bluuebunny/crossref_metadata_2025_split huggingface dataset:
Within trial comparison of survival time projections from short‐term follow‐up with long‐term follow‐up findings
Authors: Ferreira João Pedro , Claggett Brian L. , Docherty Kieran F. , Jhund Pardeep S. , Zannad Faiez , Solomon Scott D. , McMurray John J.V. 
Published: July 2022

AbstractAimsData on long‐term treatment effects are scarce, despite the intent to use new therapies for many years and the need of patients, physicians and payers to have a better understanding of the lifetime benefits of treatments. The restricted mean or median survival time (RMST) calculated using age instead of time, hypothetically enables estimation of long‐term gain in event‐free or overall survival from the short‐term (within‐trial) effects of an intervention, compared with its control. Tha aim of the study is to use trials with long‐term follow‐up available through extension studies to compare the long‐term projections estimated using RMST from within‐trial follow‐up data with the actual long‐term outcomes in the extension studies.Methods and resultsWe estimated the median long‐term survival time using age instead of follow‐up time and compared these model‐based projections with the actual long‐term estimates in the (i) SCD‐HeFT trial vs. SCD‐HeFT long‐term outcomes; (ii) SOLVD trial vs. SOLVD 12 year follow‐up; (iii) STICH trial vs. STICHES; and (iv) ACCORD study vs. ACCORDION. In the long‐term follow‐up of SCD‐HeFT, gain in survival with ICD vs. placebo over a median of 11.0 years was +1.4 years of life. The RMST model‐derived survival projection from the within‐trial data (median follow‐up of 3.4 years) gave an estimated survival gain of +1.2 years. In STICHES, over a median follow‐up of 9.8 years, coronary artery bypass grafting (CABG) vs. medical care led to a survival extension of +1.4 years in favour of CABG. RMST projections using within‐trial data from STICH (median follow‐up of 4.9 years), gave an extended survival of +2.4 years in favour of CABG in younger patients. In the long‐term follow‐up of SOLVD, enalapril vs. placebo led to a survival gain of +0.8 years over a median follow‐up of 12.1 years. The RMST projections from the within‐trial data (median follow‐up of 2.8 years) gave a survival extension of +0.3 years in favour of enalapril. In the long‐term follow‐up ACCORDION study, with a median follow‐up of 8.8 years, intensive vs. a standard anti‐hyperglycaemic treatment did not influence long‐term survival, which was concordant with the RMST projections from the short‐term ACCORD study with median follow‐up of 4.9 years.ConclusionsAge‐based survival projections using within‐trial data generally provided concordant results with the actual survival measured in long‐term follow‐up extension studies. Our findings suggest that age‐based lifetime projections may be used as means to assess the long‐term treatment effects.
Synthesis of Tri‐ and Tetrasubstituted Alkenyl Boronates from Alkynes
Authors: Altarejos Julia , Valero Antonio , Manzano Rubén , Carreras Javier 
Published: July 2022

AbstractThe synthesis of organoboron compounds have attracted the attention of the synthetic community. In particular, molecules with C(sp2)‐B bonds enable the transformation to new C−C or C‐heteroatom bonds by well‐established methodologies. Alkenyl boronates have the possibility for further conversion of the boron moiety or functionalization of the double bond. This review gives an overview on the recent methodologies for the selective preparation of the challenging highly substituted alkenyl boronates from alkynes.
An examination of the efficacy and safety of fenfluramine in adults, children, and adolescents with Dravet syndrome in a real‐world practice setting: A report from the Fenfluramine European Early Access Program
Authors: Guerrini Renzo , Specchio Nicola , Aledo‐Serrano Ángel , Pringsheim Milka , Darra Francesca , Mayer Thomas , Gil‐Nagel Antonio , Polster Tilman , Zuberi Sameer M. , Lothe Amélie , Gammaitoni Arnold , Strzelczyk Adam 
Published: July 2022

AbstractObjectiveTo examine the efficacy and safety of fenfluramine in patients with Dravet syndrome (DS) in three age groups: <6, 6‐17, and ≥18 years old, treated in a real‐world setting.MethodsPatients with DS were treated with fenfluramine in the European Union Early Access Program (EAP). Following a 28‐day baseline period to establish the pretreatment monthly convulsive seizure frequency (MCSF), fenfluramine was started at a dose chosen by the treating physician and gradually titrated based on efficacy and tolerability up to a maximum of 0.7 mg/kg/day. Seizure incidence was recorded in a written diary, and adverse events (AEs) were reported at each patient visit. Cardiovascular safety was assessed by transthoracic echocardiography before treatment started and at least every 6 months thereafter.ResultsA total of 149 patients have enrolled in the EAP and 63 were <6 years old, 62 were 6‐17 years old, and 24 were ≥18 years old. After 3 months of treatment 62%, 53%, and 50% of patients demonstrated ≥75% reduction in MCSF in the <6, 6‐17, and ≥18‐year‐old groups, respectively. This pattern of response was sustained through 12 months of treatment with 55%, 46%, and 80% of the <6, 6‐17, and ≥18‐year‐old groups, respectively, experiencing a ≥75% reduction in MCSF. Most common AEs were loss of appetite (21%) and somnolence (16%). No valvular heart disease or pulmonary artery hypertension was observed.SignificanceThe magnitude, consistency, and durability of the response to add‐on fenfluramine is consistent across age groups in patients with Dravet syndrome.
Novel mechanism of hypoxic neuronal injury mediated by non‐excitatory amino acids and astroglial swelling
Authors: Álvarez‐Merz Iris , Fomitcheva Ioulia V. , Sword Jeremy , Hernández‐Guijo Jesús M. , Solís José M. , Kirov Sergei A. 
Published: July 2022

AbstractIn ischemic stroke and post‐traumatic brain injury (TBI), blood–brain barrier disruption leads to leaking plasma amino acids (AA) into cerebral parenchyma. Bleeding in hemorrhagic stroke and TBI also release plasma AA. Although excitotoxic AA were extensively studied, little is known about non‐excitatory AA during hypoxic injury. Hypoxia‐induced synaptic depression in hippocampal slices becomes irreversible with non‐excitatory AA, alongside their intracellular accumulation and increased tissue electrical resistance. Four non‐excitatory AA (l‐alanine, glycine,l‐glutamine,l‐serine: AGQS) at plasmatic concentrations were applied to slices from mice expressing EGFP in pyramidal neurons or astrocytes during normoxia or hypoxia. Two‐photon imaging, light transmittance (LT) changes, and electrophysiological field recordings followed by electron microscopy in hippocampal CA1 st. radiatum were used to monitor synaptic function concurrently with cellular swelling and injury. During normoxia, AGQS‐induced increase in LT was due to astroglial but not neuronal swelling. LT raise during hypoxia and AGQS manifested astroglial and neuronal swelling accompanied by a permanent loss of synaptic transmission and irreversible dendritic beading, signifying acute damage. Neuronal injury was not triggered by spreading depolarization which did not occur in our experiments. Hypoxia without AGQS did not cause cell swelling, leaving dendrites intact. Inhibition of NMDA receptors prevented neuronal damage and irreversible loss of synaptic function. Deleterious effects of AGQS during hypoxia were prevented by alanine‐serine‐cysteine transporters (ASCT2) and volume‐regulated anion channels (VRAC) blockers. Our findings suggest that astroglial swelling induced by accumulation of non‐excitatory AA and release of excitotoxins through antiporters and VRAC may exacerbate the hypoxia‐induced neuronal injury.
Pharmacokinetic Evaluation of Aconiazide, A Potentially Less Toxic Isoniazid Prodrug
Authors: Peloquin Charles A. , James Gordon T. , Craig Larry D. , Kim Michael , McCarthy Eileen A. , Iklé David , Iseman Michael D. 
Published: July 2022

Study Objective. To determine the bioavailability and renal elimination of isoniazid, acetylisoniazid, monoacetylhydrazine, diacetylhydrazine, aconiazide, and 2‐formylphenoxyacetic acid.Study Design. Randomized, double‐blind, two‐period, crossover phase I study.Setting. Pharmacokinetics unit at a referral hospital that specializes in the treatment of mycobacterial infections.Subjects. Twelve healthy volunteers selected from the hospital staff.Interventions. Subjects received aconiazide tablets 650 mg (containing isoniazid 300 mg) and isoniazid tablets 300 mg. Blood and urine samples were collected over 24 hours after the dose.Measurements and Main Results. Intact aconiazide and 2‐formylphenoxyacetic acid were not detected in the serum. Compared with isoniazid tablets, aconiazide's relative bioavailability (based on the area under the serum concentration‐time curve) was 50.7%; its relative maximum serum concentration was 13.4%.Conclusions. Isoniazid is less bioavailable after aconiazide tablets than after isoniazid tablets. The optimum dose of aconiazide remains to be determined.
Is ceasing self‐injury enough? Differences in psychological health between people reporting behavioral cessation of non‐suicidal self‐injury and those who consider themselves to have stopped self‐injuring
Authors: Claréus Benjamin , Hasking Penelope A. , Gray Nicole , Boyes Mark E. 
Published: July 2022

AbstractObjectiveThis study examined the overlap between considering oneself to have stopped nonsuicidal self‐injury (NSSI) and the actual cessation of the behavior in terms of days self‐injured in the last month and last year, and how these operationalizations are associated with constructs related to NSSI recovery.MethodsA cross‐sectional survey including measures of coping, emotion dysregulation, psychological distress, general self‐efficacy, and self‐efficacy in resisting NSSI was answered by 144 adults aged 17–81 years (Mage [SD] = 21.43 [7.32]).ResultsHaving self‐injured for ≥5 days in the last year was overly inclusive of individuals who currently considered themselves as having stopped NSSI (39.02%). Considering oneself to have stopped NSSI was associated with better emotion regulation (Cohen's d = 0.45), and higher general self‐efficacy and higher self‐efficacy to resist NSSI (d = 0.59‒0.64) than behavioral cessation. Not actually engaging in NSSI was only associated with self‐efficacy to resist NSSI in risk contexts, such that fewer days self‐injured in the last year increased confidence (partial η2 = 0.085).ConclusionAccounting for whether an individual considers themselves as having stopped NSSI or not may complement estimates of behavioral cessation, and strengthen outcomes associated with NSSI recovery.
N6‐methyladenosine (m6A) modification in gynecological malignancies
Authors: Zhang Chunmei , Liu Ning 
Published: July 2022

AbstractN6‐methyladenosine (m6A) modification is one of the most abundant modifications in eukaryotic mRNA, regulated by m6A methyltransferase and demethylase. m6A modified RNA is specifically recognized and bound by m6A recognition proteins, which mediate splicing, maturation, exonucleation, degradation, and translation. In gynecologic malignancies, m6A RNA modification‐related molecules are expressed aberrantly, significantly altering the posttranscriptional methylation level of the target genes and their stability. The m6A modification also regulates related metabolic pathways, thereby controlling tumor development. This review analyzes the composition and mode of action of m6A modification‐related proteins and their biological functions in the malignant progression of gynecologic malignancies, which provide new ideas for the early clinical diagnosis and targeted therapy of gynecologic malignancies.
Lack of consensus among healthcare professionals at a large academic medical center on the use of exome sequencing for prenatal diagnosis
Authors: Johnson Kylie , Erfani Hadi , Maktabi Mohamad Ali , Van den Veyver Ignatia , Nassef Salma 
Published: July 2022

AbstractPrenatal exome sequencing (ES) is increasingly used for prenatal diagnosis because emerging data indicate it has incremental diagnostic benefit in pregnancies with fetal anomalies without identified genetic abnormalities by karyotyping and chromosomal microarray analysis. The aim of this study was to evaluate the medical community's attitude toward the clinical utility and use of exome sequencing for prenatal diagnosis and to address differences in attitudes and responses by type of practitioner, level of training, and years passed since last full‐time training. We analyzed the answers of 109 trainees and professionals in the fields of genetic counseling, laboratory science, and medicine to an online survey addressing these topics. Multiple‐choice questions asked participants about their awareness of prenatal ES and what genetic test they would choose to order in certain scenarios. Likert‐scale questions assessed participants' opinions of statements asserting when prenatal ES should be used for diagnostic testing. Attitude toward the use of prenatal ES statistically differed (p < 0.05) by type of participant and level of training. Practicing genetic counselors and physicians were more selective in their recommendations for prenatal ES than laboratory scientists. Genetic counseling students and practicing genetic counselors felt similarly about indications for the use of prenatal ES, whereas medical students were more liberal in their recommendations for prenatal ES than practicing physicians. This study shows a lack of consensus among the medical community regarding the clinical utility and indications for prenatal ES.
A seroepidemiological study across age groups before and after the 2010–2011 mumps epidemic in Japan
Authors: Morino Saeko , Satoh Hiroshi , Arai Satoru , Suzuki Motoi , Tanaka‐Taya Keiko 
Published: July 2022

AbstractIn Japan, large‐scale mumps epidemics recur every 4–6 years because of low vaccination coverage. This study aimed to describe the seroprevalence of mumps in the Japanese population and identify the age groups most affected. The prevalence of anti‐mumps antibodies was evaluated based on 1000 serum samples obtained from the Japanese National Serum Reference Bank. These samples consisted of 50 sera for each of 10 different age groups, collected during 2007–2008 (pre‐epidemic period) and 2012–2013 (post‐epidemic period). Seropositivity was lowest in the 6–11 months subgroup (3% and 0% in pre‐ and post‐epidemic periods, respectively) and highest in the 10–14 years group (66% and 72% in pre‐ and post‐epidemic periods, respectively). A comparison of anti‐mumps antibody prevalence throughout the two periods considered revealed a large rise in seropositivity among the 2004–2008 birth cohort, using that of the 1–4 years group as representative in the pre‐epidemic period (from 22% in pre‐ to 58% in post‐epidemic periods; p = 0.0002). These results indicate that most people likely gain antibodies to the mumps virus during their childhood, especially during the first epidemic that they experience after their second year of life. Therefore, children should be vaccinated against mumps soon after their first birthday for effective prevention.
Learning Curve of USgHIFU Ablation for Uterine Fibroids: A Multi‐Center Prospective Study
Authors: Liu Dang , Zhang Xinyue , Gong Xue , Yang Chao , Zhang Rong , Chen Wenzhi , Chen Jinyun 
Published: July 2022

ObjectivesTo verify the stability of high‐intensity focused ultrasound (HIFU) technology and the feasibility of training programs with learning curve cumulative summation (LC‐CUSUM).MethodsA total of 12 physicians and 720 cases were equally assigned to the learning group and the control group, with 6 physicians and 360 cases per group. The learning group was treated by physicians without HIFU experience and the control group was treated by experienced physicians. Nonperfused volume (NPV) ratio was assessed by contrast‐enhanced magnetic resonance imaging. Technical failure was defined as NPV ratio of uterine fibroids <70% and/or major complication, while <80% was set as a stricter standard of training qualification. LC‐CUSUM was used to analyze the learning curve.ResultsPhysicians with or without HIFU experience in both groups achieved matchable NPV ratios, where a NPV ratio of 92.52% (16.06) was achieved by experienced physicians and 93.82% (16.95) by inexperienced physicians. No major complication was observed. The results of LC‐CUSUM analysis showed that, with the standards of the NPV ratio of 70% or 80%, the learning group mastered the technique on the 11th case and the 16th case, respectively, while the control group was stable.ConclusionsHIFU technology stayed stable in operation, with good safety and sound effectiveness, and was easy to learn. NPV ratio of 70% was considered as an appropriate indicator of training qualification. HIFU has remarkable prospects in achieving a NPV ratio of ≥80% without safety being compromised.
Outcomes for Organ Preservation with Chemoradiation Therapy for T4 Larynx and Hypopharynx Cancer
Authors: Eita Amgad , Mohamed Nader , Rybkin Alisa , Kang Jung Julie , Fiasconaro Megan , Zhigang Zhang , Zakeri Kaveh , Yu Yao , Sadaka Emad , Sherman Eric , Dunn Lara , Cracchiolo Jennifer , Wong Richard J. , Cohen Marc , Lee Nancy Y. 
Published: July 2022

ObjectiveLimited data is available to guide non‐surgical management of Stage T4 larynx and hypopharynx cancer patients who have inoperable disease or refuse surgery. We aim to review the nonoperative management of T4 laryngeal and hypopharyngeal cancer and report the long‐term therapeutic and functional outcomes.MethodsWe reviewed the nonoperative management of T4 laryngeal (n = 44) and hypopharyngeal (n = 53) cancer from 1997 to 2015 and performed a univariate analysis (UVA).ResultsThe 2‐/5‐year OS rates were 73%/38% for larynx patients and 52%/29% for hypopharynx patients. Locoregional failure (LRF) occurred in 25% and 19% of larynx and hypopharynx patients, respectively. On UVA of the larynx subset, N3 nodal status and non‐intensity‐modulated radiation therapy were negatively associated with OS; treatment with radiation therapy alone impacted disease‐free survival; and age >70 was associated with LRF. On UVA of the hypopharynx subset, only T4b status significantly impacted OS. In the larynx and hypopharynx groups, 68% and 85% received a percutaneous endoscopic gastrostomy (PEG) tube and 32% and 40% received a tracheostomy tube, respectively. At the last follow‐up visit, 66% of our larynx cohort had neither tracheostomy or PEG placed and 40% of our hypopharynx cohort had neither.ConclusionWe report better than previously noted outcomes among T4 larynx and hypopharynx patients who have unresectable disease or refuse surgery.Level of Evidence4 Laryngoscope, 133:1138–1145, 2023
Validation of a surgical training model containing indocyanine green for near‐infrared fluorescence imaging
Authors: Nishio Naoki , Mitani Sohei , Sakamoto Kayo , Morimoto Gaku , Yokoi Sayaka , Shigeyama Mayu , Wada Akihisa , Mukoyama Nobuaki , Rosenthal Eben L. , Sone Michihiko 
Published: July 2022

AbstractObjectiveTo determine the efficacy of a surgical training model for fluorescence‐guided cancer surgery and validate its utility to detect any residual tumors after tumor resection using electrocautery.MethodsWe developed surgical training models containing indocyanine green (ICG) for near‐infrared (NIR) fluorescence imaging using a root vegetable organic material (konjac). After the fluorescence assessment for the models, the surgical simulation for fluorescence‐guided cancer surgery using electrocautery was performed. ICG‐containing tumors were divided into two surgical groups: “Enucleation” (removal of the entire visible tumor) and “Complete resection” (removal of the tumor with an appropriate 5‐mm surgical margin).ResultsAll 12 ICG‐containing tumors were clearly visible from the normal view but not from the flipped view. The tumor resection time was significantly longer in the “Complete resection” group than in the “Enucleation” group (p < .001). The ICG‐containing tumors showed a high tumor‐to background ratio from the normal (average = 45.8) and flipped (average = 19.2) views, indicating that the models including ICG‐containing tumors were useful for a surgical simulation in fluorescence‐guided surgery. The average mean fluorescence intensity of the wound bed was significantly higher in the “Enucleation” group than in the “Complete resection” group (p < .01). No decrease in fluorescence signal was found in the wound bed even at 2 days postresection.ConclusionOur surgical training model containing a fluorescent agent is safe, inexpensive, not harmful for humans, and easy to dispose after use. Our model would be beneficial for surgeons to learn NIR fluorescence imaging and to accelerate fluorescence‐guided cancer surgery into clinical application.
Martensite transformation behavior and mechanical properties of two kinds of low‐nickel austenite stainless steel
Authors: Cai C. , Wu H. , Liao L. , Li J. , Chen Y. 
Published: July 2022

AbstractIn this study, tensile tests were performed to study the effect of martensitic transformation on mechanical properties. The effect of the martensitic transformation on the growth of austenite grains was also investigated. The result indicated that, with higher martensite content, alloy 2 possessed finer austenite grains and higher tensile strength. To compare the martensitic transformation behavior of the two steels, the Ms and Md30 temperatures, austenite stacking fault energies, and driving force were calculated by empirical equations. Equilibrium phase diagrams were calculated using Thermo‐Calc software. The kinetics of martensite volume fraction versus true strain was fitted by the sigmodal model. It was found that martensite volume fraction and deformation behavior exhibited significant differences in the two low‐nickel austenitic stainless steel. Both stacking fault energy and the driving force of transforming austenite to martensite have a critical role in strain‐induced martensite deformation. Beyond that, the prediction of martensite content by the sigmoidal equation was consistent with the experimental data.
Optical and electrical properties of perovskite microrods
Authors: Ahmed M.T. , Islam S. , Ahmed F. 
Published: July 2022

AbstractOrganic‐inorganic perovskites have become widely studied materials for their superior optoelectronic applications. This research reports the synthesis of CH3NH3PbI3 perovskite microrods via one‐step deposition for optoelectronic applications. Crystalline and morphological structure, bond information, optical, and electrical characteristics have been studied. The perovskite microrods showed fine crystalinity with 90 nm–300 nm rod diameter with a high absorption coefficient over 104 cm−1. A very lesser refractive index (1.85–2.00) was observed in the visible region. A comparison among different bandgap measuring techniques has also been demonstrated and up to 5.5 % deviation in measured bandgap was observed.