bluuebunny/crossref_metadata_2025_split huggingface dataset:
Vascular imaging findings in retinopathy of prematurity
Authors: Rowe Lucas W. , Belamkar Aditya , Antman Gal , Hajrasouliha Amir R. , Harris Alon 
Published: October 2023

AbstractRetinopathy of prematurity (ROP) is a vascular disease among preterm infants involving incomplete or abnormal retinal vascularization and is a leading cause of preventable blindness globally. Measurements of ocular blood flow originating from a variety of imaging modalities, including colour Doppler imaging (CDI), fluorescein angiography (FA) and ocular coherence tomography angiography (OCTA), have been associated with changes in ROP patients. Herein, we discuss and summarize the relevant current literature on vascular imaging and ROP reviewed through December 2022. Differences in vascular imaging parameters between ROP patients and healthy controls are reviewed and summarized. The available data identify significantly increased peak systolic velocity (PSV) in the central retinal artery and ophthalmic artery as measured by CDI, increased vascular tortuosity as measured by FA, smaller foveal avascular zone (FAZ) as measured by FA and OCTA, and increased foveal vessel density (VD) and reduced parafoveal VD as measured by OCTA in ROP patients compared with controls. None of the above findings appear to reliably correlate with visual acuity. The studies currently available, however, are inconclusive and lack robust longitudinal data. Vascular imaging demonstrates the potential to aid in the diagnosis, management and monitoring of ROP, alongside retinal examination via indirect ophthalmoscopy and fundus photography.
Exploring the challenges faced by foundation doctors when prescribing high risk medicines safely during the on‐call period: A qualitative study
Authors: Alanzi Mahdi A. , Tully Mary P. , Lewis Penny J. 
Published: October 2023

AimsErrors with prescribing high‐risk medicines (HRMs) have a greater propensity to cause harm than with non‐HRMs. Prescribing errors arise due to multiple factors and it can be particularly challenging for junior doctors to prescribe safely during the on‐call period. Knowledge regarding the challenges of prescribing HRM during the on‐call period would be useful to target preventative interventions. The aim of this study was to explore the challenges encountered by foundation doctors (doctors who have graduated medical school within the last 2 years) when prescribing specific HRMs (anticoagulants, insulin and opioids) safely during the on‐call period.MethodsSix focus groups exploring the challenges of prescribing HRMs safely during the on‐call period were conducted, 3 with foundation year 1 and 3 with foundation year 2 doctors from across 3 different hospitals. A thematic framework analysis based on the London Protocol was conducted.ResultsDoctors described multiple challenges to prescribing HRMs safely during the on‐call period including a lack of prescribing support, nursing pressure, complex prescribing tasks, unknown patients as well as individual factors such as lack of knowledge and tiredness. Many of these factors exist to some extent during the day, yet the nature of the on‐call period as a fast‐paced environment heightened the challenges that prescribers faced.ConclusionThere are multiple challenges experienced by foundation doctors when prescribing HRMs during the on‐call period. The potentially devastating consequences of errors with HRMs means that closer attention and more concern from healthcare professionals, researchers and policymakers is required to improve safe prescribing of HRMs in hospitals.
Drug clustering to anticipate new aspects of drug safety profile: Application to gabapentinoids and other voltage‐gated calcium channel ligand drugs
Authors: Viguier Thibault , Agier Marie‐Sara , Jonville‐Béra Annie‐Pierre , Giraudeau Bruno , Largeau Bérenger 
Published: October 2023

AbstractAimsGabapentin and pregabalin bind to α2‐δ subunit of voltage‐gated calcium channels (Cav). Other drugs targeting Cav include cardiovascular calcium channel blockers (CCBs) and anticonvulsants (levetiracetam, ethosuximide and zonisamide). In addition to pharmacodynamics, the safety profile of gabapentinoids seems to overlap with the one of cardiovascular CCBs (oedema) and Cav‐blocking anticonvulsants (suicide and ataxia). The objective of this study was to cluster the safety profile of different Cav‐ligand drugs by focusing on whether gabapentinoids present a distinct adverse drug reaction (ADR) signature from cardiovascular CCBs and anticonvulsants.MethodsWe extracted all ADRs with at least one significant disproportionate reporting (reporting odds ratio) related to gabapentinoids, CCBs or anticonvulsants in VigiBase. After principal component analysis preprocessing, a hierarchical ascendent classification was performed to cluster gabapentinoids and other Cav‐ligand drugs that share a similar ADR signature. The robustness of the results was determined through four sensitivity analyses, varying on the dataset or the clustering method.ResultsA total of 16 drugs and 65 ADRs were included. Gabapentinoids were in Cluster #1, which included eight other drugs (isradipine, nicardipine, lacidipine, lercanidipine, ethosuximide, levetiracetam, zonisamide and nimodipine). Cluster #2 contained two drugs (diltiazem and verapamil) and Cluster #3 contained four drugs (amlodipine, felodipine, nifedipine and nitrendipine). The clustering results were consistent in all sensitivity analyses.ConclusionsThe safety profile of gabapentinoids overlaps with those of some dihydropyridine CCBs and Cav‐blocking anticonvulsants. These results could be used to anticipate some unidentified ADRs of gabapentinoids from information accumulated with older drugs and sharing a common molecular target and ADR signature.
Population pharmacokinetics of mirvetuximab soravtansine in patients with folate receptor‐α positive ovarian cancer: The antibody–drug conjugate, payload and metabolite
Authors: Tu Ya‐Ping , Hanze Eva , Zhu Fengying , Lagraauw H. Maxime , Sloss Callum M. , Method Michael , Esteves Brooke , Westin Eric H. , Berkenblit Anna 
Published: October 2023

AimsMirvetuximab soravtansine is a first‐in‐class antibody–drug conjugate recently approved for the treatment of folate receptor‐α positive ovarian cancer. The aim of this study was to develop a population pharmacokinetic model to describe the concentration–time profiles of mirvetuximab soravtansine, the payload (DM4) and a metabolite (S‐methyl‐DM4).MethodsMirvetuximab soravtansine was administered intravenously from 0.15 to 7 mg/kg to 543 patients with predominantly platinum‐resistant ovarian cancer in 3 clinical studies, and the plasma drug concentrations were analysed using a nonlinear mixed‐effects modelling approach. Stepwise covariate modelling was performed to identify covariates.ResultsWe developed a semi‐mechanistic population pharmacokinetic model that included linear and nonlinear routes for the elimination of mirvetuximab soravtansine and a target compartment for the formation and disposition of the payload and metabolite in tumour cells. The clearance and volume of the central compartment were 0.0153 L/h and 2.63 L for mirvetuximab soravtansine, 8.83 L/h and 3.67 L for DM4, and 2.04 L/h and 6.3 L for S‐methyl‐DM4, respectively. Body weight, serum albumin and age were identified as statistically significant covariates. Exposures in patients with renal or hepatic impairment and who used concomitant cytochrome P450 (CYP) 3A4 inhibitors were estimated.ConclusionThere is no need for dose adjustment due to covariate effects for mirvetuximab soravtansine administered at the recommended dose of 6 mg/kg based on adjusted ideal body weight. Dose adjustment is not required for patients with mild or moderate renal impairment, mild hepatic impairment, or when concomitant weak and moderate CYP3A4 inhibitors are used.
Post‐COVID‐19 thrombotic sequelae: The potential role of persistent platelet hyperactivity
Authors: Schieppati Francesca 
Published: October 2023

Postacute COVID‐19 sequelae affect millions of individuals, and active research into the pathophysiological mechanisms and potential treatments is underway. The report by Nara and colleagues shows persistent platelet hyperactivity in the chronic phase of the infection, suggesting a possible role of platelets in post‐COVID‐19 complications and, consequently, a possible therapeutic target.Commentary on: Nara et al. Prolonged platelet hyperactivity after COVID‐19 infection. Br J Haematol 2024;204:492‐496.
AZD9567 versus prednisolone in patients with active rheumatoid arthritis: A phase IIa, randomized, double‐blind, efficacy, and safety study
Authors: van Laar Jacob M. , Lei Alejhandra , Safy‐Khan Mary , Almquist Joachim , Belfield Graham , Edman Karl , Öberg Lisa , Angermann Bastian R. , Dillmann Inken , Berntsson Pia , Etal Damla , Dainty Ian , Astbury Carol , Belvisi Maria G. , Nemes Szilárd , Platt Adam , Prothon Susanne , Samuelsson Sara , Svanberg Petter , Keen Christina ,   the SEMRA study group
Published: October 2023

AbstractOral corticosteroid use is limited by side effects, some caused by off‐target actions on the mineralocorticoid receptor that disrupt electrolyte balance. AZD9567 is a selective, nonsteroidal glucocorticoid receptor modulator. The efficacy, safety, and tolerability of AZD9567 and prednisolone were assessed in a phase IIa study. Anti‐inflammatory mechanism of action was also evaluated in vitro in monocytes from healthy donors. In this randomized, double‐blind, parallel‐group, multicenter study, patients with active rheumatoid arthritis were randomized 1:1 to AZD9567 40 mg or prednisolone 20 mg once daily orally for 14 days. The primary end point was change from baseline in DAS28‐CRP at day 15. Secondary end points included components of DAS28‐CRP, American College of Rheumatology (ACR) response criteria (ACR20, ACR50, and ACR70), and safety end points, including serum electrolytes. Overall, 21 patients were randomized to AZD9567 (n = 11) or prednisolone (n = 10), and all completed the study. As anticipated, AZD9567 had a similar efficacy profile to prednisolone, with no clinically meaningful (i.e., >1.0) difference in change from baseline to day 15 in DAS28‐CRP between AZD9567 and prednisolone (least‐squares mean difference: 0.47, 95% confidence interval: −0.49 to 1.43). Similar results were observed for the secondary efficacy end points. In vitro transcriptomic analysis showed that anti‐inflammatory responses were similar for AZD9567, prednisolone, and dexamethasone. Unlike prednisolone, AZD9567 had no effect on the serum sodium:potassium ratio. The safety profile was not different from that of prednisolone. Larger studies of longer duration are required to determine whether AZD9567 40 mg may in the future be an alternative to prednisolone in patients with inflammatory disease.
Cytologic features of meningioma: An analysis of common and uncommon subtypes and diagnostic difficulties during intraoperative procedures
Authors: Rodríguez‐García Ana M. , Esteban‐Rodríguez Isabel , Jiménez‐Heffernan José A. , Bárcena Carmen , López‐Muñoz Samuel , López‐Ferrer Pilar 
Published: October 2023

AbstractDespite common histogenesis meningiomas have a wide morphologic spectrum, and the World Health Organization (WHO) recognizes 15 subtypes. They are the most common brain tumour in adults and typically have an extra‐axial location. Although there have been important advances in the molecular biology of meningiomas its diagnosis is based on histopathologic features. The great majority are benign WHO grade 1 tumours. There are specific criteria for assigning WHO grade 2 and 3 that can be applied to all meningioma subtypes. Regardless of these criteria, chordoid and clear cell morphologic subtypes are considered grade 2. WHO grade 3 tumours exhibit a very high mitotic index, frank anaplasia or specific molecular abnormalities. The impressive morphologic diversity shown by meningiomas makes them a diagnostic challenge, which can be even greater in intraoperative studies. The focus of this article is to describe and illustrate their main cytologic features, with emphasis on the most infrequent subtypes.
Do gender stereotypes play a role in the process of identifying gifted students in Western Balkan countries? – Case study Bosnia and Herzegovina
Authors: Milic Sanja , Simeunovic Vlado 
Published: October 2023

AbstractGender stereotypes, as a cause and consequence of deeply rooted attitudes, values and norms, directly affect the discovery and development of gifted potentials. Given the fact that high abilities are most successfully identified and properly developed in early school age, the aim of the study is to investigate the existence of gender differences in the perception of different abilities in boys and girls by teachers, parents, peers and self‐perception in multiple intelligences. The research was conducted on 115 lower primary school students in Bosnia and Herzegovina. Mann–Whitney U test was used to determine differences in various domains of giftedness between girls and boys throughout groups of evaluators. Statistically significant difference was found in 11 of the 36 variables analysed. Most statistically significant differences were found in parents' assessments (5), while 3 were found in teachers' assessments, 2 in peers' assessments, and only one in self‐assessments. Although the cultural factors, customs and traditions of the Balkan country of Bosnia and Herzegovina have a great influence on gender stereotypes, the results of research on gender discrimination in the process of identifying giftedness are largely similar to the results of developed European countries. The results of the study can be used in the context of general education as a basis for critical re‐examination of negative attitudes towards females in the direction of a particular professional orientation.
Hemispheric epilepsy surgery for hemimegalencephaly: The UCLA experience
Authors: Goel Keshav , Phillips H. Westley , Chen Jia‐Shu , Ngo Jacqueline , Edmonds Benjamin , Ha Phong X. , Wang Andrew , Weil Alexander G. , Russell Bianca E. , Salamon Noriko , Nariai Hiroki , Fallah Aria 
Published: October 2023

AbstractObjectivesHemimegalencephaly (HME) is a rare congenital brain malformation presenting predominantly with drug‐resistant epilepsy. Hemispheric disconnective surgery is the mainstay of treatment; however, little is known about how postoperative outcomes compare across techniques. Thus we present the largest single‐center cohort of patients with HME who underwent epilepsy surgery and characterize outcomes.MethodsThis observational study included patients with HME at University of California Los Angeles (UCLA) from 1984 to 2021. Patients were stratified by surgical intervention: anatomic hemispherectomy (AH), functional hemispherectomy (FH), or less‐than‐hemispheric resection (LTH). Seizure freedom, functional outcomes, and operative complications were compared across surgical approaches. Regression analysis identified clinical and intraoperative variables that predict seizure outcomes.ResultsOf 56 patients, 43 (77%) underwent FH, 8 (14%) underwent AH, 2 (4%) underwent LTH, 1 (2%) underwent unknown hemispherectomy type, and 2 (4%) were managed non‐operatively. At median last follow‐up of 55 months (interquartile range [IQR] 20–92 months), 24 patients (49%) were seizure‐free, 17 (30%) required cerebrospinal fluid (CSF) shunting for hydrocephalus, 9 of 43 (21%) had severe developmental delay, 8 of 38 (21%) were non‐verbal, and 15 of 38 (39%) were non‐ambulatory. There was one (2%) intraoperative mortality due to exsanguination earlier in this cohort. Of 12 patients (29%) requiring revision surgery, 6 (50%) were seizure‐free postoperatively. AH, compared to FH, was not associated with statistically significant improved seizure freedom (hazard ratio [HR] = .48, p = .328), although initial AH trended toward greater odds of seizure freedom (75% vs 46%, p = .272). Younger age at seizure onset (HR = .29, p = .029), lack of epilepsia partialis continua (EPC) (HR = .30, p = .022), and no contralateral seizures on electroencephalography (EEG) (HR = .33, p = .039) independently predicted longer duration of seizure freedom.SignificanceThis study helps inform physicians and parents of children who are undergoing surgery for HME by demonstrating that earlier age at seizure onset, absence of EPC, and no contralateral EEG seizures were associated with longer postoperative seizure freedom. At our center, initial AH for HME may provide greater odds of seizure freedom with complications and functional outcomes comparable to those of FH.
A global synthesis and conceptualization of the magnitude and duration of soil carbon losses in response to forest disturbances
Authors: Mayer Mathias , Baltensweiler Andri , James Jason , Rigling Andreas , Hagedorn Frank 
Published: October 2023

AbstractAimForest disturbances are increasing around the globe due to changes in climate and management, deteriorating forests' carbon sink strength. Estimates of global forest carbon budgets account for losses of plant biomass but often neglect the effects of disturbances on soil organic carbon (SOC). Here, we aimed to quantify and conceptualize SOC losses in response to different disturbance agents on a global scale.LocationGlobal.Time Period1983–2022.Major Taxa StudiedForest soils.MethodsWe conducted a comprehensive global analysis of the effects of harvesting, wildfires, windstorms and insect infestations on forest SOC stocks in the surface organic layer and top mineral soil, synthesizing 927 paired observations from 151 existing field studies worldwide. We further used global mapping to assess potential SOC losses upon disturbance.ResultsWe found that both natural and anthropogenic forest disturbances can cause large SOC losses up to 60 Mg ha−1. On average, the largest SOC losses were found after wildfires, followed by disturbances from windstorms, harvests and insects. However, initial carbon stock size, rather than disturbance agent, had the strongest influence on the magnitude of SOC losses. SOC losses were greatest in cold‐climate forests (boreal and mountainous regions) with large accumulations of organic matter on or near the soil surface. Negative effects are present for at least four decades post‐disturbance. In contrast, forests with small initial SOC stocks experienced quantitatively lower carbon losses, and their stocks returned to pre‐disturbance levels more quickly.Main ConclusionsOur results indicate that the more carbon is stored in the forest's organic layers and top mineral soils, the more carbon will be lost after disturbance. Robust estimates of forest carbon budgets must therefore consider disturbance‐induced SOC losses, which strongly depend on site‐specific stocks. Particularly in cold‐climate forests, these disturbance‐related losses may challenge forest management efforts to sequester CO2.
Categorization using the Dementia Assessment Sheet for Community‐Based Integrated Care System 8‐items (DASC‐8) based on cognitive function and activities of daily living predicts frailty, disability and mortality in older adults
Authors: Katsumata Yuu , Toyoshima Kenji , Tamura Yoshiaki , Murao Yuji , Sato Motoya , Watanabe So , Kodera Remi , Oba Kazuhito , Ishikawa Joji , Chiba Yuko , Awata Shuichi , Araki Atsushi 
Published: October 2023

AimThis longitudinal study aimed to determine whether categorization by the Dementia Assessment Sheet for Community‐based Integrated Care System 8‐items (DASC‐8) is associated with risk of frailty onset, disability, and mortality.MethodsWe analyzed longitudinal data from outpatients aged 65 years and older evaluated for the DASC‐8 at the Frailty Clinic. The outcomes during the 3‐year follow‐up period were (Study A) frailty onset (Kihon Checklist ≥8) and (Study B) disability (new certification of nursing care needs) or mortality. Multivariate Cox regression analyses were performed to examine independent associations between the DASC‐8 category and outcomes, and hazard ratios and 95% confidence intervals (CIs) were calculated after adjustment for age, sex, and the presence or absence of diabetes, hypertension, and dyslipidemia.Results(Study A) Out of the 216 patients without frailty in Categories I or II at baseline, 40 (20.4%) and 11 (55.0%) developed frailty, respectively. The adjusted hazard ratio was 3.62 (95% CI: 1.69–7.76, P < 0.001). (Study B) Out of the 350 patients who did not require long‐term care at baseline, disability or death occurred for 20 (7.3%) in Category I, 14 (23.0%) in Category II, and 9 (56.3%) in Category III. The adjusted hazard ratios were 2.40 (Category I vs. II; 95% CI: 1.13–5.11, P = 0.023) and 5.43 (Category I vs. III; 95% CI: 2.23–13.3, P < 0.001).ConclusionCategorization according to DASC‐8 is associated with the risk of frailty, disability, and mortality in older patients. Geriatr Gerontol Int 2024; 24: 150–155.
Diagnosis with confidence: deep learning for reliable classification of laryngeal dysplasia
Authors: Lubrano Mélanie , Bellahsen‐Harrar Yaëlle , Berlemont Sylvain , Atallah Sarah , Vaz Emmanuelle , Walter Thomas , Badoual Cécile 
Published: October 2023

BackgroundDiagnosis of head and neck (HN) squamous dysplasias and carcinomas is critical for patient care, cure, and follow‐up. It can be challenging, especially for grading intraepithelial lesions. Despite recent simplification in the last WHO grading system, the inter‐ and intraobserver variability remains substantial, particularly for nonspecialized pathologists, exhibiting the need for new tools to support pathologists.MethodsIn this study we investigated the potential of deep learning to assist the pathologist with automatic and reliable classification of HN lesions following the 2022 WHO classification system. We created, for the first time, a large‐scale database of histological samples (>2000 slides) intended for developing an automatic diagnostic tool. We developed and trained a weakly supervised model performing classification from whole‐slide images (WSI). We evaluated our model on both internal and external test sets and we defined and validated a new confidence score to assess the predictions that can be used to identify difficult cases.ResultsOur model demonstrated high classification accuracy across all lesion types on both internal and external test sets (respectively average area under the curve [AUC]: 0.878 (95% confidence interval [CI]: [0.834–0.918]) and 0.886 (95% CI: [0.813–0.947])) and the confidence score allowed for accurate differentiation between reliable and uncertain predictions.ConclusionOur results demonstrate that the model, associated with confidence measurements, can help in the difficult task of classifying HN squamous lesions by limiting variability and detecting ambiguous cases, taking us one step closer to a wider adoption of AI‐based assistive tools.