bluuebunny/crossref_metadata_2025_split huggingface dataset:
The effect of food and acid‐reducing agents on the pharmacokinetic profile of capivasertib: Results from a randomized, crossover study
Authors: Miller Claire , Sommavilla Roberto , Murphy Donal , Morris Thomas , Khatun Mahmuda , Cullberg Marie 
Published: June 2023

AbstractAimsThis two‐part, adaptive study assessed the effect of food and an acid‐reducing agent (rabeprazole) on the pharmacokinetics (PK) and safety of capivasertib, a potent AKT inhibitor, in clinical development for cancer treatment.MethodsIn Part 1, healthy participants (n = 24) were randomized to receive single‐dose capivasertib after overnight fasting, a high‐fat, high‐calorie meal and with rabeprazole postovernight fasting in one of six treatment sequences. Based on Part 1 results, a new group of participants (n = 24) were randomized (Part 2) to receive capivasertib after overnight fasting, a low‐fat, low‐calorie meal and modified fasting (food restricted from 2 h before dosing to 1 h postdose) in one of six treatment sequences. Blood samples were collected for PK analyses.ResultsFollowing a high‐fat, high‐calorie meal, capivasertib exposure increased versus overnight fasting (geometric mean ratio [GMR] [90% confidence interval (CI)]: area under the concentration‐time curve [AUCinf] 1.32 [1.22, 1.43], maximum concentration [Cmax] 1.23 [1.08, 1.41]), but was comparable to that postmodified fasting (GMR: AUCinf 1.13 [0.99, 1.29], Cmax 0.85 [0.70, 1.04]). AUCinf was similar and Cmax was lower with/without rabeprazole (GMR: AUCinf 0.94 [0.87, 1.02]), Cmax 0.73 [0.64, 0.84]). Capivasertib exposure was similar after a low‐fat, low‐calorie meal versus overnight fasting (GMR: AUCinf 1.14 [1.05, 1.25], Cmax 1.21 [0.99, 1.48]) or modified fasting (GMR: AUCinf 0.96 [0.88, 1.05], Cmax 0.86 [0.70, 1.06]). Safety was consistent with that in larger trials.ConclusionsThis study demonstrates that administering capivasertib with food or acid‐reducing agents does not lead to clinically relevant PK or safety profile changes.
Automated multi‐well stratigraphic correlation and model building using relative geologic time
Authors: Sylvester Zoltán 
Published: June 2023

AbstractStratigraphic correlation of geophysical well logs is one of the most important—and most time‐consuming—tasks that applied geoscientists perform on a daily basis. Using the dynamic time warping (DTW) algorithm, automated correlation of two wells is a fairly simple task; DTW can also be used to correlate a large number of wells along a single path. However, errors accumulate along a path and loops cannot be closed. To create a three‐dimensionally consistent correlation framework, we use a Python implementation of the Wheeler and Hale (2014) approach, which is based on the idea of stretching and squeezing all logs into a chronostratigraphic diagram that has relative geologic time (RGT) on itsy‐axis. The depth shifts needed for the RGT transformation are computed by translating the outputs of a large number of pairwise DTW correlations into a least‐squares optimization problem that is solved through the conjugate gradient method. The resulting chronostratigraphic diagram provides an overview of the overall stratigraphy and its variability; and the correlation framework is significantly different from what one could get from correlating based on lithologic similarity between two logs. To create geologically intuitive well‐log cross sections, we use a multi‐scale blocking method that relies on the continuous wavelet transform to identify stratigraphic units of a certain scale in one well and then propagate these boundaries to all the other wells. We demonstrate the usefulness of this approach on a data set with close to 700 wells from the Permian Basin, West Texas. Linear channel bodies in the deepwater Spraberry Formation are easily detected and clearly highlighted in maps and cross sections. The methodology is robust enough for mapping subtle stratigraphic details, previously considered feasible only through manual interpretation. More importantly, it can be used to quickly build three‐dimensional stratigraphic models for large segments of sedimentary basins where enough log data are available.
Patient perspectives on consequences of resection for colorectal cancer: A qualitative study
Authors: van Kooten Robert T. , Schutte Bianca A. M. , van Staalduinen Dorine J. , Hoeksema Jetty H. L. , Holman Fabian A. , van Dorp Chantal , Peeters Koen C. M. J. , Tollenaar Rob A. E. M. , Wouters Michel W. J. M. 
Published: June 2023

AbstractBackgroundColorectal cancer is diagnosed in approximately 500,000 patients each year in Europe, leading to a high number of patients having to cope with the consequences of resection for colorectal cancer. As treatment options tend to grow, more information on the effects of these treatments is needed to engage in shared decision‐making. This study aims to explore the impact of resection for colorectal cancer on patients' daily life.MethodsPatients (≥18 years of age) who underwent an oncological colorectal resection between 2018 and 2021 were selected. Purposeful sampling was used to include patients who differed in age, comorbidity conditions, types of (neo)adjuvant therapy, postoperative complications and the presence/absence of a stoma. Semi‐structured interviews were conducted, guided by a topic guide. Interviews were fully transcribed and subsequently thematically analysed using the framework approach. Analyses were carried out using the following predefined themes: (1) daily life and activities; (2) psychological functioning; (3) social functioning; (4) sexual functioning; and (5) healthcare experiences.ResultsSixteen patients with a follow‐up period of between 0.6 and 4.4 years after surgery were included in this study. Participants reported several challenges experienced because of poor bowel function, a stoma, chemotherapy‐induced neuropathy, fear of recurrence and sexual dysfunction. However, they reported these as not interfering much with daily life.ConclusionColorectal cancer treatment leads to several challenges and treatment‐related health deficits. This is often not recognized by generic patient‐reported outcome measures, but the findings on treatment‐related health deficits presented in this study contain valuable insights which might contribute to improving colorectal cancer care, shared decision making and value‐based health care.
Optimal staffing for a good quality inpatient diabetes service
Authors: Dashora U. , Flanagan D. , Rayman G. , Mustafa O. G. , Walden E. , Dhatariya K. ,   the Joint British Diabetes Societies
Published: June 2023

AbstractIntroductionIncreasing numbers of people admitted to hospital have diabetes and need specialist support. To date, there is no mechanism which can help teams estimate the number of health care professionals they need to provide optimal care for people with diabetes in hospitals.MethodsThe Joint British Diabetes Societies (JBDS) for Inpatient Care Group organised a survey of specialist inpatient diabetes teams in the UK for current staffing and the perception of optimal staffing using mailing lists available through their representative organisations. The results were verified and confirmed by one‐to‐one conversations with individual respondents and discussed in multiple expert‐group meetings to agree on the results.ResultsResponses were received from 17 Trusts covering 30 hospital sites. Current diabetes specialist staffing level per 100 people with diabetes in hospital (Median, IQR) for consultants was 0.24 (0.22–0.37), diabetes inpatient specialist nurses was 1.94 (1.22–2.6), dieticians was 0.00 (0.00–0.00), podiatrists was 0.19 (0.00–0.62), pharmacists was 0.00 (0.00–0.37), psychologists was 0.00 (0.00–0.00). The teams also reported that for optimal care the total staff needed for each group (Median, IQR) was much higher; consultants 0.65 (0.50–0.88), specialist nurses 3.38 (2.78–4.59), dieticians 0.48 (0.33–0.72), podiatrists, 0.93 (0.65–1.24), pharmacists, 0.65 (0.40–0.79) and psychologists 0.33 (0.27–0.58). Based on the results of the survey, the JBDS expert group produced an Excel calculator to estimate staffing needs of any hospital site in question just by populating a few of the cells.ConclusionCurrent inpatient diabetes staffing is much lower than needed in most Trusts who responded to the survey. The JBDS calculator can provide an estimate of the staffing needs of any hospital.
Neuropsychological outcomes after epilepsy surgery: A comparison of stereo electroencephalography and subdural electrodes
Authors: Arya Ravindra , Frink Clayton , Kargol Christina , Byars Anna W. , Huddleston David , Diedenhofer Donna B. , Aungaroon Gewalin , Ervin Brian , Horn Paul S. , Ihnen S. K. Z. , Tenney Jeffrey R. , Kremer Kelly , Fong Susan , Lin Nan , Liu Wei , Arthur Todd M. , Skoch Jesse , Leach James L. , Mangano Francesco T. , Glauser Tracy A. , Greiner Hansel M. , Holland Katherine D. 
Published: June 2023

AbstractBackground and purposeWe analyzed the association of neuropsychological outcomes after epilepsy surgery with the intracranial electrode type (stereo electroencephalography [SEEG] and subdural electrodes [SDE]), and electrical stimulation mapping (ESM) of speech/language.MethodsDrug‐resistant epilepsy patients who underwent comprehensive neuropsychological evaluation before and 1 year after epilepsy surgery were included. SEEG and SDE subgroups were matched by age, handedness, operated hemisphere, and seizure freedom. Postsurgical neuropsychological outcomes (adjusted for presurgical scores) and reliable change indices were analyzed as functions of electrode type and ESM.ResultsNinety‐nine patients aged 6–29 years were included with similar surgical resection/ablation volumes in the SEEG and SDE subgroups. Most of the neuropsychological outcomes were comparable between SEEG and SDE subgroups; however, Working Memory and Processing Speed were significantly improved in the SEEG subgroup. Undergoing language ESM was associated with significant improvements in Spelling, Letter–Word Identification, Vocabulary, Verbal Comprehension, Verbal Learning, and Story Memory scores, but a decline in Calculation scores.ConclusionsIntracranial evaluations with SEEG and SDE are comparable in terms of long‐term postsurgical neuropsychological outcomes. Our data suggest that SEEG may be associated with improvements in working memory and processing speed, representing cognitive domains served by spatially distributed networks. Our study also supports wider use of language ESM before epilepsy surgery, preferably using other language tasks in addition to visual naming. Rather than the type of electrode, postsurgical neuropsychological outcomes are driven by whether language ESM was performed or not, with beneficial effects of language mapping.
Connecting Women in Neurosciences: A networking project to sustain mutual empowerment in young, female clinical neuroscientists
Authors: Goeldlin Martina B. , Wenz Elena S. , Kottler Chantal , Fischer Urs , Bassetti Claudio L. A. , Aybek Selma , Heldner Mirjam R. 
Published: June 2023

AbstractSimultaneously acquiring broad clinical knowledge and scientific expertise is a major challenge for young clinical scientists. Female researchers may face additional hurdles in their career, for example, due to unconscious bias. We aimed to address clinical, research, and gender‐related challenges among young female clinical neuroscientists. We implemented a peer‐led networking group dedicated to increasing clinical and scientific knowledge, improve soft skills, and encourage exchange between fellow residents. In monthly meetings, two participants hold short presentations on a clinical topic or scientific method, followed by a discussion and feedback to the presenter. Afterwards, participants network and discuss challenges they face in their daily experience. Nine neurology residents at a Swiss University Hospital with ≤3 years of training participated in the Connecting Women in Neurosciences project from August 2020 to June 2021. In a qualitative evaluation, participants reported they felt empowered by these meetings and profited from their new network. We identified several challenges in combining clinical and research activities, some of which participants perceived to be gender‐related. In addition to women‐only meetings, we will promote events addressing all interested researchers. Peer‐to‐peer networking is an easy and low‐budget intervention to encourage female residents to engage in research activities, profit from each other's expertise, and promote interdisciplinary teamwork. It can provide a protected environment to discuss and overcome in particular gender‐related challenges. We encourage young colleagues to regularly engage in structured networking activities with their local peers.
Making migraine easier to stomach: the role of the gut−brain−immune axis in headache disorders
Authors: Sgro Marissa , Ray Jason , Foster Emma , Mychasiuk Richelle 
Published: June 2023

AbstractBackground and PurposeHeadache disorders place a significant burden on the healthcare system, being the leading cause of disability in those under 50 years. Novel studies have interrogated the relationship between headache disorders and gastrointestinal dysfunction, suggesting a link between the gut−brain−immune (GBI) axis and headache pathogenesis. Although the exact mechanisms driving the complex relationship between the GBI axis and headache disorders remain unclear, there is a growing appreciation that a healthy and diverse microbiome is necessary for optimal brain health.MethodsA literature search was performed through multiple reputable databases in search of Q1 journals within the field of headache disorders and gut microbiome research and were critically and appropriately evaluated to investigate and explore the following; the role of the GBI axis in dietary triggers of headache disorders and the evidence indicating that diet can be used to alleviate headache severity and frequency. The relationship between the GBI axis and post‐traumatic headache is then synthesized. Finally, the scarcity of literature regarding paediatric headache disorders and the role that the GBI axis plays in mediating the relationship between sex hormones and headache disorders are highlighted.ConclusionsThere is potential for novel therapeutic targets for headache disorders if understanding of the GBI axis in their aetiology, pathogenesis and recovery is increased.
Individuals with chronic epilepsy have elevated P‐wave heterogeneity comparable to patients with atrial fibrillation
Authors: Fialho Guilherme L. , Pang Trudy D. , Kong Wan Yee , Tran Anthony P. , Yu Calvin G. , Rodriguez Ivo D. , Nearing Bruce D. , Waks Jonathan W. , Maher Timothy R. , Clarke John‐Ross , Shepherd Alyssa , D'Avila Andre , Schachter Steven C. , Verrier Richard L. 
Published: June 2023

AbstractObjectiveIdentification of epilepsy patients with elevated risk for atrial fibrillation (AF) is critical given the heightened morbidity and premature mortality associated with this arrhythmia. Epilepsy is a worldwide health problem affecting nearly 3.4 million people in the United States alone. The potential for increased risk for AF in patients with epilepsy is not well appreciated, despite recent evidence from a national survey of 1.4 million hospitalizations indicating that AF is the most common arrhythmia in people with epilepsy.MethodsWe analyzed inter‐lead heterogeneity of P‐wave morphology, a marker reflecting arrhythmogenic nonuniformities of activation/conduction in atrial tissue. The study groups consisted of 96 patients with epilepsy and 44 consecutive patients with AF in sinus rhythm before clinically indicated ablation. Individuals without cardiovascular or neurological conditions (n = 77) were also assessed. We calculated P‐wave heterogeneity (PWH) by second central moment analysis of simultaneous beats from leads II, III, and aVR (“atrial dedicated leads”) from standard 12‐lead electrocardiography (ECG) recordings from admission day to the epilepsy monitoring unit (EMU).ResultsFemale patients composed 62.5%, 59.6%, and 57.1% of the epilepsy, AF, and control subjects, respectively. The AF cohort was older (66 ± 1.1 years) than the epilepsy group (44 ± 1.8 years, p < .001). The level of PWH was greater in the epilepsy group than in the control group (67 ± 2.6 vs. 57 ± 2.5 μV, p = .046) and reached levels observed in AF patients (67 ± 2.6 vs. 68 ± 4.9 μV, p = .99). In multiple linear regression analysis, PWH levels in individuals with epilepsy were mainly correlated with the PR interval and could be related to sympathetic tone. Epilepsy remained associated with PWH after adjustments for cardiac risk factors, age, and sex.SignificancePatients with chronic epilepsy have increased PWH comparable to levels observed in patients with AF, while being ~20 years younger, suggesting an acceleration in structural change and/or cardiac electrical instability. These observations are consistent with emerging evidence of an “epileptic heart” condition.
Dysfunctional sodium channel kinetics as a novel epilepsy mechanism in chromosome 15q11‐q13 duplication syndrome
Authors: Elamin Marwa , Lemtiri‐Chlieh Fouad , Robinson Tiwanna M. , Levine Eric S. 
Published: June 2023

AbstractObjectiveDuplication of the maternal chromosome 15q11.2‐q13.1 region causes Dup15q syndrome, a highly penetrant neurodevelopmental disorder characterized by severe autism and refractory seizures. Although UBE3A, the gene encoding the ubiquitin ligase E3A, is thought to be the main driver of disease phenotypes, the cellular and molecular mechanisms that contribute to the development of the syndrome are yet to be determined. We previously established the necessity of UBE3A overexpression for the development of cellular phenotypes in human Dup15q neurons, including increased action potential firing and increased inward current density, which prompted us to further investigate sodium channel kinetics.MethodsWe used a Dup15q patient‐derived induced pluripotent stem cell line that was CRISPR‐edited to remove the supernumerary chromosome and create an isogenic control line. We performed whole cell patch clamp electrophysiology on Dup15q and corrected control neurons at two time points of in vitro development.ResultsCompared to corrected neurons, Dup15q neurons showed increased sodium current density and a depolarizing shift in steady‐state inactivation. Moreover, onset of slow inactivation was delayed, and a faster recovery from both fast and slow inactivation processes was observed in Dup15q neurons. A fraction of sodium current in Dup15q neurons (~15%) appeared to be resistant to slow inactivation. Not unexpectedly, a higher fraction of persistent sodium current was also observed in Dup15q neurons. These phenotypes were modulated by the anticonvulsant drug rufinamide.SignificanceSodium channels play a crucial role in the generation of action potentials, and sodium channelopathies have been uncovered in multiple forms of epilepsy. For the first time, our work identifies in Dup15q neurons dysfunctional inactivation kinetics, which have been previously linked to multiple forms of epilepsy. Our work can also guide therapeutic approaches to epileptic seizures in Dup15q patients and emphasize the role of drugs that modulate inactivation kinetics, such as rufinamide.
The performance of socially responsible investments: A meta‐analysis
Authors: Hornuf Lars , Yüksel Gül 
Published: June 2023

AbstractIn this article, we use a meta‐analysis to examine the performance of socially responsible investing (SRI). We find that, on average, SRI neither outperforms nor underperforms the market portfolio. However, in line with modern portfolio theory, we find that global SRI portfolios outperform regional subportfolios. Moreover, high‐quality publications, publications in finance journals and authors who publish more frequently on SRI are all less likely to report SRI outperformance. In particular, we find that including more factors in a capital market model reduces the likelihood that a study will find SRI outperformance.
Phase variation and mechanical properties of waste calcium carbonate to substitute quartz in composite slab production
Authors: Baş Sedanur , Güler Taki , Özer Ali , Aktürk Selçuk , Kriven Waltraud M. 
Published: June 2023

AbstractOwing to the fast‐emerging nature and rapid advancements in the construction industry, huge volumes of marble dust (MD) are generated as reject during slab cutting in marble processing, causing significant environmental hazards. Nowadays, quartz composite slabs have increasingly been preferred in building works due to their excellent hygienic property and mechanical strength. Composite slab is produced using micronized quartz as filler, the grinding of which is an energy‐intensive process. Substitution of micronized quartz with MD at different percentages was investigated in natural form and after roasting. Natural MD offered appreciable physical properties closer to those of a quartz composite slab. Physical properties slightly retrograded by quartz supplementation in the raw form. Roasting the filler led to the formation of rounded Ca–silicate. Wollastonite was the first phase formed after sintering at the lowest MD percentage and shortest roasting times. Larnite became dominating phase first by increasing MD percentage and roasting time, and then calcio‐olivine formed. Physical characterization test results demonstrated that hardnesses of new phase and particle shape were the key parameters that improved slabs’ mechanical properties of. Hard rounded larnite particles improved mechanical behavior of slabs having the synergic effect of quartz, whereas wollastonite did not show a significant effect.
Development and validation of nomogram to improve the specificity of multiparametric MRI for clinically significant prostate cancer
Authors: Shiekh Mohsin , Houenstein Holly , Ramahi Yousuf O. , Shabir Usma , Ghadersohi Sarah , Zhu Denzel , Zhu Michael , Jing Zhe , Attwood Kristopher , Kauffman Eric , Aboumohamed Ahmed , Guru Khurshid , Hussein Ahmed A. 
Published: June 2023

ObjectiveTo develop and validate a nomogram to improve the specificity of prostate imaging reporting and data system (PI‐RADS) on multiparametric magnetic resonance imaging (MRI) for clinically significant prostate cancer on targeted fusion biopsy.MethodsA retrospective review of patients who underwent fusion biopsy for PI‐RADS 3–5 lesions using UroNav and Artemis systems between 2016 and 2022 was performed. Patients were divided into those with CS disease on fusion biopsy (Gleason grade group ≥2) versus those without. Multivariable analysis was used to identify variables associated with CS disease. A 100‐point nomogram was constructed, and ROC curve was generated.Results1485 lesions (1032 patients) were identified, 510 (34%) were PI‐RADS 3, 586 (40%) were PI‐RADS 4, and 389 (26%) were PI‐RADS 5. Of these, 11% of PI‐RADS 3, 39% of PI‐RADS 4, and 61% of PI‐RADS 5 showed CS disease. CS disease was associated with older age (OR 1.04, 95% CI 1.02–1.06, p < 0.01), previous negative biopsy (OR 0.52, 95% CI 0.36–0.74, p < 0.01), presence of multiple PI‐RADS 3–5 lesions (OR 0.61, 95% CI 0.45–0.83, p < 0.01), peripheral zone location (OR 1.88, 95% CI 1.30–2.70, p < 0.01), PSA density (OR 1.48 per 0.1 unit, 95% CI 1.33–1.64, p < 0.01), PI‐RADS score 4 (OR 3.28, 95% CI 2.21–4.87, p < 0.01), and PI‐RADS score 5 (OR 7.65, 95% CI 4.93–11.85, p < 0.01). Area under ROC curve was 82% for nomogram compared to 75% for PI‐RADS score alone.ConclusionWe report a nomogram that combines PI‐RADS score with other clinical parameters. The nomogram outperforms PI‐RADS score for the detection of CS prostate cancer.