bluuebunny/crossref_metadata_2025 huggingface dataset:
Lipoprotein(a) Atherosclerotic Cardiovascular Disease Risk Score Development and Prediction in Primary Prevention From Real-World Data
Authors: Fan Wenjun , Wu Chuyue , Wong Nathan D.
Published: January 2025

BACKGROUND:

Lipoprotein(a) [Lp(a)] is a predictor of atherosclerotic cardiovascular disease (ASCVD); however, there are few algorithms incorporating Lp(a), especially from real-world settings. We developed an electronic health record (EHR)-based risk prediction algorithm including Lp(a).

METHODS:

Utilizing a large EHR database, we categorized Lp(a) cut points at 25, 50, and 75 mg/dL and constructed 10-year ASCVD risk prediction models incorporating Lp(a), with external validation in a pooled cohort of 4 US prospective studies. Net reclassification improvement was determined among borderline-intermediate risk patients.

RESULTS:

We included 5902 patients aged ≥18 years (mean age 48.7±16.7 years, 51.2% women, and 7.7% Black). Our EHR model included Lp(a), age, sex, Black race/ethnicity, systolic blood pressure, total and high-density lipoprotein cholesterol, diabetes, smoking, and hypertension medication. Over a mean follow-up of 6.8 years, ASCVD event rates (per 1000 person-years) ranged from 8.7 to 16.7 across Lp(a) groups. A 25 mg/dL increment in Lp(a) was associated with an adjusted hazard ratio of 1.23 (95% CI, 1.10–1.37) for composite ASCVD. Those with Lp(a) ≥75 mg/dL had an 88% higher risk of ASCVD (hazard ratio, 1.88 [95% CI, 1.30–2.70]) and more than double the risk of incident stroke (hazard ratio, 2.55 [95% CI, 1.54–4.23]). C-statistics for our EHR and EHR+Lp(a) models in our EHR training data set were 0.7475 and 0.7556, respectively, with external validation in our pooled cohort (n=21 864) of 0.7350 and 0.7368, respectively. Among those at borderline/intermediate risk, the net reclassification improvement was 21.3%.

CONCLUSIONS:

We show the feasibility of developing an improved ASCVD risk prediction model incorporating Lp(a) based on a real-world adult clinic population. The inclusion of Lp(a) in ASCVD prediction models can reclassify risk in patients who may benefit from more intensified ASCVD prevention efforts.
Dynamic Importance of Genomic and Clinical Risk for Coronary Artery Disease Over the Life Course
Authors: Urbut Sarah M. , Cho So Mi Jemma , Paruchuri Kaavya , Truong Buu , Haidermota Sara , Peloso Gina M. , Hornsby Whitney E. , Philippakis Anthony , Fahed Akl C. , Natarajan Pradeep
Published: January 2025

BACKGROUND:

Earlier identification of high coronary artery disease (CAD) risk individuals may enable more effective prevention strategies. However, existing 10-year risk frameworks are ineffective at earlier identification. We sought to understand how the variable importance of genomic and clinical factors across life stages may significantly improve lifelong CAD event prediction.

METHODS:

A longitudinal study was performed using data from 2 cohort studies: the FOS (Framingham Offspring Study) with 3588 participants aged 19 to 57 years and the UKB (UK Biobank) with 327 837 participants aged 40 years to 70 years. A total of 134 765 and 3 831 734 person-time years were observed in FOS and UKB, respectively. Hazard ratios for CAD were calculated for polygenic risk score (PRS) and clinical risk factors at each age of enrollment. The relative importance of PRS and pooled cohort equations in predicting CAD events was also evaluated by age groups.

RESULTS:

The importance of CAD PRS diminished over the life course, with a hazard ratio of 3.58 (95% CI, 1.39–9.19) at the age of 19 years in FOS and a hazard ratio of 1.51 (95% CI, 1.48–1.54) by the age of 70 years in UKB. Clinical risk factors exhibited similar age-dependent trends. PRS significantly outperformed pooled cohort equations in identifying subsequent CAD events in the 40- to 45-year age group, with 3.2-fold more appropriately identified events. Overall, adding PRS improved the area under the receiving operating curve of the pooled cohort equations by an average of +5.1% (95% CI, 4.9%–5.2%) across all age groups; among individuals <55 years, PRS augmented the area under the receiver operater curve (ROC) of the pooled cohort equations by 6.5% (95% CI, 5.5%–7.5%;
P
<0.001).

CONCLUSIONS:

Genomic and clinical risk factors for CAD display time-varying importance across the lifespan. The study underscores the added value of CAD PRS, particularly among individuals younger than 55 years, for enhancing early risk prediction and prevention strategies. All results are available at
https://surbut.github.io/dynamicHRpaper/index.html
.
The Kidney-Immune-Brain Axis: The Role of Inflammation in the Pathogenesis and Treatment of Stroke in Chronic Kidney Disease
Authors: Kelly Dearbhla M. , Kelleher Eoin M. , Rothwell Peter M.
Published: January 2025

Cardiovascular diseases such as stroke are a major cause of morbidity and mortality for patients with chronic kidney disease (CKD). The underlying mechanisms connecting CKD and cardiovascular disease are yet to be fully elucidated, but inflammation is proposed to play an important role based on genetic association studies, studies of inflammatory biomarkers, and clinical trials of anti-inflammatory drug targets. There are multiple sources of both endogenous and exogenous inflammation in CKD, including increased production and decreased clearance of proinflammatory cytokines, oxidative stress, metabolic acidosis, chronic and recurrent infections, dialysis access, changes in adipose tissue metabolism, and disruptions in intestinal microbiota. This review focuses on the mechanisms of inflammation in CKD, dialysis and associated therapies, its proposed impact on stroke pathogenesis and prognosis, and the potential role of anti-inflammatory agents in the prevention and treatment of stroke in patients with CKD.
Gender Distribution of Leadership Positions in Global Environmental Politics
Authors: Downie David L.
Published: January 2025

Many institutions have called for increasing the number of women in leadership positions in global environmental politics (GEP). Little information exists, however, regarding gender distributions in such positions. This brief report begins filling in elements of our collective data gap. Men currently lead 80 percent of the fifteen global intergovernmental organizations (IGOs) that are particularly important to GEP and have held 90 percent of these positions in the past. Men currently lead 70 percent of national environmental ministries and have held approximately 78 percent of those positions. Equal numbers of men and women currently lead the twenty most prominent environmental treaty secretariats, although men have held more than 70 percent of these positions in the past. During the twenty-first century, men received 69 percent of the appointments to lead the IGOs and treaty secretariats most important to GEP. These numbers raise a series of research, ethical, and political questions.
Costly Signaling in Ancient Chinese Narratives
Authors: Weingarten Oliver
Published: January 2025

Seemingly reckless, wasteful, or self-harming actions depicted in narrative sources are embedded in the philosophical and political discourse of Warring States and early imperial China (around the third to the first century bce). Signaling theory unveils the underlying rationality of many such acts by demonstrating how they allow actors with conflicting interests to pursue their goals while reducing costs compared to alternative scenarios. Ancient Chinese thinkers did not discuss signaling theory in the abstract; they were, however, keenly aware of the underlying mechanisms, at times articulating them in the context of specific cases. Comparisons of multiple narrative versions suggest that plot elements related to signaling became more pronounced and the understanding of signaling more profound during the period, most likely due to heightened socio-political and military competition.
A Civil War by Any Other Name? Building a Qualitative Model to Support Quantitative Datasets: The Cypriot Civil War
Authors: Mansueto Tim , Varnava Andrekos
Published: January 2025

A case study of the Cypriot Civil War (1963–1967) demonstrates that existing scholarly definitions of civil war are inadequate. The arbitrary death thresholds that qualify conflicts for inclusion in civil war datasets are demonstrably biased against smaller countries and do not account for all internal conflicts that exhibit the qualitative characteristics of civil war. An alternative model of study showcases how quantitative data might be better supported by qualitative analysis through the use of relative death thresholds.
To Whom Does the Land Belong?
Authors: Jwilisi Sphesihle , Onwuegbuchulam Sunday Paul Chinazo
Published: January 2025

Land has been influential in the political discourse and policymaking of both apartheid and post-apartheid democratic South Africa. Currently, considering certain conflicts and recent calls for land expropriation in South Africa, it would seem that the land issue persists despite all efforts by the democratic government in South Africa to address it through various land reform policies. For this reason, interrogating land reform in South Africa and the prospects of peace and national unity in the country becomes pertinent. Using qualitative desktop methods and adopting a self-categorisation theoretical lens, the article interrogates the question of land reform in South Africa. The paper argues that resolving the land question will demand a diversified approach that strikes a balance between social fairness, economic progress and political stability. Achieving this will entail constructive discourse, inclusive decision-making processes, transparent governance, and targeted interventions towards addressing land-related conflicts while encouraging reconciliation and social cohesion in South Africa.
Land Reform and Industrial Development in Mexico: Practical Lessons for Zimbabwe
Authors: Tekwa Newman
Published: January 2025

Despite the different time periods, land reform in Zimbabwe and Mexico share remarkable similarities from which Zimbabwe can draw policy lessons for reindustrialisation. Occurring between 1911 and 1947, land reform in Mexico redistributed 51.4% of the country’s agricultural land to tenants, workers and peasants. The new social order lacked an economic foundation, presenting a situation of both a challenge and a response yet fulfilling the conditions necessary for industrial development. Similarly, Zimbabwe redistributed about 80% of former white freehold agricultural land to an estimated 170,000 farming households. Whereas the key historical secret to Mexico’s industrialisation lies in its agrarian reform, the same cannot be said about contemporary Zimbabwe, which experienced deindustrialisation at the turn of the millennium. Zimbabwe’s national industrial development policy makes no specific reference to the country’s land reform. I argue for a comprehensive agrarian reform strategy that can steer the country onto a sustainable reindustrialisation path.
Collaborative spaces as places-of-entrepreneuring: A phenomenological investigation of entrepreneurs’ place-making experiences and practices
Authors: Dey Pascal , Lô Amadou , Fatien Pauline
Published: January 2025

Entrepreneurship scholars have become increasingly interested in new collaborative spaces—such as incubators, makerspaces, and coworking spaces—that support entrepreneurial ventures. However, limited attention has been paid to entrepreneurs’ embodied capacity to transform these collaborative spaces into places for entrepreneuring. In response, we propose a phenomenological perspective to advance theorizing on how entrepreneurs “do place” by experiencing and shaping the meaning, affective content, and materiality of their workplace in specific ways. Based on a longitudinal qualitative study of a coworking space in Paris, we identify three regimes of entrepreneur’s place-making: (a) collectively negotiating place-meaning, (b) manipulating place as a site of practical use, and (c) place-based identity forming. Our contribution is threefold. First, drawing on a diverse literature on phenomenology, and recent practice-based research, we argue that a dual focus on the embodied experiences and practices of entrepreneurs enables a more granular understanding of how collaborative spaces are enacted as “places-of-entrepreneuring.” Second, we show how “places-of-entrepreneuring” emerge from the skillful interweaving of different regimes of place-making. Third, we recommend that owners of collaborative spaces proactively promote place-making “by design” by encouraging entrepreneurs to become active producers, rather than passive users, of their work environments.
Ben Weinstein, MD (1913–1974) and his enduring impact on the history of medicine experience in medical school
Authors: Trotter Michael C
Published: January 2025

The history of medicine as a component of the medical school curriculum has been a long-standing subject of debate and controversy. Ultimately, local factors may determine this experience and be aligned with or outside of the curriculum. The opportunity at Tulane University School of Medicine is long-standing and successful. It came to fruition through the efforts of Benjamin Bernard Weinstein, MD. A native New Orleanian, he received his undergraduate (1933) and medical (1937) degrees from Tulane as well as his training in obstetrics and gynaecology. He then joined the faculty and remained there until 1953 when he entered private practice with an interest in reproductive medicine. Weinstein was internationally known in the field, travelling the globe as a prominent educator and intersecting with world leaders. But his passion was the Tulane History of Medicine Society, founded by Weinstein in 1933 as a medical student. He became its guiding force and benefactor and built the foundation that remains highly relevant and successful 91 years later with a lengthy list of distinguished Weinstein Lecturers annually. Following his death in 1974, his family has continued to engage and support the Society. Weinstein's legacy of an enriched life through the study and knowledge of the history of medicine continues through the Society.
Creating an Ellipsys percutaneous arteriovenous fistula after a failed ipsilateral WavelinQ fistula: A case report of an endovascular approach for access restoration
Authors: Pham Son Tung , Dorbath Christian , Gunnar Heine , Brzoska Martin
Published: January 2025

The introduction of devices for endovascular dialysis access creation (WavelinQ and Ellipsys) offers practitioners more options for access management in dialysis patients. Especially in terms of reducing the usage of central venous catheters, a native fistula is desirable as an initial dialysis access. We present a case in which a failed WavelinQ type fistula was reactivated using the Ellipsys procedure on the same arm. This specific rescue method is based on the idea that the proximal part of an endoAVF from an earlier WavelinQ procedure which resulted in adequately dilated veins, comprising the perforating vein, may allow a subsequent Ellipsys procedure. This case report shows how the use of endovascular techniques such as WavelinQ and Ellipsys can be incorporated in a clinical context and create new options for the patient.
Ngā manu taketake o te ao (Indigenous birds of the world): a scoping review of research focusing on Indigenous speech-language therapy for Indigenous children, using Indigenous methodologies
Authors: Kohere-Smiler Nicky-Marie J , dos Santos Meechan Ryan JH , Malone Marie , Purdy Suzanne C , Brewer Karen M
Published: January 2025

For Indigenous children with speech, language and communication needs, providing speech-language therapy within their worldview is of vital importance. This scoping review identified speech-language therapy research undertaken internationally in the past 20 years using Indigenous methodologies. This is part of a research project conducted by tribal researchers from Te Aitanga-a-Māhaki Trust, the mandated tribal organization located in the Eastern region of New Zealand’s North Island. The review critically appraised 31 articles and theses using the CONSoliDated critERia (CONSIDER) for strengthening reporting of health research involving Indigenous peoples, to evaluate the quality of research practices in studies involving Indigenous peoples. The review revealed small pockets of speech-language therapy research for children from Indigenous communities around the English-speaking world, but insufficient research to form a robust evidence base to meet the rights of any group of Indigenous peoples, as expressed in the United Nations Declaration on the Rights of Indigenous Peoples.
Who cares?: The burdens of care borne by the loved ones of incarcerated men
Authors: McDonald Alysha , Berardi Luca , Haggerty Kevin , Bucerius Sandra
Published: January 2025

The labor and associated challenges of providing informal care have been characterized as constituting a burden of care (BoC). Despite the analytical value this concept has demonstrated in studies of nursing, psychiatry, and health administration, researchers have overlooked this phenomenon in the context of incarceration. Using 181 longitudinal interviews conducted between April 2020 and January 2021 with 29 loved ones of men incarcerated across Canada, we examine the experiences of caregivers trying to meet the outstanding needs of incarcerated people. We find that the BoC arose when caregivers compensated for the correctional system's (real or perceived) failed responsibility to fulfill the basic needs of incarcerated people relating to rehabilitation and release planning, as well as their legal advocacy requirements. We position the BoC as a component of secondary prisonization and use the framework to accentuate the roles caregivers played in reducing the care deficit incarcerated people experienced and, by extension, augmenting the functionality of the prison system. We suggest ways to promote less onerous carceral and reintegrative terms by reducing the unmet needs of incarcerated people and, by extension, the BoC that caregivers bore.
ACQUIRED MUTATIONS IN PATIENTS WITH RELAPSED/REFRACTORY CLL WHO PROGRESSED IN THE ALPINE STUDY
Authors: Brown Jennifer R. , Li Jessica , Eichhorst Barbara , Lamanna Nicole , O'Brien Susan M. , Tam Constantine S. , Qiu Lugui , Huang Ruiqi , Shi Yang , Idoine Adam , Salmi Tommi , Cohen Aileen Cleary , Shadman Mazyar
Published: January 2025

Some CLL patients who develop progressive disease (PD) during treatment with covalent Bruton tyrosine kinase inhibitors (cBTKi) acquire pathway resistance mutations in BTK or PLCG2. Here, we report gene mutation data from paired baseline and PD peripheral blood samples from 52 patients (zanubrutinib, n=24; ibrutinib, n=28) who, at an early median follow-up time of 25.7 months, progressed on zanubrutinib or ibrutinib treatment in the ALPINE trial (NCT03734016). No BTK mutations were observed at baseline; at PD, eight patients (zanubrutinib, n=5, ibrutinib, n=3) acquired a total of 17 BTK mutations. Among BTK mutations, 82.4% (zanubrutinib, n=11/14; ibrutinib, n=3/3) were at C481. Non-C481 mutations were detected in 12.5% (3/24) of zanubrutinib-treated patients (L528W: n=2, cancer cell fraction [CCF]=9.58% and 17.6%; A428D, n=1, CCF=37.03%); these were not detected in ibrutinib-treated patients. At baseline, 48/52 patients had ≥1 driver gene mutation/s, most frequently in: NOTCH1 (n=21), TP53 (n=19), BRAF (n=10), SF3B1 (n=8), and ATM (n=8). At PD, acquired driver gene mutations were observed in one zanubrutinib-treated patient (TP53, XPO1) and five ibrutinib-treated patients (TP53, n=1 patient; SETD2, n=1; SF3B1, n=1; ASXL1, n=2). Baseline driver gene mutations were not associated with later development of BTK mutations, but patients with ≥2 baseline driver gene mutations were more likely to acquire BTK mutations at PD. In conclusion, patients in this data set had a short treatment duration and a low incidence of BTK mutations, suggesting that mechanisms other than BTK/PLCG2 mutations are driving most instances of early PD. NCT03734016
TP53 Mutant Variant Allele Frequency and Cytogenetics Determine Prognostic Groups in MDS/AML for Transplantation
Authors: Lontos Konstantinos , Saliba Rima M , Kanagal-Shamanna Rashmi , Ozcan Gonca , Ramdial Jeremy Leon , Chen George Liwei , Kadia Tapan M. , Short Nicholas J , Daver Naval G. , Kantarjian Hagop M. , Marin David , Kebriaei Partow , Popat Uday R. , Champlin Richard E. , Shpall Elizabeth J , Oran Betul
Published: January 2025

Results following hematopoietic stem cell transplantation (HSCT) for TP53-mutated myeloid malignancies are disappointing. Several HSCT centers decline to perform HSCT for patients with TP53 mutation because of poor outcomes. In this study, we analyzed 240 patients with TP53-mutated myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML) that underwent HSCT. We aimed to identify the patients that benefit most from HSCT. The primary outcome was progression-free survival (PFS). Fifty-two percent of the cohort had AML and the median age of the cohort was 62. AML and MDS outcomes were similar. We identified several favorable prognostic factors for PFS including the absence of complex cytogenetics/5q deletion/7q deletion, a lower variant allele frequency (VAF), a mono-hit status and the use of a matched-related donor. Using classification and regression tree analysis, we identified VAF and cytogenetics as the two most important prognostic factors. Patients with TP53mut VAF ≥ 50% had a 2-year PFS of 3%, patients with TP53mut VAF < 50% and complex/5q/7q cytogenetics abnormalities had 2-year PFS of 22%. Patients with TP53mut VAF < 50% and without complex/5q/7q cytogenetics had 2-year PFS of 60%. This data informs clinical practice and helps patients decide whether to pursue HSCT.
Proteinuria and the risk of Incident atrial fibrillation according to glycemic stages: a nationwide population-based cohort study
Authors: Yeo Muhan , Lee So-Ryoung , Choi Eue-Keun , Choi JungMin , Lee Kyung-Yeon , Kwon Soonil , Ahn Hyo-Jeong , Kim Bong-Seong , Han Kyung-Do , Oh Seil , Lip Gregory Y. H.
Published: January 2025

Background

Diabetes mellitus (DM) and proteinuria each independently raise the risk of atrial fibrillation (AF). We aimed to investigate the relationship between proteinuria and the risk of incident AF across glycemic stages.

Methods

A cohort of 4,044,524 individuals without prior AF and type 1 DM was selected from the 2009 Korean National Health Insurance Service health checkup data. The individuals were categorized into five glycemic stages: normal, prediabetes, new-onset DM, early DM (< 5 years), and late DM (≥ 5 years). Proteinuria was graded using a urine dipstick test. The development of incident AF was tracked until 2023.

Results

Overall, the cohort (mean age 47 ± 14 years, 44.8% female) showed increasing annual AF incidence rates from 2.05 to 7.22 per 1000 person-years from normal to late DM (p < 0.001). Incidence rates increased from 2.46 to 8.18 per 1000 person-years with increasing proteinuria (p < 0.001). Adjusted Cox regression models revealed a heightened AF risk with higher proteinuria across all glycemic stages (adjusted hazard ratios for urine dipstick 3+/4+: 1.58, 1.64, 2.39, 2.12, and 2.53 for normal, prediabetes, new-onset DM, early DM, and late DM, respectively). The proteinuria-AF association was more pronounced in individuals with DM than in those without DM but was similar among the new-onset and established DM groups.

Conclusions

Proteinuria is an independent and significant risk factor for incident AF at all glycemic stages. The risk of incident AF in patients with DM can be stratified by measuring the level of proteinuria rather than comparing the duration of DM. Tailoring clinical strategies to proteinuria level could potentially mitigate this risk, improving patient outcomes.

Graphical abstract
Obesity-induced mesenteric PVAT remodelling is sexually dimorphic, but not driven by ovarian hormones
Authors: Ivatt Lisa , Paul Mhairi , Miguelez-Crespo Allende , Hadoke Patrick W. F. , Bailey Matthew A. , Morgan Ruth A. , Nixon Mark
Published: January 2025

Background

Obesity, a major risk factor for cardiovascular disease (CVD), is associated with hypertension and vascular dysfunction. Perivascular adipose tissue (PVAT), a metabolically active tissue surrounding blood vessels, plays a key role in regulating vascular tone. In obesity, PVAT becomes dysregulated which may contribute to vascular dysfunction; how sex impacts the remodelling of PVAT and thus the altered vascular contractility during obesity is unclear.

Objective

To investigate sex-specific PVAT dysregulation in the setting of obesity as a potential driver of sex differences in vascular pathologies and CVD risk.

Methods

Adult male and female C57Bl/6J mice were fed an obesogenic high-fat diet (HFD) or regular chow for 16 weeks. Mesenteric PVAT (mPVAT) was isolated for RNA-sequencing and histological analysis, and mesenteric arteries were isolated for assessment of vascular function by wire myography. In a separate study, female mice were subjected to bilateral ovariectomy prior to dietary intervention to determine the contribution of ovarian hormones to PVAT dysregulation.

Results

Transcriptomic analysis of mPVAT revealed sexually dimorphic responses to HFD, with upregulation of extracellular matrix (ECM) remodelling pathways in male but not female mice. Histological and RT-qPCR approaches demonstrated increased collagen deposition and ECM remodelling in mPVAT from obese male compared with obese female mice. Assessment of vascular function in mesenteric arteries -/+ PVAT revealed that in obesity, mPVAT impaired endothelium-mediated vasodilation in male but not female mice. Ovariectomy of female mice prior to HFD administration did not alter ECM transcript expression or collagen deposition in mPVAT compared to sham-operated female mice.

Conclusions

Obesity induces sex-specific molecular remodelling in mPVAT, with male mice exhibiting unique upregulation of ECM pathways and increased collagen deposition compared to females. Moreover, the relative protection of female mice from obesity-induced mPVAT dysregulation is not mediated by ovarian hormones. These data highlight a potential sex-specific mechanistic link between mPVAT and mesenteric artery dysfunction in obesity, and provides crucial insights for future development of treatment strategies that consider the unique cardiovascular risks in men and women.

Graphical abstract
Facile nucleophilic substitution approach for the spectrofluorimetric assay of natamycin based on diarylpyrrolone formation, evaluation of method greenness
Authors: Derayea Sayed M. , Mohammed Fatma F.
Published: January 2025

An ecofriendly, effective, and selective spectrofluorimetric approach for natamycin analysis was developed using fluorescamine as a fluorogenic probe. Natamycin is the only topical ocular antifungal medication that is presently on the market for treating keratitis, conjunctivitis, and blepharitis caused by yeast and other fungi. Owing to its primary aliphatic amino group, natamycin can easily interact with fluorescamine resulting in the formation of the highly fluorescent diaryl pyrrolone derivative. The derivatization reaction was completed within very short time at room temperature in borate buffer solution (pH 7.6). The fluorescence intensity of the reaction product was monitored at 465 nm after exciting at 390 nm. The linearity range of the spectrofluorimetric method was 0.25–4.0 µg/mL of natamycin with limit of detection (LOD) of 0.082 µg/mL. The method was applied for the determination of the cited drug in pharmaceutical eye drops and artificial aqueous humor with high percentage recoveries and low relative standard deviations. In addition, the involved analytical procedure was green based on the results of the ecology scale scores.
Identification of fine antigenic epitopes of Tamdy virus glycoprotein Gn fragment and establishment of ELISA detection method
Authors: Fu Yujiao , Liu Liping , Zhang Beibei , Chao Xiaoshan , Jin Junxia , Wang Ying , Ding Juntao
Published: January 2025

Background

Tamdy virus (TAMV) was first isolated in Uzbekistan and Turkmenistan. In 2018, it was found in China, marking its entry into the molecular research era. TAMV is linked to febrile diseases, but its epidemiology and spillover risks are poorly understood, necessitating urgent molecular research and detection method development.

Methods

The secondary structure of TAMV glycoprotein Gn was predicted, and the results showed that it had rich antigenic epitopes. According to the predicted results, glycoprotein Gn was divided into 46 truncated 16-peptides by modified synthetic peptide method, and the antigenicity of 46 truncated 16-peptides was verified by western blotting analysis.

Results

The results showed that P8, P9, P24, P25, P28, P29, and P39 had antigenicity. Subsequently, the seven positive 16-peptide sequences with antigenicity were truncated to form 8-peptide sequences with an overlap of seven amino acids. After analysis with the same method, eight fine antigenic epitopes E1 (58VINSTLDH65), E2 (65HVGSWGMP72), E3 (68SWGMPVTT75), E4 (187IRNQPFKS194), E5 (195FNVEVQ200), E6 (226AVVEHH231), E7 (228VEHHGNKA235), and E8 (310RGGRR314) were identified, all of which were located on the three-dimensional surface of glycoprotein Gn and were highly conserved in different TAMV strains.

Conclusions

Eight precise epitopes were identified, and an indirect ELISA method based on fusion multiepitope peptide (r-Gn-MEPX2) was developed and implemented, featuring high sensitivity, accuracy, and specificity.

Graphical Abstract
Expanding the frontiers of electrocatalysis: advanced theoretical methods for water splitting
Authors: Cho Seong Chan , Seok Jun Ho , Manh Hung Ngo , Seol Jae Hun , Lee Chi Ho , Lee Sang Uck
Published: January 2025

Electrochemical water splitting, which encompasses the hydrogen evolution reaction (HER) and the oxygen evolution reaction (OER), offers a promising route for sustainable hydrogen production. The development of efficient and cost-effective electrocatalysts is crucial for advancing this technology, especially given the reliance on expensive transition metals, such as Pt and Ir, in traditional catalysts. This review highlights recent advances in the design and optimization of electrocatalysts, focusing on density functional theory (DFT) as a key tool for understanding and improving catalytic performance in the HER and OER. We begin by exploring DFT-based approaches for evaluating catalytic activity under both acidic and alkaline conditions. The review then shifts to a material-oriented perspective, showcasing key catalyst materials and the theoretical strategies employed to enhance their performance. In addition, we discuss scaling relationships that exist between binding energies and electronic structures through the use of charge-density analysis and d-band theory. Advanced concepts, such as the effects of adsorbate coverage, solvation, and applied potential on catalytic behavior, are also discussed. We finally focus on integrating machine learning (ML) with DFT to enable high-throughput screening and accelerate the discovery of novel water-splitting catalysts. This comprehensive review underscores the pivotal role that DFT plays in advancing electrocatalyst design and highlights its potential for shaping the future of sustainable hydrogen production.

Graphical Abstract
Estimation of the probability of informed trading models via an expectation-conditional maximization algorithm
Authors: Ghachem Montasser , Ersan Oguz
Published: January 2025

The estimation of the probability of informed trading (PIN) model and its extensions poses significant challenges owing to various computational problems. To address these issues, we propose a novel estimation method called the expectation-conditional-maximization (ECM) algorithm, which can serve as an alternative to the existing methods for estimating PIN models. Our method provides optimal estimates for the original PIN model as well as two of its extensions: the multilayer PIN model and the adjusted PIN model, along with its restricted versions. Our results indicate that estimations using the ECM algorithm are generally faster, more accurate, and more memory-efficient than the standard methods used in the literature, making it a robust alternative. More importantly, the ECM algorithm is not limited to the models discussed and can be easily adapted to estimate future extensions of the PIN model.
Migraine diagnosis in patients with sinus headache symptoms: a cross-sectional study at Khartoum ENT Hospital
Authors: Abdelgafour Mohamed Salah Mohamed , Eltayeb Abdelgadir Ahmed , El-Awad Mohammed
Published: January 2025

Background

Sinus headache is the most common diagnosis reported by patients with migraine who received a non-migraine diagnosis. Thus, the aim of this study was to determine the prevalence of migraine among patients present with sinus headache to Khartoum ENT Hospital.

Objective

To study the prevalence of migraine (using IHS criteria) among patients present with sinus headache at Khartoum ENT Hospital.

Methods

This is a cross-sectional hospital-based study conducted at Khartoum ENT Hospital in the period between July 2022 to February 2023 including all patients with self-reported or physician diagnosed “sinus headache”, without a suspected secondary cause of headache. Diagnosis of migraine was made using the IHS criteria.

Data was collected by the researcher, entered and analyzed using SPSS.

Results

This study included 197 patients with a mean age of 33 ± 10 years, and female predominance 129 (65. 5%). The most common presentation was nasal blockage 178 (90.4%), flowed by facial pain 87 (44.7%), and nasal discharge 42 (21.3%). Autonomic symptoms included lacrimation 71 (36%), conjunctival injection 20 (10%), and eyelid edema 6 (3%), and 26 (13%) had positive family history of migraine. The prevalence of migraine was 67 (34%); 40 (20%) without aura and 27 (14%) with aura. Migraine was significantly associated with autonomic symptoms, and family history of migraine, and poor response to NSAIDs and nasal sprays compared to non-migraine headache (P-value < 0.05).

Conclusion

Migraine is not uncommon as 34% of patients with self-reported or physician diagnosed sinus headache meet the International Headache Society (IHS) criteria of Migraine. Migraine was associated with autonomic symptoms and a positive family history of migraine. The presence of good response among those who used antimigraine medications may aid the diagnosis of migraine.
Inequity in treatment access for child mental health services in England: analysis of administrative national data for 2021–2022
Authors: Pape Tom , Rixson Lauren , Pari Anees Ahmed Abdul
Published: January 2025

Aims and method

An equitable child mental health service provides access to treatment proportionally to the need of individual demographic groups. Despite qualitative and survey-based evidence of barriers disadvantaging some demographic groups, it is not well understood how these barriers translate into quantifiable inequities. We calculated the treatment access rate for English children aged 6–16 years in 2021–2022, using the patient-level Mental Health Services Data Set and Mental Health of Children and Young People Survey.

Results

The number of primary school children in treatment needs to increase nationally by 173%, the number of boys by 65% and the number of children from a White ethnic background by 31%, to achieve equity in treatment access. There was no evidence of inequities by area deprivation.

Clinical implications

Child mental health services in England should not only increase overall access rates, but also pay more attention to equity in access across different demographic groups.
Delta-Radiomics Using Machine Learning Classifiers With Auxiliary Data Sets to Predict Disease Progression During Magnetic Resonance-Guided Radiotherapy in Adrenal Metastases
Authors: Fajemisin Jesutofunmi A. , Bryant John M. , Saghand Payman G. , Mills Matthew N. , Latifi Kujtim , Moros Eduardo G. , Feygelman Vladimir , Frakes Jessica M. , Hoffe Sarah E. , Mittauer Kathryn E. , Kutuk Tugce , Kotecha Rupesh , El Naqa Issam , Rosenberg Stephen A.
Published: January 2025

PURPOSE

Adaptive radiotherapy accounts for interfractional anatomic changes. We hypothesize that changes in the gross tumor volumes identified during daily scans could be analyzed using delta-radiomics to predict disease progression events. We evaluated whether an auxiliary data set could improve prediction performance.

MATERIALS AND METHODS

We analyzed 108 patients (n = 90 internal; n = 18 external) who received ablative radiotherapy. The internal data set included 42 patients with adrenal cancer, 23 patients with lung cancer, and 25 patients with pancreatic cancer, with the clinical end point of progression-free survival events. The median dose was 50 Gy, which was delivered over five fractions. The delta features are the ratio of the features of the last to first treatment fraction, F5/F1, and the concatenation of the first and last fraction features, F1||F5. Decision tree classifier with and without auxiliary data sets, and the external data set was used exclusively for independent testing of the final models.

RESULTS

During internal training, for the F1||F5 model, the inclusion of the lung data set increased our AUC receiver operator characteristic curve (ROC) from 0.53 ± 0.12 to 0.61 ± 0.11, whereas the pancreatic data set increased our AUC-ROC to 0.60 ± 0.14. For the F5/F1 model, the inclusion of the lung auxiliary data increased our AUC-ROC from 0.52 ± 0.13 to 0.65 ± 0.11, whereas it modestly changed by 0.62 ± 0.13 with the pancreas. During external testing, for the F5/F1 model, we reported an AUC-ROC of 0.60 with the lung auxiliary data and 0.43 with the pancreatic data. Also, for the F5||F1 model, we reported an AUC-ROC of 0.70 with the lung auxiliary and 0.60 with the pancreatic data.

CONCLUSION

Decision trees provided an explainable model on the external data set. The validation of our model on an external data set may be the first step to biologically adapted radiotherapy recognizing radiomics signals for potential recurrence.
Pertuzumab Retreatment for Human Epidermal Growth Factor Receptor 2–Positive Locally Advanced/Metastatic Breast Cancer (PRECIOUS Study): Final Overall Survival Analysis
Authors: Yamamoto Yutaka , Iwata Hiroji , Saji Shigehira , Takahashi Masato , Yoshinami Tetsuhiro , Ueno Takayuki , Toyama Tatsuya , Yamanaka Takashi , Takano Toshimi , Kashiwaba Masahiro , Tsugawa Koichiro , Hasegawa Yoshie , Tamura Kenji , Tada Hiroshi , Hara Fumikata , Fujisawa Tomomi , Niikura Naoki , Taira Naruto , Morita Satoshi , Toi Masakazu , Ohno Shinji , Masuda Norikazu
Published: January 2025

In the primary analysis of the open-label phase III PRECIOUS study, pertuzumab retreatment combined with trastuzumab plus chemotherapy of physician's choice (PTC) significantly improved investigator-assessed progression-free survival (PFS) compared with trastuzumab plus physician's choice chemotherapy (TC) in patients with human epidermal growth factor receptor 2 (HER2)–positive locally advanced/metastatic breast cancer (LA/mBC). Here, we report final overall survival (OS) at the median follow-up of 25.8 months. Patients who have previously received pertuzumab-containing regimens as first-/second-line treatment for LA/mBC were randomly assigned 1:1 to two groups, PTC group (n = 110) and TC group (n = 109). Median OS was longer in the PTC group (median OS 36.2
v
26.5 months; hazard ratio [HR], 0.73 [one side 95% CI upper limit, 0.97]). Updated median investigator-assessed PFS (5.5
v
4.2 months; HR, 0.81 [one side 95% CI upper limit, 1.02]) were also better in the PTC group. Median PFS by independent review did not show the difference between the two groups (4.4
v
4.4 months; HR, 1.03 [one side 95% CI upper limit, 1.36]). These findings suggest that dual HER2 blockade with pertuzumab plus trastuzumab could contribute to improving OS in patients who have previously been treated with pertuzumab-containing regimens for HER2-positive LA/mBC.
Perioperative Supportive Care Interventions to Enhance Surgical Outcomes for Older Adults With Cancer: A Systematic Review
Authors: Lam Anh B. , Sorensen Luke , Moore Vanessa A. , Bouvette Max J. , Diaz Barba Adolfo , Clifton Shari , Wismann Andrea , Keyser Katie , Shinall Myrick C. , Nipp Ryan David
Published: January 2025

PURPOSE

Older adults with cancer have unique needs, which likely influence surgical outcomes in the geriatric oncology population. We conducted a systematic review to describe the literature focused on perioperative supportive care interventions for older adults with cancer undergoing surgery.

METHODS

Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, we performed a comprehensive search using the Ovid MEDLINE, CINAHL, and Embase databases for literature published from January 2010 to October 2023. We included randomized controlled trials (RCTs) focusing on supportive care interventions that enrolled adults older than 60 years with cancer.

RESULTS

We included 11 RCTs with 2,177 patients in this review. Patients' age ranged from 60 to 95, and the median number of patients per study was 147 (range, 44-690). Most studies included patients with colorectal cancer (81.8%). Half of the studies (54.5%) evaluated exercise interventions, and the remaining assessed geriatric assessment–guided interventions (27.2%), nutrition optimization (9.1%), and patient empowerment (9.1%). Primary outcomes included postoperative complications, quality of life, feasibility of exercise programs, inspiratory muscle endurance, and hospital length of stay, among others. All studies had postoperative complications as a primary or secondary outcome. We found implementation challenges that influenced several studies, including high dropout rates and intervention fidelity.

CONCLUSION

We found 11 studies focused on perioperative supportive care interventions in older adults with cancer undergoing surgery. Notably, interventions involved exercise, geriatric assessment–guided care, nutrition optimization, and patient empowerment. We also found heterogeneity in intervention modality and outcome assessment, thus demonstrating a need for ongoing work to address the unique needs of the geriatric oncology population.
Prevalence of FGFR2b Protein Overexpression in Advanced Gastric Cancers During Prescreening for the Phase III FORTITUDE-101 Trial
Authors: Rha Sun Young , Zhang Yanqiao , Elme Anneli , Pazo Cid Roberto , Alacacioglu Ahmet , Ziogas Dimitrios C. , Shitara Kohei , Ranceva Anastasija , Nemecek Radim , Santoro Armando , Calderon Carlos Alberto , Korphaisarn Krittiya , Davis Tracy , Zahlten-Kuemeli Anita , Conn Christopher , Tan Mengyao , Honeycutt Hayden , Wainberg Zev A.
Published: January 2025

PURPOSE

Fibroblast growth factor receptor 2 isoform IIIb (FGFR2b) protein overexpression is an emerging biomarker in gastric cancer and gastroesophageal junction cancer (GC). We assessed FGFR2b protein overexpression prevalence in nearly 3,800 tumor samples as part of the prescreening process for a global phase III study in patients with newly diagnosed advanced or metastatic GC.

METHODS

As of June 28, 2024, 3,782 tumor samples from prescreened patients from 37 countries for the phase III FORTITUDE-101 trial (ClinicalTrials.gov identifier: NCT05052801) were centrally tested for FGFR2b protein overexpression by immunohistochemistry (IHC) and had evaluable results. FGFR2b positivity was defined as both any % tumor cells (TC) and ≥10% TC exhibiting moderate-to-strong (2+/3+) membranous FGFR2b staining. Prevalence was analyzed across patient and sample characteristics.

RESULTS

FGFR2b protein overexpression at any % and ≥10%, 2+/3+ TC positivity was 37.8% (1,428/3,782 [95% CI, 36.2 to 39.3]) and 16.2% (612/3,782 [95% CI, 15 to 17.4]), respectively. Of any %, 2+/3+ TC–positive tumors, 42.9% (612/1,428 [95% CI, 40.3 to 45.4]) were FGFR2b ≥10%, 2+/3+ TC positive. FGFR2b prevalence was not notably different within multiple patient and sample characteristics examined (age, sex, collection method [biopsy
v
resection], collection site, location of primary tumor, and geographic region).

CONCLUSION

As of the data cutoff date, we report the largest prevalence assessment of FGFR2b protein overexpression in GC with more than one third (37.8%) of patients with GC exhibiting FGFR2b protein overexpression (any % TC, 2+/3+) by a validated IHC assay. Approximately 16% of patients had FGFR2b protein overexpression in ≥10% of TC. FGFR2b prevalence was similar across geographic regions and within defined patient and sample variables regardless of the level of expression.
Romosozumab Improves Tissue Thickness–Adjusted Trabecular Bone Score in Women With Osteoporosis and Diabetes
Authors: Ferrari Serge , Betah Donald , Feldman Robert G , Langdahl Bente L , Oates Mary , Timoshanko Jen , Wang Zhenxun , Dhaliwal Ruban
Published: January 2025

Context

Trabecular bone score (TBS), a gray-level texture index derived from lumbar spine (LS) dual-energy x-ray absorptiometry (DXA) scans, is decreased in patients with diabetes and is associated with increased fracture risk, independent of areal bone mineral density (aBMD), but potentially influenced by abdominal fat tissue.

Objective

Evaluate effect of romosozumab (210 mg monthly) for 12 months followed by alendronate (70 mg weekly) for 24 months vs alendronate alone (70 mg weekly) for 36 months on LS aBMD and TBS in women with type 2 diabetes (T2D) enrolled in the ARCH study.

Methods

This post hoc analysis included women from ARCH who had T2D at baseline and LS DXA scans at baseline and ≥1 postbaseline visit (romosozumab-to-alendronate, n = 165; alendronate-to-alendronate, n = 195). aBMD and TBS (determined by an updated tissue thickness–adjusted TBS algorithm [TBSTT]) were assessed on LS DXA scans at baseline and ≥1 postbaseline visit (months 12, 24, and 36).

Results

Romosozumab led to significantly greater gains in LS aBMD and TBSTT at month 12 vs alendronate, and the greater gains with romosozumab were maintained after transition to alendronate and persisted significantly at months 24 and 36 vs alendronate alone. TBSTT percentage changes weakly correlated to LS aBMD percentage changes from baseline to month 36 (romosozumab-to-alendronate, R2 = 0.1493; alendronate-to-alendronate, R2 = 0.0429).

Conclusion

In postmenopausal women with osteoporosis and T2D, 12 months of romosozumab followed by 24 months of alendronate vs alendronate alone significantly improved LS aBMD and TBSTT (independently of abdominal fat) and to a greater extent. Hence, romosozumab may improve bone strength in patients with T2D.

Trial registration

ClinicalTrials.gov—NCT01631214