bluuebunny/crossref_metadata_2025 huggingface dataset:
Health system responsiveness and its associated factors for intrapartum care in conflict affected areas in Amhara region, Ethiopia: a cross-sectional study
Authors: Atnafu Asmamaw , Dellie Endalkachew , Kebede Adane , Fetene Samrawit Mihret , Haile Tsegaye G. , Alemu Melaku Birhanu , Park Jinha , Tefera Selamawit , Alene Bruhtesfa Mouhabew , Negash Wubshet Debebe
Published: July 2024

Objective

In Ethiopia, information about health system responsiveness (HSR) in conflict-affected areas is limited. No previous local study was conducted on the assessment of HSR at the community level. Hence, the study assessed HSR for intrapartum care in conflict-affected areas in Amhara region, Ethiopia.

Design

Community-based cross-sectional study design.

Setting

Wadila, Gayint and Meket districts, Amhara region, Ethiopia.

Participants

The participants were 419 mothers who gave birth in conflict-affected areas within the last 6 months. The study included all mothers who gave birth at health facilities but excluded those who delivered at home, critically ill or unable to hear.

Outcome

HSR was the outcome variable. In this regard, the study assessed how mothers were treated and the situation in which they were cared for in relation to their experience during the conflict.

Methods

We conducted the study in the community, where we analysed eight domains of HSR to identify 30 measurement items related to intrapartum care responsiveness. The domains we looked at were dignity (4), autonomy (4), confidentiality (2), communication (5), prompt attention (5), social support (3), choice (3) and basic amenities (4). We used a multiple linear regression model to analyse the data, and in this model, we used an unstandardized β coefficient with a 95% CI and a p value of less than 0.05 to determine the factors significantly associated with HSR.

Results

The findings of our study revealed that the overall proportion of HSR in intrapartum care was 45.11% (95% CI: 40.38 to 49.92). The performance of responsiveness was the lowest in the autonomy, choice and prompt attention domains at 35.5%, 49.4% and 52.0%, respectively. Mothers living in urban areas (β=4.28; 95% CI: 2.06 to 6.50), government employees (β=4.99; 95% CI: 0.51 to 9.48), those mothers stayed at the health facilities before delivery/during conflict (β=0.22; 95% CI: 0.09 to 0.35), those who were satisfied with the healthcare service (β=0.69; 95% CI: 0.08 to 1.30) and those who perceived the quality of healthcare favourable (β=0.96; 95% CI: 0.72 to 1.19) were more likely to rate HSR positively. On the other hand, joint decision-making for health (β=−2.46; 95% CI: −4.81 to –0.10) and hospital delivery (β=−3.62; 95% CI: −5.60 to –1.63) were negatively associated with HSR.

Conclusion

In the Amhara region of Ethiopia, over 50% of mothers living in areas affected by conflict reported that health systems were not responsive with respect to intrapartum care. Therefore, all stakeholders should work together to ensure that intrapartum care is responsive to conflict-affected areas, with a focus on providing women autonomy and choice.
How should non-emergency EMS presentations be managed? A thematic analysis of politicians’, policymakers’, clinicians’ and consumers’ viewpoints
Authors: Wilkinson-Stokes Matt , Yap Celene , Crellin Di , Bange Ray , Braitberg George , Gerdtz Marie
Published: July 2024

Objective

In 2023, Australian government emergency medical services (EMS) responded to over 4 million consumers, of which over 56% were not classified as an ‘emergency’, at the cost of AU$5.5 billion. We explored the viewpoints of politicians, policymakers, clinicians and consumers on how these non-emergency requests should be managed.

Design

A realist framework was adopted; a multidisciplinary team (including paramedicine, medicine and nursing) was formed; data were collected via semistructured focus groups or interviews, and thematic analysis was performed.

Setting and participants

56 participants were selected purposefully and via open advertisement: national and state parliamentarians (n=3); government heads of healthcare disciplines (n=3); government policymakers (n=5); industry policymakers in emergency medicine, general practice and paramedicine (n=6); EMS chief executive officers, medical directors and managers (n=7); academics (n=8), frontline clinicians in medicine, nursing and paramedicine (n=8); and consumers (n=16).

Results

Three themes emerged: first, the reality of the EMS workload (theme titled ‘facing reality’); second, perceptions of what direction policy should take to manage this (‘no silver bullet’) and finally, what the future role of EMS in society should be (‘finding the right space’). Participants provided 16 policy suggestions, of which 10 were widely supported: increasing public health literacy, removing the Medical Priority Dispatch System, supporting multidisciplinary teams, increasing 24-hour virtual emergency departments, revising undergraduate paramedic university education to reflect the reality of the contemporary role, increasing use of management plans for frequent consumers, better paramedic integration with the healthcare system, empowering callers by providing estimated wait times, reducing ineffective media campaigns to ‘save EMS for emergencies’ and EMS moving away from hospital referrals and towards community care.

Conclusions

There is a need to establish consensus on the role of EMS within society and, particularly, on whether the scope should continue expanding beyond emergency care. This research reports 16 possible ideas, each of which may warrant consideration, and maps them onto the standard patient journey.
Development of a core data set for describing, measuring and reporting the learning curve in studies of novel invasive procedures: study protocol
Authors: Ramirez Jozel , Hoffmann Christin , Corrigan Neil , Kobetic Matthew , Macefield Rhiannon , Elliott Daisy , Blazeby Jane , Potter Shelley , Stocken Deborah D , Avery Kerry , Blencowe Natalie S
Published: July 2024

Introduction

The introduction of novel surgical techniques and procedures remains poorly regulated and standardised. Although the learning curve associated with invasive procedures is a critical part of innovation, it is currently inconsistently defined, measured and reported. This study aims to develop a core data set that can be applied in all studies describing or measuring the learning curve in novel invasive procedures.

Methods

A core data set will be developed using methods adapted from the Core Outcome Measures in Effectiveness Trials initiative. The study will involve three phases: (1) Identification of a comprehensive list of data items through (a) an umbrella review of existing systematic reviews on the learning curve in surgery and (b) qualitative interviews with key stakeholders. (2) Key stakeholders (eg, clinical innovators, clinicians, patients, methodologists, statisticians, journal editors and governance representatives) will complete a Delphi survey to score the importance of each data item, generating a shortened list. (3) Consensus meeting(s) with stakeholders to discuss and agree on the final core data set.

Ethics and dissemination

The study is approved by an Institutional Ethics Committee at the University of Bristol (ref: 111362). Participants will complete written informed consent to participate. Dissemination strategies include scientific meeting presentations, peer-reviewed journal publications, patient engagement events, use of social media platforms, workshops and other events.
General practitioners retiring or relocating and its association with healthcare use and mortality: a cohort study using Norwegian national data
Authors: Vinjerui Kristin Hestmann , Asheim Andreas , Sarheim Anthun Kjartan , Carlsen Fredrik , Mjølstad Bente Prytz , Nilsen Sara Marie , Pape Kristine , Bjørngaard Johan Håkon
Published: July 2024

Background

Continuity in the general practitioner (GP)-patient relationship is associated with better healthcare outcomes. However, few studies have examined the impact of permanent discontinuities on all listed patients when a GP retires or relocates.

Aim

To investigate changes in the Norwegian population’s overall healthcare use and mortality after discontinuity due to Regular GPs retiring or relocating.

Methods

Linking national registers, we compared days with healthcare use and mortality for matched individuals affiliated with Regular GPs who retired or relocated versus continued. We included list patients 3 years prior to exposure and followed them up to 5 years after. We assessed changes over time employing a difference-in-differences design with Poisson regression.

Results

From 2011 to 2020, we identified 819 Regular GPs retiring and 228 moving, affiliated with 1 165 295 people. Relative to 3 years before discontinuity, the rate ratio (RR) of daytime GP contacts, increased 3% (95% CI 2 to 4) in year 1 after discontinuity, corresponding to 148 (95% CI 54 to 243) additional contacts per 1000 patients. This increase persisted for 5 years. Out-of-hours GP contacts increased the first year, RR 1.04 (95% CI 0.99 to 1.09), corresponding to 16 (95% CI −5 to 37) contacts per 1000 patients. Planned hospital contacts increased 3% (95% CI 2 to 4) in year 1, persisting into year 5. Acute hospital contacts increased 5% (95% CI 3 to 7), primarily in the first year. These 1-year effects corresponded to 51 (95% CI 18 to 83) planned and 13 (95% CI 7 to 18) acute hospital contacts per 1000 patients. Mortality was unchanged up to 5 years after discontinuity.

Conclusion

Regular GPs retirement and relocation were associated with small to moderate increases in healthcare use among listed patients, while mortality was unaffected.
Firearm ownership for protection in the USA, 2023: results from a nationally representative survey
Authors: Degli Esposti Michelle , Sokol Rebeccah L , Lee Daniel B , Wiebe Douglas J , Cunningham Rebecca M , Hawryszkiewycz Alice , Carter Patrick M
Published: July 2024

Objective

This study aims to characterise the motivations of firearm owners and examine whether firearm ownership motivations and carriage varied by state stand your ground law status. 

Methods

Using a nationally representative survey of US adults in 2023, we asked firearm owners (n=2477) about their firearm motivations and behaviours, including reason(s) for ownership.

Results

Of all firearm owners, 78.8% (95% CI 76.0% to 81.0%) owned a firearm for protection, and 58.1% (95% CI 54.3% to 62.0%) carried a firearm outside their home in the last 12 months. Firearm ownership for protection was not significantly associated with stand your ground laws, but firearm carriage was more prevalent in states with stand your ground laws (50.1% (95% CI 47.0% to 53.0%) vs 34.9% (95% CI 25.0% to 46.0%)). Gender (women) and race (minority groups) emerged as key correlates for firearm ownership for protection (vs other ownership motivations). For example, black and Asian women (98.8%) almost exclusively owned firearms for protection.

Conclusions

Protection was the dominant reason for firearm ownership in 2023, motivating 65 million Americans to own firearms and appealing to different strata of the population.
Phase I study of the safety and clinical activity of the interleukin-8 inhibitor AMY109 combined with atezolizumab in patients with advanced solid cancers
Authors: Yamamoto Noboru , Kitano Shigehisa , Koyama Takafumi , Ikeda Masafumi , Mizugaki Hidenori , Narikiyo Takatsugu , Yamaguchi Yuki , Ishida Takaaki , Takubo Ryoko , Ogami Chika , Sekiya Mayuko , Nakagawa Yuki , Kuboki Yasutoshi
Published: July 2024

Background

Immunosuppressive conditions within the tumor microenvironment (TME) can allow tumors to evade the immune system, including by hampering programmed death ligand 1 (PD-L1) inhibitor activity. Interleukin (IL)-8 contributes to immunosuppression and fibrosis in the TME. AMY109, a humanized anti-IL-8 monoclonal antibody, reduced fibrosis and decreased immunosuppressive cells in tumor tissue in animals. Combining AMY109 with atezolizumab (anti-PD-L1 antibody) may enhance its antitumor effects by making the TME more favorable to PD-L1 inhibition.

Methods

This multicenter, open-label, dose-escalation study evaluated the safety, pharmacokinetics, and clinical activity of AMY109 plus atezolizumab in patients with previously treated advanced solid tumors and Eastern Cooperative Oncology Group performance status 0 or 1. Patients received AMY109 (2–45 mg/kg) plus atezolizumab (1200 mg) intravenously every 3 weeks in part 1, and AMY109 (15–45 mg/kg) plus atezolizumab (1200 mg) in part 2. Primary endpoints were the dose-limiting toxicity (DLT), safety, and pharmacokinetics of AMY109 and atezolizumab in Part 1, and safety and antitumor activity per investigator-assessed Response Evaluation Criteria in Solid Tumors 1.1 in part 2. Exploratory analyses of peripheral and tumor biomarker were conducted.

Results

Overall, 38 patients (18 in part 1 and 20 in part 2) were enrolled. Part 1 showed no DLTs and a dose-proportional increase in AMY109 exposure over 2–45 mg/kg, with no apparent change in mean atezolizumab serum concentrations across AMY109 dosing. Plasma IL-8 concentration accumulation was seen in all dose cohorts after AMY109 initiation. Grade 1–3 treatment-related adverse events (AEs) occurred in 21 of 38 patients (55%). Treatment-related serious AEs occurred in two patients (5%). No AEs led to treatment withdrawal. Partial responses (PRs) occurred in 2 of 38 patients; the confirmed objective response rate was 5%. These patients had uterocervical and pancreatic cancer, respectively, and had been treated for >500 days at the cut-off date: one had received 45 mg/kg of AMY109 throughout, and the other received 30 mg/kg of AMY109 until cycle 5, then 45 mg/kg thereafter.

Conclusions

With no DLTs, AMY109 plus atezolizumab was well tolerated in patients with advanced solid tumors, with no new safety signals. AMY109 showed a dose-proportional increase in exposure. The PRs in two patients were durable.
TG6050, an oncolytic vaccinia virus encoding interleukin-12 and anti-CTLA-4 antibody, favors tumor regression via profound immune remodeling of the tumor microenvironment
Authors: Azar Fadi , Deforges Jules , Demeusoit Christelle , Kleinpeter Patricia , Remy Christelle , Silvestre Nathalie , Foloppe Johann , Fend Laetitia , Spring-Giusti Clémentine , Quéméneur Eric , Marchand Jean-Baptiste
Published: July 2024

Background

TG6050 was designed as an improved oncolytic vector, combining the intrinsic properties of vaccinia virus to selectively replicate in tumors with the tumor-restricted expression of recombinant immune effectors to modify the tumor immune phenotype. These properties might be of particular interest for “cold” tumors, either poorly infiltrated or infiltrated with anergic T cells.

Methods

 TG6050, an oncolytic vaccinia virus encodes single-chain human interleukin-12 (hIL-12) and full-length anti-cytotoxic T-lymphocyte-associated antigen-4 (@CTLA-4) monoclonal antibody. The relevant properties of TG6050 (replication, cytopathy, transgenes expression and functionality) were extensively characterizedin vitro. The biodistribution and pharmacokinetics of the viral vector, @CTLA-4 and IL-12, as well as antitumoral activities (alone or combined with immune checkpoint inhibitors) were investigated in several “hot” (highly infiltrated) and “cold” (poorly infiltrated) syngeneic murine tumor models. The mechanism of action was deciphered by monitoring both systemic and intratumoral immune responses, and by tumor transcriptome analysis. The safety of TG6050 after repeated intravenous administrations was evaluated in cynomolgus monkeys, with a focus on the level of circulating IL-12.

Results

Multiplication and propagation of TG6050 in tumor cellsin vitroandin vivowere associated with local expression of functional IL-12 and @CTLA-4. This dual mechanism translated into a strong antitumoral activity in both “cold” and “hot” tumor models (B16F10, LLC1 or EMT6, CT26, respectively) that was further amplified when combined with anti-programmed cell death protein-1. Analysis of changes in the tumor microenvironment (TME) after treatment with TG6050 showed increases in interferon-gamma, of CD8+T cells, and of M1/M2 macrophages ratio, as well as a drastic decrease of regulatory T cells. These local modifications were observed alongside bolstering a systemic and specific antitumor adaptive immune response. In toxicology studies, TG6050 did not display any observable adverse effects in cynomolgus monkeys.

Conclusions

TG6050 effectively delivers functional IL-12 and @CTLA-4 into the tumor, resulting in strong antitumor activity. The shift towards an inflamed TME correlated with a boost in systemic antitumor T cells. The solid preclinical data and favorable benefit/risk ratio paved the way for the clinical evaluation of TG6050 in metastatic non-small cell lung cancer (NCT05788926trial in progress).
Treatment-free survival and partitioned survival analysis of patients with advanced renal cell carcinoma treated with nivolumab plus ipilimumab versus sunitinib: 5-year update of CheckMate 214
Authors: Mantia Charlene M , Jegede Opeyemi A , Plimack Elizabeth R , Powles Thomas , Motzer Robert J , Tannir Nizar M , Lee Chung-Han , Tomita Yoshihiko , Voss Martin H , Choueiri Toni K , Rini Brian I , Hammers Hans J , Escudier Bernard , Albigès Laurence , Rosenblatt Lisa , Atkins Michael B , Regan Meredith M , McDermott David F
Published: July 2024

Background

Immunotherapy can be associated with prolonged disease control even after cessation of treatment without the need for further cancer-directed therapy. Treatment-related adverse events (TRAEs) can also persist after discontinuation of therapy. Treatment-free survival (TFS) with and without toxicity as a component of a partitioned survival model can characterize patient survival time, which is not captured by standard outcome measures.

Methods

Data from 1096 patients with advanced renal cell carcinoma treated with first-line nivolumab plus ipilimumab (NIVO+IPI) versus sunitinib (SUN) in the CheckMate 214 trial were analyzed. TFS was defined as the area between two Kaplan-Meier curves for time from randomization to protocol therapy discontinuation and time from randomization to subsequent systemic therapy initiation or death, estimated as the difference in 60-month restricted mean times with confidence intervals (CIs) obtained using bootstrap sampling. Time on protocol therapy and TFS were further characterized as time with and without grade 2+ and 3+TRAEs. Survival functions were estimated in subgroups including International Metastatic Renal Cell Carcinoma Database Consortium risk groups using the Kaplan-Meier method.

Results

At 5 years from randomization, 48% of patients treated with NIVO+IPI and 37% of patients treated with SUN were alive. In the intent-to-treat population, 18% of the NIVO+IPI-treated and 5% of SUN-treated patients are surviving treatment-free. For favorable-risk patients, the 60-month mean TFS was 14.4 months for NIVO+IPI versus 5.5 months for SUN (difference 8.9 months (95% CI 4.9 to 12.8)). TFS for NIVO+IPI versus SUN with grade 2+TRAEs was 5.0 and 2.1 months, respectively, and with grade 3+TRAEs was 1.2 and 0.3 months, respectively. For intermediate/poor-risk patients, the 60-month mean TFS was 10.1 months for NIVO+IPI versus 4.1 months for SUN (difference 6.1 months (95% CI 4.2 to 7.9)). TFS for NIVO+IPI versus SUN with grade 2+TRAEs was 4.0 versus 2.0 months, respectively, and 0.6 versus 0.3 months with grade 3+TRAEs.

Conclusions

Although overall survival was similar, favorable-risk patients treated with NIVO+IPI spent more time surviving treatment-free with and without toxicity versus SUN after 60 months of follow-up. Intermediate/poor-risk patients treated with NIVO+IPI had longer survival and longer TFS without toxicity versus SUN.

Trial registration number

NCT02231749.
Study of quasi-projectile properties at Fermi energies in $$^{48}$$Ca projectile systems
Authors:   FAZIA Collaboration, Upadhyaya S. , Mazurek K. , Kozik T. , Gruyer D. , Casini G. , Piantelli S. , Baldesi L. , Barlini S. , Borderie B. , Bougault R. , Camaiani A. , Ciampi C. , Cicerchia M. , Ciemała M. , Dell’Aquila D. , Dueñas J. A. , Fable Q. , Frankland J. D. , Gramegna F. , Henri M. , Hong B. , Kordyasz A. , Kweon M. J. , Neindre N. Le , Lombardo I. , Lopez O. , Marchi T. , Nam S. H. , Park J. , Pârlog M. , Pasquali G. , Valdré S. , Verde G. , Vient E. , Vigilante M.
Published: July 2024

A systematic analysis of the data obtained by the FAZIA collaboration during a recent experiment with a neutron rich projectile is presented. The main goal was to compare the experimental results with the HIPSE event generator simulations to investigate the influence of the neutron rich entrance channel on the quasi-projectile fragment properties. The full isotopic range of charged particles detected in this experiment was within the limit of the resolution of the FAZIA detector. A majority of quasi-projectile fragments were detected thanks to the forward angular acceptance of the experimental setup which was confirmed through the HIPSE calculations. Essentially, the lowering of N/Z of quasi-projectile fragments with the beam energy was found to be present since the initial phase of the reaction. Thus, pre-equilibrium neutron emissions might be a possible candidate to explain such an effect.
The Static Noise Margin (SNM) of Quaternary SRAM using Quantum SWS-FET
Authors: Saman B. , Heller E. , Jain F. C.
Published: July 2024

Static random-access memory (SRAM) is an essential component in the architecture of modern microprocessors and VLSI circuits. The problems of high power consumption, large area, circuit complexity, and data stability against noise are among the most important indicators of performance and obstacles to the current use of SRAM. Ternary, quaternary, and higher-order logic (MLV) systems have shown the potential in overcoming these limitations in increasing the information density compared to the traditional binary system. The quantum dot channel field-effect transistor (QDC-FET) and quantum well Spatial Wavefunction Switched field-effect transistor (SWS-FET) are a new alternative with multiple operating states, low power consumption, and smaller footprints. This work presents a new four-state SRAM design that uses SWS-FET and compares it with Voltage-Mode CMOS Quaternary logic design. In addition, this work studies the noise margin in the memory circuit of the quadrilateral logic system and its effect on data stability. Furthermore, this study shows the reliability of quaternary SRAM design by evaluating the impact of errors.
An Interdisciplinary Survey on Origin-destination Flows Modeling: Theory and Techniques
Authors: Rong Can , Ding Jingtao , Li Yong
Published: July 2024

Origin-destination (OD) flow modeling is an extensively researched subject across multiple disciplines, such as the investigation of travel demand in transportation and spatial interaction modeling in geography. However, researchers from different fields tend to employ their own unique research paradigms and lack interdisciplinary communication, preventing the cross-fertilization of knowledge and the development of novel solutions to challenges. This article presents a systematic interdisciplinary survey that comprehensively and holistically scrutinizes OD flows from utilizing fundamental theory to studying the mechanism of population mobility and solving practical problems with engineering techniques, such as computational models. Specifically, regional economics, urban geography, and sociophysics are adept at employing theoretical research methods to explore the underlying mechanisms of OD flows. They have developed three influential theoretical models: the gravity model, the intervening opportunities model, and the radiation model. These models specifically focus on examining the fundamental influences of distance, opportunities, and population on OD flows, respectively. In the meantime, fields such as transportation, urban planning, and computer science primarily focus on addressing four practical problems: OD prediction, OD construction, OD estimation, and OD forecasting. Advanced computational models, such as deep learning models, have gradually been introduced to address these problems more effectively. We have constructed the benchmarks for these four problems at https://github.com/tsinghua-fib-lab/OD_benckmark. Finally, based on the existing research, this survey summarizes current challenges and outlines future directions for this topic. Through this survey, we aim to break down the barriers between disciplines in OD flow related research, fostering interdisciplinary perspectives and modes of thinking.
Empirical Disability Legal Studies
Authors: Dorfman Doron
Published: July 2024

Disability studies is an interdisciplinary field investigating the nature of disability as a social and cultural phenomenon. Since the mid-2000s, legal scholars have been employing a disability studies lens to explore legal doctrine and the treatment of people with disabilities under the law. This article identifies a nascent scholarly movement I call empirical disability legal studies: utilizing both a disability studies lens and empirical methods associated with the social sciences to study disability law. Legal scholars have used empirical methods, involving an analysis of quantitative or qualitative data, to explore three main themes: the experiences of disabled individuals within the formal legal system, the negotiations of disability rights in everyday life outside of formal legal institutions, and the construction of disability in legal texts. This article calls for more scholars to do work in the empirical disability legal studies tradition and puts forward new unexplored paths to expand such inquiry into the legal treatment of disability.
Statelessness: A Radical Rethinking of the Dominant Citizenism Paradigm
Authors: Kochenov Dimitry V.
Published: July 2024

A new approach to statelessness has emerged in the literature on the topic. Taking citizenism as a starting point and pioneered by Swider and Bloom, this approach offers a completely fresh paradigm for studying and understanding the statelesseness phenomenon. In the contemporary global context where citizenships are deeply unequal and racialized, the focus on rights invites us to dismiss the baseless presumption that fighting statelessness is always in the interests of the populations concerned, let alone that it is directly connected to the protection of human and citizenship rights. It is the world's inequitable neo-feudal citizenism arrangement that is a problem, not the fact that some people do not fit neatly into the citizenism hierarchy and find themselves in a position of statelessness. Shedding light on the role of citizenship and statelessness in the world today as tools of preservation of racialized hierarchies and inequitable exclusion of most of the world's population from rights at home and abroad, the new scholarship questions the UN High Commissioner for Refugees's mission and actions in this domain and takes issue with the self-serving parochialism of dominant Western citizenship and statelessness literatures.
Hypertension disrupts the vascular clock in both sexes
Authors: Visniauskas Bruna , Ogola Benard O. , Kilanowski-Doroh Isabella , Harris Nicholas R. , Diaz Zaidmara T. , Horton Alec C. , Blessinger Sophia A. , McNally Alexandra B. , Zimmerman Margaret A. , Arnold Amy C. , Lindsey Sarah H.
Published: July 2024

This study reveals that ANG II-induced hypertension disrupts the circadian rhythm of blood pressure in both male and female mice, with parallel effects on vascular clock gene and estrogen receptor diurnal patterns. Notably, sex-specific responses to hypertension in terms of locomotor activity, heart rate, and baroreflex sensitivity are revealed. These findings pave the way for chronotherapeutic strategies tailored to mitigate cardiovascular risks associated with disrupted circadian rhythms in hypertension.
The bottlenose dolphin (Tursiops truncatus): a novel model for studying healthy arterial aging
Authors: Bernaldo de Quirós Yara , Mahoney Sophia A. , VanDongen Nicholas S. , Greenberg Nathan T. , Venkatasubramanian Ravinandan , Saavedra Pedro , Bossart Greg , Brunt Vienna E. , Clayton Zachary S. , Fernández Antonio , Seals Douglas R.
Published: July 2024

We demonstrate that, unlike serum of midlife/older adult humans, age-matched dolphin serum elicits higher endothelial function ex vivo in young mouse carotid arteries, suggesting that the circulating milieu of bottlenose dolphins may be geroprotective. We propose that dolphins are a novel model to investigate potential novel therapeutic strategies to mitigate age-related endothelial dysfunction in humans.
The Relationship between Emotional Intelligence, Job Satisfaction, and Organizational Commitment among First‐Line Nurse Managers in Qatar
Authors: Othman Mutaz I. , Khalifeh Anas , Oweidat Islam , Nashwan Abdulqadir J.
Published: July 2024

Background. Emotional responses and the ability to regulate emotions among nurses, especially first‐line nurse managers, can influence various workplace dynamics. However, there is a knowledge gap regarding emotional intelligence, job satisfaction, and organizational commitment among nurses in Qatar, particularly first‐line nurse managers. Objectives. The primary aim of this study is to determine if there is a significant relationship between emotional intelligence, job satisfaction, and organizational commitment among first‐line nurse managers (FLNMs) in Qatar. Design. This is a descriptive cross‐sectional correlational study. Settings. The research took place at Hamad Medical Corporation in Qatar. Participants. A total of 203 first‐line nurse managers participated in the study. Methods. Participants were recruited using a convenience sample method. Data were collected using the Genos Emotional Intelligence Inventory—Concise, the three‐component model Employee Commitment Survey, and the short‐form Minnesota Satisfaction Questionnaire (MSQ). Results. The findings showed that participants had average levels of emotional intelligence, job satisfaction, and organizational commitment. Notably, a significant, moderately positive relationship was observed between emotional intelligence and organizational commitment, as well as between job satisfaction and organizational commitment. A weak positive relationship was identified between emotional intelligence and job satisfaction. Differences in emotional intelligence were observed based on variables such as gender, age, and unit specialty. Organizational commitment varied based on the current position and hospital type, while job satisfaction differed based on the current position and education level. Conclusions. The findings suggest that enhancing the emotional intelligence of first‐line nurse managers can potentially improve organizational commitment, job satisfaction, and, subsequently, healthcare outcomes. There is a need for further research to delve deeper into these factors and devise strategies aiming to boost the emotional intelligence and job satisfaction of first‐line nurse managers. Implications for Nursing Management. The study provides empirical data from Qatar’s healthcare system, shedding light on FLNMs’ emotional intelligence, job satisfaction, and organizational commitment.
Penetrating Posterior Urethral Injuries: Case Report and Management Strategies
Authors: Tabei Seyed Sajjad , Lippold Brandon , Baas Wesley , Murphy Gregory
Published: July 2024

Penetrating posterior urethral trauma from gunshot wounds (GSW) is rare and requires prompt treatment to minimize complications. Data regarding the management of such cases is scarce in the literature and poorly addressed in the guidelines. Different management approaches exist, including urinary diversion with immediate versus delayed urethroplasty/fistula repair. We present our case series to add to our experience to the literature. Three patients aged 18–44 presented with ballistic posterior urethra injuries from GSW. Initial management involved urethral catheter placement, with one patient requiring operative placement of urethral and suprapubic catheters (SPTs). Complications included recurrent membranous stricture, urinary retention, rectourethral fistula, and erectile dysfunction (ED). Posterior urethral injuries from GSW are complex as they can be either isolated or affect adjacent organs. Bladder, ureteral, and urethral injuries must be ruled out. Unlike bladder neck injuries, immediate urethroplasty/fistula repair would be very challenging and not advised for standard prostatic or membranous injuries. Urethral catheter or suprapubic tube is recommended and can result in fistula closure and urethral patency. It is critical to maintain close follow‐up with the patient due to the possibility of stricture recurrence. Urethroplasty in a delayed fashion can be very successful.
Optimization of Traffic Flow by Allowing Private Cars to Merge into the Bus Lane at Specific Locations
Authors: Yin Zhentao , Yuan Kai , Zheng Shenshen
Published: July 2024

A dedicated bus lane is designed to give priority to buses over private cars on the road. However, this approach might waste road traffic capacity when bus demand is low and private car demand is high. Thus, it is essential to utilize bus lanes more effectively. Previous work focuses on allowing private cars to use bus lanes which may cause bus delays. To strike a balance, some approaches involve mandating private cars to leave bus lanes and limiting the number of private cars entering bus lanes. However, these highly rely on transportation infrastructure and emerging technologies. Hence, we propose a simple method of a partially space‐shared bus lane, which allows private cars to merge into the bus lane at specific locations. Lane‐changing decision is modeled as a result of speed difference between adjacent lanes. Traffic flow is simulated by the LWR model in the Lagrangian coordinate system. Two scenarios are set up—dedicated bus lane and partially space‐shared bus lane—to evaluate the partially space‐shared system. The only optimization variable is the location that allows private cars to conduct lane‐changing. We use the genetic algorithms to optimize the system. Finally, simulation results show that the partially space‐shared bus lane reduces private‐car delays and total delays of the system. The buses would experience an increase of delays, inevitably. But the bus delay increase could be limited in a small range, which maintains the bus priority. In addition, a multiple lane‐changing position strategy is better than the single position one. This approach is suitable for traffic situations with low bus demand and high private car demand. Our work is expected to contribute to the design of future urban bus lanes and improve overall traffic operations.
A Phase II Placebo-Controlled Study of the Effect and Safety of Nanvuranlat in Patients with Advanced Biliary Tract Cancers Previously Treated by Systemic Chemotherapy
Authors: Furuse Junji , Ikeda Masafumi , Ueno Makoto , Furukawa Masayuki , Morizane Chigusa , Takehara Tetsuo , Nishina Tomohiro , Todaka Akiko , Okano Naohiro , Hara Kazuo , Nakai Yousuke , Ohkawa Kazuyoshi , Sasaki Takashi , Sugimori Kazuya , Yokoyama Naoyuki , Yamamoto Kouji
Published: July 2024

Purpose:

To evaluate the efficacy and safety of nanvuranlat [an L-type amino acid transporter 1 inhibitor] monotherapy as a later-line treatment in advanced, metastatic, and refractory biliary tract cancers.

Patients and Methods:

A multicenter, randomized, double-blind, placebo-controlled phase II study was conducted across fourteen leading Japanese cancer centers and hospitals. Nanvuranlat 25 mg/m2/day or placebo was given intravenously in cycles of 5 consecutive days, followed by 9 days off. The primary endpoint was progression-free survival (PFS). Secondary endpoints included overall survival and disease control rate. Subgroup analysis was performed in patients with high L-type amino acid transporter 1 expression and biliary tract cancer subtypes.

Results:

A total of 211 patients were screened, of which 105 eligible patients were randomized. Among these, 70 received nanvuranlat and 35 received placebo. Nanvuranlat demonstrated an improvement in PFS when compared with placebo (HR, 0.56; 95% confidence interval, 0.34–0.90; P = 0.02). Grade 3 or higher adverse events were reported in 30.0% and 22.9% of those in the nanvuranlat and placebo groups, respectively. The overall survival was not statistically different between nanvuranlat- and placebo-treated patients. An exploratory analysis indicated that nanvuranlat is warranted to evaluate its long-term clinical benefit in patients with intrahepatic cholangiocarcinoma, extrahepatic cholangiocarcinoma, and gallbladder cancer.

Conclusions:

Compared with placebo, nanvuranlat improved PFS in patients with advanced and refractory biliary tract cancer with an acceptable safety profile. Further studies of this promising compound are warranted in the population of patients who are exhausted from treatment options.
Ipatasertib plus Paclitaxel for Patients with PIK3CA/AKT1/PTEN-Altered Locally Advanced Unresectable or Metastatic Triple-Negative Breast Cancer in the IPATunity130 Phase III Trial
Authors: Dent Rebecca A. , Kim Sung-Bae , Oliveira Mafalda , Barrios Carlos , O’Shaughnessy Joyce , Isakoff Steven J. , Saji Shigehira , Freitas-Junior Ruffo , Philco Manuel , Bondarenko Igor , Lian Qinshu , Bradley Denise , Hinton Heather , Wongchenko Matthew J. , Reilly Sarah-Jayne , Turner Nicholas
Published: July 2024

Purpose:

In the randomized phase II LOTUS trial, combining ipatasertib with first-line paclitaxel for triple-negative breast cancer (TNBC) improved progression-free survival (PFS), particularly in patients with PIK3CA/AKT1/PTEN-altered tumors. We aimed to validate these findings in a biomarker-selected TNBC population.

Patients and Methods:

In Cohort A of the randomized double-blind placebo-controlled phase III IPATunity130 trial, taxane-eligible patients with PIK3CA/AKT1/PTEN-altered measurable advanced TNBC and no prior chemotherapy for advanced disease were randomized 2:1 to ipatasertib (400 mg, days 1–21) or placebo, both plus paclitaxel (80 mg/m2, days 1, 8, and 15), every 28 days until disease progression or unacceptable toxicity. The primary endpoint was investigator-assessed PFS.

Results:

Between February 2018 and April 2020, 255 patients were randomized (168 to ipatasertib, 87 to placebo). At the primary analysis, there was no significant difference between treatment arms in PFS [hazard ratio 1.02, 95% confidence interval (CI), 0.71–1.45; median 7.4 months with ipatasertib vs. 6.1 months with placebo]. The final analysis showed no difference in overall survival between treatment arms (hazard ratio 1.08, 95% CI, 0.73–1.58; median 24.4 vs. 24.9 months, respectively). Ipatasertib was associated with more grade ≥3 diarrhea (9% vs. 2%) and adverse events leading to dose reduction (39% vs. 14%) but similar incidences of grade ≥3 adverse events (51% vs. 46%). Exploratory subgroup analyses by PAM50 and Burstein gene expression showed inconsistent results.

Conclusions:

Adding ipatasertib to paclitaxel did not improve efficacy in PIK3CA/AKT1/PTEN-altered advanced TNBC. Biomarkers for benefit from PI3K/AKT pathway inhibition in TNBC remain poorly understood.
Organ-Specific Immune Setpoints Underlie Divergent Immune Profiles across Metastatic Sites in Breast Cancer
Authors: Egelston Colt A. , Guo Weihua , Simons Diana L. , Ye Jian , Avalos Christian , Solomon Shawn T. , Nwangwu Mary , Nelson Michael S. , Tan Jiayi , Bacon Eliza R. , Ihle Kena , Schmolze Daniel , Tumyan Lusine , Waisman James R. , Lee Peter P.
Published: July 2024

Immune composition within the tumor microenvironment (TME) plays a central role in the propensity of cancer cells to metastasize and respond to therapy. Previous studies have suggested that the metastatic TME is immune-suppressed. However, limited accessibility to multiple metastatic sites within patients has made assessing the immune TME difficult in the context of multiorgan metastases. We utilized a rapid postmortem tissue collection protocol to assess the immune composition of numerous sites of breast cancer metastasis and paired tumor-free tissues. Metastases had comparable immune cell densities and compositions to paired tumor-free tissues of the same organ type. In contrast, immune cell densities in both metastatic and tumor-free tissues differed significantly between organ types, with lung immune infiltration being consistently greater than that in the liver. These immune profiling results were consistent between flow cytometry and multiplex immunofluorescence–based spatial analysis. Furthermore, we found that granulocytes were the predominant tumor-infiltrating immune cells in lung and liver metastases, and these granulocytes comprised most PD–L1–expressing cells in many tissue sites. We also identified distinct potential mechanisms of immunosuppression in lung and liver metastases, with the lung having increased expression of PD-L1+ antigen-presenting cells and the liver having higher numbers of activated regulatory T cells and HLA-DRlow monocytes. Together, these results demonstrate that the immune contexture of metastases is dictated by organ type and that immunotherapy strategies may benefit from unique tailoring to the tissue-specific features of the immune TME.
Oral Supplementation with l-Cystine, Serenoa repens, Cucurbita pepo, and Pygeum africanum in Chronic Telogen Effluvium and Androgenetic Alopecia: A Double-Blind, Placebo-Controlled, Randomized Clinical Study
Authors: Piquero-Casals Jaime , Saceda-Corralo David , Aladren Sonia , Bustos Javier , Fernández-Botello Alfonso , Navasa Albert , Logusso Georgina , Jourdan Eric , Mir-Bonafé Juan Francisco , Morgado-Carrasco Daniel
Published: July 2024

Introduction: Chronic telogen effluvium (TE) and androgenetic alopecia represent two prevalent forms of hair loss that can significantly impact individuals’ quality of life. Insufficiency of essential micronutrients has been associated with hair loss. The objective of this study was to evaluate the safety and efficacy of an oral supplement containing l-Cystine, Serenoa repens, Cucurbita pepo, Pygeum africanum, vitamins, and micronutrients in chronic TE (CTE) and androgenetic alopecia (AGA). Methods: Eighty patients of both sexes aged 18–60 years with CTE or AGA were randomized to receive one capsule daily of the oral supplement or placebo for 6 months. Dermatological evaluations, clinical pictures and phototrichograms were done at baseline, 3 months and 6 months. The overall hair volume and appearance were assessed before and after treatment as well as subject’s self-assessment via standardized questionnaire. Results: Hair density increased by 9.9 hairs/cm2 after 3 months and 12.3 hairs/cm2 after 6 months in the oral supplement group and it is statistically significant when compared to placebo. Overall hair volume after 1, 3, and 6 months is better in the supplement group than in the placebo group. The oral supplement was well tolerated. No moderate or severe adverse events were reported. Conclusion: Oral supplementation can increase hair density, anagen hairs, and overall hair appearance in patients with AGA or CTE.
Endoscopic Artificial Intelligence for Image Analysis in Gastrointestinal Neoplasms
Authors: Kikuchi Ryosuke , Okamoto Kazuaki , Ozawa Tsuyoshi , Shibata Junichi , Ishihara Soichiro , Tada Tomohiro
Published: July 2024

Background: Artificial intelligence (AI) using deep learning systems has recently been utilized in various medical fields. In the field of gastroenterology, AI is primarily implemented in image recognition and utilized in the realm of gastrointestinal (GI) endoscopy. In GI endoscopy, computer-aided detection/diagnosis (CAD) systems assist endoscopists in GI neoplasm detection or differentiation of cancerous or noncancerous lesions. Several AI systems for colorectal polyps have already been applied in colonoscopy clinical practices. In esophagogastroduodenoscopy, a few CAD systems for upper GI neoplasms have been launched in Asian countries. The usefulness of these CAD systems in GI endoscopy has been gradually elucidated. Summary: In this review, we outline recent articles on several studies of endoscopic AI systems for GI neoplasms, focusing on esophageal squamous cell carcinoma (ESCC), esophageal adenocarcinoma (EAC), gastric cancer (GC), and colorectal polyps. In ESCC and EAC, computer-aided detection (CADe) systems were mainly developed, and a recent meta-analysis study showed sensitivities of 91.2% and 93.1% and specificities of 80% and 86.9%, respectively. In GC, a recent meta-analysis study on CADe systems demonstrated that their sensitivity and specificity were as high as 90%. A randomized controlled trial (RCT) also showed that the use of the CADe system reduced the miss rate. Regarding computer-aided diagnosis (CADx) systems for GC, although RCTs have not yet been conducted, most studies have demonstrated expert-level performance. In colorectal polyps, multiple RCTs have shown the usefulness of the CADe system for improving the polyp detection rate, and several CADx systems have been shown to have high accuracy in colorectal polyp differentiation. Key Messages: Most analyses of endoscopic AI systems suggested that their performance was better than that of nonexpert endoscopists and equivalent to that of expert endoscopists. Thus, endoscopic AI systems may be useful for reducing the risk of overlooking lesions and improving the diagnostic ability of endoscopists.
Multicenter, open-label, prospective study shows safety and therapeutic benefits of a defined ginkgo biloba extract for adults with Major Neurocognitive Disorder
Authors: Chowdhury Debashish , Roy Ajit Kumar , Reddy V. Radhika , Gupta Yogesh Kumar , Nigam Pushkar , Hoerr Robert
Published: July 2024

Introduction: Safety and therapeutic effects of gingko biloba extract EGb 761® to treat cognitive decline have been demonstrated in numerous clinical trials. However, trials in Indian populations have been lacking.
Methods: This open-label, multicenter, single-arm, phase IV trial enrolled 150 patients aged ≥50 years with Major Neurocognitive Disorder due to Alzheimer’s disease, major vascular neurocognitive disorder, or mixed forms of both according to the Diagnostic and Statistical Manual of Mental Disorders, 5th edition (DSM-5) criteria and a Mini-Mental State Examination (MMSE) score of 12–24. Patients took 120 mg EGb 761® twice daily for 18 weeks. Therapeutic effects were assessed by CERAD Constructional Praxis and Recall of Constructional Praxis (CERAD CP, CERAD Recall of CP), Trail-Making Test (TMT), Behavioral Pathology in Alzheimer's Disease (BEHAVE-AD), Clinical Global Impressions (CGI) scale and 11-point box scales for tinnitus and vertigo. Safety assessment was based on the occurrence of adverse events as well as changes in clinical, laboratory and functional parameters.
Results: After 18 weeks, significant improvements compared to baseline were found in constructional praxis (CERAD CP, p<0.0001), memory (CERAD Recall of CP, p<0.0001), speed and executive functioning (TMT A, p<0.0001; TMT B, p<0.0001), and behavioral symptoms (BEHAVE-AD, p<0.0001). Forty-five adverse events were reported in 33 (22.0%) patients in total, including ten presumed adverse drug reactions in 9 (6.0%) patients. Headache and diarrhea of mild-to-moderate severity were the most frequent events. Two serious adverse events, both considered unrelated to the study drug, occurred in 2 (1.3%) patients.
Conclusion: This study confirmed the favorable safety profile and suggested therapeutic benefits of EGb 761® in Indian patients with Major Neurocognitive Disorder.