bluuebunny/crossref_metadata_2025 huggingface dataset:
Association of relationship satisfaction with blood pressure: a cross-sectional study of older adults in rural Burkina Faso
Authors: Jaspert Felicitas Maria , Harling Guy , Sie Ali , Bountogo Mamadou , Bärnighausen Till , Ditzen Beate , Fischer Melanie Sandy
Published: November 2024

Objectives

The objective of this study is to examine the association between relationship satisfaction and blood pressure (BP) in a low-income setting and to screen for gender moderation in this context. Research conducted in high-income settings suggests that relationship satisfaction is associated with better physical and mental health outcomes.

Design

A cross-sectional study design was employed, using both questionnaire and physical measurement data. Multiple linear regression models were calculated for systolic and diastolic BP and adjusted for age, gender, demographics/socioeconomics and other health-related variables. Gender moderation was tested using interaction terms in multivariable analyses.

Setting

A household survey was conducted in 2018 in rural northwestern Burkina Faso.

Participants

Final analysis included 2114 participants aged over 40 who were not pregnant, reported being in a partnership and had valid BP readings.

Main outcome measures

Systolic and diastolic BP levels.

Results

A significant positive association existed between relationship satisfaction (Couples Satisfaction Index-4 score) and systolic BP (B=0.23, 95% CI (0.02 to 0.45), p=0.03) when controlling for demographics/socioeconomics. Nevertheless, this relationship lost statistical significance when additional adjustments were made for health-related variables (B=0.21, 95% CI (−0.01 to 0.42), p=0.06). There was no significant association of relationship satisfaction and diastolic BP and no evidence of gender moderation.

Conclusion

In contrast to many higher-income settings, we found a positive association between relationship satisfaction and systolic BP in very low-income rural Burkina Faso. Our results add to the evidence regarding the contextual nature of the association between relationship satisfaction and health, as high relationship satisfaction may not act as a health promotor in this socioeconomic context.
Oxygen extraction–guided transfusion strategy in critically ill patients: study protocol for a randomised, open-labelled, controlled trial
Authors: Fogagnolo Alberto , Azzolina Danila , Taccone Fabio Silvio , Pedarzani Emma , Pasa Gianluca , Marianello Daniele , Valpiani Giorgia , Marchesini Chiara , Annoni Filippo , Moureau Anthony , Volta Carlo Alberto , Franchi Federico , Spadaro Savino
Published: November 2024

Introduction

In critically ill patients, individualised strategies for red blood cell transfusion (RBCT) are lacking. The objective of this study is to demonstrate the potential advantages of employing an individualised transfusion strategy compared with a restrictive approach, in unselected intensive care unit (ICU) patients.

Methods

This will be a randomised, multicentre, international trial. Two open-label parallel groups will be compared with an allocation ratio of 1:1. The trial is designed to investigate the superiority of the individualised intervention group compared with the standard intervention group. The study will be performed in three mixed, academic ICUs located in two different countries. In the individualised group, prescription of RCBT is restricted to patients who present haemoglobin (Hb) ≤9.0 g/dL and oxygen extraction ratio (O2ER) ≥ 30%, for a minimum Hb value of ≤6.0 g/dL. In the control group, prescription of RBCT is guided by thresholds proposed by recent guidelines, regardless of O2ER values.

Ethics and dissemination

This trial is approved by the Comitato Etico Area Vasta Centro della Regione Emilia-Romagna (protocol number 350/2023/Sper/AOUFe/PRBCT, date of approval 18/05/2023) and ethic boards at all participating sites. Our results will be published and shared with relevant organisations and healthcare professionals.

Trial registration number

Clinicaltrials.govNCT06102590
Intranasal insulin for the treatment of olfactory dysfunction: a protocol for a systematic review and meta-analysis
Authors: He Xiaoquan , Chen Xi , Mou Daili , Chen Feifei , Xie Yan , Cui Wanling , Wang Yuezhou , Jiang Luyun
Published: November 2024

Introduction

Olfactory dysfunction (OD) is a prevalent nasal affliction that has detrimental effects on the patients’ quality of life and safety. Conventional therapeutic strategies have various limitations such as high costs, prolonged treatment durations and adverse side effects. Intranasal insulin is a novel intervention for the management of OD. To date, few systematic reviews have been conducted to evaluate the efficacy of this intervention. This study aims to critically assess the therapeutic efficacy and safety profile of intranasal insulin administration in patients with OD.

Methods and analysis

A systematic literature search will be performed on several databases, including PubMed, the Cochrane Central Register of Controlled Trials, Embase, SinoMed and China National Knowledge Infrastructure (CNKI), to identify studies investigating the efficacy of intranasal insulin in treating OD. The search will span from database inception to 1 April 2024, including publication in Chinese and English languages. Data will be retrieved from the literature by two independent investigators. Subsequently, the data will be processed using RevMan V.5.3.5. The meta-analysis will be performed in line with the Cochrane Handbook guidelines. The clinical efficacy and safety of intranasal insulin for OD will be appraised based on various outcomes, including overall symptom improvement, the Connecticut Chemosensory Clinical Research Center score, variations in serum glucose levels, body mass index variations and the incidence of adverse events.

Ethics and dissemination

This will be a systematic review of available literature; thus, no ethical clearance is required. The results of this study will be shared through journal publication or presented at an academic conference.

Trial registration number

According to the guidelines, our systematic review protocol was registered with the International Prospective Register of Systematic Reviews (PROSPERO) on 16 May 2024 (registration number CRD42024543438).
Supplemental oxygen for pulmonary embolism (SO-PE): study protocol for a mechanistic, randomised, blinded, cross-over study
Authors: Lyhne Mads Dam , Liteplo Andrew S , Zeleznik Oana Alina , Dudzinski David M , Andersen Asger , Shokoohi Hamid , Al Jalbout Nour , Eke Onyinyechi Franca , Morone Christina C , Huang Calvin K , Heyne Thomas F , Kalra Mannudeep K , Kabrhel Christopher
Published: November 2024

Background

Acute pulmonary embolism (PE) mortality is linked to abrupt rises in pulmonary artery (PA) pressure due to mechanical obstruction and pulmonary vasoconstriction, leading to right ventricular (RV) dilation, increased RV wall tension and oxygen demand, but compromised right coronary artery oxygen supply. Oxygen is a known pulmonary vasodilator, and in preclinical animal models of PE, supplemental oxygen reduces PA pressures and improves RV function. However, the mechanisms driving these interactions, especially in humans, remain poorly understood. The overall objective of the supplemental oxygen in pulmonary embolism (SO-PE) study is to investigate the mechanisms of supplemental oxygen in patients with acute PE.

Methods and analysis

This randomised, double-blind, cross-over trial at Massachusetts General Hospital will include adult patients with acute PE and evidence of RV dysfunction but without hypoxaemia (SaO2≥90% on room air). We will enrol 80 patients, each serving as their own control, with 40 randomised to start on supplemental oxygen, and 40 randomised to start on room air. Over 180 min, patients will alternate between supplemental oxygen delivered by non-rebreather mask (60% FiO2) and room air (21% FiO2). The primary outcome will be the difference in pulmonary artery systolic pressure with and without oxygen. Secondary outcomes include additional echocardiographic measures, metabolomic profiles, vital signs and dyspnoea scores. Echocardiographic data will be compared by a paired t-test or Wilcoxon signed-rank test. For metabolomic analyses, we will perform multivariable mixed effects logistic regression models and calculate false discovery rate (q-value ≤0.05) to account for multiple comparisons. Data will be collected in compliance with National Institutes of Health and National Heart Lung and Blood Institute (NHLBI) policies for data and safety monitoring.

Ethics and dissemination

The SO-PE study is funded by the NHLBI and has been approved by the Institutional Review Board of Mass General Brigham (no. 2023P000252). The study will comply with the Helsinki Declaration on medical research involving human subjects. All participants will provide prospective, written informed consent.

Trial registration number

NCT05891886.
Factors associated with exclusive breast feeding among mothers in formal employment in Dar es Salaam, Tanzania: a cross-sectional study
Authors: Mkono Nsiah , Chirande Lulu , Moshiro Robert , Noorani Mariam
Published: November 2024

Objectives

In Tanzania, only 45% of babies are still exclusively breast feeding at 4–5 months of age and maternal employment contributes to suboptimal breastfeeding practices. The objective of this study was to determine the prevalence and factors associated with exclusive breast feeding up to 6 months among mothers in formal employment in Dar es Salaam, Tanzania.

Design

This was a cross-sectional study.

Setting

The study was conducted at reproductive and child health clinics of three hospitals in Dar es Salaam, Tanzania.

Participants

327 mothers in formal employment were recruited during their infants’ 9-month vaccination visit.

Primary and secondary outcome measures

A self-administered questionnaire was used to collect data on exclusive breast feeding and associated factors. Pearson’s χ2was used to test for association and multivariable logistic regression was used to determine independent variables associated with exclusive breast feeding.

Results

The prevalence of exclusive breast feeding up to 6 months was 38.5% (95% CI 33%, 44%). Having rooms to express milk, breastfeeding policies and flexible work schedules were associated with exclusive breast feeding in χ2analysis. In multivariable analysis, mothers who had flexible schedules were two times more likely to practice exclusive breast feeding compared with those who did not have flexible schedules: aOR 2.58 (95% CI 1.15, 5.78).

Conclusion

Rates of exclusive breast feeding among mothers in formal employment are lower than the national average. Policies and programmes that offer flexible work schedules to this population can support exclusive breast feeding.
FUPEC study, a prospective open-cohort on severe pre-eclampsia and cardiovascular risk factors based in the Netherlands
Authors: van der Bijl Marte F , Al-Hassany Linda , Wijtzes Anne I , Verdonk Koen , Duvekot Johannes J , Roeters van Lennep Jeanine
Published: November 2024

Purpose

The FUPEC (Follow-Up Pre-EClampsia) study aims to investigate the presence and development of cardiovascular risk factors, cardiovascular disease, as well as cardiovascular health following a pregnancy complicated by severe pre-eclampsia.

Participants

The FUPEC study is an open-cohort study conducted within routine care at the FUPEC clinic at Erasmus Medical Center in the Netherlands. This clinic is specifically designed for the cardiovascular follow-up of patients who have experienced severe pre-eclampsia. Women with a history of severe pre-eclampsia are invited to the FUPEC clinic at 6 weeks, 3 months, 1 year and every 2 years thereafter postpartum until they are 50 years of age. Clinical and biochemical data are routinely collected, encompassing pregnancy characteristics and outcomes, anthropometric measurements, cardiovascular risk factors, cardiovascular health scores, carotid intima-media thickness—including vascular age and ambulatory blood pressure measurements. Additionally, blood and urine samples are collected and stored in a biobank.

Findings to date

The first patient was enrolled in April 2011. As of March 2024, a total number of 1268 women have been enrolled in the FUPEC study, with an annual enrolment rate of 100–150 new patients. At inclusion, women had a median age of 33.5 years (IQR 30.1–37.9). At their first FUPEC visit, women were a median of 4.9 months (1.9–29.4) after delivery. At the first visit, the median body mass index was 25.7 (IQR 23.0–29.9) kg/m2, 23.4% of participants were using antihypertensive medication and 6.4% were smoking. Preliminary analyses of 24-hour blood pressure patterns and carotid intima-media thickness have previously been conducted on a subset of the cohort, with details provided in the ‘Findings to Date’ section.

Future plans

The FUPEC cohort serves as a robust clinical data source and biobank that can be used for future studies and collaborative research answering, for example, questions on the aetiology, risk factors and short-term and long-term complications of pregnancies complicated by severe pre-eclampsia. Since the FUPEC cohort is integrated with routine care, there is no strict completion of data collection, allowing for flexible data acquisition.
Prevalence and risk factors for Achilles tendon rupture in the military population from 2006 to 2015: a retrospective cohort study
Authors: Fraser John J , A Zellers J , K Sullivan C , F Janney C
Published: November 2024

Introduction

Achilles tendon rupture (ATR) is a serious musculoskeletal injury that results in substantial functional decline, especially in highly physically demanding occupations such as service in the military. The purpose of this retrospective cohort study was to evaluate the prevalence and associated factors of ATR in US military service members.

Methods

The Defence Medical Epidemiology Database was used to identify all diagnosed ATR in military personnel from 2006 to 2015. The prevalence of ATR was calculated and compared by year, service branch and military rank. Unadjusted and adjusted assessments of risk were calculated.

Results

Officers incurred 15 978 episodes at a prevalence of 7.43/1000 (male: 8.11/1000; female: 3.89/1000). Among enlisted personnel, there were 59 242 episodes of ATR that occurred at a prevalence of 6.23 episodes per 1000 (male enlisted: 6.49/1000; female enlisted: 4.48/1000). Apart from enlisted aviation specialists (where there was no significant difference in risk between men and women), both female officers and enlisted service members had significantly lower risk of ATR compared with their male counterparts in all occupations (prevalence ratio (PR): 0.26–0.73). Aviation and service officers demonstrated significantly lower risk of ATR episodes (PR: 0.87–0.91) and administration, operations, intelligence and logistic officers demonstrated increased risk (PR: 1.16–1.31) compared with ground and naval gunfire officers. Among enlisted specialties, all but mechanised/armour and combat engineers had significantly higher risk of ATR risk compared with infantry (PR: 1.14–2.13), with the highest risk observed in the administration, intelligence and communication fields.

Conclusions

ATR was ubiquitous in the US military, with multiple risk factors identified, including male sex, older age, rank, military occupation and service branch. These findings highlight the populations that can most greatly benefit from preventive screening and care.
An Empirical Study on the Suitability of Test-based Patch Acceptance Criteria
Authors: Zemin Luciano , Gutiérrez Brida Simón , Godio Ariel , Cornejo César , Degiovanni Renzo , Regis Germán , Aguirre Nazareno , Frias Marcelo
Published: November 2024

In this article, we empirically study the suitability of tests as acceptance criteria for automated program fixes, by checking patches produced by automated repair tools using a bug-finding tool, as opposed to previous works that used tests or manual inspections. We develop a number of experiments in which faulty programs from
IntroClass
, a known benchmark for program repair techniques, are fed to the program repair tools GenProg, Angelix, AutoFix, and Nopol, using test suites of varying quality, including those accompanying the benchmark. We then check the produced patches against formal specifications using a bug-finding tool. Our results show that, in the studied scenarios, automated program repair tools are significantly more likely to accept a spurious program fix than producing an actual one. Using bounded-exhaustive suites larger than the originally given ones (with about 100 and 1,000 tests) we verify that overfitting is reduced but (a) few new correct repairs are generated and (b) some tools see their performance reduced by the larger suites and fewer correct repairs are produced. Finally, by comparing with previous work, we show that overfitting is underestimated in semantics-based tools and that patches not discarded using held-out tests may be discarded using a bug-finding tool.
A Simple Yet Effective Corpus Construction Framework for Indonesian Grammatical Error Correction
Authors: Lin Nankai , Zeng Meiyu , Huang Wentao , Jiang Shengyi , Xiao Lixian , Yang Aimin
Published: November 2024

Currently, the majority of research in grammatical error correction (GEC) is concentrated on universal languages, such as English and Chinese. Many low-resource languages lack accessible evaluation corpora. How to efficiently construct high-quality evaluation corpora for GEC in low-resource languages has become a significant challenge. To fill these gaps, in this article, we present a framework for constructing GEC corpora. Specifically, we focus on Indonesian as our research language and construct an evaluation corpus for Indonesian GEC using the proposed framework, addressing the limitations of existing evaluation corpora in Indonesian. Furthermore, we investigate the feasibility of utilizing existing large language models (LLMs), such as GPT-3.5-Turbo and GPT-4, to streamline corpus annotation efforts in GEC tasks. The results demonstrate significant potential for enhancing the performance of LLMs in low-resource language settings. Our code and corpus can be obtained from
https://github.com/GKLMIP/GEC-Construction-Framework
.
The Role of B Cells in Solid Tumors
Authors: Silva Harrison , Sherwin Delaney , Pylayeva-Gupta Yuliya
Published: November 2024

A surge of recent studies have identified B cells as pivotal contributors to shaping the tumor microenvironment (TME) within solid tumors. B cells can both directly and indirectly antagonize tumor growth via antibody production, antigen presentation, and cytokine secretion, potentially through the formation of tertiary lymphoid structures. However, certain B cell states have demonstrated the ability to promote tumor growth via immunoregulatory mechanisms such as the production of immunosuppressive cytokines and the expression of immune checkpoints, both of which dampen T cell–dependent antitumor responses. Here, we discuss the dichotomy of B cell function in solid tumors, underscoring both the pro- and antitumor roles that B cells play in the TME. Furthermore, we summarize ongoing efforts to reprogram protumorigenic B cells and/or to promote the activity and abundance of effector B cells as potential immunotherapy approaches in solid tumors.
Awakening the Genome: CRISPR Activation to Unravel the Origin and Vulnerabilities of Cancer
Authors: La Marca John E. , Diepstraten Sarah T. , Kelly Gemma L. , Herold Marco J.
Published: November 2024

CRISPR activation (CRISPRa) co-opts nuclease-dead Cas-molecule DNA-binding capabilities to direct transcriptional activators to specific loci, driving gene expression. CRISPRa technology has advanced rapidly in the past few years, and it is now applicable to a wide range of biological questions, including the study of cancer. In this review, we discuss the different forms of CRISPRa technologies, their in vitro and in vivo applications, and recent studies that have used CRISPRa in their cancers of choice in highly diverse studies. We further discuss the different CRISPRa tools that are available, including mouse models and single-guide RNA libraries. Finally, we examine the maturation of CRISPRa, as its potential therapeutic applications are beginning to be explored.
The Lymphatic Vasculature in Lung Homeostasis and Disease
Authors: Maisel Katharina , Outtz Reed Hasina
Published: November 2024

The lymphatic vasculature maintains lung homeostasis via fluid drainage in the form of lymph and by facilitating immune surveillance and leukocyte trafficking to the draining lymph nodes. Previous studies in both humans and animal models have demonstrated an important role for lymphatics in lung function from the neonatal period through adulthood. In addition, changes in the lymphatic vasculature have been observed in many respiratory diseases, and there is emerging evidence of a causative role for lymphatic dysfunction in the initiation and progression of lung pathology. Despite advances in the field, there are still many unanswered questions, and a more comprehensive understanding of the mechanisms by which the lymphatics affect lung homeostasis and the response to lung injury is needed. In this review, we discuss our current knowledge of the structure, function, and role of the lymphatics in the lung and how these vessels are involved in respiratory disease.
Infectious Disease Modeling
Authors: Huang Jing , Morris Jeffrey S.
Published: November 2024

Infectious diseases pose a persistent challenge to public health worldwide. Recent global health crises, such as the COVID-19 pandemic and Ebola outbreaks, have underscored the vital role of infectious disease modeling in guiding public health policy and response. Infectious disease modeling is a critical tool for society, informing risk mitigation measures, prompting timely interventions, and aiding preparedness for healthcare delivery systems. This article synthesizes the current landscape of infectious disease modeling, emphasizing the integration of statistical methods in understanding and predicting the spread of infectious diseases. We begin by examining the historical context and the foundational models that have shaped the field, such as the SIR (susceptible, infectious, recovered) and SEIR (susceptible, exposed, infectious, recovered) models. Subsequently, we delve into the methodological innovations that have arisen, including stochastic modeling, network-based approaches, and the use of big data analytics. We also explore the integration of machine learning techniques in enhancing model accuracy and responsiveness. The review identifies the challenges of parameter estimation, model validation, and the incorporation of real-time data streams. Moreover, we discuss the ethical implications of modeling, such as privacy concerns and the communication of risk. The article concludes by discussing future directions for research, highlighting the need for data integration and interdisciplinary collaboration for advancing infectious disease modeling.
Tensors in High-Dimensional Data Analysis: Methodological Opportunities and Theoretical Challenges
Authors: Auddy Arnab , Xia Dong , Yuan Ming
Published: November 2024

Large amounts of multidimensional data represented by multiway arrays or tensors are prevalent in modern applications across various fields such as chemometrics, genomics, physics, psychology, and signal processing. The structural complexity of such data provides vast new opportunities for modeling and analysis, but efficiently extracting information content from them, both statistically and computationally, presents unique and fundamental challenges. Addressing these challenges requires an interdisciplinary approach that brings together tools and insights from statistics, optimization, and numerical linear algebra, among other fields. Despite these hurdles, significant progress has been made in the past decade. This review seeks to examine some of the key advancements and identify common threads among them, under a number of different statistical settings.
Zang Siwei Qingfei Mixture Alleviates Pulmonary Arterial Hypertension in Rats: Integrated Network Pharmacology and Metabolomics
Authors: Lei Si , Wu Shangjie
Published: November 2024

Purpose: Pulmonary arterial hypertension (PAH) is a fatal condition characterized by poor control of pulmonary hemodynamics and vascular development. Zang Siwei Qingfei mixture (ZSQM) is a traditional Chinese medicine formula used for the treatment of chronic respiratory diseases. However, the underlying mechanism of ZSQM for treating PAH remains unclear.

Methods: A PAH rat model was established after monocrotaline (MCT) injection, and pulmonary hemodynamic features and pathological changes were evaluated. The candidate targets of ZSQM against PAH were discovered using network pharmacology. Then, molecular docking was used to validate the discovered key targets. Moreover, serum metabolomics was used to identify differential metabolites. The metabolomics and network pharmacology integrated network was constructed.

Results: ZSQM alleviated MCT‐induced pulmonary vascular injury and vascular remodeling. We found ZSQM core component chrysin and six hub genes according to network pharmacology, including CYP2C19, CASP8, PTK2, VEGFA, FLT4, and TNNI3. Molecular docking revealed strong binding affinities between key targets and chrysin. Meanwhile, western blotting results validated significant changes in the expression of these key targets. Subsequently, we confirmed that chrysin existed in the ZSQM by HPLC–MS. In addition, a total of 19 metabolites with potential significance were identified to be implicated in the therapeutic mechanisms of ZSQM. The further integrated analysis indicated an interconnection between these key targets, their related core metabolites (12(S)HETE, ascorbate, succinate, vitamin C, and L‐arginine), and metabolic pathways.

Conclusion: The study, employing metabolomics and network pharmacology, has concluded that ZSQM has the potential to enhance the treatment of PAH by targeting multiple pathways and molecular targets. This finding suggests that ZSQM could serve as a promising alternative therapy for PAH.
Differential Pattern of Consequences of Self‐Compassion Across Gender
Authors: Musabiq Sugiarti , Santoso Guritnaningsih Prayitno Amir , Takwin Bagus , Poerwandari Elizabeth Kristi
Published: November 2024

Self‐compassion is a crucial factor in psychological well‐being, particularly among young adults facing various life challenges. This study investigates the multidimensional nature of self‐compassion and its impact on flourishing and life satisfaction in 994 college students. We found that the Self‐Compassion Scale is best understood as comprising separate “protective” (e.g., self‐acceptance and kindness) and “vulnerability” (e.g., self‐criticism) factors. Both men and women interpreted the scale similarly, suggesting a shared understanding of self‐compassion. However, gender differences emerged in how these dimensions relate to well‐being. The “protective” dimension positively influenced flourishing and life satisfaction for both genders. Notably, for women, managing “vulnerability” was a stronger predictor of life satisfaction compared to men. This highlights the importance of fostering self‐compassion, particularly by addressing the vulnerability factor, to enhance women’s overall well‐being. The study emphasizes the need to consider the multidimensional nature of self‐compassion and gender differences when examining its relationship with well‐being.
The circRNA cEMSY Induces Immunogenic Cell Death and Boosts Immunotherapy Efficacy in Lung Adenocarcinoma
Authors: Zhang Yijian , Song Xuming , Feng Yipeng , Qian Yuxian , Chen Bing , Zhang Te , Wang Hui , Chen Yuzhong , Yu Xinnian , Ding Hanlin , Li Rutao , Ge Pengfei , Xu Lin , Dong Gaochao , Jiang Feng
Published: November 2024

Immunogenic cell death (ICD) induces an active immune response. Activating ICD represents a potential approach to boost the antitumor activity of immunotherapy, highlighting the need to identify effective and safe ICD inducers. In this study, we identified a conserved, ICD-related circular RNA cEMSY by systematically screening ICD models induced by multiple cell stressors in lung adenocarcinoma. cEMSY triggered ICD in lung adenocarcinoma cells both in vitro and in vivo, leading to the release of damage-associated molecular patterns and promoting T-cell cross-priming by dendritic cells. Notably, the intratumoral delivery of lipid nanoparticle–encapsulated cEMSY induced a potent antitumor immune response in an immunosuppressed tumor model, which synergized with PD-1 blockade to facilitate long-term antitumor immunity with no apparent toxicities. Mechanistically, cEMSY mediated mitochondrial aggregation of the RNA-binding protein TDP-43 that enabled leakage of mitochondrial DNA to stimulate the cGAS–STING pathway, activating the antiviral immune response. Clinically, elevated expression of cEMSY correlated with enhanced infiltration of dendritic cells and CD8+ T cells and favorable immunotherapy response in lung adenocarcinoma. Together, these findings support the dual potential of cEMSY as a target and biomarker for improving immune checkpoint inhibitor responses in lung adenocarcinoma.

Significance: cEMSY is a safe and effective immunogenic cell death inducer that synergizes with PD-1 blockade in lung adenocarcinoma, providing a potential strategy to enhance the efficacy of tumor immunotherapy.
Targeting T-Cell Costimulation to the Surface of Tumor Cells
Authors: Eguren-Santamaría Iñaki , Sanmamed Miguel F. , Molero-Glez Paula , Perez-Gracia Jose Luis , Melero Ignacio
Published: November 2024

Bispecific agents targeting tumor-cell surface antigens and activating receptors on T lymphocytes are being developed for solid tumors. Effective and safe strategies depend on target specificity and at least relative tumor-tissue confinement of T-cell activation. Novel evidence suggests that constructs targeting HER2 on tumor cells with the aim of providing costimulation (signal 2) to T lymphocytes via cluster of differentiation 137 (4-1BB) are safe and can meaningfully invigorate antitumor responses in a proportion of patients.

See related article by Piha-Paul et al., p. 288
Kinetics of Nirogacestat-Mediated Increases in B-cell Maturation Antigen on Plasma Cells Inform Therapeutic Combinations in Multiple Myeloma
Authors: Shearer Todd , Comstock Melissa , Williams Rex L. , Johnson Mark C. , Cendrowicz Ewa , Leonowens Cathrine , Smith Margaret , Baughman Todd M. , Breitbach Caroline J. , Cheng Shinta , Green Damian J.
Published: November 2024

B-cell maturation antigen (BCMA) is the target of several investigational and approved drugs for multiple myeloma. BCMA expressed on plasma cells (PC) and multiple myeloma cells is cleaved by the enzyme γ-secretase, reducing membrane-bound BCMA (mbBCMA) receptor density. γ-Secretase inhibitors (GSI) have been shown to increase mbBCMA density and may enhance efficacy of BCMA-targeted therapies. The pharmacodynamic profile of the GSI nirogacestat was evaluated in multiple myeloma cell lines and a phase I study in healthy volunteers. In multiple myeloma cell lines, mbBCMA density and soluble BCMA concentrations were measured before and after short-duration nirogacestat exposure and at serial time points following washout. In the phase I study, 23 participants were administered a single oral dose of nirogacestat 50, 150, or 300 mg or repeated doses of 100 mg every 12 hours for up to 48 hours; mbBCMA density on PCs (from whole blood and bone marrow) and nirogacestat plasma concentrations were measured at baseline and postdose. After single-dose administration, serum nirogacestat concentrations rapidly increased (Tmax ∼1 hour), and a two-compartment model with linear absorption and clearance best described nirogacestat pharmacokinetics. In multiple myeloma cells and healthy volunteers’ PCs, nirogacestat resulted in rapid and robust increases in mbBCMA density, with increases up to 20-fold within 4 to 8 hours of exposure. Concomitant decreases in soluble BCMA were observed. Nirogacestat is currently being evaluated in combination with several BCMA-directed therapeutic agents in patients with multiple myeloma. Elucidating the kinetics of BCMA in response to nirogacestat is key to guiding dosing and therapeutic strategies in multiple myeloma.

Significance:

GSIs can enhance multiple myeloma therapies targeting BCMA by increasing mbBCMA on plasma cells. In response to the GSI nirogacestat, mbBCMA rapidly and robustly increased in vitro and in vivo. Elucidating nirogacestat’s effects on BCMA kinetics will guide potential multiple myeloma dosing strategies.
An Update on the Diagnosis and Management of Faltering Growth and Catch-Up Growth in Young Children
Authors: Meyer Rosan
Published: November 2024

Background:: The term “faltering growth” (FG) is widely used to refer to a slower rate of weight gain in childhood than expected for age and gender. The prevalence varies depending on the definition and the studied population. Early recognition is important when considering the short- and long-term consequences, which include reduced cognitive development and increased risk of morbidity and mortality. Summary:: The causes of FG are traditionally classified into being either illness- or non-illness-related. However, such a rigid classification does not acknowledge the fact that poor growth may be multifactorial. While many definitions for FG exist, a recent consensus document suggested that a drop of weight-for-height of 1 z-score warrants the consideration for FG. The nutritional assessment supports the calculation of energy and protein requirements, which should be tailored to the underlying cause.
Immediate Care for Common Conditions in Term and Preterm Neonates: The Evidence
Authors: Jiang Li , Dominguez Georgia , Cummins Aoife , Muralidharan Oviya , Harrison Leila , Vaivada Tyler , Bhutta Zulfiqar A.
Published: November 2024

Background: Several interventions provided to newborns at birth or within 24 h after birth have been proven critical in improving neonatal survival and other birth outcomes. We aimed to provide an update on the effectiveness and safety of these interventions in low- and middle-income countries (LMICs). Summary: Following a comprehensive scoping of the literature, we updated or re-analyzed the LMIC-specific evidence for included topics. Ninety-four LMIC studies were identified. Delayed cord clamping with immediate neonatal care after cord clamping resulted in a lower risk of blood transfusion in newborns <32–34 gestational weeks and a lower occurrence of anemia in term newborns but did not have significant effect on neonatal mortality or other common morbidities both in preterm and term newborns. Immediate thermal care using plastic wrap/bag led to a 38% lower risk of hypothermia and a higher axillary temperature in preterm newborns without increasing the risk of hyperthermia. Kangaroo mother care initiated immediately (iKMC) or early after birth (eKMC, within 24 h) significantly reduced neonatal mortality and the occurrence of hypothermia in preterm or low-birth-weight neonates. For delayed first bath in newborns, no pooled estimate was generated due to high heterogeneity of included studies. Trials from high-income countries demonstrated anti-D’s effectiveness in lowering the incidence of Rhesus D alloimmunization in subsequent pregnancy if given within 72 h postpartum. Key Messages: We generated the most updated LMIC evidence for several immediate newborn care interventions. Despite their effectiveness and safety in improving some of the neonatal outcomes, further high-quality trials are necessary.
Basosquamous Carcinoma Arising from the Vulva: A Case Report
Authors: Saadallah Fatma , Ghazouani Ayoub , Zemni Ines , Turki Haykel , Mansouri Houyem , Sahraoui Ghada , Ben Dhiab Tarek
Published: November 2024

Introduction: Basosquamous carcinoma (BSC) of the vulva is an uncommon tumor that primarily consists of basal cell carcinoma with squamous differentiation. Also known as metatypical basal cell carcinoma, BSC is typically classified as a skin cancer and represents only 2% of non-melanoma skin malignancies. This type of carcinoma has a poorer prognosis than basal cell carcinoma due to its increased local aggressiveness and metastatic potential. Case Presentation: We present the case of a 59-year-old woman with a 3-year history of a slow-growing and painful vulvar lesion. Clinical examination revealed a 35-mm nodular, ulcerating, and non-pigmented lesion located on the labia majora. A biopsy confirmed the diagnosis of BSC, and staging assessments indicated no evidence of metastasis. The patient underwent partial radical vulvectomy and sentinel lymph node biopsy, with histological analysis revealing distinct features characteristic of BSC, including basaloid cell islands and areas of significant squamous differentiation. The excision margins were tumor-free, and all six lymph nodes examined were negative for metastases. Regular surveillance for 6 months was conducted without signs of recurrence. Conclusion: After reviewing the literature, this case represents the sixth documented instance of vulvar BSC. Compared to basal cell carcinoma, BSC has a poorer prognosis, with a higher potential for recurrences and metastases. While basal cell carcinoma is much more prevalent among vulvar and skin malignancies, recognizing the squamous differentiation component is crucial for ensuring wider margins during surgical excision.
High-Grade Sarcoma of the Pulmonary Artery That Mimicked a Pulmonary Embolism in a 39-Year-Old Patient with Recurrent Miscarriages: A Case Report
Authors: Cravero John Corbyn , Wahab Laith , Wilson Dirk T. , Alani Ali , Bredeweg Arthur , Aguirre Roberto
Published: November 2024

Introduction: Primary pulmonary artery sarcoma is a rare malignancy with a poor prognosis, undefined treatment guidelines, and is often mistaken for a pulmonary embolism (PE) based on similar clinical presentation and radiographic findings. Case Presentation: We present a case of a 39-year-old female with a past medical history of recurrent miscarriages who presented with a chief complaint of dyspnea. Due to a history of recurrent miscarriages, a predisposing coagulopathic condition was suspected for a PE. A V/Q scan showed high probability for a PE with bilateral perfusion defects. Subsequent CT angiographic imaging of the chest was read as positive for a massive PE. The patient was transferred to the medical ICU for tPA administration but developed worsening hypoxic respiratory failure and was transferred to an outside hospital for expert surgical consultation and thrombectomy. Intraoperative reports during thrombectomy commented on a mass within the pulmonary artery. Subsequent pathology showed a high-grade sarcoma. The patient was started on adjuvant chemotherapy with doxorubicin, ifosfamide, and MESNA; however, due to multiple comorbidities, the patient ultimately succumbed to her illness. Conclusion: This case underscores the diagnostic difficulty in distinguishing pulmonary artery sarcomas from a PE, especially in the presence of other confounders and biases.
External Beam Radiotherapy for Malignant Central Airway Obstruction in a Remote Rural Patient: A Case Study
Authors: Collins Eoin , Mitra Druva , Carruthers Scott
Published: November 2024

Introduction: Malignant central airway obstruction (MCAO) is a challenging therapeutic scenario, caused by tumour burden which limits airflow within the large airways. Squamous cell carcinoma (SCC) of the lung accounts for 50% of MCAO seen in the setting of non-small cell lung cancer. Here, we present the challenging case of a 63-year-old Indigenous Australian Female rom a remote rural community with background history of metastatic SCC of presumed pulmonary origin, who presented with a 1-week history of dyspnoea, stridor, and hoarse voice. Case Presentation: A CT chest and neck demonstrated a superior mediastinal mass compressing the trachea to a narrowest diameter of 3 mm. The patient was stabilised in her local health centre, then transferred to our tertiary care facility for further evaluation and management. This stenotic lesion was not amenable to bronchoscopic or surgical intervention but was instead treated successfully with a short course of external beam radiotherapy, to total dose of 25Gy delivered over 10 fractions. The patient had almost complete resolution of respiratory symptoms with no significant radiotherapy related toxicity. Conclusion: Here, we discuss a challenging case of MCAO in a remote rural Australian patient and demonstrate the utility of external beam radiotherapy in this setting. We also discuss aspects of cancer related healthcare disparities which exist for Indigenous Australians. In doing so, we wish to highlight the need for improved cancer healthcare for such communities.
The association between body mass index and mortality in breast cancer patients receiving pembrolizumab
Authors: Chiang Cho-Han , Xu Xiaocao , Shahid Ahmed , Song Junmin , Chi Kuan-Yu , Chang Yu-Cheng , Chang Yu , Chiang Cho-Hung , Lin Shuwen
Published: November 2024

Introduction: A higher body mass index (BMI) has been associated with a better response and overall survival in patients with lung cancer or melanoma receiving immune checkpoint inhibitors (ICIs). Pembrolizumab has been approved for the use of breast cancer but its relationship with survival outcomes is unclear.
Methods: We conducted a retrospective, propensity score-matched cohort study using the TriNetX Analytics Network database, which contains de-identified data from over 120 participating healthcare institutions. We included all adult female patients with breast cancer who received pembrolizumab. We excluded patients who were prescribed endocrine or human epidermal growth factor receptor 2 targeted therapies. We compared the 1-year all-cause mortality between patients who were overweight or obese (BMI ≥ 25 kg/m2) and those who were normal weight (BMI < 25 kg/m2). We matched patients on predetermined variables including age, race, breast cancer-directed therapy, cardiovascular and diabetes medications, and underlying comorbidities.
Results: We identified 1628 eligible patients, of whom 1163 had a BMI ≥ 25 kg/m2 and 465 had a BMI < 25 kg/m2. After propensity score matching, 410 patients in each cohort were well-balanced for demographics, breast cancer-directed therapy, and underlying comorbidities. The mean ages for patients with BMI ≥ 25 kg/m2 and BMI < 25 kg/m2 were 56.7±14.0 and 56.9±15.0, respectively. Over a median follow-up of 1 year, 28 and 53 patients died in the BMI ≥ 25 kg/m2 and BMI < 25 kg/m2 cohorts, respectively. Patients with BMI ≥ 25 kg/m2 had a 49% lower risk of all-cause mortality compared with those with BMI < 25 kg/m2 (Hazard ratio (HR), 0.51 [95% CI: 0.33-0.81]).
Conclusions: A BMI ≥ 25 kg/m2 was associated with a lower all-cause mortality among breast cancer patients receiving pembrolizumab.
Career Interest and Readiness among Grade 10 Students of A Private University in Cebu City
Authors: Boctot Jenalyn B. , Cabatingan Alicia P , Polinar Mark Anthony N.
Published: November 2024

This descriptive-correlational study aimed to identify the students’ awareness regarding their career interests and career readiness regarding the learning experience, learning outcomes, and pre-college experience of Grade 10 students at a private university in Cebu City. Using Slovin’s formula, there should be 206 respondents; however, 198 have participated. Also, several statistical treatments were applied to the study’s findings. The findings regarding the profile and the career interests of the students, as well as their age, gender, total income, parents' educational attainment, and occupation, found no relationship. Another finding regarding the profile and career readiness revealed that both the mother and father's age and educational attainment have a significant relationship. Career interest and career readiness have a solid positive relationship. Thus, the finding shows that the relationship between the two variables is solid, and it also indicates that interest will influence the student's career readiness and how ready they are to step up to the next level of their studies. The findings disclosed that the student's career interest is a significant factor (computed value 14.4) in pursuing their major field of specialization, primarily supported by their career readiness. The more the student is interested in a particular field, the more the student is ready to pursue his dream career. Based on the findings and conclusion, it is suggested that all grade levels should be given a career interest survey and ready to think, prepare, and choose what career path they need to take in the future. As much as possible, parents should also play a significant role in selecting the students' careers so that they can guide their students in what career is best suited for them.
Rostros de Oceanía en el Museo de La Plata: itinerarios de una colección
Authors: Sardi Marina Laura , Farro Máximo Ezequiel , Bucci Piero Javier
Published: November 2024

Molding and casting faces, hands, and feet were part of the various knowledge-making strategies of anthropologists since the 19th century. This study focuses on a collection of facial masks obtained by the German anthropologist Otto Finsch from live subjects of native people from Oceania and held by the Museo de La Plata, Argentina. We’ve analysed the materials, archives, and catalogues; also, oral testimonies of museum workers that were in contact with this collection. Firstly, we revise how these masks came to be, how they were acquired by this museum, how they were exhibited and what happened with them after they were removed from the exhibition. Second, we remark on some points of discussion around this collection on the assumption that these materials represent scientific heritage that not only accounts for the history of anthropology and the context in which it was constituted but that it is also feasible to be reactivated into new narratives.
Personality dimensions in the common octopus (Octopus vulgaris)
Authors: Mazza Valeria , Pacchiarotti Giulia , Strinati Claudia , Carlini Alessandro , Mather Jennifer A. , Carere Claudio
Published: November 2024

Understanding the origin, universality, and maintenance of among-individual variation in behaviour is a current focus of behavioural ecology and comparative psychology. Research on animal personality emphasising the central role of the individual contributes to conservation efforts and animal welfare by tailoring guidelines and interventions at the individual level. Cephalopods are understudied in this respect, despite being the only invertebrate group currently included in international directives for the protection of animals used for scientific purposes. Here, we assessed among-individual variation in behavioural responses (i.e., animal personality) of 21 common octopuses (Octopus vulgaris) temporarily kept in captivity. We performed a battery of tests across three different experimental contexts, namely a Startle test, a Foraging test, and a Disturbance test, each repeated for four consecutive days, adapting established protocols from other cephalopods. Behavioural variables were moderately repeatable. Results of a principal component analysis revealed a three-component structure, with components we labelled Alertness, Exploration, and Boldness. The components were also moderately repeatable. The components Exploration and Boldness predicted each other across experimental contexts, suggesting a behavioural syndrome. Overall, findings indicate marked individual differences in common octopuses, and provide evidence of personality dimensions in a widely used animal model in neurophysiology and cognition. Our findings thus contribute to the study of the evolution of personality structure from a comparative perspective, and may help individual-level welfare refinement.