Uruguay. The 3D restoration was performed directly on the material based on anatomical information provided by the living coelacanth Latimeria and previous two‐dimensional restorations of the head of Mawsonia. The montage was then scanned with computed tomography and virtually adjusted to generate an interactive online resource for future anatomical, taxonomic and biomechanical research. In general terms, the model constitutes a tool to improve both the anatomical knowledge of this genus and its comparison with other coelacanths. It also facilitates the evaluation of possible evolutionary trends and the discussion of particular features with potential palaeobiological implications, such as the anterior position of the eye and the development of the pseudomaxillary fold. Regarding the body size, a previous model for body size estimation based on the gular plate was submitted to OLS, RMA, segmented linear and PGLS regressions (including the evaluation of regression statistics, variance analysis, t‐tests and residual analysis). The results point to a power relationship between gular and total lengths showing a better support than a simple linear relationship. The new resulting equations were applied to the studied individual and are provided for future estimates. Although an isometric evolutionary growth cannot be rejected with the available evidence, additional models developed with other bones will be necessary to evaluate possible hidden evolutionary allometric trends in this group of fishes, thus avoiding overestimates.
Effective improvement methods for striae distensae: A novel approach utilizing laser‐induced micro‐jet injectors with poly‐d,l‐lactic acid
Authors: Seo Suk Bae , Kim Soo‐Bin , Yi Kyu‐Ho 
Published: May 2024

AbstractIntroductionStriae distensae (SD), or stretch marks, result from rapid stretching of the skin due to various factors. Conventional treatments often yield unsatisfactory results, leading to the exploration of alternative methods. Laser‐induced microjet technology offers a promising approach for drug delivery to target areas. This study investigates the efficacy of using a microjet injector with poly‐d,l‐lactic acid for treating SD.MethodsFour female participants with SD were treated with poly‐d,l‐lactic acid solution using a microjet injector over five sessions. Patients were assessed based on severity scales before and after treatment. Topical anesthetics were applied to minimize discomfort. Injection techniques were optimized to reduce side effects such as bleeding and pain.ResultsAll patients showed significant improvement in SD appearance after 5–7 treatments. Assessment scales indicated positive outcomes both immediately after treatment and at the 32‐week follow‐up. Minimal side effects, primarily petechiae, were observed.DiscussionLaser‐induced microjet technology offers several advantages, including rapid drug delivery and mechanotransduction effects, promoting skin regeneration. Poly‐d,l‐lactic acid injections demonstrated effectiveness in treating SD, particularly when delivered via microjet injectors. Patients expressed high satisfaction due to the procedure's minimal invasiveness and quick recovery.ConclusionUtilizing a needleless microjet injector with poly‐d,l‐lactic acid shows promise as a treatment for SD, typically requiring 5–7 sessions for optimal results. Mild petechiae may occur as a common side effect. This approach offers an effective and minimally invasive alternative for addressing this common cosmetic concern.