bluuebunny/crossref_metadata_2025_split huggingface dataset:
Usage and limitations of medical consultation with patients’ families using online video calls: a prospective cohort study
Authors: Hayashi Tetsuro , Bito Seiji 
Published: May 2024

Abstract
Background
Few studies have been conducted on the usage of telehealth focusing on consultations between patients’ families and physicians. This study aimed to identify the usage and limitations of online medical consultations with patients’ families compared to the traditional in-person consultations.

Methods
We conducted a prospective cohort study from April 1, 2020, to September 30, 2021, at an educational acute-care hospital in Japan. The study included hospitalized patients aged 20 years or older and their family members for whom an online or in-person medical consultation between the family member and physician was conducted during the hospitalization period. The primary endpoints assessed were three topics pertaining to medical consultation: medical conditions and treatment plans, policies for life-threatening events, and post-discharge support. The secondary endpoint was the number of consultations required.

Results
Online consultations and traditional in-person consultations were provided to 58 and 53 patients’ families, respectively. Of the patients in the online consultation group who underwent multiple consultations, 46 (79%) also underwent in-person consultations. Regarding the topics, all the patients’ families in both consultation groups had consultations on medical conditions and treatment plans; regarding the policy for life-threatening events, 47% of patient families in the online consultation group were consulted compared to 53% of those in the in-person group. Regarding post-discharge support, 59% of patient families in the online group were consulted compared to 40% in the in-person group. In the online consultation group of 58 patients’ families, 188 consultations were conducted, including 95 online and 93 in-person consultations. Consultations on policy for life-threatening events were significantly more frequent in in-person consultations than in online consultations (p < 0.05). Regarding post-discharge support, online consultations were significantly more frequent than in-person consultations (p < 0.05). The number of family members who attended online consultations was significantly higher than those who attended in-person consultations (p < 0.05).

Conclusions
Online consultation between the physician and patient’s family may be an alternative to in-person consultation for explaining medical conditions and treatment plans. However, in-person consultation still plays an important role in sensitive topics, such as policy consultation for life-threatening events.
Establishment of disulfidptosis-related LncRNA signature as biomarkers in colon adenocarcinoma
Authors: Yao Hongfei , Liu Peng , Yao Linli , Li Xiao 
Published: May 2024

Abstract
Purpose
Metabolic reprogramming is a hallmark of cancer and plays a key role in precision oncology treatment. Long non-coding RNAs (lncRNAs) regulate cancer cell behavior, including metabolism. Disulfidptosis, a newly identified form of regulated cell death triggered by glucose starvation, has yet to be fully understood in colon adenocarcinoma (COAD). This study aimed to confirm the existence and role of disulfidptosis in COAD and identify disulfidptosis-related lncRNAs that may be targeted to induce disulfidptosis in COAD.

Methods
PI and F-actin staining were used to observe disulfidptosis in COAD cell lines. Disulfidptosis-related lncRNAs were identified based on the expression of disulfidptosis-associated genes in the TCGA-COAD database. A four-lncRNA signature for disulfidptosis was established. Subsequently, loss-of-function assays explored the roles of AC013652.1 and MCM3AP-AS1 in disulfidptosis.

Results
Disulfidptosis was observed in COAD cells under glucose starvation and could be reversed by agents that prevent disulfide stress, such as dithiothreitol (DTT) and tris-(2-carboxyethyl)-phosphine (TCEP). The prognostic value of disulfidptosis-associated genes in COAD patients was confirmed, with higher expression indicating longer survival. A disulfidptosis-related lncRNA signature comprising four lncRNAs was established based on the expression of these genes. Among these, AC013652.1 and MCM3AP-AS1 predicted worse prognoses. Furthermore, inhibiting AC013652.1 or MCM3AP-AS1 increased disulfidptosis-associated gene expression and cellular death, which could be reversed by DTT and TCEP.

Conclusions
This study provides hitherto undocumented evidence of the existence of disulfidptosis and the prognostic value of disulfidptosis-associated genes in COAD. Importantly, we identified lncRNAs AC013652.1 and MCM3AP-AS1, which suppress disulfidptosis and may serve as potential therapeutic targets for COAD.
A cross-sectional analysis of the relationship between the non-high density to high density lipoprotein cholesterol ratio (NHHR) and kidney stone risk in American adults
Authors: Du Yuan-Zhuo , Dong Qian-Xi , Hu Hong-Ji , Guo Biao , Li Yi-He , Zhang Ji , Li Fu-Chun , Guo Ju 
Published: May 2024

Abstract
Background
Recent interest in the Non-High Density to High Density Lipoprotein Cholesterol ratio (NHHR) has emerged due to its potential role in metabolic disorders. However, the connection between NHHR and the development of kidney stones still lacks clarity. The primary goal of this research is to explore how NHHR correlates with kidney stone incidence.

Methods
An analysis was conducted on the data collected by the National Health and Nutrition Examination Survey (NHANES) between 2007 and 2018, focusing on adults over 20 years diagnosed with kidney stones and those with available NHHR values. Employing weighted logistic regression and Restricted Cubic Spline (RCS) models, NHHR levels’ correlation with kidney stone risk was examined. Extensive subgroup analyses were conducted for enhanced reliability of the findings.

Results
The findings indicate a heightened kidney stone risk for those at the highest NHHR levels relative to those at the lowest (reference group). A notable non-linear correlation of NHHR with kidney stone incidence has been observed, with a significant P-value (< 0.001), consistent across various subgroups.

Conclusion
A clear link exists between high NHHR levels and increased kidney stone risk in the American adult population. This study highlights NHHR’s significance as a potential indicator in kidney stone formation.
A SU6668 pure nanoparticle-based eyedrops: toward its high drug Accumulation and Long-time treatment for corneal neovascularization
Authors: Wu Han , Ye Jinfa , Zhang Minjie , Zhang Lingyu , Lin Sijie , Li Qingjian , Liu Yanbo , Han Yun , Huang Caihong , Wu Yiming , Cheng Yuhang , Cai Shundong , Ke Lang , Liu Gang , Li Wei , Chu Chengchao 
Published: May 2024

AbstractCorneal neovascularization (CNV) is one of the common blinding factors worldwide, leading to reduced vision or even blindness. However, current treatments such as surgical intervention and anti-VEGF agent therapy still have some shortcomings or evoke some adverse effects. Recently, SU6668, an inhibitor targeting angiogenic tyrosine kinases, has demonstrated growth inhibition of neovascularization. But the hydrophobicity and low ocular bioavailability limit its application in cornea. Hereby, we proposed the preparation of SU6668 pure nanoparticles (NanoSU6668; size ~135 nm) using a super-stable pure-nanomedicine formulation technology (SPFT), which possessed uniform particle size and excellent aqueous dispersion at 1 mg/mL. Furthermore, mesenchymal stem cell membrane vesicle (MSCm) was coated on the surface of NanoSU6668, and then conjugated with TAT cell penetrating peptide, preparing multifunctional TAT-MSCm@NanoSU6668 (T-MNS). The T-MNS at a concentration of 200 µg/mL was treated for CNV via eye drops, and accumulated in blood vessels with a high targeting performance, resulting in elimination of blood vessels and recovery of cornea transparency after 4 days of treatment. Meanwhile, drug safety test confirmed that T-MNS did not cause any damage to cornea, retina and other eye tissues. In conclusion, the T-MNS eye drop had the potential to treat CNV effectively and safely in a low dosing frequency, which broke new ground for CNV theranostics.
Multifunctional elastin-like polypeptide nanocarriers for efficient miRNA delivery in cancer therapy
Authors: Hong Jisan , Sim Dahye , Lee Byung-Heon , Sarangthem Vijaya , Park Rang-Woon 
Published: May 2024

Abstract
Background
The exogenous delivery of miRNA to mimic and restore miRNA-34a activity in various cancer models holds significant promise in cancer treatment. Nevertheless, its effectiveness is often impeded by challenges, including a short half-life, propensity for off-target accumulation, susceptibility to inactivation by blood-based enzymes, concerns regarding patient safety, and the substantial cost associated with scaling up. As a means of overcoming these barriers, we propose the development of miRNA-loaded Tat-A86 nanoparticles by virtue of Tat-A86's ability to shield the loaded agent from external environmental factors, reducing degradation and inactivation, while enhancing circulation time and targeted accumulation.

Results
Genetically engineered Tat-A86, featuring 16 copies of the interleukin-4 receptor (IL-4R)-binding peptide (AP1), Tat for tumor penetration, and an elastin-like polypeptide (ELP) for presenting target ligands and ensuring stability, served as the basis for this delivery system. Comparative groups, including Tat-E60 and A86, were employed to discern differences in binding and penetration. The designed ELP-based nanoparticle Tat-A86 effectively condensed miRNA, forming stable nanocomplexes under physiological conditions. The miRNA/Tat-A86 formulation bound specifically to tumor cells and facilitated stable miRNA delivery into them, effectively inhibiting tumor growth. The efficacy of miRNA/Tat-A86 was further evaluated using three-dimensional spheroids of lewis lung carcinoma (LLC) as in vitro model and LLC tumor-bearing mice as an in vivo model. It was found that miRNA/Tat-A86 facilitates effective cell killing by markedly improving miRNA penetration, leading to a substantial reduction in the size of LLC spheroids. Compared to other controls, Tat-A86 demonstrated superior efficacy in suppressing the growth of 3D cellular aggregates. Moreover, at equivalent doses, miRNA-34a delivered by Tat-A86 inhibited the growth of LLC cells in allograft mice.

Conclusions
Overall, these studies demonstrate that Tat-A86 nanoparticles can deliver miRNA systemically, overcoming the basic hurdles impeding miRNA delivery by facilitating both miRNA uptake and stability, ultimately leading to improved therapeutic effects.

Graphical Abstract
Human and financial resource needs for universal access to WHO-PEN interventions for diabetes and hypertension care in Eswatini: results from a time-and-motion and bottom-up costing study
Authors: Harkare Harsh Vivek , Osetinsky Brianna , Ginindza Ntombifuthi , Cindzi Bongekile Thobekile , Mncina Nomfundo , Akomolafe Babatunde , Marowa Lisa-Rufaro , Ntshalintshali Nyasatu , Tediosi Fabrizio 
Published: May 2024

Abstract
Background
Eswatini faces persistent challenges in providing care for diabetes and hypertension, exacerbated by a shortage of healthcare workers. The implementation of WHO-PEN interventions aimed to address these issues, yet their effects on healthcare worker time requirements and associated costs remain unclear.

Methods
This study employed a time-and-motion analysis and a bottom-up cost assessment to quantify the human and financial resources required for scaling up WHO-PEN interventions nationally in Eswatini for all estimated diabetic and hypertensive patients.

Results
Findings reveal that healthcare workers in intervention-arm clinics reported longer workday durations compared to those in control-arm clinics, yet spent less time per patient while seeing more patients. The implementation of WHO-PEN interventions increased the workload on healthcare workers but also led to a notable increase in patient care utilization. Furthermore, a morning peak in patient visits was identified, suggesting potential opportunities for optimizing patient flow. Notably, scaling up care provision nationally with WHO-PEN interventions proved to be more cost saving than expanding standard-of-care treatment.

Conclusion
WHO-PEN interventions hold promise in improving access to diabetes and hypertension care in Eswatini while offering an efficient solution. However, addressing challenges in healthcare workforce creation and retention is crucial for sustained effectiveness. Policy makers must consider all aspects of the WHO-PEN intervention for informed decision-making.
Trial registration US Clinical Trials Registry. NCT04183413. Trial registration date: December 3, 2019. https://ichgcp.net/clinical-trials-registry/NCT04183413
Trends in the geographic inequality of advanced practice nursing workforce in cancer care in Japan from 1996 to 2022: a panel data analysis
Authors: Tamaki Tomoko , Morioka Noriko , Machida Ako , Kashiwagi Masayo 
Published: May 2024

Abstract
Background
Cancer was ranked as the second leading cause of global mortality in 2019, with an increasing incidence. An adequate workforce of healthcare professionals with special skills and knowledge in cancer care is vital for addressing the disparities in cancer prognosis. This study aimed to elucidate the trends in the advanced practice nursing workforce (APNW) in cancer care, which included certified nurse specialists (CNSs) and certified nurses (CNs) in each prefecture of Japan from the system's inception to the present. Further, it sought to analyze the regional disparities and compare these trends with other healthcare resources to identify contributing factors associated with the APNW in cancer care in each prefecture.

Methods
We performed a panel data analysis using publicly available data on the APNW in cancer care in each prefecture of Japan from 1996 to 2022. Gini coefficients were calculated to examine the trends in geographic equality. Univariate and multivariable fixed effect panel data regression models were used to examine regional factors associated with an APNW in cancer care.

Results
From 1996 to 2012, the APNW in cancer care increased from four to 6982 staff, while their Gini coefficients decreased from 0.79 to 0.43. However, from 2012 to 2022, the Gini coefficients decreased slightly from 0.43 to 0.41. The coefficient value was comparable to that for the disparity between hospital doctors (0.43) but more pronounced compared to those for other medical resources, such as hospitals (0.34), hospital nurses (0.37), and designated cancer care hospitals (0.29). The APNW in cancer care in each prefecture was significantly associated with a higher number of designed cancer care hospitals in the previous year (see first quartile, the coefficient for second quartile: 0.31, 95% confidence interval (CI) 0.21–0.40), and a fewer number of hospital doctors (− 1.89, 95%CI − 2.70 to − 1.09).

Conclusions
The size of the APNW in cancer care has increased since the system was established in 1996 up till 2022. With the increase in numbers, geographic inequality narrowed until 2012 and has since then remained stagnant.
Decentralization of the health system – experiences from Pakistan, Portugal and Brazil
Authors: Mahmood Shafaq , Sequeira Rita , Siddiqui Muhammad Muneeb Ullah , Herkenhoff Marcos Batista Araujo , Ferreira Patrícia Pita , Fernandes Adalberto Campos , Sousa Paulo 
Published: May 2024

Abstract
Background
Decentralization of a health system is a complex and multidimensional phenomenon that demands thorough investigation of its process logistics, predisposing factors and implementation mechanisms, within the broader socio-political environment of each nation. Despite its wide adoption across both high-income countries (HICs) and low-and-middle-income countries (LMICs), empirical evidence of whether decentralization actually translates into improved health system performance remains inconclusive and controversial. This paper aims to provide a comprehensive description of the decentralization processes in three countries at different stages of their decentralization strategies – Pakistan, Brazil and Portugal.

Main body
This study employed a systematic analysis of peer-reviewed academic journals, official government reports, policy documents and publications from international organizations related to health system decentralization. A comprehensive search was conducted using reputable databases such as PubMed, Google Scholar, the WHO repository and other relevant databases, covering the period up to the knowledge cutoff date in June 2023. Information was systematically extracted and organized into the determinants, process mechanics and challenges encountered during the planning, implementation and post-decentralization phases. Although decentralization reforms have achieved some success, challenges persist in their implementation. Comparing all three countries, it was evident that all three have prioritized health in their decentralization reforms and aimed to enhance local decision-making power. Brazil has made significant progress in implementing decentralization reforms, while Portugal and Pakistan are still in the process. Pakistan has faced significant implementation challenges, including capacity-building, resource allocation, resistance to change and inequity in access to care. Brazil and Portugal have also faced challenges, but to a lesser extent. The extent, progress and challenges in the decentralization processes vary among the three countries, each requiring ongoing evaluation and improvement to achieve the desired outcomes.

Conclusion
Notable differences exist in the extent of decentralization, the challenges faced during implementation and inequality in access to care between the three countries. It is important for Portugal, Brazil and Pakistan to address these through reinforcing implementation strategies, tackling inequalities in access to care and enhancing monitoring and evaluation mechanism. Additionally, fostering knowledge sharing among these different countries will be instrumental in facilitating mutual learning.
Enhancing the delivery of comprehensive care for people living with HIV in Canada: insights from citizen panels and a national stakeholder dialogue
Authors: Wilson Michael G. , Mattison Cristina , Waddell Kerry , Bacon Jean , Becker Marissa , Bibeau Christine , Lavis John N. , Rosenes Ron , Kendall Claire E. 
Published: May 2024

Abstract
Background
People living with human immunodeficiency virus (HIV) are living longer with health-related disability associated with ageing, including complex conditions. However, health systems in Canada have not adapted to meet these comprehensive care needs.

Methods
We convened three citizen panels and a national stakeholder dialogue. The panels were informed by a plain-language citizen brief that outlined data and evidence about the challenge/problem, elements of an approach for addressing it and implementation considerations. The national dialogue was informed by a more detailed version of the same brief that included a thematic analysis of the findings from the panels.

Results
The 31 citizen panel participants emphasized the need for more prevention, testing and social supports, increased public education to address stigma and access to more timely data to inform system changes. The 21 system leaders emphasized the need to enhance person-centred care and for implementing learning and improvement across provinces, territories and Indigenous communities. Citizens and system leaders highlighted that policy actions need to acknowledge that HIV remains unique among conditions faced by Canadians.

Conclusions
Action will require a national learning collaborative to support spread and scale of successful prevention, care and support initiatives. Such a collaborative should be grounded in a rapid-learning and improvement approach that is anchored on the needs, perspectives and aspirations of people living with HIV; driven by timely data and evidence; supported by appropriate decision supports and aligned governance, financial and delivery arrangements; and enabled with a culture of and competencies for rapid learning and improvement.
Estimation and probabilistic projection of age- and sex-specific mortality rates across Brazilian municipalities between 2010 and 2030
Authors: Gonzaga Marcos R. , Queiroz Bernardo L. , Freire Flávio H.M.A. , Monteiro-da-Silva José H.C. , Lima Everton E.C. , Silva-Júnior Walter P. , Diógenes Victor H. D. , Flores-Ortiz Renzo , da Costa Lilia C. C. , Pinto-Junior Elzo P. , Ichihara Maria Yury , Teixeira Camila S. S. , Alves Flávia J. O. , Rocha Aline S. , Ferreira Andrêa J. F. , Barreto Maurício L. , Katikireddi Srinivasa Vittal , Dundas Ruth , Leyland Alastair H. 
Published: May 2024

Abstract
Background
Mortality rate estimation in small areas can be difficult due the low number of events/exposure (i.e. stochastic error). If the death records are not completed, it adds a systematic uncertainty on the mortality estimates. Previous studies in Brazil have combined demographic and statistical methods to partially overcome these issues. We estimated age- and sex-specific mortality rates for all 5,565 Brazilian municipalities in 2010 and forecasted probabilistic mortality rates and life expectancy between 2010 and 2030.

Methods
We used a combination of the Tool for Projecting Age-Specific Rates Using Linear Splines (TOPALS), Bayesian Model, Spatial Smoothing Model and an ad-hoc procedure to estimate age- and sex-specific mortality rates for all Brazilian municipalities for 2010. Then we adapted the Lee-Carter model to forecast mortality rates by age and sex in all municipalities between 2010 and 2030.

Results
The adjusted sex- and age-specific mortality rates for all Brazilian municipalities in 2010 reveal a distinct regional pattern, showcasing a decrease in life expectancy in less socioeconomically developed municipalities when compared to estimates without adjustments. The forecasted mortality rates indicate varying regional improvements, leading to a convergence in life expectancy at birth among small areas in Brazil. Consequently, a reduction in the variability of age at death across Brazil’s municipalities was observed, with a persistent sex differential.

Conclusion
Mortality rates at a small-area level were successfully estimated and forecasted, with associated uncertainty estimates also generated for future life tables. Our approach could be applied across countries with data quality issues to improve public policy planning.
Influence of intersignaling crosstalk on the intracellular localization of YAP/TAZ in lung cells
Authors: Govorova I. A. , Nikitochkina S. Y. , Vorotelyak E. A. 
Published: May 2024

AbstractA cell is a dynamic system in which various processes occur simultaneously. In particular, intra- and intercellular signaling pathway crosstalk has a significant impact on a cell’s life cycle, differentiation, proliferation, growth, regeneration, and, consequently, on the normal functioning of an entire organ. Hippo signaling and YAP/TAZ nucleocytoplasmic shuttling play a pivotal role in normal development, homeostasis, and tissue regeneration, particularly in lung cells. Intersignaling communication has a significant impact on the core components of the Hippo pathway and on YAP/TAZ localization. This review describes the crosstalk between Hippo signaling and key lung signaling pathways (WNT, SHH, TGFβ, Notch, Rho, and mTOR) using lung cells as an example and highlights the remaining unanswered questions.