bluuebunny/crossref_metadata_2025_split huggingface dataset:
Venetoclax pharmacokinetics in participants with end‐stage renal disease undergoing haemodialysis
Authors: Noorani Behnam , Menon Rajeev M. , Chen Xin , Marsh Kennan C. , Huang Weize , Gupta Shelly , Dobkowska Edyta , Marbury Thomas , Salem Ahmed Hamed 
Published: October 2023

AimsRenal insufficiency is a common comorbidity in patients with haematological malignancies. This study aimed to assess how end‐stage renal disease (ESRD) might affect the pharmacokinetics of venetoclax, a Bcl‐2 inhibitor, in participants with ESRD undergoing haemodialysis.MethodsVenetoclax was administered as a single 100‐mg dose to 6 female participants with ESRD (estimated glomerular filtration rate <15 mL/min) both prior to haemodialysis and between haemodialysis days and 7 healthy female participants with normal renal function (estimated glomerular filtration rate >90 mL/min). Intensive pharmacokinetic and protein binding samples were collected from all participants. Arterial and venous samples were collected from ESRD participants during haemodialysis to assess the effect of haemodialysis on venetoclax pharmacokinetics. Pharmacokinetic parameters were estimated using noncompartmental methods.ResultsThere was no difference in plasma venetoclax concentrations between arterial and venous samples, suggesting that haemodialysis did not affect the pharmacokinetics of venetoclax. The fraction unbound (fu) of venetoclax was ~2‐fold higher for participants with ESRD compared to participants with normal renal function. The unbound maximum plasma concentration and area under the plasma concentration–time curve from time 0 to 48 h were comparable between ESRD and normal function groups. The mean half‐life ranged from 10.4 to 12.2 h across groups, demonstrating that ESRD did not affect the half‐life of venetoclax. No new safety signals were observed during this study.ConclusionESRD and dialysis do not alter unbound venetoclax plasma concentrations. No pharmacokinetics driven dose adjustment is needed for patients with renal insufficiency.
Synthesis and anti‐tumor activity evaluation of 1H‐pyrrolo[2,3‐b]pyridine‐2‐carboxamide derivatives with phenyl sulfonamide groups as potent RSK2 inhibitors
Authors: Zhang Xiaoyu , Zheng Guochuang , Gao Shang , Zhou Feng , Pan Tao , Shi Qiqi , Li Jiani , Zhang Xiaomeng , Huang Zhangjian , Quan Xu 
Published: October 2023

AbstractRibosome S6 Protein Kinase 2 (RSK2) is involved in many signal pathways such as cell growth, proliferation, survival and migration in tumors. Also, RSK2 can phosphorylate YB‐1, which induces the expression of tumor initiating cells, leading to poor prognosis of triple negative breast cancer. Herein, phenyl sulfonamide was introduced to a series of 1H‐pyrrolo[2,3‐b]pyridine‐2‐carboxamide derivatives to obtain novel RSK2 inhibitors which were evaluated RSK2 inhibitory activity and proliferation inhibitory activity against MDA‐MB‐468. The newly introduced sulfonamide group was observed to form a hydrogen bond with target residue LEU‐74 which played crucial role in activity. The results showed that most of compounds exhibited RSK2 enzyme inhibitory with IC50 up to 1.7 nM. Compound B1 exhibited the strongest MDA‐MB‐468 cell anti‐proliferation activity (IC50 = 0.13 μM). The in vivo tumor growth inhibitory activities were evaluated with compounds B1‐B3 in MDA‐MB‐468 xenograft model which gave up to 54.6% of TGI.
The impact of the COVID‐19 pandemic on families of children with medical complexity: A qualitative study of caregivers' experiences
Authors: Tager Julia B. , Kenney Ansley E. , Lim Paulina S. , Everhart Samantha A. , Johaningsmeir Sarah , Balistreri Kathryn A. , Morgan‐Tautges Amy , Berridge Kevin E. , Brophey Maura , Rothschild Charles B. , Scanlon Matthew C. , Davies W. Hobart , Lee K. Jane , Schnell Jessica L. 
Published: October 2023

AbstractBackgroundFamilies of children with medical complexity (CMC) have been negatively affected by the COVID‐19 pandemic, experiencing challenges such as decreased access to services, increased financial hardship and increased isolation. However, there are few qualitative studies which explore parental experiences. The aim of the present study was to describe the impact of the COVID‐19 pandemic on families of CMC.MethodsCaregivers of CMC were recruited from a large hospital in the Midwestern United States. They completed a semistructured qualitative interview assessing the impact of COVID‐19 on their child's care, which was analysed using interpretive phenomenological analysis.ResultsTwenty caregivers who were predominantly White, married and female participated. Emergent themes included the importance of protecting their child's health to ensure their physical safety, greater social isolation and missed medical services related to concerns about exposure, clinic closures and/or other logistical changes. Participants noted that the convenience of telehealth was a positive outcome of COVID‐19 that facilitated care while reducing time and resource challenges.ConclusionsThis study highlights the importance of protecting the health of CMC through continued safe access to in‐person or telehealth services. It is important to prioritise emotional support services for families of CMC as they have experienced increased stress and social isolation during and after the COVID‐19 pandemic. This topic should be explored among diverse families with CMC across multiple healthcare systems.
Selection of planning unit size in dynamic management strategies to reduce human–wildlife conflict
Authors: Welch Heather , Liu Owen R. , Riekkola Leena , Abrahms Briana , Hazen Elliott L. , Samhouri Jameal F. 
Published: October 2023

AbstractConservation planning traditionally relies upon static reserves; however, there is increasing emphasis on dynamic management (DM) strategies that are flexible in space and time. Due to its novelty, DM lacks best practices to guide design and implementation. We assessed the effect of planning unit size in a DM tool designed to reduce entanglement of protected whales in vertical ropes of surface buoys attached to crab traps in the lucrative U.S. Dungeness crab (Metacarcinus magister) fishery. We conducted a retrospective analysis from 2009 to 2019 with modeled distributions of blue (Balaenoptera musculus) and humpback (Megaptera novaeangliae) whales and observed fisheries effort and revenue to evaluate the effect of 7 planning unit sizes on DM tool performance. We measured performance as avoided whale entanglement risk and protected fisheries revenue. Small planning units avoided up to $47 million of revenue loss and reduced entanglement risk by up to 25% compared to the large planning units currently in use by avoiding the incidental closure of areas with low biodiversity value and high fisheries revenue. However, large planning units were less affected by an unprecedented marine heat wave in 2014–2016 and by delays in information on the distributions of whales and the fishery. Our findings suggest that the choice of planning unit size will require decision‐makers to navigate multiple socioecological considerations—rather than a one‐size‐fits‐all approach—to separate wildlife from threats under a changing climate.
The importance of equity in payments to encourage coexistence with large mammals
Authors: Hamm Joseph , Holmes George , Martin‐Ortega Julia 
Published: October 2023

AbstractLarge mammals often impose significant costs such as livestock depredation or crop foraging on rural communities, and this can lead to the retaliatory killing of threatened wildlife populations. One conservation approach—payments to encourage coexistence (PEC)—aims to reduce these costs through financial mechanisms, such as compensation, insurance, revenue sharing, and conservation performance payments. Little is known about the equitability of PEC, however, despite its moral and instrumental importance, prevalence as a conservation approach, and the fact that other financial tools for conservation are often inequitable. We used examples from the literature to examine the capability of PEC—as currently perceived and implemented—to be inequitable. We recommend improving the equitability of current and future schemes through the cooperative design of schemes that promote compensatory equity and greater consideration of conservation performance payments and by changing the international model for funding PEC to reduce global coexistence inequalities. New and existing programs must address issues of equitability across scales to ensure that conservation efforts are not undermined by diminished social legitimacy.
Parental socioeconomic status weakly predicts specific cognitive and academic skills beyond general cognitive ability
Authors: Bignardi Giacomo , Mareva Silvana , Astle Duncan E. 
Published: October 2023

AbstractParental socioeconomic status (SES) is a well‐established predictor of children's neurocognitive development. Several theories propose that specific cognitive skills are particularly vulnerable. However, this can be challenging to test, because cognitive assessments are not pure measures of distinct neurocognitive processes, and scores across different tests are often highly correlated. Aside from one previous study by Tucker‐Drob, little research has tested if associations between SES and cognition are explained by differences in general cognitive ability rather than specific cognitive skills. Using structural equation modelling (SEM), we tested if parental SES is associated with individual cognitive test scores after controlling for latent general cognitive ability. Data from three large‐scale cohorts totalling over 16,360 participants from the UK and USA (ages 6–19) were used. Associations between SES and cognitive test scores are mainly (but not entirely) explained through general cognitive ability. Socioeconomic advantage was associated with particularly strong vocabulary performance, unexplained by general ability. When controlling for general cognitive ability, socioeconomic disadvantage was associated with better executive functions. Better characterizing relationships between cognition and adversity is a crucial first step toward designing interventions to narrow socioeconomic gaps.Research Highlights
Understanding environmental influences on cognitive development is a crucial goal for developmental science—parental socioeconomic status (SES) is one of the strongest predictors.
Several theories have proposed that specific cognitive skills, such as language or certain executive functions, are particularly susceptible to socioeconomic adversity.
Using structural equation modelling, we tested whether SES predicts specific cognitive and academic tests after controlling for latent general cognitive ability across three large‐scale cohorts.
SES moderately predicted latent general cognitive ability, but associations with specific cognitive skills were mainly small, with a few exceptions.
Gastrointestinal adverse events and weight reduction in people with type 2 diabetes treated with tirzepatide in the SURPASS clinical trials
Authors: Patel Hiren , Khunti Kamlesh , Rodbard Helena W. , Bajaj Harpreet S. , Bray Ross , Kindracki Zbigniew , Rodríguez Ángel 
Published: October 2023

AbstractAimsTo evaluate gastrointestinal adverse events (AEs) and the impact of nausea, vomiting or diarrhoea (N/V/D) and any gastrointestinal (GI) AEs overall on weight change with tirzepatide across the SURPASS‐1 to ‐5 clinical trials.Materials and MethodsParticipants with type 2 diabetes were randomized to receive once‐weekly tirzepatide (5, 10 or 15 mg) or comparator (placebo, semaglutide 1 mg once weekly, or titrated daily basal insulins) as monotherapy or added on to background antihyperglycaemic medication(s). This post hoc analysis subdivided participants within each trial into subgroups that self‐reported (yes/no) any N/V/D or GI AEs. Change from baseline in body weight at the primary timepoint was assessed within each trial and subgroup. Mediation analyses were conducted to evaluate the contribution of direct and indirect (mediated by N/V/D or GI AEs) effects of tirzepatide on weight change versus comparators.ResultsAcross the SURPASS‐1 to ‐5 trials (N = 6263), nausea (12%‐24%), diarrhoea (12%‐22%), and vomiting (2%‐13%) were the most common GI AEs reported with tirzepatide; these were transient and of mild‐to‐moderate severity. Mean weight reduction at the primary timepoint with tirzepatide was consistent between participants who reported N/V/D (−6.2 to −14.9 kg) and those who did not report N/V/D (−6.2 to −13.3 kg). Mean weight reduction was significantly (P < 0.01) greater with tirzepatide compared with placebo, semaglutide 1 mg, and basal insulins within the N/V/D and GI AEs subgroups. Mediation analyses suggested minimal contribution (<6%) of N/V/D and GI AEs to the overall difference in weight change between tirzepatide and comparators.ConclusionsSuperior weight reduction with tirzepatide versus comparators appears to be independent of reported N/V/D or GI AEs.
Natural ocean iron fertilization and climate variability over geological periods
Authors: Jiang Hai‐Bo , Hutchins David A. , Ma Wentao , Zhang Rui‐Feng , Wells Mark , Jiao Nianzhi , Wang Yuntao , Chai Fei 
Published: October 2023

AbstractMarine primary producers are largely dependent on and shape the Earth's climate, although their relationship with climate varies over space and time. The growth of phytoplankton and associated marine primary productivity in most of the modern global ocean is limited by the supply of nutrients, including the micronutrient iron. The addition of iron via episodic and frequent events drives the biological carbon pump and promotes the sequestration of atmospheric carbon dioxide (CO2) into the ocean. However, the dependence between iron and marine primary producers adaptively changes over different geological periods due to the variation in global climate and environment. In this review, we examined the role and importance of iron in modulating marine primary production during some specific geological periods, that is, the Great Oxidation Event (GOE) during the Huronian glaciation, the Snowball Earth Event during the Cryogenian, the glacial–interglacial cycles during the Pleistocene, and the period from the last glacial maximum to the late Holocene. Only the change trend of iron bioavailability and climate in the glacial–interglacial cycles is consistent with the Iron Hypothesis. During the GOE and the Snowball Earth periods, although the bioavailability of iron in the ocean and the climate changed dramatically, the changing trend of many factors contradicted the Iron Hypothesis. By detangling the relationship among marine primary productivity, iron availability and oceanic environments in different geological periods, this review can offer some new insights for evaluating the impact of ocean iron fertilization on removing CO2 from the atmosphere and regulating the climate.
The experiences of people with liver disease of palliative and end‐of‐life care in the United Kingdom—A systematic literature review and metasynthesis
Authors: Beresford Cathy J. , Gelling Leslie , Baron Sue , Thompson Linda 
Published: October 2023

AbstractBackgroundLiver disease is a growing health concern and a major cause of death. It causes multiple symptoms, including financial, psychological and social issues. To address these challenges, palliative care can support people alongside active treatment, and towards the end of life, but little is known about the care experiences of individuals with liver disease in the United Kingdom. This review aimed to explore the palliative and end‐of‐life care experiences of people with liver disease in the United Kingdom.MethodA systematic review was conducted using a five‐stage process and following Preferred Reporting Items for Systematic Reviews and Meta Analyses guidelines. Searches were across Web of Science, Scopus, EBSCO and grey literature until 10 May 2023. The review was registered through International Prospective Register of Systematic Reviews (PROSPERO). NVivo 12.5 was used to facilitate data analysis (systematic review registration: PROSPERO CRD42022382649).ResultsOf 6035 papers (excluding duplicates) found from searches, five met the inclusion criteria of primary research related to adults with liver disease receiving palliative and/or end‐of‐life care in the United Kingdom, published in English. Reflexive thematic analysis of the data was conducted. The themes identified were the experiences of people with liver disease of relating to healthcare professionals, using services, receiving support, and experiences of information and communication. These were connected by an overarching concept of disempowerment versus empowerment, with the notion of person‐centred care as an important feature.ConclusionThis review has found variations in the care experiences of people with advanced liver disease towards the end of life and an overall lack of access to specialist palliative care services. Where services are designed to be person‐centred, experiences are more empowering. Further research is needed but with recognition that it is often unclear when care for people with liver disease is palliative or end‐of‐life.Patient and Public ContributionAn online public involvement workshop was held on 18 April 2023 through Voice (2023). This included four people with liver disease and four carers to discuss the review findings and to design a qualitative research study to further explore the topic.
Quick links: Apprenticeship project
Authors: Greenfield Katy 
Published: October 2023

AbstractThis project was designed to support people to find information, resources, and evidence independently within Health Education England (now NHS England Workforce Training and Education) and allow the Knowledge Management team more time to focus on other services offered. This project aimed to pull together a number of resources in to one simple ‘Quick links’ page, with relevant information, resources and further training, providing people with opportunities to build on their own knowledge and skills.
Solar ultraviolet radiation exposure in workers with outdoor occupations: a systematic review and call to action
Authors: Slavinsky Victoria , Helmy John , Vroman Jenna , Valdebran Manuel 
Published: October 2023

AbstractChronic solar ultraviolet radiation (sUVR) exposure leads to an increased incidence of non‐melanoma skin cancer (NMSC) development, particularly when accumulated over decades. Workers in certain industries, such as construction, agriculture, postal workers, and the military, are at higher risk due to cumulative sUVR exposure in their line of work. By assessing the relationship between sUVR exposure in outdoor workers and their skin cancer risk and defining methods of prevention, clinicians can offer focused sun protection counseling to this unique population. PubMed was used to perform a literature review to address the following research questions: 1. How is ultraviolet radiation measured? 2. What is the modern utility of the ultraviolet index in modifying sun protection behaviors in outdoor industry workers? 3. What is the risk of non‐melanoma skin cancer development in individuals working in outdoor occupations? 4. What is the prevalence of skin cancer among outdoor workers? 5. Is the number of nevi and solar lentigines elevated among individuals employed in outdoor occupations? The literature suggests that individuals in outdoor occupations are exposed to UV levels that often surpass safety limits for occupational UVR exposure, increasing their risk of developing skin cancer and precursor and pigmented lesions. Individuals in high‐risk occupations experience significantly higher levels of sUVR exposure than their indoor worker counterparts, increasing their risk of malignant cutaneous transformation. Accordingly, these individuals must be counseled on effective solar protection methods, and employers should advocate for actionable change.
The Perception of the Passage of Time among Death‐Involved Hospital Patients*
Authors: Neuringer Charles , Harris Robert M. 
Published: October 2023

ABSTRACTThe present study attempted to evaluate the extent of the relationship between death involvement and temporal orientation among hospitalized suicidal, terminal, geriatrically ill, and normal patients. Their perception of the passage of time was evaluated by (a) behavioral estimations of elapsed time and (b) a survey of their opinions concerning the passage of time. The latter method included an evaluation of various consequences of the rate of time passage. The results indicated that the suicidal patients, closely followed by the geriatrically ill, overestimated time intervals to a much greater extent than did the normal and terminal patients. The suicidal subjects expressed a great deal of impulsiveness and described themselves as feeling miserable to a much greater degree than did the other groups.
Very high‐power short‐duration catheter ablation for treatment of cardiac arrhythmias: Insights from the FAST and FURIOUS study series
Authors: Heeger Christian‐H. , Kuck Karl‐Heinz , Tilz Roland R. 
Published: October 2023

AbstractThe QDOT MICRO™ Catheter is a novel open‐irrigated contact force‐sensing radiofrequency ablation catheter. It offers very high‐power short‐duration (vHPSD) ablation with 90 W for 4 s to improve safety and efficacy of catheter ablation procedures. Although the QDOT MICRO™ Catheter was mainly designed for pulmonary vein isolation (PVI) its versatility to treat atrial fibrillation (AF) and other types of arrhythmias was recently evaluated by the FAST and FURIOUS study series and other studies and will be presented in this article. Available study and registry data as well as case reports concerning utilization of the QDOT MICRO™ Catheter for the treatment of cardiac arrhythmias including AF, focal and macroreentry atrial tachycardia, typical atrial flutter by cavotricuspid isthmus block, premature ventricular contractions, and accessory pathways were reviewed and summarized. In summary, the QDOT MICRO™ Catheter showed safety and efficacy for PVI and is able to treat also other types of arrhythmias as is was recently evaluated by case reports and the FAST and FURIOUS studies.
Relationship mindfulness, negative relationship quality, and physical health
Authors: Morris Katherine L. , McDowell Chrystal N. , Tawfiq Dania , Outler Carson , Kimmes Jonathan G. 
Published: October 2023

AbstractRomantic relationships have the potential to be a great source of support or a significant stressor depending on the quality of the relationship. Given the importance of these relationships, it is important to explore possible predictors of relationship quality, primarily if such predictors can be targeted in a clinical setting. Relationship mindfulness, or the propensity to be mindful in the setting of a romantic relationship, is one such option. The current study explored the associations between relationship mindfulness, negative relationship quality, and physical health. An online assessment was completed by 116 middle‐aged different‐sex couples that measured the variables of interest. In addition, an Actor‐Partner Interdependence Mediation Model was utilized to determine significant associations between relationship mindfulness, negative relationship quality, and physical health for both actors and partners. The clinical implications are that relationship mindfulness may help to decrease negative relationship quality and subsequently benefit individual physical health.