bluuebunny/crossref_metadata_2025 huggingface dataset:
Ocular motor disorders in children and adults with mTBI: a scoping review protocol
Authors: Theis Jacqueline , Chen Angela M , Burgher Allegra P , Greenspan Lynn D , Morgenstern Andrew , Salzano Aaron D , Yap Tiong Peng , Scheiman Mitchell , Roberts Tawna L
Published: October 2023

Introduction

Ocular motor function is susceptible to neurological injury because it requires a large portion of brain circuitry including every lobe of the brain, brainstem, thalamus, basal ganglia, cerebellum, cranial nerves and visual tracts. While reports of a high frequency of ocular motor dysfunctions after mild traumatic brain injury (mTBI) span multidisciplinary journals, there is no scoping review of the signs, diagnostic assessments and criteria, and appropriate management of ocular motor disorders post-mTBI. Post-mTBI ocular motor dysfunction has been reported to respond to active treatment. The objective of this scoping review is to map the available evidence on the diagnostic assessment and treatment modalities currently used in the management of mTBI-related ocular motor disorders in children and adults. This scoping review also aims to identify gaps in the current literature and provide suggestions for future research.

Methods and analysis

This review will include populations with reported concussion and/or mTBI without restrictions on age, race, sex or time since injury. The review will evaluate the reported symptoms related to ocular motor dysfunction, types of assessments and diagnostic criteria used, reported treatments, and the level of evidence supporting the reported treatments. This review will exclude literature on brain injury of non-traumatic aetiology and moderate/severe traumatic brain injury. Ocular motor dysfunction after mTBI appears in journals across multiple disciplines. Thus, multiple databases will be evaluated including Pubmed, Embase, PEDro, OVID, Clinical Key, Google Scholar and REHABDATA. Literature will be searched from inception to present day. Evidence sources will include experimental study designs including randomised controlled trials, non-randomised controlled trials and interrupted time-series. Additionally, analytical observational studies including prospective and retrospective cohort studies, case series, cross-sectional studies and clinical practice guidelines will be considered for inclusion. Data will be extracted on clinical presentation, frequency, assessment, diagnostic criteria management strategies and outcomes of concussion and mTBI-related ocular motor disorders.

Ethics and dissemination

This scoping review will use data from existing publications and does not require ethical approval by an institutional review board. Results will be disseminated through publication in a peer-reviewed scientific journal and presented at relevant conferences and as part of future workshops with professionals involved with diagnosis and management of patients with mTBI.
LitCog Caregiver Cohort: a prospective, observational cohort study investigating US caregivers’ health literacy, self-care skills and cognitive function
Authors: O'Conor Rachel , Bonham Morgan , Opsasnick Lauren , Magnuson Grace , Yoshino Benavente Julia , Curtis Laura M , Morrissey Kwasny Mary , Wolf Michael
Published: October 2023

Introduction

Many older adults receive assistance in managing chronic conditions. Yet complicating the utility of caregiver support is whether caregivers have sufficient skills to aid in a patient’s self-care. Health literacy and cognition are important determinants of older adults’ health outcomes, but few studies have examined caregiver health literacy, cognition and self-care skills and their relations to patient outcomes.

Methods and analysis

We will expand an ongoing cognitive ageing cohort study (LitCog) to enroll a parallel caregiver cohort. Caregivers are eligible if they are (1) ≥18 years of age, (2) provided care for ≥6 months and (3) assisted with at least one activity of daily living, instrumental activity of daily living or health management task. Caregivers will complete interviews at time points corresponding with the LitCog participant interviews. Caregivers will complete assessments of health literacy, self-care skills, cognitive function, caregiver healthcare task difficulty, caregiver burden, caregiver self-efficacy, activation, technology use, busyness and routine and relationship quality. Caregivers will self-report the nature and intensity of care provided, and their own health status. Associations between caregiver presence and caregiver capacity with patient outcomes will be examined in a series of regression models, and mediating and moderating factors will be tested.

Ethics and dissemination

The Institutional Review Board at Northwestern University has approved the study protocol (STU00026255). Results will be published in peer-reviewed journals and summaries will be provided to the funders of the study as well as patients and caregivers.
Refining the provider payment system of India’s government-funded health insurance programme: an econometric analysis
Authors: Prinja Shankar , Bahuguna Pankaj , Singh Maninder Pal , Guinness Lorna , Goyal Aarti , Aggarwal Vipul
Published: October 2023

Objectives

Reimbursement rates in national health insurance schemes are frequently weighted to account for differences in the costs of service provision. To determine weights for a differential case-based payment system under India’s publicly financed national health insurance scheme, the Ayushman Bharat Pradhan Mantri Jan Arogya Yojana (PM-JAY), by exploring and quantifying the influence of supply-side factors on the costs of inpatient admissions and surgical procedures.

Design

Exploratory analysis using regression-based cost function on data from a multisite health facility costing study—the Cost of Health Services in India (CHSI) Study.

Setting

The CHSI Study sample included 11 public sector tertiary care hospitals, 27 public sector district hospitals providing secondary care and 16 private hospitals, from 11 Indian states.

Participants

521 sites from 57 healthcare facilities in 11 states of India.

Interventions

Medical and surgical packages of PM-JAY.

Primary and secondary outcome measures

The cost per bed-day and cost per surgical procedure were regressed against a range of factors to be considered as weights including hospital location, presence of a teaching function and ownership. In addition, capacity utilisation, number of beds, specialist mix, state gross domestic product, State Health Index ranking and volume of patients across the sample were included as variables in the models. Given the skewed data, cost variables were log-transformed for some models.

Results

The estimated mean costs per inpatient bed-day and per procedure were 2307 and 10 686 Indian rupees, respectively. Teaching status, annual hospitalisation, bed size, location of hospital and average length of hospitalisation significantly determine the inpatient bed-day cost, while location of hospital and teaching status determine the procedure costs. Cost per bed-day of teaching hospitals was 38–143.4% higher than in non-teaching hospitals. Similarly, cost per bed-day was 1.3–89.7% higher in tier 1 cities, and 19.5–77.3% higher in tier 2 cities relative to tier 3 cities, respectively. Finally, cost per surgical procedure was higher by 10.6–144.6% in teaching hospitals than non-teaching hospitals; 12.9–171.7% higher in tier 1 cities; and 33.4–140.9% higher in tier 2 cities compared with tier 3 cities, respectively.

Conclusion

Our study findings support and validate the recently introduced differential provider payment system under the PM-JAY. While our results are indicative of heterogeneity in hospital costs, other considerations of how these weights will affect coverage, quality, cost containment, as well as create incentives and disincentives for provider and consumer behaviour, and integrate with existing price mark-ups for other factors, should be considered to determine the future revisions in the differential pricing scheme.
Quality improvement initiative for a sustained increase in human milk donation during the hospital stay
Authors: Jain Suksham , Bansal Akanksha , Khurana Supreet , Chawla Deepak
Published: October 2023

Background

The demand for donors' human milk is much more than the availability of the same due to the myriad challenges faced during the collection process.

Methods

Baseline milk volume donation done in a human milk bank facility located in tertiary care government institute in a low-middle income country was assessed. It was initially aimed to increase the absolute quantity of milk volume donation by 30% over a period of 6 months, which was subsequently continued following COVID-19 emergence (over another 12 months) along with a particular emphasis on the sustenance of milk donation activities.

Interventions

Counselling of both the healthcare workers and stakeholders, standardising the timing of milk donation and other policies, equipment in proportion to demand and supply and addition of human resource were done as a multiprong approach to have sustained increase in human milk donation.

Results

The median control line (MCL) showed a shift of 27.8%; from a baseline of 5032 mL to 6971 mL during intervention phase I comprising of five plan do study act cycles spread over a period of 6 months. During the sustenance phase I even though the monthly collection was non-uniform, there was a further 16% upward shift in MCL to 8122 mL. During the second intervention phase, each component of the Ishikawa diagram was worked on (people, policy, place, procedure) resulting in a more than 100% increase from sustenance phase I taking the MCL to 17 181 mL with an overall increase of 3.41 times from the baseline.

Conclusion

Dedicated counselling and constant motivation have been conventionally considered as the utmost measure to increase milk volume donation in milk bank. Our study highlights the need to introduce scheduled timings along with sufficient equipment and manpower to overcome the shortage of milk donation in human milk bank facilities.
Quality improvement initiative improves the empiric antibiotic prescribing practices in a tertiary care children’s hospital in India
Authors: Kushala  , Pemde Harish , Kumar Virendra , Datta Vikram , Saxena Sonal
Published: October 2023

Introduction

Infections are a common cause of paediatric morbidity. Antibiotics are vital in treating them. Erratic prescribing practices are an important cause for the development of antibiotic resistance. Our objective was to estimate the effectiveness of educational interventions to improve empirical antibiotic prescribing practices among paediatric trainees. We aimed to improve the compliance to antibiotic protocols and to sustain it over 6 months.

Methods

It is a time interrupted non-randomised trial conducted in a tertiary hospital in India. Initially, 200 admitted children were selected randomly. Their antibiotic prescriptions, adherence of prescriptions to the then existing antibiotics guidelines, course during hospital stay and the final outcome were noted. The existing antibiotic policy and its use were reviewed. It was then considered essential to prepare a fresh antibiotic policy based on national guidelines, local sensitivity patterns and with inputs from microbiologists. This was distributed to the residents through seminars, posters and cellphone friendly documents. Compliance to the policy was also tracked twice a week. The adherence to guideline was recorded in the subsequent 6 months.

Results

The adherence of empirical antibiotic prescriptions was 59% before intervention which improved to 72% in the first month, 90% in the second month, 86% and 78% in the third and sixth months, respectively. There was no significant difference in duration of stay and the outcome at discharge in the patients in adherent and non-adherent groups.

Conclusion

Educational interventions and frequent monitoring improved antibiotic prescribing practices among residents with no negative impact on patient outcomes. Quality improvements need persistent reinforcement and frequent monitoring to be sustainable.
Sustaining extended Kangaroo mother care in stable low birthweight babies in NICU: a quality improvement collaborative of six centres of Karnataka
Authors: Murthy Raksha , Kallesh Anil , Somasekhara Aradhya Abhishek , Bharadwaj Shruthi K , Venkatagiri Praveen , Jagadish Meena , Rao Poornachandra , Chandramouli Divya , Hema Doddarangaiah , Chaithra S N , Glory Hellan , Purkayastha Jayashree
Published: October 2023

Background

Kangaroo mother care (KMC) is a proven intervention for intact survival in preterms. Despite evidence, its adoption has been low. We used a point of care quality improvement (QI) approach to implement and sustain KMC in stable low birthweight babies from a baseline of 1.5 hours/baby/day to above 4 hours/baby/day through a series of plan-do-study-act (PDSA) cycles over a period of 53 weeks.

Methods

All babies with birth weight <2000 g not on any respiratory support or phototherapy and or umbilical lines were eligible. The key quantitative outcome was KMC hours/baby/day. A QI collaborative was formed between six centres of Karnataka mentored by a team with a previous QI experience on KMC. The potential barriers for extended KMC were evaluated using fishbone analysis. Baseline data were collected over 3 weeks. A bundled approach consisting of a variety of parent centric measures (such as staff awareness, making KMC an integral part of treatment order, foster KMC, awareness sessions to parents weekly, recognising KMC champions) was employed in multiple PDSA cycles. The data were aggregated biweekly and the teams shared their implementation experiences monthly.

Results

A total of 1443 parent–baby dyads were enrolled. The majority barriers were similar across the centres. Bundled approach incorporating foster KMC helped in the quick implementation of KMC even in outborns. Parental involvement and empowering nurses helped in sustaining KMC. Two centres had KMC rates above 10 hours/baby/day, while remaining four centres had KMC rates sustained above 6 hours/baby/day. Cross-learnings from team meetings helped to sustain efforts. Extended KMC could be implemented and sustained by low intensity training and QI collaboration.

Conclusions

Formation of a QI collaborative with mentoring helped in scaling implementation of extended KMC. Extended KMC could be implemented by parent centric best practices in all the centres without any additional need of resources.
Identifying value in healthcare transformation initiatives: an evaluation of an approach to benefits realisation
Authors: Vas Venessa , Gyambibi Loretta , Eftychiou Linda , Al-Omari Hassan , Glass James , Smith Mark , Matthew Dionne
Published: October 2023

Benefits realisation management (BRM) aims to facilitate the process of identifying, measuring and tracking desired benefits derived from a project. Improvement methodology frameworks often describe BRM as integral to identifying and measuring value derived from transformation initiatives within the National Health Service and beyond. Despite this, reporting of benefits realisation plans and methodological approaches to identifying and measuring benefits remains surprisingly scarce.

This project aimed to pilot and evaluate the application of a purpose-designed benefits mapping template with seven newly funded transformation projects across three hospitals in the UK. The scope of the template was to identify key project benefits and metrics associated with the project initiatives. Plan-do-study-act (PDSA) cycles were used to capture the approach and utilisation of the template by project teams. These methods also enabled critical review of the template as an enabler to identifying relevant benefits and project metrics.

Stakeholder engagement with the templates was variable. This was attributed to clinical pressures induced by the second wave of COVID-19 in the UK. Despite this, teams were able to produce completed templates outlining a number of wide-ranging benefits. Themes of benefits drawn from the maps include patient experience, patient outcomes, staff experience, access to care and efficiency. Qualitative feedback from teams included the reported value of a structured template to help recognise all the potential benefits associated with each project initiative. The PDSA cycles highlighted the template as an early step in BRM. Further components to this process are recommended to include consensus of the key metrics to be measured, a tool that summarises the reporting details of those metrics, and an effective means to collate reported metrics overtime.
Randomised trial of general practitioner online education for prescribing and test ordering
Authors: Bonney Andrew , Kobel Conrad , Mullan Judy , Metusela Christine , Rhee Joel J , Barnett Stephen , Batterham Marijka
Published: October 2023

Introduction

Potentially inappropriate medicine prescriptions and low-value diagnostic testing pose risks to patient safety and increases in health system costs. The aim of the Clinical and Healthcare Improvement through My Health Record usage and Education in General Practice study was to evaluate a scalable online quality improvement intervention, integrating online education regarding a national shared electronic health record and rational prescribing, pathology and imaging ordering by Australian general practitioners (GPs).

Methods

The study was a parallel three-arm randomised trial comprising a prescribing education arm, a pathology education arm and an imaging education arm. Currently practising GPs in Australia were eligible to participate and randomised on a 1:1:1 basis to the study arms after consenting. The response to the intervention in reducing potentially unnecessary medicine prescriptions and tests in each arm was assessed using the other two arms as controls. The primary outcome was the cost per 100 consultations of predefined medication prescriptions, pathology and radiology test ordering 6 months following the intervention, compared with 6 months prior. Outcomes were assessed on intention-to-treat and post hoc per-protocol bases using multilevel regression models, with the analysts blinded to allocation.

Results

In total, 106 GPs were enrolled and randomised (prescribing n=35, pathology n=36, imaging n=35). Data were available for 97 GPs at the end of trial (prescribing n=33, pathology n=32, imaging n=32) with 44 fully completing the intervention. In intention-to-treat analysis, there were no significant differences in the rates of change in costs across the three arms. Per protocol, there was a statistically significant difference in the rate of change in pathology costs (p=0.03). In the pathology arm, the rate of increase in pathology costs was significantly lower by $A187 (95% CI −$A340, −$A33) than the prescribing arm, and non-significantly $A9 (95% CI −$A128, $A110) lower than the imaging arm.

Discussion

This study provides some evidence for reductions in costs for low-value pathology test ordering in those that completed the relevant online education. The study experienced slow uptake and low completion of the education intervention during the COVID-19 pandemic. Changes were not significant for the primary endpoint, which included all participants. Improving completion rates and combining real-time feedback on prescribing or test ordering may increase the overall effectiveness of the intervention. Given the purely online delivery of the education, there is scope for upscaling the intervention, which may provide cost-effectiveness benefits.

Trial registration number

ACTRN12620000010998.
Creating and sustaining a digital community of practice for quality improvement in South-East Asia during the COVID-19 pandemic
Authors: Datta Vikram , Srivastava Sushil , Lalwani Komal , Garde Rahul , Patnaik Suprabha K , Venkatagiri Praveen , Pradeep Jeena , Bangal Vidhyadhar , Pemde Harish , Kumar Achala , Sooden Ankur , Vijayan Shreeja , Sawleshwarkar Kedar , Mehta Rajesh , Raina Neena , Khanna Rajesh , Singh Vivek , Singh Priyanka , Saha Khushboo , Sharma Chhavi , Jain Sonam
Published: October 2023

Introduction

Ensuring quality of care in Low and Middle Income countries (LMICs) is challenging. Despite the implementation of various quality improvement (QI) initiatives in public and private sectors, the sustenance of improvements continues to be a major challenge. A team of healthcare professionals in India developed a digital community of practice (dCoP) focusing on QI which now has global footprints.

Methodology

The dCoP was conceptualised as a multitiered structure and is operational online atwww.nqocncop.orgfrom August 2020 onwards. The platform hosts various activities related to the quality of care, including the development of new products, and involves different cadres of healthcare professionals from primary to tertiary care settings. The platform uses tracking indicators, including the cost of sustaining the dCoP to monitor the performance of the dCoP.

Result

Since its launch in 2020, dCoP has conducted over 130 activities using 13 tools with 25 940 registration and 13 681 participants. From April 2021, it has expanded to countries across the South-East Asia region and currently has participants from 53 countries across five continents. It has developed 20 products in four thematic areas for a targeted audience. dCoP is supporting mentoring of healthcare professionals from five countries in the South-East Asia region in their improvement journey. Acquiring new knowledge and improvement in their daily clinical practice has been reported by 93% and 80% of participants, respectively. The dCoP and its partners have facilitated the publication of nearly 40 articles in international journals.

Conclusion

This dCoP platform has become a repository of knowledge for healthcare professionals in the South-East Asia region. The current paper summarises the journey of this innovative dCoP in an LMIC setting for a wider global audience.
Academy for Quality and Safety Improvement (AQSI) project to improve diagnosis and documentation of malnutrition in a community hospital
Authors: Parkash Om , Jamil Saad , Chudzinski Valarie , Tahir Nayha , Gole Shrey , Deleon Jacqueline , Forde Cindy , Zahra Farah
Published: October 2023

Background

Malnutrition is a significant public health problem that affects many patients in inpatient settings. Timely identification and addressing malnutrition in an inpatient setting presents an opportunity to improve patient care and reduce costs. There is a clear link between malnutrition, increased length of hospital stay, higher risk of readmissions and infections, skin breakdown, and higher hospital costs due to complications.

Methods

We conducted a quality improvement project to increase the number of times patients were accurately diagnosed and successfully coded as malnourished. We used the Define, Measure, Analyse, Intervene, Control (DMAIC) process to complete this project. Data were collected for nearly a year using the Epic Report Tool developed explicitly for the project. Initial data showed that our hospital performed at 20% of patients diagnosed as malnourished, while the industry standard was 33%. A multidisciplinary team of physicians, nurses and dietitians identified critical areas of improvement, including incomplete nutritional assessments by nurses, delayed evaluations by dietitians and lack of documentation by physicians. We addressed these issues by partnering with nurse managers to provide education and individual accountability for missed screenings, expanding dietitian workflows to include an in-person assessment within 24 hours of consultation, and updating physician note templates to include smart phrases that automatically inserted nutritional evaluations from registered dietitians into notes. We also worked with hospital executives and administration to increase buy-in from participating care team members.

Results

Our interventions resulted in 100% of malnutrition screening tool being completed, 33% of patients being screened at risk of malnutrition, 98% of nutrition assessments being done within 24 hours of patient admission and 100% of providers documenting malnutrition findings.

Conclusions

Our study found an immediate and significant increase in the number of times malnutrition was diagnosed and ultimately coded during billing with our interventions. This highlights the importance of timely identification and addressing malnutrition in an inpatient setting to improve patient care and reduce costs. The DMAIC process and multidisciplinary team approach proved to be effective in identifying and addressing the barriers to malnutrition diagnosis in our hospital setting.
Epidemiology of injuries in elite Women’s Artistic Gymnastics: a retrospective analysis of six seasons
Authors: Charpy Séréna , Billard Pierre , Dandrieux Pierre-Eddy , Chapon Joris , Edouard Pascal
Published: October 2023

Background

Women’s Artistic Gymnastics (WAG) is a sport well known for requiring a heavy and difficult training load from a younger age to reach a high level of performance. This also is associated with an injury risk. Epidemiological studies are thus needed to improve injury prevention strategies.

Objective

We aimed to determine the injury epidemiology in French high-level WAG.

Methods

We conducted a retrospective analysis of injury data collected prospectively over six seasons from the 2014–2015 season to the 2019–2020 season among French high-level Women’s Artistic Gymnasts from the France Gymnastics National Centre of Saint-Etienne. We performed descriptive analyses, including the calculation of the 1-year injury prevalence.

Results

43 gymnasts were included in this study, representing 111 gymnast-seasons. A total of 285 injuries were collected over the study period, that was, an average of 2.6 injuries per gymnast per season. On average, 91.4% of gymnasts had at least one injury per season. The estimated injury incidence rate was 1.8 injuries per 1000 hours of gymnastics practice. The knee was the most affected joint (16%), followed by the elbow (12%) and the ankle (12%). The most frequent injury type was physis pathologies (16%) and bone injuries (15%). Eighty-eight per cent of injuries required a modification of the gymnastics practice.

Conclusions

The results of this study allowed a description of the epidemiology of injuries in this population of young and elite gymnasts. This very high injury prevalence supports the need to improve injury risk reduction strategies in WAG.
Quality improvement project demonstrating a sustained increase in the assessment and sampling of ascites for hospitalised patients with cirrhosis
Authors: Herrle Elizabeth L , Thim Monica , Buttarazzi Matthew S , Ptaschinski Jenna , Molina Victoria , Channell Natalie , Gordon Lesley B
Published: October 2023

Objective

Using quality improvement techniques, we aimed to improve the rate of assessment and sampling of ascitic fluid for the purpose of diagnosing spontaneous bacterial peritonitis in patients with cirrhosis admitted to the hospitalist service of our institution.

Design/methods

Based on stakeholder needs assessment, we implemented interventions targeting provider knowledge, procedure workflows and clinical decision support. We analysed key metrics during preintervention (September–December 2020), intervention roll-out (January–April 2021), postintervention (May–September 2021) and sustainability (September–December 2022) periods for admissions of patients with cirrhosis to our hospitalist service at Maine Medical Center, a 700-bed tertiary-care academic hospital in Portland, Maine, USA.

Results

Among patients with cirrhosis admitted to our service, documentation of assessment for paracentesis increased from a preintervention baseline of 60.1% to 93.5% (p<0.005) postintervention. For patients with ascites potentially amenable to paracentesis, diagnostic paracentesis rate increased from 59.7% to 93% (p<0.005), with the rate of paracentesis within 24 hours increasing from 52.6% to 77.2% (p=0.01). These improvements persisted during our sustainability period. Complication rate was low (1.2%) across all study periods.

Conclusion

Our quality improvement project led to a sustained improvement in the identification of patients with cirrhosis needing diagnostic paracentesis and an increased procedure completion rate. This improvement strategy serves as a model for needed work toward closing a national performance gap for patients with cirrhosis.
Targeting the ferroptosis crosstalk: novel alternative strategies for the treatment of major depressive disorder
Authors: Wang Luyao , Xu Rongyang , Huang Chengying , Yi Guozhong , Li Zhiyong , Zhang Huayang , Ye Rongxu , Qi Songtao , Huang Guanglong , Qu Shanqiang
Published: October 2023

Depression is a major contributor to poor global health and disability, with a recently increasing incidence. Although drug therapy is commonly used to treat depression, conventional antidepressant drugs have several disadvantages, including slow onset, low response rates and severe adverse effects. Therefore, developing effective therapies for depression remains challenging. Although various aetiological theories of depression exist, the underlying mechanisms of depression are complex, and further research is crucial. Moreover, oxidative stress (OS)-induced lipid peroxidation has been demonstrated to trigger ferroptosis. Both OS and ferroptosis are pivotal mechanisms implicated in the pathogenesis of neurological disorders, and investigation of the mediators involved in these processes has emerged as a prominent and active research direction. One previous study revealed that regulatory proteins involved in ferroptosis are implicated in the pathogenesis of depression, and antidepressant drugs could reverse depressive symptoms by inhibiting ferroptosisin vivo, suggesting an important role of ferroptosis in the pathogenesis of depression. Hence, our current comprehensive review offers an up-to-date perspective on the intricate mechanisms involved, specifically concerning ferroptosis and OS in the context of depression, along with promising prospects for using molecular mediators to target ferroptosis. We delineate the key targets of molecular mediators involved in OS and ferroptosis implicated in depression, most notably reactive oxygen species and iron overload. Considering the pivotal role of OS-induced ferroptosis in the pathogenesis of neurological disorders, delving deeper into the underlying subsequent mechanisms will contribute significantly to the identification of novel therapeutic targets for depression.
Divergent tumor and immune cell reprogramming underlying immunotherapy response and immune-related adverse events in lung squamous cell carcinoma
Authors: Chen Minjiang , Ma Pengfei , Zhang Yongchang , Wang Dong , Yu Zhuang , Fu Yujie , Zhao Xiaojing , Wang Mengzhao , Zhuang Guanglei , Jing Ying
Published: October 2023

Background

Lung squamous cell carcinoma (LUSC) remains a leading cause of cancer-related deaths with few therapeutic strategies. Immune checkpoint inhibitors (ICIs) have demonstrated promising efficacy in patients with LUSC. However, ICIs could also lead to a unique spectrum of immune-related adverse events (irAEs), which dampen the clinical outcome. In-depth characterization of the immune hallmarks of antitumor responses and irAEs remains an unmet need to maximize ICI-treatment benefits of patients.

Methods

We performed single-cell RNA sequencing (scRNA-seq) on pre-ICI and on-ICI treatment tumor biopsies. We used bulk RNA-seq data of matched pretreatment/on-treatment tumors and irAE affected organs to validate observations from scRNA-seq analysis. Two independent patient cohorts were collected to determine circulating tumor necrosis factor (TNF) protein expression levels.

Results

We found that increased proportions of a macrophage subcluster with highly expressed secreted phosphoprotein 1 (SPP1) and two tumor cell subclusters in irAE patients, whereas proportions of two cytotoxic CD8+ T cell subclusters were higher in patients with partial response (PR). TNF signaling pathway was conversely associated with treatment efficacy and irAE development in most macrophage and tumor cell subclusters. Cell–cell communications for TNF ligand-receptor pairs between macrophage/T cells and tumor cells were also bidirectionally remodeled in responders versus non-responders and irAE versus non-irAE patients. Bulk RNA-seq analysis on matched pretreatment/on-treatment tumors and irAE affected organs revealed remarkably enhanced macrophage abundance and TNF signaling pathway in on-treatment tumors and organs developed irAEs. Furthermore, we observed significantly increased circulating TNF protein in plasma or serum of irAE patients but not ICI responders, based on analysis of two independent LUSC patient cohorts and one published ICI patient cohort.

Conclusions

Our data depicts specific reprogramming of macrophage, T cells and tumor cells associated with ICI response and irAEs, elucidates divergent roles of TNF signaling in antitumor immunity and irAEs, and highlights the significance of TNF expression in irAE development in the LUSC setting.
Suicide booths and assistance without moral expression: a response to Braun
Authors: Donaldson Thomas
Published: October 2023

In a recent paper, Braun argued for an autonomy-based approach to assisted suicide as a way to avoid the expressivist objection to assisted dying laws. In this paper, I will argue that an autonomy-based approach actually extends the expressivist objection to assisted dying because it is not possible for one agent to assist another in pursuit of a goal without expressing that it would be good for that goal to come about. Braun argued that assisted dying should be viewed purely as an individual’s autonomous action, but this requires the assistance of the medical professional to be understood as that of a non-moral automaton, such as a suicide booth. Instead, it will be argued that a beneficent motivation to promote human flourishing provides moral reasons for both non-interference in the actions, for example, suicide, of competent agents and for considering whether assisting another agent with their goal will promote their flourishing.
Identification and assessment of classification criteria attributes for systemic lupus erythematosus in a regional medical record data network
Authors: Forrest Noah , Jackson Kathryn L , Tran Steven , Pacheco Jennifer A , Mitrovic Vesna , Furmanchuk A'lona , Kho Abel N , Ramsey-Goldman Rosalind , Walunas Theresa L
Published: October 2023

Objective

To assess the application and utility of algorithms designed to detect features of SLE in electronic health record (EHR) data in a multisite, urban data network.

Methods

Using the Chicago Area Patient-Centered Outcomes Research Network (CAPriCORN), a Clinical Data Research Network (CDRN) containing data from multiple healthcare sites, we identified patients with at least one positively identified criterion from three SLE classification criteria sets developed by the American College of Rheumatology (ACR) in 1997, the Systemic Lupus International Collaborating Clinics (SLICC) in 2012, and the European Alliance of Associations for Rheumatology and the ACR in 2019 using EHR-based algorithms. To measure the algorithms’ performance in this data setting, we first evaluated whether the number of clinical encounters for SLE was associated with a greater quantity of positively identified criteria domains using Poisson regression. We next quantified the amount of SLE criteria identified at a single healthcare institution versus all sites to assess the amount of SLE-related information gained from implementing the algorithms in a CDRN.

Results

Patients with three or more SLE encounters were estimated to have documented 2.77 (2.73 to 2.80) times the number of positive SLE attributes from the 2012 SLICC criteria set than patients without an SLE encounter via Poisson regression. Patients with three or more SLE-related encounters and with documented care from multiple institutions were identified with more SLICC criteria domains when data were included from all CAPriCORN sites compared with a single site (p<0.05).

Conclusions

The positive association observed between amount of SLE-related clinical encounters and the number of criteria domains detected suggests that the algorithms used in this study can be used to help describe SLE features in this data environment. This work also demonstrates the benefit of aggregating data across healthcare institutions for patients with fragmented care.
Occupational exposures of firefighting and urinary tract cancer risk among men in the Norwegian Fire Departments Cohort
Authors: Marjerrison Niki , Grimsrud Tom K , Hansen Johnni , Martinsen Jan Ivar , Nordby Karl-Christian , Olsen Raymond , Veierød Marit B , Kjærheim Kristina
Published: October 2023

Objectives

Increased risks of bladder cancer and mesothelioma were the strongest evidence for the recent reclassification of firefighting as carcinogenic (Group 1) by the International Agency for Research on Cancer. Our study aim was to develop indicators for specific firefighting exposures and examine associations with urinary tract cancer (UTC), including bladder cancer.

Methods

We developed indicators for exposure from employment at a fire department or in firefighting jobs, to fire and smoke, and to diesel exhaust for men in the Norwegian Fire Departments Cohort (n=4250). Incident UTC cases were obtained from the Cancer Registry of Norway (1960–2021). Poisson regression was used to estimate incidence rate ratios (IRR) with cumulative exposures grouped into tertiles (reference: lowest exposed tertile) with 0-year, 10-year and 15-year lagging of exposures.

Results

During 125 090 person-years of follow-up, there were 76 cases of UTC. IRRs were mostly non-significantly increased in the middle tertile and at or below 1 in the highest tertile for total duration of employment, number of fires attended and fire exposure score with and without lags. In the middle tertile for diesel exhaust exposure, UTC risk was elevated over twofold with 10-year (IRR 2.27, 95% CI 1.22 to 4.20) and 15- year (2.21, 1.18 to 4.16) lags, and near 1 in the highest tertile. Findings for bladder cancer were similar to those for UTC.

Conclusions

Dose-response associations between the exposure indicators and UTC were not observed. Future studies using the indicators with more cases are needed.
Linear stability of a Couette flow for non-monotone stress-power law models
Authors: Calusi Benedetta , Fusi Lorenzo , Farina Angiolo
Published: October 2023

In this paper we investigate the linear stability of a Couette flow driven by a shear stress imposed on the top surface of a fluid layer, assuming that the material obeys an “S-shaped” stress-power law model. The perturbation equation is solved numerically by means of a spectral collocation scheme based on Chebyshev polynomials. We show that there exists a range of Reynolds numbers in which multiple flows are possible. In particular, our results highlight that the solutions belonging to the ascending branches of the constitutive law are unconditionally stable, while those in the descending branch are unconditionally unstable.

Graphic abstract
On Proper Separation Theorems by Means of the Quasi-Relative Interior with Applications
Authors: Amahroq Tijani , Khatite Hassan , Oussarhan Abdessamad
Published: October 2023

In this paper, we establish several proper separation theorems for an element and a convex set and for two convex sets in terms of their quasi-relative interiors. Then, we prove that the separation theorem given by [Cammaroto, F and B Di Bella (2007). On a separation theorem involving the quasi-relative. Proceedings of the Edinburgh Mathematical Society, 50(3), 605–610] in Theorem 2.5, is in fact a proper separation theorem for two convex sets in which the classical interior is replaced by the quasi-relative interior. Besides, we extend some known results in the literature, such as [Adán, M and V Novo (2004). Proper efficiency in vector optimization on real linear spaces. Journal of Optimization Theory and Applications, 121, 515–540] in Theorem 2.1 and [Edwards, R (1965). Functional Analysis: Theory and Applications. New York: Reinhart and Winston] in Corollary 2.2.2, through the quasi-relative interior and the quasi-interior, respectively. As an application, we provide Karush–Kuhn–Tucker multipliers for quasi-relative solutions of vector optimization problems. Several examples are given to illustrate the obtained results.
Biological modeling with nonlocal advection–diffusion equations
Authors: Painter Kevin J. , Hillen Thomas , Potts Jonathan R.
Published: October 2023

The employment of nonlocal PDE models to describe biological aggregation and other phenomena has gained considerable traction in recent years. For cell populations, these methods grant a means of accommodating essential elements such as cell adhesion, critical to the development and structure of tissues. For animals, they can be used to describe how the nearby presence of conspecifics and/or heterospecifics influence movement behaviour. In this review, we will focus on classes of biological movement models in which the advective (or directed) component to motion is governed by an integral term that accounts for how the surrounding distribution(s) of the population(s) impact on a member’s movement. We recount the fundamental motivation for these models: the intrinsic capacity of cell populations to self-organise and spatially sort within tissues; the wide-ranging tendency of animals towards spatial structuring, from the formations of herds and swarms to territorial segregation. We examine the derivation of these models from an individual level, illustrating in the process methods that allow models to be connected to data. We explore a growing analytical literature, including methods of stability and bifurcation analysis, and existence results. We conclude with a short section that lays out some future challenges and connections to the modelling of sociological phenomena including opinion dynamics.
Stability and pair production of scalars in the charged Einstein–ModMax black hole spacetime
Authors: Siahaan Haryanto M.
Published: October 2023

This study has established the stability of Reissner–Nordström black holes within a specific parameter range against charged scalar perturbations. Additionally, the near-extremal Reissner–Nordström black holes exhibit a phenomenon known as the Schwinger effect for black holes, involving the production of charged scalar particles. This paper explores the stability and Schwinger effect in the context of static charged black holes within the Einstein–ModMax theory. Our approach closely aligns with the existing literature methods. We aim to investigate how the nonlinearity inherent in the theory may impact both the stability regime and the rate of charged scalar pair production by the black hole.
Systematics of Maxwellian-averaged neutron capture cross-sections (MACS) at 30keV
Authors: Djerboua Youcef , Musacchio-González Elizabeth , Mastinu Pierfrancesco , Amrani Naima
Published: October 2023

A formula for Maxwellian-Averaged Cross-Sections (MACS) at 30[Formula: see text]keV is derived. Based on the presented formula, a linear relationship was found between the log [Formula: see text] and [Formula: see text] of the target nucleus. From this relationship, a good agreement between the calculated MACS and the experimental data can be observed. It seems therefore possible to use this systematic law in order to analyze the experimental data. It would be useful in estimating the MACS of neighboring isotopes for which no experimental data are available.
EFFECT OF MACHINABILITY OF GNP–GFRP COMPOSITES ON TENSILE STRENGTH AND FATIGUE BEHAVIOR
Authors: TOPKAYA TOLGA , ÇELİK YAHYA HIŞMAN , KILICKAP EROL
Published: October 2023

The paper focuses on the cutting behavior of Glass Fiber Reinforced Polymer (GFRP) composites and GNP–GFRP composites that contain varying amounts of Graphene Nano Platelets (GNP). GFRP composites are increasingly being used in a variety of industrial applications due to their excellent mechanical properties, such as high strength, stiffness, and low weight. However, their machining and cutting behavior can be challenging due to the presence of the reinforcing fibers. Therefore, the study aims to investigate the machining behavior of GFRP composites and the effect of adding GNP on their cutting behavior. The effect of different parameters such as cutting speed, feed rate and reinforcement rate on cutting forces and delamination factor is investigated. In addition, the tensile strength and fatigue behavior of the composite materials with the best and worst delamination factors were also determined. Addition of up to 0.2 wt.% of GNP to GFRP composites resulted in an increase in cutting forces and delamination factor when drilling GFRP composites. While the cutting force and delamination factor decreased with the increase in cutting speed, the cutting force and delamination factor increased with the increase in the feed rate. Analysis of variance (ANOVA) was performed to determine the effects of drilling parameters and reinforcement ratio on cutting force and delamination factor according to full factorial experimental design. The most efficient factor on the cutting forces is found to be feed rate (84.97%), followed by the reinforced rate (6.48%) and cutting speed (6.13%). The most efficient factor on the delamination factor is determined to be feed rate for (44.49%), followed by the reinforced rate (29.20%) and cutting speed (21.73%).
INVESTIGATING MAGNETIC, DIELECTRIC, OPTIC AND MORPHOLOGIC PROPERTIES OF NANO-NICKEL OXIDE-DOPED NdFeO3
Authors: ZENKIN KUBRA , DURMUS SEFA , DEMIR AHMET
Published: October 2023

In this investigation, [Formula: see text]-Fe2O3 was prepared via co-precipitation and nano-NiO and NdFeO3 were synthesized using the sol–gel method. For NdFe[Formula: see text]Ni[Formula: see text]O3 synthesis, Nd2O3, [Formula: see text]-Fe2O3, and nano-NiO compounds were mixed via the solid state method. The effect of each component and that of nano-NiO on the NdFe[Formula: see text]Ni[Formula: see text]O3 crystal properties was characterized by using X-ray diffraction (XRD), scanning electron microscopy-energy dispersive X-ray (SEM-EDX), ultraviolet-visible (UV–Vis), vibrating sample magnetometer (VSM), impedance and bandgap analyses. The orthorhombic perovskite structure was confirmed by the XRD data. With the doping of nano-NiO, the unit cell volume was found to decrease. The UV–Vis spectroscopy showed that the nano-NiO-doped optical bandgap ([Formula: see text]) had increased. The VSM analysis demonstrated that by doping nano-NiO to weak ferromagnetic NdFeO3, the resulting NdFe[Formula: see text]Ni[Formula: see text]O3 was rendered superparamagnetic. The real and imaginary parts of dielectric permittivity ([Formula: see text]′ and [Formula: see text]″) and the loss tangent (tan[Formula: see text]) characteristic of the compounds were measured at AC-signaled frequencies of 100 Hz–10 MHz and a voltage range of 0–20 V DC. The increase in active charge transmission with the doping of nano-NiO reduced the [Formula: see text]′ values. In addition, the large differences between the [Formula: see text]′ values were thought to be caused by the breakdown voltage ([Formula: see text]) effect of the compounds. The [Formula: see text]″ and tan[Formula: see text] changes revealed the dipole formation of the compounds at different voltages, their relaxation regions and their polarization mechanism type. The dielectric loss behavior of the compounds demonstrated their good dielectric material properties. This study investigated the effect of method difference and doped material particle size on magnetic and dielectric properties.