bluuebunny/crossref_metadata_2025_split huggingface dataset:
2834 Frailty in randomised controlled trials of glucose-lowering therapies for type 2 diabetes
Authors: Wightman H , Butterly E , Wei L , McChrystal R , Sattar N , Adler A , Phillipo D , Dias S , Welton N , Clegg A , Witham M , Rockwood K , McAllister D , Hanlon P 
Published: January 2025

Abstract

Background
The representation of frailty in type 2 diabetes trials is unclear. This study used individual patient data (IPD) from trials of newer glucose-lowering therapies to quantify frailty and assess the association between frailty and efficacy and adverse events.

Method
We analysed IPD from 34 trials of SGLT2 inhibitors, GLP1 receptor agonists and DDP4 inhibitors. Frailty was quantified using a cumulative deficit frailty index (FI). For each trial, we quantified the distribution of frailty; assessed interactions between frailty and treatment efficacy (HbA1c and major adverse cardiovascular events [MACE], pooled using random-effects network meta-analysis); and associations between frailty and withdrawal, adverse events, and hypoglycaemic episodes.

Findings
Trial participants numbered 25,208. Mean age 53·8 to 74·2 years. Using FI &gt; 0·24 to indicate frailty, median prevalence was 1·9% (IQR 0·8% to 6·1%). Prevalence was higher in trials of older people and people with renal impairment. For SGLT2i and GLP1ra, there was a small attenuation in efficacy on HbA1c with increasing frailty (0·07%-point and 0·14%-point smaller reduction, respectively, per 0·1-point increase in FI). Findings for MACE had high uncertainty (few events). A 0·1-point increase in the FI was associated with more adverse events (incidence rate ratio, IRR 1·43, 95% confidence interval 1·34 to 1·53), treatment-related adverse events (1·35, 1·22 to 1·50), serious adverse events (2·04, 1·80 to 2·30), hypoglycaemia (1·18, 1·04 to 1·34), MACE (hazard ratio 3·02, 2·49 to 3·68) and withdrawal (odds ratio 1·45, 1·30 to 1·62).

Interpretation
Frailty is associated very modest attenuation of treatment efficacy for glycaemic outcomes and with greater incidence of both adverse events and MACE. Frailty was rare in most trials. While these findings support calls to relax HbA1c-based targets in people living with frailty, they also highlight the need for inclusion of people living with frailty in trials as the absolute balance of risks and benefits remains uncertain.
2846 How can simulation training be used to teach skills in human factors (HF)?
Authors: Matharu EK , Jegard J , Hague S , Roj B , Kaneshamoorthy M 
Published: January 2025

Abstract

Introduction
Simulation training is a valuable resource to teach clinical skills and mimic emergency settings. Human factors (HF) are non-technical skills that are affected by human attitudes and behaviours. Weaknesses in human factors can cause fatal medical errors. We wanted to assess if simulation can be used as a tool to improve these. We conducted two simulation training days for medical higher specialty trainees (HST) focusing on HF.

Methods
20 HSTs participated in 10 simulated scenarios. Scenarios involved using a high-fidelity manikin and actors. The scenarios were a mixture of long and short cases, including both clinical and non-clinical scenarios with a HF focus. Pre- and post-session questionnaires were used to rate confidence levels in a series of specific HF. A 10-point Likert scale was used.

Results
The majority of participants had a firm understanding of the importance of human factors in healthcare, especially the importance of teamwork, compassion, communication and situational awareness. 70% of participants felt that human factors training may not be adequately considered in current training pathways due to limited formal exposure, limited time, and its importance being underestimated. There was an increase in confidence in: managing disagreements (31%), negative emotions (38%), prioritisation (28%), delegation (23%), teamwork (34%) and leadership skills (30%), dealing with uncertainty (29%), challenging hierarchy (27%), anticipation (31%). 100% felt simulation training helped to develop their attainment of human factor skills.

Conclusion
This form of simulation training was successful in improving confidence and understanding of human factors in healthcare and showcased the value of using high-fidelity training to realistically recreate the clinical environment. Going forward, this type of teaching could be integrated within the specialty training curriculum to formally improve skills in human factors and therefore improve patient outcomes and relationships between team members, thus contributing to a more positive working environment.
Immune-related adverse events in older adults receiving immune checkpoint inhibitors: a comprehensive analysis of the Food and Drug Administration Adverse Event Reporting System
Authors: Esen Buğra Han , Bektas Sevval Nur , Topcu Umur , Köylü Bahadır , Kuvvet Fadime Buket Bayram , Bahat Gulistan , Selçukbiricik Fatih 
Published: January 2025

Abstract

Background
Immune checkpoint inhibitors (ICIs) have revolutionised cancer therapy, yet they carry a unique spectrum of immune-related adverse events (irAEs). Given the ageing global population and the underrepresentation of older adults in clinical trials for ICIs, we investigated the occurrence and characteristics of irAEs in older versus younger adults as well as among different age subsets within the older adult population.

Methods
We analysed the U.S. Food and Drug Administration Adverse Event Reporting System database reports from 2015 to 2023, focusing on ICIs. We categorised irAEs into 11 distinct types and performed descriptive and multivariate analyses to compare the prevalence and clinical characteristics of irAEs across different age groups, adjusting for potential confounding factors.

Results
Among 47 513 patients aged 18–100 reporting irAEs, the 65–74 and 75–84 age groups had significantly increased risks compared to 18–64 (OR 1.13, 95% CI [1.09–1.18]; 1.15 [1.1–1.21]). Cardiovascular irAEs rose with age, peaking at 75–84, while endocrine irAEs decreased. Hepatobiliary, gastrointestinal and ocular irAEs decreased with age, but renal and musculoskeletal irAEs increased, showing higher risks in older adults. Serious outcomes slightly decreased in the 85+ group, while the proportion of deaths increased with age.

Conclusion
We discuss the potential changes in the immune system contributing to the decreased prevalence of irAEs in the oldest age group. Additionally, conservative treatment approaches and underreporting of irAEs in older patients may influence these findings. Our findings highlight the need for personalised decision-making for ICI therapies, considering performance status and comorbidities rather than age alone.
Goals of care discussions and treatment limitation decisions in European acute geriatric units: a one-day cross-sectional study
Authors: Piers Ruth , Pautex Sophie , Rexach Cano Lourdes , Leners Jean-Claude , Vali Ahmed Marc , De Brauwer Isabelle , Kayhan Koçak Fatma Ö , Hrnciarikova Dana , Cwynar Marcin , Alves Mariana , Pilgram Erwin H , van Bruchem-Visser Rozemarijn L 
Published: January 2025

Abstract

Background
It is important to pursue goal-concordant care and to prevent non-beneficial interventions in older people.

Aim
To describe serious illness communication and decision-making practices in hospitalised older people in Europe.

Setting/participants
Data on advance directives, goals of care (GOC) discussions and treatment limitation decisions were collected about patients aged 75-years and older admitted to 23 European acute geriatric units (AGUs).

Results
In this cohort of 590 older persons [59.5% aged 85 and above, 59.3% female, median premorbid Clinical Frailty Score (CFS) 6], a formal advance directive was recorded in 3.3% and a pre-hospital treatment limitation in 14.0% with significant differences between European regions (respectively P &lt; 0.001 and P = 0.018).
Most prevalent GOC was preservation of function (46.8%). GOC were discussed with patients in 64.0%, with families in 73.0%, within the interprofessional hospital team in 67.0% and with primary care in 13.4%. The GOC and the extent to which it was discussed differed between European regions (both P &lt; 0.001). The prevalence of treatment limitation decisions was 53.7% with a large difference within and between countries (P &lt; 0.001). The odds of having a treatment limitation decision were higher for patients with pre-hospital treatment limitation decisions (OR 39.1), residing in Western versus Southern Europe (OR 4.8), belonging to an older age category (OR 3.2), living with a higher number of severe comorbidities (OR 2.2) and higher premorbid CFS (OR 1.3).

Conclusions
There is large variability across European AGUs concerning GOC discussions and treatment limitation decisions. Sharing of information between primary and hospital care about patient preferences is noticeably deficient.
Impact of Sensitive Skin on Quality of Life, Anxiety, and Depression: A Cross-Sectional Study
Authors: Park Jinseo , Cameron Shona , Flohr Carsten , Choi Mingyu , Lee Soyeon , Chung Boyoung , Park Chunwook , Kim Hyeone 
Published: January 2025

Abstract

Background
Sensitive skin (SS) is a common condition reported by many people worldwide. Patient interviews reveal that individuals with SS experience diminished quality of life, anxiety, and depression. Nonetheless, the impact of SS on mental health remains unclear.

Objective
To assess whether SS affects mental health and the relationship between symptom severity and its impact.

Methods
A cross-sectional study was conducted at Hallym University Kangnam Sacred Heart Hospital, Seoul, Korea, between June 2022 and March 2023. The Sensitive-Scale 10 (SS-10) was used for SS diagnosis and severity scoring; the Dermatology Life Quality Index (DLQI) and the Hospital Anxiety and Depression Scale (HADS) assessed mental health. Participants were categorized as ‘non-sensitive’ (&lt;20), ‘sensitive’ (20–49), and ‘extremely sensitive’(≥50) based on SS-10 scores. Objective measurements included transepidermal water loss (TEWL), stratum corneum hydration (SCH), erythema, and demodex density.

Results
Of 200 participants, 146 completed the study. Participants were predominantly female (79.45%) with a mean age of 36.86 years (SD = 12.25). DLQI scores were higher in more sensitive groups (non-sensitive: 6.25, sensitive: 14.46, extremely sensitive: 18.86; P &lt;.001). HADS-A and HADS-D scores also increased with severity (HADS-A: 4.94 in non-sensitive to 7.80 in extremely sensitive, HADS-D: 3.88 to 8.54; P &lt;.05 for HADS-A, P &lt;.001 for HADS-D). DLQI was significantly influenced by discomfort and redness, HADS-A by TEWL (negatively) and flushes, and HADS-D by flushes.

Conclusion
SS is associated with lower quality of life and increased anxiety and depression. Symptoms of sensitive skin substantially impact patients’ psychological well-being.
Synthesis of amide-terminated cis-stereoregular polyacetylenes
Authors: Adriani Nina , Echizen Kensuke , Nishimura Tatsuya , Maeda Katsuhiro , Taniguchi Tsuyoshi 
Published: January 2025

Abstract
Inspired by the reaction between organorhodium species and isocyanates to give amides, we have developed a new method of the synthesis of cis-stereoregular amide-terminated polyacetylene derivatives using isocyanates as terminating reagents in rhodium-mediated living polymerization of acetylene derivatives. The present termination reaction was applied to phenylacetylene derivatives having pendant functional groups and a nonaromatic N-propargylamide to provide the corresponding amide-terminated cis-stereoregular polyacetylenes.
Experimental evidence of bargaining power in agricultural land markets
Authors: Kionka Marlene , Kuethe Todd , Mußhoff Oliver , Ritter Matthias , Odening Martin 
Published: January 2025

Abstract
There is public concern about the degree to which rising farmland rental rates are driven by the perceived market influence of non-agricultural actors. We conduct a structural estimation to analyse the potential bargaining power of different types of actors in the farmland market. It allows us to infer their latent reservation utilities by exploiting equilibrium conditions, derived from a stochastic ultimatum game. Reservation utilities reflect outside options in negotiations, as they are determinants of bargaining power. We conduct economic experiments in the rental market. Our findings show that farmers and local actors have more bargaining power than non-farmers and absentee actors, respectively.
High burden of abnormal cervical smears in South African primary health care: health programmes implications
Authors: Omole Olufemi B , Francis Joel M , Musonda John M , Sodo Pumla P , Reji Elizabeth , Phukuta Nyundu S J , Mabuza Honey L M , Musonda Joyce S , Akii Jimmy , Ndimande John V , Ayo-Yusuf Olalekan A 
Published: January 2025

Abstract
Cervical cancer is the second most common malignancy among South African women and the load of abnormal cervical smears has clinical, programmatic and policy implications. This cross-sectional study of women who presented for cervical cancer screening aimed to determine the prevalence of abnormal cervical smears and associated factors in primary health care (PHC) facilities in Gauteng—the most densely populated province in South Africa. A questionnaire collected data on socio-demography, tobacco use, sexual behaviours, HIV status, past treatment for sexually transmitted infections (STI) and cervical cancer screening in the past 10 years. Cytology reports were extracted from the laboratory reports. Of 749 participants, most were black (89.7%), aged 30–49 years (62.2%), single (57.5%) and attained high school education (76.8%). About 43.9% were HIV positive with almost all (97.2%) on antiretroviral therapy. Cytology results were available for 612 (81.9%) participants. Of these, 25.8% (159) were abnormal: 13.2% low-grade squamous intraepithelial lesion; 5.7% atypical squamous cells of undetermined significance and 4.9% high-grade squamous intraepithelial lesion. In bivariate and multivariable analysis, abnormal cervical cytology was not associated with any sociodemographic characteristics, HIV status, tobacco use status, sexual behaviours or past treatment for STI. In conclusion, the prevalence of abnormal cervical smears is high across all demographic groups and irrespective of HIV status and highlights the need to increase screening uptake, including advocacy for self-sampling. It also calls for capacity building to allow for the devolution of some downstream clinical care from specialist to district hospitals and large PHC facilities.
Dynamics of bacterial growth, and life-history tradeoffs, explain differences in soil carbon cycling due to land-use
Authors: Wattenburger Cassandra J , Wang Evangeline , Buckley Daniel H 
Published: January 2025

Abstract
Soil contains a considerable fraction of Earth’s organic carbon. Bacterial growth and mortality drive the microbial carbon pump, influencing carbon use efficiency and necromass production, key determinants for organic carbon persistence in soils. However, bacterial growth dynamics in soil are poorly characterized. We used an internal standard approach to normalize 16S ribosomal RNA gene sequencing data allowing us to quantify growth dynamics for 30 days following plant litter input to soil. We show that clustering taxa into three groups optimized variation of bacterial growth parameters in situ. These three clusters differed significantly with respect to their lag time, growth rate, growth duration, and change in abundance due to growth (ΔNg) and mortality (ΔNd), matching predictions of Grime’s CSR life-history framework. In addition, we show a striking relationship between ΔNg and ΔNd, which reveals that growth in soil is tightly coupled to death. This result suggests a fitness paradox whereby some bacteria can optimize fitness in soil by minimizing mortality rather than maximizing growth. We hypothesized that land-use constrains microbial growth dynamics by favoring different life-history strategies and that these constraints control carbon mineralization. We show that life-history groups vary in prevalence with respect to land-use, and that bacterial growth dynamics correlated with carbon mineralization rate and net growth efficiency. Meadow soil supported more bacterial growth, greater mortality, and higher growth efficiency than agricultural soils, pointing toward more efficient conversion of plant litter into microbial necromass, which should promote long-term C stabilization.
Information-blocking trends following regulatory action
Authors: Everson Jordan , Healy Daniel 
Published: January 2025

Abstract

Objective
To describe the prevalence of and trends in practices that interfere with the exchange of patient health information (potential information blocking) 2 years after implementation of information-blocking regulations.

Materials and Methods
Drawing from the American Hospital Association Information Technology (IT) Supplement and a national survey of health information organizations (HIOs), we described rates and methods of potential information blocking from these organizations’ perspectives in 2023 and compared them to prior years.

Results
Twenty-seven percent of hospitals sometimes or often observed potential information blocking by any actor in 2023, down from 42% in 2021 and 33% in 2022. Thirty percent of HIOs routinely observed potential information blocking by health IT developers, down from 50% in 2015. 13% of HIOs routinely observed potential information blocking by hospitals and health systems, down from 25% in 2015. According to both hospitals and HIOs, the most prevalent method of potential information blocking by developers in 2023 was through price, while the most prevalent by healthcare providers/health systems was by focusing exchange on strategic affiliations. Few hospitals and HIOs that experienced potential information blocking said that they had reported it to the Department of Health and Human Services.

Discussion
Hospitals and HIOs perceived lower rates of potential information blocking in 2023 than in prior years indicating some impact of regulations addressing information blocking. However, both respondent types reported that substantial potential information blocking persisted in 2023 and negatively impacted the exchange of information.

Conclusion
While potential information-blocking practices have decreased, they have not been eliminated, indicating the value of continued and robust enforcement of information-blocking regulations.
Biocatalytic diversification of abietic acid in Streptomyces
Authors: McCadden Caitlin A , Alsup Tyler A , Ghiviriga Ion , Rudolf Jeffrey D 
Published: January 2025

Abstract

Biocatalysis provides access to synthetically challenging molecules and commercially and pharmaceutically relevant natural product analogs while adhering to principles of green chemistry. Cytochromes P450 (P450s) are among the most superlative and versatile oxidative enzymes found in nature and are desired regio- and stereoselective biocatalysts, particularly for structurally complex hydrocarbon skeletons. We used 10 genome-sequenced Streptomyces strains, selected based on their preponderance of P450s, to biotransform the bioactive diterpenoid abietic acid. We isolated and structurally characterized seven oxidized abietic acid derivatives from three different strains, including four products that are new bacterial biotransformants or enzymatic products. Oxidations (hydroxylation, dehydrogenation, and aromatization) were seen on both the B and C rings of abietic acid and five products had multiple modifications. Notable conversions observed in the study were that of abietic acid to 15-hydroxy-7-oxo-8,11,13-abietatrien-18-oic acid, 7, which involves multiple hydroxylation reactions and dehydrogenation. The findings from this study will lead to identifying P450s or other enzymes that may act as general biocatalysts to modify abietanes and other labdane-type diterpenoid skeletons.

One-Sentence Summary
Genome-guided biotransformation of the bioactive diterpenoid abietic acid in Streptomyces yielded seven oxidized derivatives including four that have not been previously seen from bacteria.
Adult Neurogenesis
Authors: Shtrahman Matthew , Parylak Sarah L. , Toda Tomohisa , Gage Fred H. 
Published: January 2025

Abstract
This chapter explores the field of adult neurogenesis. It explains adult-born dentate granule cells (DGCs) are generated throughout most of the mammalian class, likely including humans. Many of the key molecular signals orchestrating the generation of adult-born DGCs guide a developmental program in which new neurons form functional connections with the existing hippocampal circuitry. The chapter discusses the goal of developing noninvasive tools for monitoring neurogenesis and understanding how this process is altered with aging and various disease states. It notes the possibility of understanding the regenerative potential of the neurogenic niche to improve memory and mood while treating psychiatric and neurological disorders.
Stress and the Hippocampus
Authors: McEwen Bruce S. , Chattarji Sumantra 
Published: January 2025

Abstract
This chapter describes how stress affects the hippocampus across biological scales. The discovery of stress hormone receptors in the hippocampus provided a gateway into studying structural and functional plasticity of the developing, adult, and aging hippocampus. The same framework has been utilized for studies of other brain areas that interact with the hippocampus in the context of stress effects on the brain, such as the amygdala and prefrontal cortex. It also outlines findings that have broadened the definition of stress to include epigenetic factors, immune system mediators, and sex and metabolic hormones, that determine how the brain and body interact with each other. It discusses the concepts of allostasis and allostatic load that include adaptations to a changing environment, and to health-promoting and health-damaging behaviors.
Faces of Clinical Depression
Authors: Fogel Barry S. , Jiang Xiaoling 
Published: January 2025

Abstract
Current diagnostic criteria for major depressive disorder (MDD) do not capture the diversity of phenotypes of clinically significant depression. Culture can entail suppression, normalization, or concealment of depressive symptoms. Clinically depressed people who are “subsyndromal” by MDD criteria often fall in a “middle zone” between normal negative emotion and frank mental illness. Alternative criteria for clinical depression are proposed that better accommodate cultural differences as well as variations in personality and pathophysiology. Such criteria validate the illness of people whose subsyndromal depression entails functional impairment, persistent distress, or suicide risk. Appreciation of middle zone depression by clinicians and the public could reduce the stigma of depression and facilitate its timely treatment. Questionnaire-based screening tests like the nine-item Patient Health Questionnaire, the Center for Epidemiologic Studies Depression Scale, and the Beck Depression Inventory function better if cut points are modified according to culture and if their translations from English to other languages consider connotations as well as explicit meanings of items.