bluuebunny/crossref_metadata_2025_split huggingface dataset:
Implementation of advance care planning in the routine care for acutely admitted patients in geriatric units: protocol for a cluster randomized controlled trial
Authors: Romøren Maria , Hermansen Karin Berg , Sævareid Trygve Johannes Lereim , Brøderud Linn , Westbye Siri Færden , Wahl Astrid Klopstad , Thoresen Lisbeth , Rostoft Siri , Førde Reidun , Ahmed Marc , Aas Eline , Midtbust May Helen , Pedersen Reidar 
Published: February 2024

Abstract
Background
Acutely ill and frail older adults and their next of kin are often poorly involved in treatment and care decisions. This may lead to either over- or undertreatment and unnecessary burdens. The aim of this project is to improve user involvement and health services for frail older adults living at home, and their relatives, by implementing advance care planning (ACP) in selected hospital wards, and to evaluate the clinical and the implementation interventions.

Methods
This is a cluster randomized trial with 12 hospital units. The intervention arm receives implementation support for 18 months; control units receive the same support afterwards. The ACP intervention consists of 1. Clinical intervention: ACP; 2. Implementation interventions: Implementation team, ACP coordinator, network meetings, training and supervision for health care personnel, documentation tools and other resources, and fidelity measurements with tailored feedback; 3. Implementation strategies: leadership commitment, whole ward approach and responsive evaluation. Fidelity will be measured three times in the intervention arm and twice in the control arm. Here, the primary outcome is the difference in fidelity changes between the arms. We will also include 420 geriatric patients with one close relative and an attending clinician in a triadic sub-study. Here, the primary outcomes are quality of communication and decision-making when approaching the end of life as perceived by patients and next of kin, and congruence between the patient’s preferences for information and involvement and the clinician’s perceptions of the same. For patients we will also collect clinical data and health register data. Additionally, all clinical staff in both arms will be invited to answer a questionnaire before and during the implementation period. To explore barriers and facilitators and further explore the significance of ACP, qualitative interviews will be performed in the intervention units with patients, next of kin, health care personnel and implementation teams, and with other stakeholders up to national level. Lastly, we will evaluate resource utilization, costs and health outcomes in a cost-effectiveness analysis.

Discussion
The project may contribute to improved implementation of ACP as well as valuable knowledge and methodological developments in the scientific fields of ACP, health service research and implementation science.

Trial registration
ClinicalTrials.gov Identifier NCT05681585. Registered 03.01.23.
Newborn and child health national and provincial clinical practice guidelines in South Africa, Nigeria and Malawi: a scoping review
Authors: Mthethwa Mashudu , Mbeye Nyanyiwe Masingi , Effa Emmanuel , Arikpo Dachi , Blose Ntombifuthi , Brand Amanda , Chibuzor Moriam , Chipojola Roselyn , Durao Solange , Esu Ekpereonne , Kallon Idriss Ibrahim , Kunje Gertrude , Lakudzala Suzgika , Naude Celeste , Leong Trudy D. , Lewin Simon , Mabetha Denny , McCaul Michael , Meremikwu Martin , Vandvik Per Olav , Kredo Tamara 
Published: February 2024

Abstract
Background
Low and middle-income countries remain disproportionately affected by high rates of child mortality. Clinical practice guidelines are essential clinical tools supporting implementation of effective, safe, and cost-effective healthcare. High-quality evidence-based guidelines play a key role in improving clinical management to impact child mortality. We aimed to identify and assess the quality of guidelines for newborn and child health published in South Africa, Nigeria and Malawi in the last 5 years (2017–2022).

Methods
We searched relevant websites (June–July 2022), for publicly available national and subnational de novo or adapted guidelines, addressing newborn and child health in the three countries. Pairs of reviewers independently extracted information from eligible guidelines (scope, topic, target population and users, responsible developers, stakeholder consultation process, adaptation description, assessment of evidence certainty). We appraised guideline quality using the Appraisal of Guidelines for Research & Evaluation (AGREE II) instrument.

Results
We identified 40-guidelines from the three countries. Of these, 8/40 reported being adopted from a parent guideline. More guidelines (n = 19) provided guidance on communicable diseases than on non-communicable diseases (n = 8). Guidelines were most often developed by national health ministries (n = 30) and professional societies (n = 14). Eighteen guidelines reported on stakeholder consultation; with Nigeria (10/11) and Malawi (3/6) faring better than South Africa (5/23) in reporting this activity. The Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) approach was used in 1/7 guidelines that reported assessing certainty of evidence. Overall guidelines scored well on two AGREE II domains: scope and purpose median (IQR) score 68% (IQR 47–83), and clarity of presentation 81% (67–94). Domains critical for ensuring credible guidance scored below 20%: rigour of development 11% (4–32) and editorial independence 6% (0–27).

Conclusion
National ministries and professional societies drive guideline activities in Malawi, Nigeria and South Arica. However, the methods and reporting do not adhere to global standards. We found low AGREE II scores for rigour of guideline development and editorial independence and limited use of GRADE or adaptation methods. This undermines the credibility of available guidelines to support evidence-informed care. Our findings highlight the importance of ongoing efforts to strengthen partnerships, capacity, and support for guideline development.
Predicting thresholds for population replacement gene drives
Authors: Janzen Anna , Pothula Ratnasri , Sychla Adam , Feltman Nathan R. , Smanski Michael J. 
Published: February 2024

Abstract
Background
Threshold-dependent gene drives (TDGDs) could be used to spread desirable traits through a population, and are likely to be less invasive and easier to control than threshold-independent gene drives. Engineered Genetic Incompatibility (EGI) is an extreme underdominance system previously demonstrated in Drosophila melanogaster that can function as a TDGD when EGI agents of both sexes are released into a wild-type population.

Results
Here we use a single generation fitness assay to compare the fecundity, mating preferences, and temperature-dependent relative fitness to wild-type of two distinct genotypes of EGI agents. We find significant differences in the behavior/performance of these EGI agents that would not be predicted a priori based on their genetic design. We report a surprising temperature-dependent change in the predicted threshold for population replacement in an EGI agent that drives ectopic expression of the developmental morphogen pyramus.

Conclusions
The single-generation fitness assay presented here could reduce the amount of time required to estimate the threshold for TDGD strategies for which hybrid genotypes are inviable. Additionally, this work underscores the importance of empirical characterization of multiple engineered lines, as behavioral differences can arise in unique genotypes for unknown reasons.
Risk-based lung cancer screening in heavy smokers: a benefit–harm and cost-effectiveness modeling study
Authors: Liu Yin , Xu Huifang , Lv Lihong , Wang Xiaoyang , Kang Ruihua , Guo Xiaoli , Wang Hong , Zheng Liyang , Liu Hongwei , Guo Lanwei , Chen Qiong , Liu Shuzheng , Qiao Youlin , Zhang Shaokai 
Published: February 2024

Abstract
Background
Annual screening through low-dose computed tomography (LDCT) is recommended for heavy smokers. However, it is questionable whether all individuals require annual screening given the potential harms of LDCT screening. This study examines the benefit–harm and cost-effectiveness of risk-based screening in heavy smokers and determines the optimal risk threshold for screening and risk-stratified screening intervals.

Methods
We conducted a comparative cost-effectiveness analysis in China, using a cohort-based Markov model which simulated a lung cancer screening cohort of 19,146 heavy smokers aged 50 ~ 74 years old, who had a smoking history of at least 30 pack-years and were either current smokers or had quit for < 15 years. A total of 34 risk-based screening strategies, varying by different risk groups for screening eligibility and screening intervals (1-year, 2-year, 3-year, one-off, non-screening), were evaluated and were compared with annual screening for all heavy smokers (the status quo strategy). The analysis was undertaken from the health service perspective with a 30-year time horizon. The willingness-to-pay (WTP) threshold was adopted as three times the gross domestic product (GDP) of China in 2021 (CNY 242,928) per quality-adjusted life year (QALY) gained.

Results
Compared with the status quo strategy, nine risk-based screening strategies were found to be cost-effective, with two of them even resulting in cost-saving. The most cost-effective strategy was the risk-based approach of annual screening for individuals with a 5-year risk threshold of ≥ 1.70%, biennial screening for individuals with a 5-year risk threshold of 1.03 ~ 1.69%, and triennial screening for individuals with a 5-year risk threshold of < 1.03%. This strategy had the highest incremental net monetary benefit (iNMB) of CNY 1032. All risk-based screening strategies were more efficient than the status quo strategy, requiring 129 ~ 656 fewer screenings per lung cancer death avoided, and 0.5 ~ 28 fewer screenings per life-year gained. The cost-effectiveness of risk-based screening was further improved when individual adherence to screening improved and individuals quit smoking after being screened.

Conclusions
Risk-based screening strategies are more efficient in reducing lung cancer deaths and gaining life years compared to the status quo strategy. Risk-stratified screening intervals can potentially balance long-term benefit–harm trade-offs and improve the cost-effectiveness of lung cancer screenings.
Neuregulin-1 and ALS19 (ERBB4): at the crossroads of amyotrophic lateral sclerosis and cancer
Authors: Adashek Jacob J. , Pandya Chinmayi , Maragakis Nicholas J. , De Pradip , Cohen Philip R. , Kato Shumei , Kurzrock Razelle 
Published: February 2024

Abstract
Background
Neuregulin-1 (NRG1) is implicated in both cancer and neurologic diseases such as amyotrophic lateral sclerosis (ALS); however, to date, there has been little cross-field discussion between neurology and oncology in regard to these genes and their functions.

Main body
Approximately 0.15–0.5% of cancers harbor NRG1 fusions that upregulate NRG1 activity and hence that of the cognate ERBB3/ERBB4 (HER3/HER4) receptors; abrogating this activity with small molecule inhibitors/antibodies shows preliminary tissue-agnostic anti-cancer activity. Notably, ERBB/HER pharmacologic suppression is devoid of neurologic toxicity. Even so, in ALS, attenuated ERBB4/HER4 receptor activity (due to loss-of-function germline mutations or other mechanisms in sporadic disease) is implicated; indeed, ERBB4/HER4 is designated ALS19. Further, secreted-type NRG1 isoforms may be upregulated (perhaps via a feedback loop) and could contribute to ALS pathogenesis through aberrant glial cell stimulation via enhanced activity of other (e.g., ERBB1-3/HER1-3) receptors and downstream pathways. Hence, pan-ERBB inhibitors, already in use for cancer, may be agents worthy of testing in ALS.

Conclusion
Common signaling cascades between cancer and ALS may represent novel therapeutic targets for both diseases.
Platycodin D2 enhances P21/CyclinA2-mediated senescence of HCC cells by regulating NIX-induced mitophagy
Authors: Sun Lili , Li Yaru , Zhao Renshuang , Fan Qinlei , Liu Fei , Zhu Yilong , Han Jicheng , Liu Yunyun , Jin Ningyi , Li Xiao , Li Yiquan 
Published: February 2024

Abstract
Background
Hepatocellular carcinoma (HCC) cells usually show strong resistance to chemotherapy, which not only reduces the efficacy of chemotherapy but also increases the side effects. Regulation of autophagy plays an important role in tumor treatment. Cell senescence is also an important anti-cancer mechanism, which has become an important target for tumor treatment. Therefore, it is of great clinical significance to find anti-HCC drugs that act through this new mechanism. Platycodin D2 (PD2) is a new saponin compound extracted from the traditional Chinese medicine Platycodon grandiflorum.

Purpose
Our study aimed to explore the effects of PD2 on HCC and identify the underlying mechanisms.

Methods
First, the CCK8 assay was used to detect the inhibitory effect of PD2 on HCC cells. Then, different pathways of programmed cell death and cell cycle regulators were measured. In addition, we assessed the effects of PD2 on the autophagy and senescence of HCC cells by flow cytometry, immunofluorescence staining, and Western blotting. Finally, we studied the in vivo effect of PD2 on HCC cells by using a mouse tumor-bearing model.

Results
Studies have shown that PD2 has a good anti-tumor effect, but the specific molecular mechanism has not been clarified. In this study, we found that PD2 has no obvious toxic effect on normal hepatocytes, but it can significantly inhibit the proliferation of HCC cells, induce mitochondrial dysfunction, enhance autophagy and cell senescence, upregulate NIX and P21, and downregulate CyclinA2. Gene silencing and overexpression indicated that PD2 induced mitophagy in HCC cells through NIX, thereby activating the P21/CyclinA2 pathway and promoting cell senescence.

Conclusions
These results indicate that PD2 induces HCC cell death through autophagy and aging. Our findings provide a new strategy for treating HCC.

Graphical Abstract
Breakfast quality and its sociodemographic and psychosocial correlates among Italian children, adolescents, and adults from the Italian Nutrition & HEalth Survey (INHES) study
Authors: Martinez Claudia Francisca , Ruggiero Emilia , Di Castelnuovo Augusto , Esposito Simona , Costanzo Simona , Cerletti Chiara , Donati Maria Benedetta , de Gaetano Giovanni , Iacoviello Licia , Bonaccio Marialaura ,   INHES Study Investigators
Published: February 2024

Abstract
Background
Breakfast quality, together with regularity of breakfast, has been suggested to be associated with cardiometabolic health advantages. We aimed to evaluate the quality of breakfast and its socioeconomic and psychosocial correlates in a large sample of the Italian population.

Methods
Cross-sectional analyses on 7,673 adult and 505 children/adolescent regular breakfast eaters from the Italian Nutrition & Health Survey (INHES; 2010-2013). Dietary data were collected through a single 24-h dietary recall. Breakfast quality was assessed through the Breakfast Quality Index (BQI) combining intake of ten food groups, energy, and nutrients of public health concern, and potentially ranging from 0 to 10. The association of sociodemographic and psychosocial factors with BQI were analyzed by multivariable-adjusted linear regression models.

Results
The average BQI was 4.65 (SD ± 1.13) and 4.97 (SD ± 1.00) in adults and children/adolescents, respectively. Amongst adults, older age (β = 0.19; 95%CI 0.06 to 0.31 for > 65 vs. 20–40 years) and having a high educational level (β = 0.13; 0.03 to 0.23; for postsecondary vs. up to elementary) were independent predictors of better breakfast quality, while men reported lower BQI (β = -0.08; -0.14 to -0.02 vs. women). Perceived stress levels at home and work and financial stress were inversely associated with BQI. Children/adolescents living in Central and Southern Italian regions had lower BQI compared to residents in Northern Italy (β = -0.55; -0.91 to -0.19 and β = -0.24; -0.47 to -0.01, respectively).

Conclusions
In adults, breakfast quality was associated with age, sex, and educational level. Perceived stress levels were inversely associated with the quality of breakfast. In children/adolescents, a north-south gradient in breakfast quality was observed.
Kinematic difference and asymmetries during level walking in adolescent patients with different types of mild scoliosis
Authors: Ji Run , Liu Xiaona , Liu Yang , Yan Bin , Yang Jiemeng , Lee Wayne Yuk-wai , Wang Ling , Tao Chunjing , Kuai Shengzheng , Fan Yubo 
Published: February 2024

Abstract
Background
Adolescent idiopathic scoliosis (AIS), three-dimensional spine deformation, affects body motion. Previous research had indicated pathological gait patterns of AIS. However, the impact of the curve number on the walking mechanism has not been established. Therefore, this study aimed to compare the gait symmetry and kinematics in AIS patients with different curve numbers to healthy control.

Results
In the spinal region, double curves AIS patients demonstrated a smaller sagittal symmetry angle (SA) and larger sagittal convex ROM of the trunk and lower spine than the control group. In the lower extremities, the single curve patients showed a significantly reduced SA of the knee joint in the frontal plane, while the double curves patients showed a significantly reduced SA of the hip in the transverse plane.

Conclusion
The curve number indeed affects gait symmetry and kinematics in AIS patients. The double curves patients seemed to adopt a more "careful walking" strategy to compensate for the effect of spinal deformation on sensory integration deficits. This compensation mainly occurred in the sagittal plane. Compared to double curves patients, single curve patients unitized a similar walking strategy with healthy subjects.
A comprehensive review on Moringa oleifera nanoparticles: importance of polyphenols in nanoparticle synthesis, nanoparticle efficacy and their applications
Authors: Perumalsamy Haribalan , Balusamy Sri Renukadevi , Sukweenadhi Johan , Nag Sagnik , MubarakAli Davoodbasha , El-Agamy Farh Mohamed , Vijay Hari , Rahimi Shadi 
Published: February 2024

AbstractMoringa oleifera is one of the popular functional foods that has been tremendously exploited for synthesis of a vast majority of metal nanoparticles (NPs). The diverse secondary metabolites present in this plant turn it into a green tool for synthesis of different NPs with various biological activities. In this review, we discussed different types of NPs including silver, gold, titanium oxide, iron oxide, and zinc oxide NPs produced from the extract of different parts of M. oleifera. Different parts of M. oleifera take a role as the reducing, stabilizing, capping agent, and depending on the source of extract, the color of solution changes within NP synthesis. We highlighted the role of polyphenols in the synthesis of NPs among major constituents of M. oleifera extract. The different synthesis methods that could lead to the formation of various sizes and shapes of NPs and play crucial role in biomedical application were critically discussed. We further debated the mechanism of interaction of NPs with various sizes and shapes with the cells, and further their clearance from the body. The application of NPs made from M. oleifera extract as anticancer, antimicrobial, wound healing, and water treatment agent were also discussed. Small NPs show better antimicrobial activity, while they can be easily cleared from the body through the kidney. In contrast, large NPs are taken by the mono nuclear phagocyte system (MPS) cells. In case of shape, the NPs with spherical shape penetrate into the bacteria, and show stronger antibacterial activity compared to the NPs with other shapes. Finally, this review aims to correlate the key characteristics of NPs made from M. oleifera extract, such as size and shape, to their interactions with the cells for designing and engineering them for bio-applications and especially for therapeutic purposes.
Graphical Abstract
“I don’t think of it as a shelter. I say I’m going home”: a qualitative evaluation of a low-threshold shelter for women who use drugs
Authors: Beaugard Corinne A. , Khudairi Fay , Yesufu Oluwatoyin , Farina Andrea , Laks Jordana 
Published: February 2024

Abstract
Background
In 2021–2022, encampments in a downtown Boston neighborhood reached record heights, increasing the visibility of drug use and homelessness in the city. In response, the city planned a “sweep” (i.e., eradication of encampments) and requested support from social services and medical providers to pilot low-threshold shelters. Low-threshold shelters reduce barriers to staying in traditional congregate shelters with more flexible regulations, longer-term bed assignments, and secured storage for contraband (e.g., drugs, weapons) instead of forced disposal. One homeless service provider opened a harm reduction-focused shelter for women who use drugs. This report describes the low-threshold shelter design and program evaluation.

Methods
This program evaluation had two primary aims: (1) to examine guests’ beliefs about shelter policies and practices; and (2) to understand the staff’s experiences working in a low-threshold model. We conducted semi-structured qualitative interviews with 16 guests and 12 staff members during the summer 2022. Interviews were thematically analyzed.

Results
Guests expressed overwhelming approval for the shelter’s policies, which they stated supported their autonomy, dignity, and safety. They emphasized the staff’s willingness to build relationships, thus demonstrating true commitment to the guests. Guests highlighted the value of daytime access to the shelter, as it granted them autonomy over their time, reduced their substance use, and helped them build relationships with staff and other guests. The co-directors and staff designed the shelter quickly and without US models for reference; they turned to international literature, local harm reduction health care providers, and women living in encampments for guidance on the shelter policies. The staff were passionate and committed to the health and stability of the guests. Most staff found value in the low-threshold model, though some were challenged by it, believing it enabled drug use and did not require the guests to “get better.”

Conclusions
This evaluation indicates the value of low-threshold, harm reduction shelters as alternatives to traditional models. While these shelters do not mitigate the need for overarching housing reform, they are important measures to meet the needs of women experiencing unsheltered homelessness who face intersectional oppression.