bluuebunny/crossref_metadata_2025 huggingface dataset:
Factors influencing time management skills among nurses in North West Bank, Palestine
Authors: Zyoud Raj’a Nayef
Published: October 2023

Background

In today’s companies, time management abilities have grown as a significant predictor of nurses’ success. Organizations have simplified their internal operations and flattened their organizational structures in an effort to increase productivity and cut expenses. As a result, successful time management skills are particularly crucial for nurses in recently restructured healthcare organizations. This study aimed at exploring factors influencing time management skills among Palestinian nurses.

Methods

Cross-sectional quantitative study of all nurses (715) working in private and government hospitals and primary healthcare centers in north Palestine was conducted. Time management skills were measured on a continuous scale using the Nursing Time Management Scale (NTMS), Arabic version. The scale measures various aspects of time management including goal setting, planning, scheduling, and organizing activities. The relationship between time management skills and background variables was assessed using the multivariate linear regression.

Results

The average total score for NTMS scale was 63.39 out of a total score of 90. This score indicates relatively good time management skills among the respondents. The multivariate linear regression results showed that females obtained slightly lower scores than males, coefficient = -2.36, p = 0.043. Nurses in primary care centers had significantly higher scores than nurses who work at hospitals, coefficient = 4.47, p = 0.004. The type of healthcare organization emerged as a significant factor predicting time management skills. Nurses in private hospitals had worse time management skills than nurses in government hospitals, coefficient = -12.27, p < 0.001. Nurse supervisors had better time management skills than staff nurses, coefficient = 4.01, p = 0.023. Nurses working in non-teaching hospitals had worse time management skills than nurses in teaching hospitals, coefficient = − 3.86, p = 0.001. Nurses who did not attend a time management course had worse time management skills than nurses who attended time management course, coefficient = − 4.05, p = p < 0.001.

Conclusions

Healthcare institutions should consider organizational and individual factors to improve the time management skills of their staff. Time management training interventions are proven and effective policies that are recommended to be adopted by all healthcare centers.
Defensive medicine through the lens of the managerial perspective: a literature review
Authors: Pischedda Gianfranco , Marinò Ludovico , Corsi Katia
Published: October 2023

Purpose

Several studies have been carried out on defensive medicine, but research from the managerial viewpoint is still scarce. Therefore, the aim of the present study is to conduct a literature review to better understand defensive medicine from a managerial perspective.

Design/methodology/approach

A literature review was conducted of studies focusing on the organisational (meso) level of healthcare providers and managerial practices. A final sample of 28 studies was processed.

Findings

Defensive medicine has mainly been studied in the USA, and scholars have principally used quantitative surveys. High-risk specialities have been a critical field of investigation, and a large portion of the papers are published in journals that cover medicine, health policy, education and law fields. The analysis showed that operations and the organisation of staffing were the most discussed managerial practices. No study considered planning and budgeting aspects.

Originality/value

The review confirmed that the managerial aspect of defensive medicine has not been fully addressed. Stimulated by this gap, this study analyses the managerial background of the defensive medicine phenomenon and shows which managerial practices have been most analysed. This paper also contributes to developing the literature on defensive medicine from the managerial side. Areas for future research include qualitative studies to investigate the behaviour of managers of healthcare companies to give a different perspective on defensive medicine and organisations’ decision-making.

Research limitations/implications

Some important publications might have been missed in this work because of the choice of only two databases. A further limit could be imposed by the use of the English language as an inclusion criterion.
Association between antenatal care facility readiness and provision of care at the client level and facility level in five low- and middle-income countries
Authors: Sheffel Ashley , Carter Emily , Zeger Scott , Munos Melinda K.
Published: October 2023

Background

Despite growing interest in monitoring improvements in quality of care, data on service quality in low-income and middle-income countries (LMICs) is limited. While health systems researchers have hypothesized the relationship between facility readiness and provision of care, there have been few attempts to quantify this relationship in LMICs. This study assesses the association between facility readiness and provision of care for antenatal care at the client level and facility level.

Methods

To assess the association between provision of care and various facility readiness indices for antenatal care, we used multilevel, multivariable random-effects linear regression models. We tested an inflection point on readiness scores by fitting linear spline models. To compare the coefficients between models, we used a bootstrapping approach and calculated the mean difference between all pairwise comparisons. Analyses were conducted at client and facility levels.

Results

Our results showed a small, but significant association between facility readiness and provision of care across countries and most index constructions. The association was most evident in the client-level analyses that had a larger sample size and were adjusted for factors at the facility, health worker, and individual levels. In addition, spline models at a facility readiness score of 50 better fit the data, indicating a plausible threshold effect.

Conclusions

The results of this study suggest that facility readiness is not a proxy for provision of care, but that there is an important association between facility readiness and provision of care. Data on facility readiness is necessary for understanding the foundations of health systems particularly in countries with the lowest levels of service quality. However, a comprehensive view of quality of care should include both facility readiness and provision of care measures.
A co-produced service evaluation of ethnic minority community service user experiences of a specialist mental health service during the COVID-19 pandemic
Authors: Kaur Kiranpal , Mutanda Daniel , Almond Palo , Pandey Aparajita , Young Paris , Levitan Tony , Bibby-Jones Anna-Marie
Published: October 2023

Background

For ethnic minority communities in the UK, the COVID-19 pandemic amplified existing health inequalities and created other consequential disadvantages like increased vulnerability to COVID-19, higher rates of hospital admissions, increased mortality and poorer mental health outcomes. While longer-term impacts of COVID-19 are considered, it is crucial for NHS mental health services to understand the specific barriers and needs of ethnic minority communities to provide consistent and equitable access to mental health services. These aspects were the focus of a service evaluation of a Sussex-wide mental health service conducted in co-production with experts-by-experience, public members, health professionals and researchers from ethnic minority communities.

Methods

Co-designed creative workshops (n = 13) and semi-structured qualitative interviews (n = 13) were used to explore experiences of accessing specialist mental health services during the COVID-19 pandemic. Participants were: Sussex Partnership NHS Foundation Trust (SPFT) service users recruited between October 2021 and January 2022; aged 16+; from ethnic minority community backgrounds. Data was analysed using Thematic Analysis.

Results

The analysis yielded five overarching themes contextualising service users’ experiences: (1) limited awareness of SPFT mental health services; (2) effects of COVID-19 in gaining access to SPFT; (3) SPFT reaching out to ethnic minorities; (4) being supported, 4a) hiding my mental health status from friends and families, 4b) lack of ethnic diversity in services, and 4c) better provision of information and support services, (5) relationship between childhood experiences and current mental health. These findings led to seven key recommendations for future service developments within SPFT.

Conclusions

Although this evaluation was set in the context of COVID-19, findings have highlighted specific mental health service needs for ethnic minorities that are applicable beyond the confines of the pandemic. Many benefited from online sessions seen as more inclusive. Mental health advocates, outreach and joint working with communities could help further reduce stigmatising attitudes and improve engagement with mental health services. Improved service awareness of the impact of childhood or historical traumas experienced by ethnic minority communities on current mental health, the role of cultural awareness training and availability of culturally adapted therapies is also needed. Many service improvement recommendations provided could impact all service users.
Midwife-led birthing centres in four countries: a case study
Authors: Bazirete Oliva , Hughes Kirsty , Lopes Sofia Castro , Turkmani Sabera , Abdullah Abu Sayeed , Ayaz Tasleem , Clow Sheila E. , Epuitai Joshua , Halim Abdul , Khawaja Zainab , Mbalinda Scovia Nalugo , Minnie Karin , Nabirye Rose Chalo , Naveed Razia , Nawagi Faith , Rahman Fazlur , Rasheed Saad Ibrahim , Rehman Hania , Nove Andrea , Forrester Mandy , Mandke Shree , Pairman Sally , Homer Caroline S. E.
Published: October 2023

Background

Midwives are essential providers of primary health care and can play a major role in the provision of health care that can save lives and improve sexual, reproductive, maternal, newborn and adolescent health outcomes. One way for midwives to deliver care is through midwife-led birth centres (MLBCs). Most of the evidence on MLBCs is from high-income countries but the opportunity for impact of MLBCs in low- and middle-income countries (LMICs) could be significant as this is where most maternal and newborn deaths occur. The aim of this study is to explore MLBCs in four low-to-middle income countries, specifically to understand what is needed for a successful MLBC.

Methods

A descriptive case study design was employed in 4 sites in each of four countries: Bangladesh, Pakistan, South Africa and Uganda. We used an Appreciative Inquiry approach, informed by a network of care framework. Key informant interviews were conducted with 77 MLBC clients and 33 health service leaders and senior policymakers. Fifteen focus group discussions were used to collect data from 100 midwives and other MLBC staff.

Results

Key enablers to a successful MLBC were: (i) having an effective financing model (ii) providing quality midwifery care that is recognised by the community (iii) having interdisciplinary and interfacility collaboration, coordination and functional referral systems, and (iv) ensuring supportive and enabling leadership and governance at all levels.

Conclusion

The findings of this study have significant implications for improving maternal and neonatal health outcomes, strengthening healthcare systems, and promoting the role of midwives in LMICs. Understanding factors for success can contribute to inform policies and decision making as well as design tailored maternal and newborn health programmes that can more effectively support midwives and respond to population needs. At an international level, it can contribute to shape guidelines and strengthen the midwifery profession in different settings.
The triglyceride-glucose index is a predictor for cardiovascular and all-cause mortality in CVD patients with diabetes or pre-diabetes: evidence from NHANES 2001–2018
Authors: Zhang Qin , Xiao Shucai , Jiao Xiaojuan , Shen Yunfeng
Published: October 2023

Background

The association between the triglyceride-glucose (TyG) index and mortality in cardiovascular disease (CVD) patients with diabetes or pre-diabetes remains unclear. This study aimed to investigate the relationship between baseline TyG index and all-cause and cardiovascular (CV) mortality in CVD patients with diabetes or pre-diabetes among American adults. .

Methods

This study enrolled 1072 CVD patients with diabetes or pre-diabetes from the National Health and Nutrition Examination Survey (2001–2018). Mortality outcomes were determined by linking to National Death Index (NDI) records up to December 31, 2019. Multivariate Cox proportional hazards models were constructed to analyze explore the associations between baseline TyG index and mortality. Non-linear correlations were explored using restricted cubic splines, and a two-piecewise Cox proportional hazards model for both sides of the inflection point was constructed.

Results

During 7541 person-years of follow-up, a total of 461 all-cause deaths and 154 CVD-related deaths were recorded. The restricted cubic splines revealed a U-shaped association between the baseline TyG index with all-cause and CVD mortality in CVD patients with diabetes or pre-diabetes. Specifically, baseline TyG index lower than the threshold values (TyG index < 9.05 in all-cause mortality and < 8.84 in CVD mortality) was negatively associated with mortality (HR 0.47, 95% CI = 0.27–0.81 for all-cause mortality and HR 0.25, 95% CI = 0.07–0.89 for CVD mortality). In contrast, baseline TyG index higher than the threshold values (TyG index > 9.05 in all-cause mortality and > 8.84 in CVD mortality) was positively associated with mortality (HR 1.42, 95% CI = 1.02–1.99 for all-cause mortality and HR 1.77, 95% CI = 1.08–2.91 for CVD mortality).

Conclusions

A U-shaped association was observed between the baseline TyG index with CVD and all-cause mortality in CVD patients with diabetes or pre-diabetes in a American population. The thresholds of 8.84 and 9.05 for CVD and all-cause mortality, respectively.
How do health system factors (funding and performance) impact on access to healthcare for populations experiencing homelessness: a realist evaluation
Authors: Siersbaek Rikke , Ford John , Ní Cheallaigh Clíona , Thomas Steve , Burke Sara
Published: October 2023

Background

People experiencing long-term homelessness face significant difficulties accessing appropriate healthcare at the right time and place. This study explores how and why healthcare performance management and funding arrangements contribute to healthcare accessibility or the lack thereof using long-term homeless adults as an example of a population experiencing social exclusion.

Methods

A realist evaluation was undertaken. Thirteen realist interviews were conducted after which data were transcribed, coded, and analysed.

Results

Fourteen CMOCs were created based on analysis of the data collected. These were then consolidated into four higher-level CMOCs. They show that health systems characterised by fragmentation are designed to meet their own needs above the needs of patients, and they rely on practitioners with a special interest and specialised services to fill the gaps in the system. Key contexts identified in the study include: health system fragmentation; health service fragmentation; bio-medical, one problem at a time model; responsive specialised services; unresponsive mainstream services; national strategy; short health system funding cycles; and short-term goals.

Conclusion

When health services are fragmented and complex, the needs of socially excluded populations such as those experiencing homelessness are not met. Health systems focus on their own metrics and rely on separate actors such as independent NGOs to fill gaps when certain people are not accommodated in the mainstream health system. As a result, health systems lack a comprehensive understanding of the needs of all population groups and fail to plan adequately, which maintains fragmentation. Policy makers must set policy and plan health services based on a full understanding of needs of all population groups.
Program managers’ perspectives on using knowledge to support population health management initiatives in their development towards health and wellbeing systems: a qualitative study
Authors: van Vooren N. J. E. , Drewes H. W. , de Weger E. , Bongers I. M. B. , Baan C. A.
Published: October 2023

Background

Population health management (PHM) initiatives are more frequently implemented as a means to tackle the growing pressure on healthcare systems in Western countries. These initiatives aim to transform healthcare systems into sustainable health and wellbeing systems. International studies have already identified guiding principles to aid this development. However, translating this knowledge to action remains a challenge. To help address this challenge, the study aims to identify program managers’ experiences and their expectations as to the use of this knowledge to support the development process of PHM initiatives.

Methods

Semi-structured interviews were held with program managers of ten Dutch PHM initiatives. These Dutch PHM initiatives were all part of a reflexive evaluation study and were selected on the basis of their variety in focus and involved stakeholders. Program managers were asked about their experiences with, and expectations towards, knowledge use to support the development of their initiative. The interviews with the program managers were coded and clustered thematically.

Results

Three lessons for knowledge use for the development of PHM initiatives were identified: (1) being able to use knowledge regarding the complexity of PHM development requires (external) expertise regarding PHM development and knowledge about the local situation regarding these themes; (2) the dissemination of knowledge about strategies for PHM development requires better guidance for action, by providing more practical examples of actions and consequences; (3) a collective learning process within the PHM initiative is needed to support knowledge being successfully used for action.

Conclusions

Disseminating and using knowledge to aid PHM initiatives is complex due to the complexity of the PHM development itself, and the different contextual factors affecting knowledge use in this development. The findings in this study suggest that for empirical knowledge to support PHM development, tailoring knowledge to only program managers’ use might be insufficient to support the initiatives’ development, as urgency for change amongst the other involved stakeholders is needed to translate knowledge to action. Therefore, including more partners of the initiatives in knowledge dissemination and mobilization processes is advised.
Neurotrophin-3 promotes peripheral nerve regeneration by maintaining a repair state of Schwann cells after chronic denervation via the TrkC/ERK/c-Jun pathway
Authors: Xu Xiong , Song Lili , Li Yueying , Guo Jin , Huang Shuo , Du Shuang , Li Weizhen , Cao Rangjuan , Cui Shusen
Published: October 2023

Background

Maintaining the repair phenotype of denervated Schwann cells in the injured distal nerve is crucial for promoting peripheral nerve regeneration. However, when chronically denervated, the capacity of Schwann cells to support repair and regeneration deteriorates, leading to peripheral nerve regeneration and poor functional recovery. Herein, we investigated whether neurotrophin-3 (NT-3) could sustain the reparative phenotype of Schwann cells and promote peripheral nerve regeneration after chronic denervation and aimed to uncover its potential molecular mechanisms.

Methods

Western blot was employed to investigate the relationship between the expression of c-Jun and the reparative phenotype of Schwann cells. The inducible expression of c-Jun by NT-3 was examined both in vitro and in vivo with western blot and immunofluorescence staining. A chronic denervation model was established to study the role of NT-3 in peripheral nerve regeneration. The number of regenerated distal axons, myelination of regenerated axons, reinnervation of neuromuscular junctions, and muscle fiber diameters of target muscles were used to evaluate peripheral nerve regeneration by immunofluorescence staining, transmission electron microscopy (TEM), and hematoxylin and eosin (H&E) staining. Adeno-associated virus (AAV) 2/9 carrying shRNA, small molecule inhibitors, and siRNA were employed to investigate whether NT-3 could signal through the TrkC/ERK pathway to maintain c-Jun expression and promote peripheral nerve regeneration after chronic denervation.

Results

After peripheral nerve injury, c-Jun expression progressively increased until week 5 and then began to decrease in the distal nerve following denervation. NT-3 upregulated the expression of c-Jun in denervated Schwann cells, both in vitro and in vivo. NT-3 promoted peripheral nerve regeneration after chronic denervation, mainly by upregulating or maintaining a high level of c-Jun rather than NT-3 itself. The TrkC receptor was consistently presented on denervated Schwann cells and served as NT-3 receptors following chronic denervation. NT-3 mainly upregulated c-Jun through the TrkC/ERK pathway.

Conclusion

NT-3 promotes peripheral nerve regeneration by maintaining the repair phenotype of Schwann cells after chronic denervation via the TrkC/ERK/c-Jun pathway. It provides a potential target for the clinical treatment of peripheral nerve injury after chronic denervation.
Evaluating a scalable ARCHES (Addressing Reproductive Coercion in Health Settings) model in government health facilities in Uasin Gishu county, Kenya: study protocol for a cluster-randomized controlled trial
Authors: Pearson Erin , Uysal Jasmine , Menzel Jamie , Undie Chi-Chi , Odwe George , Liambila Wilson , Silverman Jay G.
Published: October 2023

Background

Since 2013, the World Health Organization has recommended that reproductive coercion (RC) and intimate partner violence (IPV) be addressed within reproductive health services and, in 2018, the Lancet Commission on Sexual and Reproductive Health and Rights found that RC and IPV were significant contributors to unmet need for family planning (FP) and unintended pregnancy. In Kenya, the Ministry of Health (MOH) has made reduction of unintended pregnancy and gender-based violence a primary objective. Despite this need and guidance, no clinic-based intervention models outside of the U.S. (apart from the one described here) have demonstrated efficacy to improve FP use and reduce IPV or RC thereby reducing unintended pregnancy. ARCHES (Addressing Reproductive Coercion in Health Settings) is a brief, clinic-based intervention delivered by existing FP providers aiming to: (1) Increase women’s ability to use FP without interference, (2) Provide a safe and supportive environment for IPV disclosure and referral to support services, and (3) Improve quality of FP counseling, including addressing RC and IPV. The objective of this study is to generate evidence on scaling integrated FP services (including FP, RC, and IPV) in public sector health facilities in Uasin Gishu county, Kenya via adaptation and implementation of ARCHES in partnership with the Kenya MOH.

Methods

A cluster-randomized controlled trial paired with concurrent implementation science assessments will test effectiveness of the ARCHES model, adapted for scale by the Kenya MOH, in reducing unintended pregnancy. Female FP clients aged 15–49 years at selected sites will complete baseline surveys (immediately prior to receiving care), immediately post-visit exit surveys, and 6-month follow-up surveys. Provider surveys will assess changes in gender-equitable attitudes and self-efficacy to address violence reported by their clients. Costs associated with scaling ARCHES will be tracked and utilized in combination with results of the effectiveness trial to assess costs and cost-effectiveness relative to the standard of care.

Discussion

This study will provide evidence of the effectiveness of a facility-based intervention to address RC and IPV within public sector FP services at scale, as adapted and implemented in Uasin Gishu county, Kenya.

Trial registration Trial registered on 28 September 2023 with clinicaltrials.gov NCT06059196.
Decoding the immune landscape following hip fracture in elderly patients: unveiling temporal dynamics through single-cell RNA sequencing
Authors: Lu Yining , Luo Yang , Zhang Qi , Chen Wei , Zhang Ning , Wang Ling , Zhang Yingze
Published: October 2023

Background

Hip fractures in the elderly have significant consequences, stemming from the initial trauma and subsequent surgeries. Hidden blood loss and stress due to concealed injury sites could impact the whole osteoimmune microenvironment. This study employs scRNA-seq technique to map immune profiles in elderly hip fracture patients from post-trauma to the recovery period, investigating the dynamic changes of immune inflammation regulation subgroups.

Methods

We collected peripheral blood samples from four elderly hip fracture patients (two males and two females, all > 75 years of age) at three different time points (24 h post-trauma, 24 h post-operation, and day 7 post-operation) and applied scRNA-seq technique to analyze the cellular heterogeneity and identify differentially expressed genes in peripheral blood individual immune cells from elderly hip fracture patients.

Results

In this study, we analyzed the composition and gene expression profiles of peripheral blood mononuclear cells (PBMCs) from elderly hip fracture patients by scRNA-seq and further identified new CD14 monocyte subpopulations based on marker genes and transcriptional profiles. Distinct gene expression changes were observed in various cell subpopulations at different time points. C-Mono2 monocyte mitochondria-related genes were up-regulated and interferon-related and chemokine-related genes were down-regulated within 24 h post-operation. Further analysis of gene expression profiles at day 7 post-operation showed that C-Mono2 monocytes showed downregulation of inflammation-related genes and osteoblast differentiation-related genes. However, the expression of these genes in cytotoxic T cells, Treg cells, and B cell subsets exhibited a contrasting trend. GZMK+CD8+ cytotoxic T cells showed downregulation of chemokine-related genes, and Treg cells showed upregulation of genes related to the JAK/STAT signaling pathway. Furthermore, we examined interactions among diverse immune cell subsets, pinpointing specific ligand-receptor pairs. These findings imply cross-talk and communication between various cell types in the post-traumatic immune response.

Conclusions

Our study elucidates the notable alterations in immune cell subpopulations during different stages of hip fracture in elderly patients, both in terms of proportions and differential gene expressions. These changes provide significant clinical implications for tissue repair, infection prevention, and fracture healing in clinic.
Partial sternectomy with reconstruction of a giant cell tumor of the sternum, a case report, Saudi, Arabia
Authors: Eldaabossi Safwat , Al-Ghoneimy Yasser , Antar Ahmad , Lotfy Elsaid , Aljawad Hameed , Abish Yasser G. , Helyl Mohammed , Oraby Haytham , Soliman Hesham , Abdullatif Bassam , Nour Sameh O. , Lotfi Ahmad
Published: October 2023

Background

Giant cell tumor (GCT) is a relatively common and locally aggressive benign bone tumor that rarely affects the sternum.

Case presentation

We report a case of giant cell tumor of the sternum in a 28-year-old Saudi with painful swelling at the lower part of the sternum. Subtotal sternectomy and reconstruction with a neosternum using two layers of proline mesh, a methyl methacrylate prosthesis, and bilateral pectoralis muscle advancement flaps were performed.

Conclusions

Giant cell tumor of the sternum is a rare diagnosis. Surgical resection with negative margins is the ideal management. To avoid defects or instability of the chest wall, reconstruction of the chest wall with neosternum should be considered.
Exploring hematic crasis variations in cancer patients following SARS-CoV-2 vaccination: a real-practice study
Authors: Montella Liliana , Dell’Aversana Carmela , Pacella Daniela , Troise Simona , Russo Paola , Cacciapuoti Valentina , Ottaiano Alessandro , Di Marino Luigi , Coppola Paola , Liguori Carmela , Berretta Massimiliano , Maddaluno Salvatore , Altucci Lucia , Facchini Gaetano
Published: October 2023

SARS-CoV-2 vaccination is strongly recommended, particularly for fragile patients such as those undergoing active oncological treatments. It is crucial to conduct post-marketing surveillance in this patient population. In our study, we conducted a retrospective analysis of real-world data, including 136 patients who received SARS-CoV-2 vaccines and were undergoing anticancer treatments between March 1st and June 30th, 2021. All patients received mRNA vaccines, namely Pfizer-BioNTech’s COMIRNATY (BNT162b2 mRNA) and Moderna’s mRNA-1273 COVID-19 vaccines. We collected blood samples from the patients one week to 10 days before and after vaccine administration to assess full blood count with white cell differentials. Additionally, we monitored serology titers to detect any previous SARS-CoV-2 infection before hospital admission and tracked changes over time. Our findings revealed a significant occurrence of leukopenia following both the first and second vaccine doses among patients receiving chemotherapy and chemo-immunotherapy. Importantly, this effect was independent of demographic factors such as sex, age, and Body Mass Index. In the chemo-immunotherapy treated group, we observed that concomitant immune-mediated diseases were significantly associated with leukopenia following the second vaccine dose. Notably, in healthy subjects, transient neutropenia was recognized as an adverse event following vaccination. The observed lymphocytopenia during SARS-CoV-2 infection, combined with the impact on leukocyte counts observed in our study, underscores the need for larger post-marketing surveillance studies. Despite a treatment delay occurring in 6.6% of patients, the administration of mRNA vaccines did not have a significant impact on the treatment schedule in our series. These findings from a real-world setting provide valuable insights and suggest avenues for further prospective studies to explore potential complex interactions specific to this patient population.
KDM4C-mediated senescence defense is a targetable vulnerability in gastric cancer harboring TP53 mutations
Authors: Wang Kaiqing , Gong Zhicheng , Chen Yanyan , Zhang Meimei , Wang Suzeng , Yao Surui , Liu Zhihui , Huang Zhaohui , Fei Bojian
Published: October 2023

Background

Gastric cancer patients harboring a TP53 mutation exhibit a more aggressive and chemoresistant phenotype. Unfortunately, efforts to identify the vulnerabilities to overcome these aggressive malignancies have made minimal progress in recent years. Therefore, there is an urgent need to explore the novel therapeutic strategies for this subclass. Histone methylation modulators are critical epigenetic targets for cancer therapies that help maintain the malignancies of cancers harboring TP53 mutations and senescence evasion. Triggering senescence is now considered to benefit multiple cancer therapies. Furthermore, senescence-based “one-two punch” therapy was validated in clinical trials. Therefore, we hypothesized that screening epigenetic modulators might help identify a novel vulnerability to trigger senescence in gastric cancer harboring TP53 mutations.

Results

We developed a novel efficient approach to identify senescence inducers by sequentially treating cells with drug candidates and senolytic agents. Based on this, we demonstrated that QC6352 (a selective KDM4C inhibitor) efficiently triggered cellular senescence in gastric cancer harboring TP53 mutations. More importantly, the “one-two punch’ therapy consisting of QC6352 and SSK1 eliminates tumor cells harboring TP53 mutations. This finding highlights a potential therapeutic strategy for the aggressive subgroup of gastric cancer. Besides, the functions of QC6352 were totally unknown. We demonstrated that QC6352 might possess far more powerful anti-tumor capacities compared to the traditional genotoxic drugs, 5-Fu and Oxaliplatin.

Conclusions

This initial investigation to identify a senescence inducer revealed that QC6352 triggers senescence in gastric cancer cells harboring TP53 mutations by regulating the SP1/CDK2 axis through suppressing KDM4C. QC6352 and senolytic agent-SSK1 represent a novel ‘one-two punch’ therapeutic strategy for the more malignant gastric cancer subtypes.
Cellular vimentin regulates the infectivity of Newcastle disease virus through targeting of the HN protein
Authors: Lu Xiaolong , Liu Kaituo , Chen Yu , Gao Ruyi , Hu Zenglei , Hu Jiao , Gu Min , Hu Shunlin , Ding Chan , Jiao Xinan , Wang Xiaoquan , Liu Xiufan , Liu Xiaowen
Published: October 2023

The haemagglutinin-neuraminidase (HN) protein plays a crucial role in the infectivity and virulence of Newcastle disease virus (NDV). In a previous study, the mutant HN protein was identified as a crucial virulence factor for the velogenic variant NDV strain JS/7/05/Ch, which evolved from the prototypic vaccine strain Mukteswar. Furthermore, macrophages are the main susceptible target cells of NDV. However, the possible involvement of cellular molecules in viral infectivity remains unclear. Herein, we elucidate the crucial role of vimentin, an intermediate filament protein, in regulating NDV infectivity through targeting of the HN protein. Using LC‒MS/MS mass spectrometry and coimmunoprecipitation assays, we identified vimentin as a host protein that differentially interacted with prototypic and mutant HN proteins. Further analysis revealed that the variant NDV strain induced more significant rearrangement of vimentin fibres compared to the prototypic NDV strain and showed an interdependence between vimentin rearrangement and virus replication. Notably, these mutual influences were pronounced in HD11 chicken macrophages. Moreover, vimentin was required for multiple infection processes of the variant NDV strain in HD11 cells, including viral internalization, fusion, and release, while it was not necessary for those of the prototypic NDV strain. Collectively, these findings underscore the pivotal role of vimentin in NDV infection through targeting of the HN protein, providing novel targets for antiviral treatment strategies for NDV.
Effects of CPAP and FiO2 on respiratory effort and lung stress in early COVID-19 pneumonia: a randomized, crossover study
Authors: Giosa Lorenzo , Collins Patrick Duncan , Sciolla Martina , Cerrone Francesca , Di Blasi Salvatore , Macrì Matteo Maria , Davicco Luca , Laguzzi Andrea , Gorgonzola Fabiana , Penso Roberto , Steinberg Irene , Muraccini Massimo , Perboni Alberto , Russotto Vincenzo , Camporota Luigi , Bellani Giacomo , Caironi Pietro
Published: October 2023

Background

in COVID-19 acute respiratory failure, the effects of CPAP and FiO2 on respiratory effort and lung stress are unclear. We hypothesize that, in the compliant lungs of early Sars-CoV-2 pneumonia, the application of positive pressure through Helmet-CPAP may not decrease respiratory effort, and rather worsen lung stress and oxygenation when compared to higher FiO2 delivered via oxygen masks.

Methods

In this single-center (S.Luigi Gonzaga University-Hospital, Turin, Italy), randomized, crossover study, we included patients receiving Helmet-CPAP for early (< 48 h) COVID-19 pneumonia without additional cardiac or respiratory disease. Healthy subjects were included as controls. Participants were equipped with an esophageal catheter, a non-invasive cardiac output monitor, and an arterial catheter. The protocol consisted of a random sequence of non-rebreather mask (NRB), Helmet-CPAP (with variable positive pressure and FiO2) and Venturi mask (FiO2 0.5), each delivered for 20 min. Study outcomes were changes in respiratory effort (esophageal swing), total lung stress (dynamic + static transpulmonary pressure), gas-exchange and hemodynamics.

Results

We enrolled 28 COVID-19 patients and 7 healthy controls. In all patients, respiratory effort increased from NRB to Helmet-CPAP (5.0 ± 3.7 vs 8.3 ± 3.9 cmH2O, p < 0.01). However, Helmet’s pressure decreased by a comparable amount during inspiration (− 3.1 ± 1.0 cmH2O, p = 0.16), therefore dynamic stress remained stable (p = 0.97). Changes in static and total lung stress from NRB to Helmet-CPAP were overall not significant (p = 0.07 and p = 0.09, respectively), but showed high interpatient variability, ranging from − 4.5 to + 6.1 cmH2O, and from − 5.8 to + 5.7 cmH2O, respectively. All findings were confirmed in healthy subjects, except for an increase in dynamic stress (p < 0.01). PaO2 decreased from NRB to Helmet-CPAP with FiO2 0.5 (107 ± 55 vs 86 ± 30 mmHg, p < 0.01), irrespective of positive pressure levels (p = 0.64). Conversely, with Helmet’s FiO2 0.9, PaO2 increased (p < 0.01), but oxygen delivery remained stable (p = 0.48) as cardiac output decreased (p = 0.02). When PaO2 fell below 60 mmHg with VM, respiratory effort increased proportionally (p < 0.01, r = 0.81).

Conclusions

In early COVID-19 pneumonia, Helmet-CPAP increases respiratory effort without altering dynamic stress, while the effects upon static and total stress are variable, requiring individual assessment. Oxygen masks with higher FiO2 provide better oxygenation with lower respiratory effort.

Trial registration Retrospectively registered (13-May-2021): clinicaltrials.gov (NCT04885517), https://clinicaltrials.gov/ct2/show/NCT04885517.
Reliability-aware failure recovery for cloud computing based automatic train supervision systems in urban rail transit using deep reinforcement learning
Authors: Zhu Li , Zhuang Qingheng , Jiang Hailin , Liang Hao , Gao Xinjun , Wang Wei
Published: October 2023

As urban rail transit construction advances with information technology, modernization, information, and intelligence have become the direction of development. A growing number of cloud platforms are being developed for transit in urban areas. However, the increasing scale of urban rail cloud platforms, coupled with the deployment of urban rail safety applications on the cloud platform, present a huge challenge to cloud reliability.One of the key components of urban rail transit cloud platforms is Automatic Train Supervision (ATS). The failure of the ATS cloud service would result in less punctual trains and decreased traffic efficiency, making it essential to research fault tolerance methods based on cloud computing to improve the reliability of ATS cloud services. This paper proposes a proactive, reliability-aware failure recovery method for ATS cloud services based on reinforcement learning. We formulate the problem of penalty error decision and resource-efficient optimization using the advanced actor-critic (A2C) algorithm. To maintain the freshness of the information, we use Age of Information (AoI) to train the agent, and construct the agent using Long Short-Term Memory (LSTM) to improve its sensitivity to fault events. Simulation results demonstrate that our proposed approach, LSTM-A2C, can effectively identify and correct faults in ATS cloud services, improving service reliability.
Upregulation of BMP1 through ncRNAs correlates with adverse outcomes and immune infiltration in clear cell renal cell carcinoma
Authors: Gong Mancheng , Feng Shengxing , Zhou Dongsheng , Luo Jinquan , Lin Tianxin , Qiu Shaopeng , Yuan Runqiang , Dong Wenjing
Published: October 2023

Background

Renal cell carcinoma (RCC) accounts for approximately 2–3% of all adult malignancies. Clear cell renal cell carcinoma (ccRCC), which comprises 70–80% of all RCC cases, is the most common histological subtype.

Methods

ccRCC transcriptome data and clinical information were downloaded from the TCGA database. We used the TCGA and GEPIA databases to analyze relative expression of BMP1 in various types of human cancer. GEPIA was used to perform survival analysis for BMP1 in various cancer types. Upstream binding miRNAs of BMP1 were obtained through several important target gene prediction tools. StarBase was used to predict candidate miRNAs that may bind to BMP1 and candidate lncRNAs that may bind to hsa-miR-532-3p. We analyzed the association between expression of BMP1 and immune cell infiltration levels in ccRCC using the TIMER website. The relationship between BMP1 expression levels and immune checkpoint expression levels was also investigated.

Results

BMP1 was upregulated in GBM, HNSC, KIRC, KIRP and STAD and downregulated in KICH and PRAD. Combined with OS and DFS, BMP1 can be used as a biomarker for poor prognosis among patients with KIRC. Through expression analysis, survival analysis and correlation analysis, LINC00685, SLC16A1-AS1, PVT1, VPS9D1-AS1, SNHG15 and the CCDC18-AS1/hsa-miR-532-3p/BMP1 axis were established as the most potential upstream ncRNA-related pathways of BMP1 in ccRCC. Furthermore, we found that BMP1 levels correlated significantly positively with tumor immune cell infiltration, biomarkers of immune cells, and immune checkpoint expression.

Conclusion

Our results demonstrate that ncRNA-mediated high expression of BMP1 is associated with poor prognosis and tumor immune infiltration in ccRCC.
Counterfeits on dark markets: a measurement between Jan-2014 and Sep-2015
Authors: Soldner Felix , Kleinberg Bennett , Johnson Shane D.
Published: October 2023

Counterfeits harm consumers, governments, and intellectual property holders. They accounted for 3.3% of worldwide trades in 2016, having an estimated value of $509 billion in the same year. Estimations in the literature are mostly based on border seizures, but in this paper, we examined openly labeled counterfeits on darknet markets, which allowed us to gather and analyze information from a different perspective. Here, we analyzed data from 11 darknet markets for the period Jan-2014 and Sep-2015. The findings suggest that darknet markets harbor similar counterfeit product types to those found in seizures but that the share of watches is higher while the share of electronics, clothes, shoes, and Tobacco is lower on darknet markets. Also, darknet market counterfeits seem to have similar shipping origins as seized goods, with some exceptions, such as a relatively high share (5%) of dark market counterfeits originating from the US. Lastly, counterfeits on dark markets tend to have a relatively low price and sales volume. However, based on preliminary estimations, the equivalent products on the surface web appear to be advertised for a multiple of the prices found for darknet markets. We provide some suggestions on how information about darknet market counterfeits could be used by companies and authorities for preventative purposes, showing that insight gathering from the dark web is valuable and could be a cost-effective alternative (or compliment) to border seizures. Thus, monitoring darknet markets can help us understand the counterfeit landscape better.
Early modern knitted caps (fifteenth to sixteenth centuries): analyzing dyes in archaeological samples using microspectrofluorimetry complemented by HPLC–MS
Authors: Nabais Paula , Malcolm-Davies Jane , Melo Maria João , Teixeira Natércia , Behlen Beatrice
Published: October 2023

The knitted cap was the ubiquitous and most visible garment men wore throughout early modern society, from apprentices to royals. Documentary evidence also suggests that red was a conventional color for specific garments in the sixteenth century, including knitted caps. However, most knitted caps in museum collections are now a muddy brown characteristic of archaeological textiles, and their original color has seldom been studied. Considering the potential of microspectrofluorimetry for analyzing dyes in ancient textiles and manuscript illuminations, this technique was tested on six caps dating from the fifteenth to sixteenth centuries examined in the Knitting in Early Modern Europe research project. The colors are in good preservation condition in two samples, whereas the others show extensive degradation. The emission and excitation spectra acquired allowed the identification of the similarities and differences between samples, grouping them into different dye sources such as cochineal-based and madder-based (RED1 and RED2, respectively). For the coif cap and split-brimmed cap in good condition, analysis through HPLC–MS confirmed the sources of the dyes as Rubia tinctorum and cochineal. It also disclosed the source for another coif cap as Kermes vermilio (RED4). The other knitted items are possibly madder-based (RED3), but HPLC–MS did not allow confirmation of the madder source. The continuing development of a database of excitation and emission spectra acquired from historical textiles, such as the knitted caps, will support the identification of dye sources and specific formulations. Although this technique demands a comprehensive database of references for comparison with the complex signals identified, it allows for rapid spectra acquisition, providing tremendously valuable information.
Invasive lobular carcinoma of the breast with colonic metastasis: a case series of three patients
Authors: Otsuka Shinya , Komuro Kazuteru , Suzuoki Masato , Hayasaka Shuhei , Tsuda Momoko , Kubo Kimitoshi , Ueki Tomone , Moriya Yumi , Kimura Noriko , Ohara Masanori
Published: October 2023

Background

Although metastatic spread of breast cancer to the gastrointestinal tract is very rare, it is more likely to occur in invasive lobular carcinoma (ILC) than in ductal carcinoma. Colonic metastasis is particularly rare, and the treatment strategies for these cases are not clearly defined. Herein, we report three cases of ILC with various abdominal symptoms associated with colonic metastasis.

Case presentation

Case 1 A 70-year-old female patient with vomiting and melena was referred to our hospital. Endoscopic examination revealed a Dieulafoy ulcer in the rectum and an elevated lesion in the descending colon. She also had two breast nodules, and was diagnosed as ILC with colonic metastasis. Considering her general condition, the best supportive care (BSC) was offered. The patient died 4 months after confirmation of the diagnosis. Case 2 An 80-year-old female patient presented with diarrhea and vomiting. She was diagnosed with ILC with colonic metastasis, and a coloscopy revealed stenosis of the transverse colon with a metastatic lesion. Ileosigmoid bypass surgery was performed for intestinal obstruction, and systemic treatment for breast cancer was initiated. The patient developed peritoneal carcinomatosis and died 1 year and 2 months after surgery. Case 3 A 56-year-old female patient underwent left total mastectomy for ILC, and laparoscopic transverse colectomy was conducted for a colonic lesion 9 years and 2 months after. The diagnosis as colonic metastasis was not confirmed at that time. Two years and 2 months later, torose lesions were detected in the hepatic flexural and descending colon, and histopathological findings indicated that all colon tumors, including the previously resected tumor, were metastatic spread of ILC. Systemic treatment was continued, but the transverse colonic lesion penetrated the abdominal wall, and an abscess formed 2 years and 11 months after the resection. The fistula improved by continuous suction drainage following ileostomy but recurred, and the patient died 3 years and 8 months after colectomy.

Conclusions

Colonic metastases from breast cancer can trigger various abdominal symptoms, and the prognosis in these cases is generally poor. In selected cases, surgical treatment for abdominal symptoms and subsequent systemic therapy can contribute to a prolonged prognosis.