bluuebunny/crossref_metadata_2025 huggingface dataset:
Symbiont plasticity as a driver of plant success
Authors: Zobel Martin , Koorem Kadri , Moora Mari , Semchenko Marina , Davison John
Published: February 2024

We discuss which plant species are likely to become winners, that is achieve the highest global abundance, in changing landscapes, and whether plant‐associated microbes play a determining role. Reduction and fragmentation of natural habitats in historic landscapes have led to the emergence of patchy, hybrid landscapes, and novel landscapes where anthropogenic ecosystems prevail. In patchy landscapes, species with broad niches are favoured. Plasticity in the degree of association with symbiotic microbes may contribute to broader plant niches and optimization of symbiosis costs and benefits, by downregulating symbiosis when it is unnecessary and upregulating it when it is beneficial. Plasticity can also be expressed as the switch from one type of mutualism to another, for example from nutritive to defensive mutualism with increasing soil fertility and the associated increase in parasite load. Upon dispersal, wide mutualistic partner receptivity is another facet of symbiont plasticity that becomes beneficial, because plants are not limited by the availability of specialist partners when arriving at new locations. Thus, under conditions of global change, symbiont plasticity allows plants to optimize the activity of mutualistic relationships, potentially allowing them to become winners by maximizing geographic occupancy and local abundance.
Content analysis of oral (mouth) cancer‐related posts on Instagram
Authors: Al Karadsheh Omar , Atef Alaa , Alqaisi Dua’a , Zabadi Siraj , Hassona Yazan
Published: February 2024

Objective

To examine the content of Instagram posts about oral cancer and assess its usefulness in promoting oral cancer awareness and early detection practices.

Methods

A systematic search of Instagram for posts about oral (mouth) cancer was conducted using the hashtags #oral cancer and #mouth cancer. Posts usefulness in promoting awareness and early detection was assessed using the early detection usefulness score, and caption readability was assessed using the Flesch Kincaid readability score.

Results

A total of 81,000 posts were identified, and 200 posts were thoroughly evaluated. Included posts gathered a total of 48,118 (mean = 420.59 likes) and 27,898 views. Most posts (81.5%) were educational to the lay person, and India and the UK were the major contributors. The most discussed topics were prevention and early detection (55%). Representative clinical images were present in 35.5% of posts. Only 9.5% of posts mentioned the source of information, and the mean usefulness score was only 2.1 out of 10. The mean reading ease score was 56.7 ± 43.8 (range from 1 to 98 out of 100).

Conclusion

Instagram shows potential for promoting oral cancer awareness, particularly in prevention and early detection. However, concerns regarding content quality, scientific validity, and clarity persist.
A data‐driven adaptive geospatial hotspot detection approach in smart cities
Authors: Yan Yuchen , Quan Wei , Wang Hua
Published: February 2024

Hotspot detection from geo‐referenced urban data is critical for smart city research, such as traffic management and policy making. However, the classical clustering or classification approach for hotspot detection mainly aims at identifying “hotspot areas” rather than specific points, and the setting of global parameters such as search bandwidth can lead to inaccurate results when processing multi‐density urban data. In this article, a data‐driven adaptive hotspot detection (AHD) approach based on kernel density analysis is proposed and applied to various spatial objects. The adaptive search bandwidth is automatically calculated depending on the local density. Window detection is used to extract the specific hotspots in AHD, thus realizing a small‐scale characterization of urban hotspots. Through the trajectory data of Harbin City taxis and New York City crime data, Geo‐information Tupu is used to analyze the obtained specific hotspots and verify the effectiveness of AHD, providing new ideas for further research.
CPK28 is a modulator of purinergic signaling in plant growth and defense
Authors: Sowders Joel M. , Jewell Jeremy B. , Tanaka Kiwamu
Published: February 2024

Extracellular ATP (eATP) is a key signaling molecule that plays a pivotal role in plant growth and defense responses. The receptor P2K1 is responsible for perceiving eATP and initiating its signaling cascade. However, the signal transduction mechanisms downstream of P2K1 activation remain incompletely understood. We conducted a comprehensive analysis of the P2K1 interactome using co‐immunoprecipitation‐coupled tandem mass spectrometry, leading to the identification of 121 candidate proteins interacting with P2K1. In silico analysis narrowed down the candidates to 47 proteins, including Ca2+‐binding proteins, ion transport‐related proteins, and receptor kinases. To investigate their involvement in eATP signaling, we employed a screening strategy based on changes in gene expression in response to eATP in mutants of the identified interactors. This screening revealed several Ca2+‐dependent protein kinases (CPKs) that significantly affected the expression of eATP‐responsive genes, suggesting their potential roles in eATP signaling. Notably, CPK28 and CPK6 showed physical interactions with P2K1 both in yeast and plant systems. Calcium influx and gene expression studies demonstrated that CPK28 perturbed eATP‐induced Ca2+ mobilization and some early transcriptional responses. Overexpression of CPK28 resulted in an antagonistic physiological response to P2K1‐mediated eATP signaling during both plant growth and defense responses to the necrotrophic pathogen Botrytis cinerea. Our findings highlight CPK28, among other CPKs, as a modulator of P2K1‐mediated eATP signaling, providing valuable insights into the coordination of eATP signaling in plant growth and immunity.
Development of pro‐angiogenic skin substitutes for wound healing
Authors: Song Hengyue , Hao Dake , Zhou Jianda , Farmer Diana , Wang Aijun
Published: February 2024

Wounds pose significant challenges to public health, primarily due to the loss of the mechanical integrity and barrier function of the skin and impaired angiogenesis, causing physical morbidities and psychological trauma to affect patients. Reconstructing the vasculature of the wound bed is crucial for promoting wound healing, reducing scar formation and enhancing the quality of life for patients. The development of pro‐angiogenic skin substitutes has emerged as a promising strategy to facilitate vascularization and expedite the healing process of burn wounds. This review provides an overview of the various types of skin substitutes employed in wound healing, explicitly emphasising those designed to enhance angiogenesis. Synthetic scaffolds, biological matrices and tissue‐engineered constructs incorporating stem cells and primary cells, cell‐derived extracellular vesicles (EVs), pro‐angiogenic growth factors and peptides, as well as gene therapy‐based skin substitutes are thoroughly examined. The review summarises the existing challenges, future directions and potential innovations in pro‐angiogenic dressing for skin substitutes. It highlights the need for continued research to develop new technologies and combine multiple strategies and factors, and to overcome obstacles and advance the field, ultimately leading to improved outcomes for wound patients.
Principles of synaptic encoding of brainstem circadian rhythms
Authors: Ragozzino Forrest J. , Karatsoreos Ilia N. , Peters James H.
Published: February 2024

Circadian regulation of autonomic tone and reflex pathways pairs physiological processes with the daily light cycle. However, the underlying mechanisms mediating these changes on autonomic neurocircuitry are only beginning to be understood. The brainstem nucleus of the solitary tract (NTS) and adjacent nuclei, including the area postrema and dorsal motor nucleus of the vagus, are key candidates for rhythmic control of some aspects of the autonomic nervous system. Recent findings have contributed to a working model of circadian regulation in the brainstem which manifests from the transcriptional, to synaptic, to circuit levels of organization. Vagal afferent neurons and the NTS possess rhythmic clock gene expression, rhythmic action potential firing, and our recent findings demonstrate rhythmic spontaneous glutamate release. In addition, postsynaptic conductances also vary across the day producing subtle changes in membrane depolarization which govern synaptic efficacy. Together these coordinated pre‐ and postsynaptic changes provide nuanced control of synaptic transmission across the day to tune the sensitivity of primary afferent input and likely govern reflex output. Further, given the important role for the brainstem in integrating cues such as feeding, cardiovascular function and temperature, it may also be an underappreciated locus in mediating the effects of such non‐photic entraining cues. This short review focuses on the neurophysiological principles that govern NTS synaptic transmission and how circadian rhythms impacted them across the day.
Competencias TIC en profesores de comunicación en tiempos de COVID-19
Authors: Quintero-León Margarita , Ortiz Záccaro Zulma Zoraida , Díaz-Santana Daivy Dalila , Espinel Rubio Gladys Adriana , Bohórquez-Pereira Giovanni , Baltar-Moreno Adolfo
Published: February 2024

Se exploran las percepciones de los estudiantes sobre las competencias digitales de sus docentes en cinco universidades de Colombia. La metodología aplicada es cuantitativa, con una encuesta aplicada a 606 estudiantes de comunicación social, quienes evaluaron las competencias (comunicativa, TIC y pedagógica) de los profesores de acuerdo con lo establecido por el Ministerio de Educación Nacional, desde tres niveles de dominio: explorador, integrador e innovador. Los docentes fueron valorados positivamente, siendo la competencia comunicativa la que obtuvo mayor registro (91,30 %). Se propone transitar, del aprendizaje de la tecnología, al aprendizaje con la tecnología.
El deber de declaración-respuesta en los seguros de vida y enfermedad: entre el fraude del asegurado y la negligencia del asegurador
Authors: Carbajo Cascón Fernando
Published: February 2024

La declaración de riesgo previa a la contratación de una póliza de seguro es un deber legal del tomador o asegurado en los contratos de seguro que se hace más relevante si cabe en los seguros de vida y enfermedad. Pero la declaración precontractual de riesgo se convierte en un deber compartido en la medida en que requiere necesariamente del concurso diligente de la compañía aseguradora con la presentación de un cuestionario riguroso y, en su caso, con la ayuda de los empleados al tomador para diligenciar dicho documento. Tanto la ocultación maliciosa de información por parte del tomador como la negligencia de la compañía en la presentación de un cuestionario suficiente y la ayuda para diligenciarlo provocan conflictos entre las partes que son resueltos por los tribunales de justicia, lo que ha dado pie a una rica Jurisprudencia fundamental para interpretar el contenido y alcance del deber precontractual de conducta compartida entre tomador y asegurador.
Omisiones del asegurado y reticencia. impacto en el contrato de seguros en las legislaciones española y costarricense
Authors: Arias Mora Nancy
Published: February 2024

Las declaraciones que deben hacer los consumidores de seguros, contienen implícita la obligación de decir verdad en cumplimiento del principio de máxima buena fe que informa los contratos de seguros. Los ordenamientos jurídicos incluyen la sanción ante el incumplimiento de ésta.

La sanción para el asegurado, siendo la parte débil del contrato, hace que pierda el derecho a la indemnización y, en algunos casos, implica la nulidad del contrato, con lo cual además pierde la prima que ha pagado.

En contraposición, no se encuentra establecida legalmente la obligación de hacer una buena selección del riesgo por parte de las aseguradoras pues ante la reticencia del asegurado, se liberan del pago de la indemnización y en ocasiones, retener las primas pagadas.

Se compara la legislación española con la costarricense, reflexionando sobre el desequilibrio que genera la reticencia para el consumidor y sus derechos frente a la aseguradora.
ODS 3, Legal Design y nuevas tecnologías en seguros de vida y salud
Authors: Novaes da Silva Anthony Charles de , Acosta Olivo Carlos
Published: February 2024

Este trabajo explora el Objetivo de Desarrollo Sostenible 3 (ODS 3) respecto a garantizar una vida sana y promover el bienestar para todas las personas, basándose en el potencial transformador de las nuevas tecnologías y la innovación en el ámbito de los seguros de vida y salud.

A través de un enfoque interdisciplinar, este documento explora las sinergias entre el ODS3, el legal design y las nuevas tecnologías, a ejemplo de la Inteligencia Artificial, destacando su potencial para revolucionar el sector de los seguros de vida y salud. De esta manera, el sector de los seguros puede desempeñar un papel fundamental en el avance del ODS 3 y en el avance del bienestar general de las personas y la comunidad a nivel mundial.
La subrogación del reasegurador en Colombia
Authors: Coronado Sabogal Diego Alejandro
Published: February 2024

Atendiendo la evolución jurídica y negocial del reaseguro, las vicisitudes judiciales que ha enfrentado recientemente el gremio reasegurador en Colombia y la creciente colocación de programas de seguros mediante el esquema del fronting, resulta oportuno examinar la posibilidad que tiene el reasegurador de subrogarse en la posición de la compañía aseguradora (cedente), con el fin de ejercer sus derechos litigiosos en contra del responsable del siniestro, una vez el asegurado original es efectivamente indemnizado. El presente escrito, procura auscultar y esclarecer los posibles caminos para ejercer una eventual subrogación por parte del reasegurador bajo la legislación colombiana, tratándose de un tema que ha sido parcialmente explorado por la doctrina nacional y que apunta a convertirse en una herramienta de vital repercusión para el reasegurador en la etapa post-siniestral, es decir, una vez reconocida la indemnización derivada del contrato de reaseguro a la cedente (compañía de seguros) o directamente al asegurado original.
El seguro sobre la vida. Aspectos neurálgicos
Authors: Jaramillo J. Carlos Ignacio
Published: February 2024

El propósito del presente escrito, estriba en abordar los aspectos más salientes del seguro sobre la vida, sabedores de que este tipo aseguraticio, ciertamente, es uno de los más resonantes, a la par que de amplio espectro temático, motivo por el cual, por entendibles razones de espacio, no podremos auscultar toda su problemática, a plenitud, como lo hubiéramos deseado. Ello explica, en consecuencia, su indicativo rótulo: 'El seguro sobre la vida. Aspectos neurálgicos'.

Por consiguiente, conscientes de la descrita realidad, abordaremos entonces los temas más neurálgicos de tan trascendente seguro, el que sin perjuicio de existir hace varias centurias, stricto sensu, y de traducirse en uno de los más grandilocuentes, signado por su indiscutida función social, sigue ocupando, y con razón, un sitial de preferencia en la esfera aseguraticia y reaseguraticia nacional e internacional.

De ahí, en concreto, que analizaremos temas tales como su importancia preliminar, sus antecedentes históricos (primera y segunda etapa), su marco normativo, su noción aproximativa, su naturaleza, las partes contratantes, y el régimen concerniente al beneficiario, tanto en el Derecho colombiano, como en el Derecho comparado, en lo pertinente.
Fragility Analysis and Resilience Assessment of the Single-Column Pier Steel-Concrete Composite Bridge Subjected to Seismic Loads
Authors: Wang Tong , Gao Qingfei , Dong Yidian , Xu Hao , Liu Yang
Published: February 2024

With the advantages of a small footprint, wide under-bridge view, and beautiful appearance, single-column pier bridges are widely used in urban bridge networks. However, single-column pier bridges are prone to damage during earthquakes or heavy vehicle use, which can seriously affect normal operations and postdisaster recoveries. Therefore, there is an urgent need to carry out seismic resilience assessments of single-column pier bridges and formulate disaster prevention and mitigation measures from the aspects of design, maintenance, and postearthquake recovery. This paper first establishes a resilience assessment framework for the single-column pier bridge and optimizes a functionality recovery model after an earthquake. Then, a numerical model of a sample bridge is built for resilience fragility analysis. Nonlinear dynamic time history analysis is performed to build a probabilistic seismic demand model, and moment–curvature analysis is performed to build a probabilistic seismic capacity model. Finally, a seismic resilience assessment of the single-column pier bridge is obtained based on the seismic fragility, and a sensitivity analysis is carried out for the pier height, pier section dimension, span and vehicle load level to improve the resilience of the single-column pier bridge.
Generation of streptocarbazoles with cytotoxicities by pathway engineering and insights into their biosynthesis
Authors: Xiao Fei , Xu Mingyuan , Cheng Yongmeng , Li Tong , Hong Kui , Li Wenli
Published: February 2024

Streptocarbazoles are a class of indolocarbazole (ICZ) compounds produced by
Streptomyces
strains that feature unique cyclic
N
-glycosidic linkages between the 1,3-carbon atoms of the glycosyl moiety and the two indole nitrogen atoms. Although several streptocarbazole compounds display effective cytotoxic activity, their biosynthesis remains unclear. Herein, through the inactivation of the aminotransferase gene
spcI
in the staurosporine biosynthetic gene cluster
spc
followed by heterologous expression, two new streptocarbazole derivatives (
1
and
3
) and three known ICZs (
2
,
4
, and
5
) were generated. Their structures were determined by a combination of spectroscopic methods, circular dichroism measurements, and single-crystal X-ray diﬀraction. Compounds
1–4
displayed moderate cytotoxicity against HCT-116 cell line, and compounds
3
and
4
were effective against Huh 7 cell line. Double-gene knockout experiments allowed us to propose a biosynthetic pathway for streptocarbazole productions. Furthermore, by overexpression of the involving key enzymes, the production of streptocarbazoles
1
and
3
were improved by approximately 1.5–2.5 fold.

IMPORTANCE

Indolocarbazoles (ICZs) are a group of antitumor agents, with several analogs used in clinical trials. Therefore, the identification of novel ICZ compounds is important for drug discovery. Streptocarbazoles harbor unique
N
-glycosidic linkages (N13-C1′ and N12-C3′), distinguishing them from the representative ICZ compound staurosporine; however, their biosynthesis remains unclear. In this study, two new streptocarbazoles (
1
and
3
) with cytotoxic activities were obtained by manipulating the staurosporine biosynthetic gene cluster
spc
followed by heterologous expression. The biosynthetic pathway of streptocarbazoles was proposed, and their productions were improved through the overexpression of the key enzymes involved. This study enriches the structural diversity of ICZ compounds and would facilitate the discovery of new streptocarbazoles via synthetic biological strategies.
Measuring patients’ experience of nursing quality in acute hospitals: review of existing scales and development and psychometric validation of a new scale
Authors: Blume Kai Svane , Kirchner-Heklau Uta , Winter Vera , Meyer Gabriele , Fleischer Steffen
Published: February 2024

Objective

To provide an overview of existing instruments measuring patient-perceived quality of nursing care and to develop and psychometrically evaluate a new multidimensional scale applicable to the German acute care sector.

Design

We conducted a scale development and validation study involving the following phases: (1) performing a structured literature search to identify existing scales, (2) generating an initial pool of items using the results of the literature search and expert interviews, (3) coding/categorising the item pool, (4) organising a peer researcher workshop to select relevant items, (5) drafting the survey questionnaire and conducting cognitive pretesting, (6) pilot testing the survey questionnaire, (7) administering the survey to a large sample of hospital patients and (8) conducting a psychometric evaluation comprising exploratory factor analysis using the survey results, followed by confirmatory factor analysis and reliability and validity assessment of the resulting draft scale.

Survey participants

17 859 recently hospitalised patients discharged from non-intensive care in non-paediatric and non-psychiatric hospital units in Germany between May and October 2019.

Results

We identified 32 instruments comprising 635 items on nursing care quality. Alongside 135 indicators derived from expert interviews, these formed our initial item pool, which we coded into 15 categories. From this pool, 36 items were selected in the peer researcher workshop for pretesting and psychometric evaluation. Based on the results of our exploratory and confirmatory factor analyses, we propose a second-order scale to measure Patients’ Experience of Nursing Quality in Acute Hospitals (PENQuAH), including the two higher-order dimensions ‘patients’ perception of direct nursing care activities’ and ‘patients’ perception of guidance provided by nurses’. The results of various tests suggest the scale has sufficient goodness of fit, reliability and validity.

Conclusions

The PENQuAH scale is promising in terms of its psychometric properties, the plausibility and meaningfulness of its dimensions, and its ease of use.
Pivotal relationship between heavy metal, PM2.5exposures and tuberculosis in Bangladeshi children: protocol paper of a case–control study
Authors: Haque Rehnuma , Hanson Molly , Shariful Islam Md , Akter Nazrin , Moniruzzaman Mohammad , Alam Md Jahangir , Kamruzzaman Md , Rahman Mahbubur , Chisti Mohammod Jobayer , Raqib Rubhana , Rahman Syed Moshfiqur
Published: February 2024

Introduction

Air pollution is a global issue that poses a significant threat to public health. Children, due to their developing physiology, are particularly susceptible to the inhalation of environmental pollutants. Exposure can trigger immune modulation and organ damage, increasing susceptibility to respiratory diseases. Therefore, we aim to examine the association between heavy metal and particulate matter exposure with tuberculosis in children.

Methods and analysis

As a case–control study, we will include children diagnosed with pulmonary tuberculosis (n=60) and matched healthy controls (n=80) recruited from the same communities in Dhaka, Bangladesh. Exposure data for both cases and controls will be collected by a trained field team conducting home visits. They will administer an exposure questionnaire, measure child anthropometry, collect blood and household dust samples and instal 48-hour air quality monitors. The blood samples will be analysed by inductively coupled plasma mass spectrometry for serum heavy metal concentrations (lead, cadmium, arsenic, mercury and chromium), as a representative marker of exposure, and the presence of inflammatory biomarkers. Descriptive and inferential statistics, including independent samples t-tests, analysis of variance and conditional regression analysis, will be used to quantify heavy metal and particulate matter exposure status in tuberculosis cases compared with healthy controls, while accounting for potential confounders. Dust samples and air quality results will be analysed to understand household sources of heavy metal and particulate matter exposure. To test the study hypothesis, there is a positive association between exposure and tuberculosis diseases, we will also measure the accumulated effect of simultaneous exposures using Bayesian statistical modelling.

Ethics and dissemination

This study has been approved by International Centre for Diarrhoeal Disease Research, Bangladesh’s Institutional Review Board (PR-22030). The study findings will be disseminated at conferences and published in peer-reviewed journals.
Elevated prevalence and treatment of sleep disorders from 2011 to 2020: a nationwide population-based retrospective cohort study in Korea
Authors: Ahn Eunkyoung , Baek Younghwa , Park Ji-Eun , Lee Siwoo , Jin Hee-Jeong
Published: February 2024

Objectives

This study used National Health Insurance claims data from Korea to report the prevalence of sleep disorders and treatment status, including traditional Korean medicine, in the last 10 years.

Methods

This is a retrospective cohort study in Korea. All diagnosis and prescription data, including herbal medicine claims, from the Health Insurance Review and Assessment Service from 2011 to 2020 were reviewed. Prevalence estimation, direct medical expenses and prescribed amounts for sleep disorders were recorded.

Results

The prevalence of sleep disorders increased from 3 867 975 (7.62%) in 2011 to 7 446 846 (14.41%) in 2020, nearly doubling over 10 years. Insomnia was observed in 91.44% (n=9 011 692) of the patients. The mean number of hospital visits per patient for sleep disorders was 11.5 (±26.62). Benzodiazepines are the most commonly prescribed medications for sleep disorders, and gamma-isoyosan is the most frequently prescribed herbal medicine.

Conclusions

Sleep disorders are continuously increasing, as is the use of medical services—personal and social medical expenses are also increasing accordingly. Sleep disorders should be recognised as a significant health problem that needs to be actively addressed to improve quality of life.
Perioperative treatment with tranexamic acid in melanoma (PRIME): protocol for a Danish multicentre randomised controlled trial investigating the prognostic and treatment-related impact of the plasminogen–plasmin pathway
Authors: Kristjansen Karoline Assifuah , Engel Krag Andreas , Schmidt Henrik , Hölmich Lisbet Rosenkrantz , Bønnelykke-Behrndtz Marie Louise
Published: February 2024

Introduction

Inflammation is a hallmark of cancer and is involved in tumour growth and dissemination. However, the hallmarks of cancer are also the hallmarks of wound healing, and modulating the wound inflammatory response and immune contexture in relation to cancer surgery may represent effective targets of therapies.

Repurposing anti-inflammatory drugs in a cancer setting has gained increasing interest in recent years. Interestingly, the known and thoroughly tested antifibrinolytic drug tranexamic acid reduces the risk of bleeding, but it is also suggested to play important roles in anti-inflammatory pathways, improving wound healing and affecting anti-carcinogenic mechanisms.

As a novel approach, we will conduct a randomised controlled trial using perioperative treatment with tranexamic acid, aiming to prevent early relapses by >10% for patients with melanoma.

Methods and analysis

Design: investigator-initiated parallel, two-arm, randomised, blinded, Danish multicentre superiority trial.

Patients: ≥T2 b melanoma and eligible for sentinel lymph node biopsy (n=1204).

Project drug: tranexamic acid or placebo.

Treatment: before surgery (intravenous 15 mg/kg) and daily (peroral 1000 mg x 3) through postoperative day 4.

Primary outcome: relapse within 2 years after surgery.

Primary analysis: risk difference between the treatment arms (χ2test).

Secondary outcomes: postoperative complications, adverse events and survival.

Inclusion period: summer 2023 to summer 2026.

Ethics and dissemination

The trial will be initiated during the summer of 2023 and is approved by the National Committee on Health Research Ethics, the Danish Medicine Agency, and registered under the Data Protection Act. The study will be conducted in accordance with the principles of the Declaration of Helsinki and Good Clinical Practice. Patients included in the study will adhere to normal Danish treatment protocols and standards of care, and we expect only mild and temporary side effects. Positive and negative results will be published in peer-reviewed journals, with authorships adhering to the Vancouver rules.

Trial registration number

NCT05899465; ClinicalTrials.gov Identifier.
Early ICD implantation following out-of-hospital cardiac arrest: a retrospective cohort study from the Swedish Registry for Cardiopulmonary Resuscitation
Authors: Sultanian Pedram , Lundgren Peter , Rawshani Aidin , Möller Sebastian , Jafari Arash Hadi , David Laura , Yassinson Shavan , Myredal Anna , Rorsman Cecilia , Taha Amar , Ravn-Fischer Annica , Martinsson Andreas , Herlitz Johan , Rawshani Araz
Published: February 2024

Background

It is unclear whether an implantable cardioverter-defibrillator (ICD) is generally beneficial in survivors of out-of-hospital cardiac arrest (OHCA).

Objective

We studied the association between ICD implantation prior to discharge and survival in patients with cardiac aetiology or initial shockable rhythm in OHCA.

Design

We conducted a retrospective cohort study in the Swedish Registry for Cardiopulmonary Resuscitation. Treatment associations were estimated using propensity scores. We used gradient boosting, Bayesian additive regression trees, neural networks, extreme gradient boosting and logistic regression to generate multiple propensity scores. We selected the model yielding maximum covariate balance to obtain weights, which were used in a Cox regression to calculate HRs for death or recurrent cardiac arrest.

Participants

All cases discharged alive during 2010 to 2020 with a cardiac aetiology or initial shockable rhythm were included. A total of 959 individuals were discharged with an ICD, and 2046 were discharged without one.

Results

Among those experiencing events, 25% did so within 90 days in the ICD group, compared with 52% in the other group. All HRs favoured ICD implantation. The overall HR (95% CI) for ICD versus no ICD was 0.38 (0.26 to 0.56). The HR was 0.42 (0.28 to 0.63) in cases with initial shockable rhythm; 0.18 (0.06 to 0.58) in non-shockable rhythm; 0.32 (0.20 to 0.53) in cases with a history of coronary artery disease; 0.36 (0.22 to 0.61) in heart failure and 0.30 (0.13 to 0.69) in those with diabetes. Similar associations were noted in all subgroups.

Conclusion

Among survivors of OHCA, those discharged with an ICD had approximately 60% lower risk of death or recurrent cardiac arrest. A randomised trial is warranted to study this further.
Effectiveness of an adaptive, multifaceted intervention to enhance care for patients with complex multimorbidity in general practice: protocol for a pragmatic cluster randomised controlled trial (the MM600 trial)
Authors: Holm Anne , Lyhnebeck Anna Bernhardt , Rozing Maarten , Buhl Sussi Friis , Willadsen Tora Grauers , Prior Anders , Christiansen Ann-Kathrin Lindahl , Kristensen Jette , Andersen John Sahl , Waldorff Frans Boch , Siersma Volkert , Brodersen John Brandt , Reventlow Susanne
Published: February 2024

Introduction

Patients with complex multimorbidity face a high treatment burden and frequently have low quality of life. General practice is the key organisational setting in terms of offering people with complex multimorbidity integrated, longitudinal, patient-centred care. This protocol describes a pragmatic cluster randomised controlled trial to evaluate the effectiveness of an adaptive, multifaceted intervention in general practice for patients with complex multimorbidity.

Methods and analysis

In this study, 250 recruited general practices will be randomly assigned 1:1 to either the intervention or control group. The eligible population are adult patients with two or more chronic conditions, at least one contact with secondary care within the last year, taking at least five repeat prescription drugs, living independently, who experience significant problems with their life and health due to their multimorbidity. During 2023 and 2024, intervention practices are financially incentivised to provide an extended consultation based on a patient-centred framework to eligible patients. Control practices continue care as usual. The primary outcome is need-based quality of life. Outcomes will be evaluated using linear and logistic regression models, with clustering considered. The analysis will be performed as intention to treat. In addition, a process evaluation will be carried out and reported elsewhere.

Ethics and dissemination

The trial will be conducted in compliance with the protocol, the Helsinki Declaration in its most recent form and good clinical practice recommendations, as well as the regulation for informed consent. The study was submitted to the Danish Capital Region Ethical Committee (ref: H-22041229). As defined by Section 2 of the Danish Act on Research Ethics in Research Projects, this project does not constitute a health research project but is considered a quality improvement project that does not require formal ethical approval. All results from the study (whether positive, negative or inconclusive) will be published in peer-reviewed journals.

Trial registration number

NCT05676541.
Implementing adaptive e-learning for newborn care in Tanzania: an observational study of provider engagement and knowledge gains
Authors: Meaney Peter Andrew , Hokororo Adolfine , Ndosi Hanston , Dahlen Alex , Jacob Theopista , Mwanga Joseph R , Kalabamu Florence Salvatory , Joyce Christine Lynn , Mediratta Rishi , Rozenfeld Boris , Berg Marc , Smith Zachary Haines , Chami Neema , Mkopi Namala , Mwanga Castory , Diocles Enock , Agweyu Ambrose
Published: February 2024

Introduction

To improve healthcare provider knowledge of Tanzanian newborn care guidelines, we developed adaptive Essential and Sick Newborn Care (aESNC), an adaptive e-learning environment. The objectives of this study were to (1) assess implementation success with use of in-person support and nudging strategy and (2) describe baseline provider knowledge and metacognition.

Methods

6-month observational study at one zonal hospital and three health centres in Mwanza, Tanzania. To assess implementation success, we used the Reach, Efficacy, Adoption, Implementation and Maintenance framework and to describe baseline provider knowledge and metacognition we used Howell’s conscious-competence model. Additionally, we explored provider characteristics associated with initial learning completion or persistent activity.

Results

aESNC reached 85% (195/231) of providers: 75 medical, 53 nursing and 21 clinical officers; 110 (56%) were at the zonal hospital and 85 (44%) at health centres. Median clinical experience was 4 years (IQR 1–9) and 45 (23%) had previous in-service training for both newborn essential and sick newborn care. Efficacy was 42% (SD ±17%). Providers averaged 78% (SD ±31%) completion of initial learning and 7% (SD ±11%) of refresher assignments. 130 (67%) providers had ≥1 episode of inactivity >30 day, no episodes were due to lack of internet access. Baseline conscious-competence was 53% (IQR: 38%–63%), unconscious-incompetence 32% (IQR: 23%–42%), conscious-incompetence 7% (IQR: 2%–15%), and unconscious-competence 2% (IQR: 0%–3%). Higher baseline conscious-competence (OR 31.6 (95% CI 5.8 to 183.5)) and being a nursing officer (aOR: 5.6 (95% CI 1.8 to 18.1)), compared with medical officer, were associated with initial learning completion or persistent activity.

Conclusion

aESNC reach was high in a population of frontline providers across diverse levels of care in Tanzania. Use of in-person support and nudging increased reach, initial learning and refresher assignment completion, but refresher assignment completion remains low. Providers were often unaware of knowledge gaps, and lower baseline knowledge may decrease initial learning completion or activity. Further study to identify barriers to adaptive e-learning normalisation is needed.
Understanding and addressing femicide in Africa: a systematic review of empirical research
Authors: Variava Tarique , Dekel Bianca
Published: February 2024

Context

Against the backdrop of a high prevalence rate of femicide across Africa, it is crucial to gain methodological insights into the existing research on femicide.

Objective

To develop evidence-based strategies to address the complex and multifaceted nature of femicide in Africa, ultimately contributing to its prevention and reduction.

Data sources

Empirical research was searched for using four electronic research databases (ProQuest, Web of Science, EBSCO and PubMed).

Eligibility criteria

Full-text empirical articles (ie, observational or retrospective studies) published in English between the period of 1 January 1992 and 30 July 2021, which sampled femicide victims and/or perpetrators in Africa, were included in the review.

Data extraction

Data were extracted using predefined data fields, including study quality indicators.

Data synthesis

Thomas and Harden’s (2008) thematic synthesis method was used to analyse 22 empirical articles that met the inclusion criteria in this study.

Results

This review highlights the significant focus on femicide research in South Africa. Most studies of femicides have used cross-sectional research designs. This review also demonstrates that crime dockets have benefited significantly from forensic contributions and police investigations. Furthermore, research efforts have uncovered various contextual factors that contribute to femicide, such as the high prevalence of early childhood trauma and the loss of primary caregivers among femicide offenders.

Conclusion

This systematic review offers a thorough synthesis of the current understanding of femicide in an African context, focusing on South Africa. Despite acknowledging the strengths and limitations of the existing knowledge, this review emphasises the urgency of addressing femicide and calls for international attention and action to effectively combat this pressing issue.
What works for whom and why? Treatment effects and their moderators among forcibly displaced people receiving psychological and psychosocial interventions: study protocol for an individual patient data meta-analysis
Authors: Kurath Jennifer , Akhtar Aemal , Karyotaki Eirini , Sijbrandij Marit , Cuijpers Pim , Bryant Richard , Morina Naser
Published: February 2024

Introduction

Forcibly displaced people (FDP) have a high risk of developing mental disorders such as post-traumatic stress (PTS) disorder. Providing adequate mental healthcare for FDP is crucial but despite overall efficacy of many existing interventions, a large proportion of FDP does not benefit from treatment, highlighting the necessity of further investigating factors contributing to individual differences in treatment outcome. Yet, the few studies that have explored moderators of treatment effects are often insufficiently powered. Therefore, the present Individual Patient Data meta-analysis (IPD-MA) will investigate treatment effects and their moderators—variables related to beneficiaries, providers, intervention and study characteristics in relation to PTS outcomes.

Methods and analysis

A systematic literature search will be conducted from database inception in the databases PsycINFO, Cochrane, Embase, PTSDpubs and Web of Science. Only studies published in English, German, French, Spanish, Portuguese, and Dutch will be considered. Retrieved records will be screened for eligibility. Randomised controlled trials on adult FDP receiving psychological and psychosocial interventions aimed at alleviating symptoms such as PTS compared with a control condition without intervention will be included in this IPD-MA. Subsequently, authors of eligible studies will be contacted to request individual patient data (IPD). All datasets obtained will be synthesised into one large dataset which will be analysed using a one-stage approach by conducting mixed-effects linear regression models (ie, primary analysis). Additionally, aggregate data meta-analyes will be run using a two-stage approach by conducting multivariate regression models including all IPD (transformed) and available meta-data from study reports (ie, secondary analysis). PTS will serve as primary outcome measure, while mental health outcomes other than PTS, attendance, attrition, treatment non-response and adverse outcomes will be examined as secondary outcomes.

Ethics and dissemination

This IPD-MA does not require ethical approval. The results will be published in international peer-reviewed journals.

PROSPERO registration number

CRD42022299510.
Study protocol of short-course radiotherapy combined with CAPOX and PD-1 inhibitor for locally advanced colon cancer: a randomised, prospective, multicentre, phase II trial (TORCH-C)
Authors: Zhang Hui , Li Yaqi , Xia Fan , Sun Yiqun , Shen Lijun , Wan Juefeng , Chen Yajie , Wang Yaqi , Zhou Menglong , Wu Ruiyan , Zhou Shujuan , Wang Yan , Liu Fangqi , Cai Sanjun , Zhang Zhen
Published: February 2024

Introduction

The preliminary result of the TORCH trial has shown a promising complete response (CR) for managing locally advanced rectal cancer with neoadjuvant short-course radiotherapy (SCRT) combined with chemotherapy and PD-1 inhibitor. For locally advanced colon cancer (LACC) with bulky nodal disease and/or clinically T4, neoadjuvant chemotherapy followed by colectomy with en bloc removal of regional lymph nodes is the suggested treatment. However, the CR rate is less than 5%. TORCH-C will aim to investigate neoadjuvant SCRT combined with chemotherapy and PD-1 inhibitor in LACC.

Methods and analysis

TORCH-C is a randomised, prospective, multicentre, double-arm, open, phase II trial of SCRT combined with chemotherapy and immunotherapy in LACC with microsatellite stable (MSS) patients and cT4 or bulky nodes. Eligible patients will be identified by the multidisciplinary team. 120 patients will be randomised 1:1 to the intervention or control arm. The patients in the control arm will receive four cycles of capecitabine plus oxaliplatin (CAPOX). The patients in the intervention arm will receive SCRT, followed by four cycles of CAPOX and PD-1 inhibitor (serplulimab). Both arms will receive curative surgery, followed by four cycles of CAPOX. The primary endpoint is pathological complete regression.

TORCH-C (TORCH-colon) trial aims to investigate whether the combination of immunotherapy and chemoradiotherapy improves the treatment effect in LACC with MSS. TORCH-C will establish the TORCH platform, a key part of our long-term strategy to develop neoadjuvant treatment for colorectal cancer.

Ethics and dissemination

This study was approved by the Ethics Committee of Fudan University Shanghai Cancer Center (approval number: 2211265-12).

Trial registration number

NCT05732493
Excess winter mortality in Finland, 1971–2019: a register-based study on long-term trends and effect modification by sociodemographic characteristics and pre-existing health conditions
Authors: Suulamo Ulla , Remes Hanna , Tarkiainen Lasse , Murphy Michael , Martikainen Pekka
Published: February 2024

Objectives

Excess winter mortality is a well-established phenomenon across the developed world. However, whether individual-level factors increase vulnerability to the effects of winter remains inadequately examined. Our aim was to assess long-term trends in excess winter mortality in Finland and estimate the modifying effect of sociodemographic and health characteristics on the risk of winter death.

Design

Nationwide register study.

Setting

Finland.

Participants

Population aged 60 years and over, resident in Finland, 1971–2019.

Outcome measures

Age-adjusted winter and non-winter death rates, and winter-to-non-winter rate ratios and relative risks (multiplicative interaction effects between winter and modifying characteristics).

Results

We found a decreasing trend in the relative winter excess mortality over five decades and a drop in the series around 2000. During 2000–2019, winter mortality rates for men and women were 11% and 14% higher than expected based on non-winter rates. The relative risk of winter death increased with age but did not vary by income. Compared with those living with at least one other person, individuals in institutions had a higher relative risk (1.07, 95% CI 1.05 to 1.08). Most pre-existing health conditions did not predict winter death, but persons with dementia emerged at greater relative risk (1.06, 95% CI 1.04 to 1.07).

Conclusions

Although winter mortality seems to affect frail people more strongly—those of advanced age, living in institutions and with dementia—there is an increased risk even beyond the more vulnerable groups. Protection of high-risk groups should be complemented with population-level preventive measures.
Phase 1/2 study of monalizumab plus durvalumab in patients with advanced solid tumors
Authors: Patel Sandip P , Alonso-Gordoa Teresa , Banerjee Susana , Wang Ding , Naidoo Jarushka , Standifer Nathan E , Palmer Doug C , Cheng Lin-Yang , Kourtesis Panagiotis , Ascierto Maria L , Das Mayukh , Diamond Jennifer R , Hellmann Matthew D , Carneiro Benedito A
Published: February 2024

Background

The combination of monalizumab (anti-NKG2A/CD94) and durvalumab (anti-programmed death ligand-1) may promote antitumor immunity by targeting innate and adaptive immunity. This phase 1/2 study of monalizumab and durvalumab evaluated safety, antitumor activity, and pharmacodynamics in patients with advanced solid tumors.

Main body

Immunotherapy-naïve patients aged ≥18 years with advanced disease, Eastern Cooperative Oncology Group performance status of 0–1, and 1–3 prior lines of systemic therapy in the recurrent/metastatic setting were enrolled. In part 1 (dose escalation), patients received durvalumab 1500 mg every 4 weeks (Q4W) with increasing doses of monalizumab Q2W/Q4W (n=15). Dose expansion in part 1 included patients with cervical cancer (n=15; durvalumab 1500 mg Q4W and monalizumab 750 mg Q2W) or metastatic microsatellite stable (MSS)-colorectal cancer (CRC) (n=15; durvalumab 1500 mg Q4W and monalizumab 750 mg Q4W). In part 2 (dose expansion), patients with MSS-CRC (n=40), non-small cell lung cancer (NSCLC; n=20), MSS-endometrial cancer (n=40), or ovarian cancer (n=40) received durvalumab 1500 mg Q4W and monalizumab 750 mg Q2W. The primary endpoint was safety. Secondary endpoints included antitumor activity per Response Evaluation Criteria In Solid Tumors version 1.1 (RECIST v1.1). Exploratory analyses included assessment of T-cell and natural killer (NK) cell activation and proliferation in peripheral blood and the tumor microenvironment (TME). The study enrolled 185 patients (part 1, 45; part 2, 140). No dose-limiting toxicities were observed and the maximum tolerated dose was not reached. In part 2, the most common treatment-related adverse events were fatigue (12.1%), asthenia (9.3%), diarrhea (9.3%), pruritus (7.9%), and pyrexia (7.1%). In the expansion cohorts, response rates were 0% (cervical), 7.7% (MSS-CRC), 10% (NSCLC), 5.4% (ovarian), and 0% (MSS-endometrial). Sustained NK cell activation, CD8+T-cell proliferation, increased serum levels of CXCL10 (C-X-C motif chemokine ligand 10) and CXCL11, and increased tumor infiltration of CD8+and granzyme B+cells were observed.

Conclusions

Although efficacy was modest, monalizumab plus durvalumab was well tolerated and encouraging immune activation was observed in the peripheral blood and TME.

Trial registration number

NCT02671435.