bluuebunny/crossref_metadata_2025 huggingface dataset:
A Scoping Review of Literature on Deep Learning Techniques for Face Recognition
Authors: Nemavhola Andisani , Viriri Serestina , Chibaya Colin
Published: January 2025

Deep learning has led to the creation of facial recognition technologies using convolutional neural networks (CNNs). This preliminary study explores the application of CNN architectures in face recognition to gain a deeper understanding of the challenges and methodologies in the field. The study systematically reviewed relevant literature using the Preferred Reporting Items for Systematic reviews and Meta‐Analyses extension for Scoping Reviews (PRISMA‐ScR) framework. Out of 3622 eligible papers, 266 were included in the review, with 47% proposing new techniques and 1% focusing on method implementation and comparison. Most studies used images rather than video as training or testing data, with 78% using clean data and only 7% utilizing occluded and clean data. It was observed that traditional CNN architectures were predominantly employed. The study identified a lack of research on the implementation and definition of CNN architectures, the development of facial recognition models using both clean and occluded images and videos, and the exploration of nontraditional CNN architectures. The challenges affecting facial recognition included occlusion, distance from the camera, camera angle, and lighting conditions. This preliminary assessment provides an insight into the use of CNN in face recognition and suggests that nontraditional CNN architectures could be further explored in future research.
Australian Grandparents Raising Grandchildren: Understanding the Complexities of Intergenerational and Vicarious Trauma
Authors: McPherson Lynne , Day Kylie , Gatwiri Kathomi , Mitchell Janise , Macnamara Noel , Kim Samara
Published: January 2025

Grandparents have a long history of assuming caregiving responsibilities, particularly in Indigenous communities, where the concepts of “kin” and “care” are expansive. In Australia, there has been a rise in grandparents becoming custodial carers for their grandchildren who cannot live with their parents, biological or otherwise. Placement with relatives or family friends is known as kinship care, with most of these families headed by grandparents raising grandchildren. Children being raised by kin are widely considered the preferred option compared to nonrelative institutional or foster care, as kinship care provides a connection to family, community, and culture and fosters a sense of belonging and identity, while also offering the potential for stable living arrangements. This paper reports on an Australian study involving 428 grandparent carers sharing their experiences of caring for their grandchildren as survey respondents, with nine of those carers participating in an individual in‐depth interview. Findings suggest that the pleasure of watching their grandchildren grow was a privilege for many. Alongside this privilege, many experienced multiple and complex levels of stress, distress and trauma, exacerbated by a service system that did not appear to want to hear or understand. Implications for policy, practice and further research are highlighted.
Antibiotic Resistance Profile of Enterovirulent E. coli Isolates Harboring Broad‐Spectrum Beta‐Lactamase Genes in Cancer Patients at the Laquintinie Hospital in Douala, Littoral Region, Cameroon
Authors: Kengne Michael F. , Mbaveng Armelle T. , Marbou Wiliane J. T. , Karimo Ousenu , Dadjo Ballue S. T. , Fonjou Delano G. T. , Tsobeng Ornella D. , Kuete Victor
Published: January 2025

Cases of antibiotic‐resistant Escherichia coli (E. coli) infections are becoming increasingly frequent and represent a major threat to our ability to treat cancer patients. The emergence of antimicrobial resistance threatens the treatment of E. coli infections. In this study, the antimicrobial profiles, virulent genes, and the frequency of extended‐spectrum beta‐lactamase (ESBL) gene carriage in fecal E. coli isolates from cancer patients at the Laquintinie Hospital in Douala (Cameroon) were determined. 507 participants were recruited from October 2021 to March 2023, of whom 307 (60.55%) had cancer and 200 (39.45%) did not. Two hundred and two E. coli were isolated from fecal samples of one hundred and fifteen cancer patients and 47 (87) noncancer patients using EMB LEVINE agar. The antimicrobial resistance profile of the isolates was determined using the Kirby–Bauer disk diffusion method. Virulence and resistance genes were detected by simplex polymerase chain reaction (PCR). E. coli showed significant rates of resistance to amoxicillin, cefotaxime, ceftazidime, piperacillin, tetracycline, and ciprofloxacin in cancer patients compared to noncancer patients. The rate of multidrug resistance (MDR) was significantly (p < 0.05) higher in cancer patients than in noncancer patients. Fifty‐five enterovirulent E. coli were identified, of which 24 (43.63%) were EPEC, 13 (23.63%) were EAEC, 6 (10.90%) were ETEC, 10 (18.18%) were STEC, and 2 (3.63%) were EIEC. The frequency of beta‐lactamase genes in the 55 ESBL‐producing enterovirulent E. coli isolates was determined, and 94.54% harbored at least one ESBL gene, distributed as follows: 80.00% for blaTEM, 67.27% for blaCTX−M, 24.63 for blaOXA, and 36.36% for blaSHV genes. Several associations were observed between virulence factors, resistance genes, and the antimicrobial resistance phenotype. This study revealed the real existence of fecal carriage of ESBL‐producing enterovirulent E. coli isolates from cancer patients with a high rate of MDR in the latter.
Clinical Outcomes and Resource Efficiency of a Telehealth Model for New Lower Gastrointestinal Bleeding Referrals: A Tertiary Colorectal Outpatient Service Audit
Authors: Naseem Zainab , Butt Qamar M. , Shaukat Amina , Grenfell-Dexter Rachael , Zhu Junzhe , D’Souza Basil , Strugnell Neil
Published: January 2025

Introduction: Amidst the COVID‐19 pandemic, telehealth (TH) has gained increasing relevance in colorectal patient care, prompting an audit of the TH clinic at a tertiary colorectal unit. This study evaluated telephone‐based consultations’ clinical efficacy and diagnostic thresholds for new lower gastrointestinal (LGI) bleeding referrals.

Methods: We conducted a quality assurance audit of the per rectal (PR) bleeding TH clinic at Northern Hospital Victoria, evaluating new LGI bleeding referrals. Data from July 2021 to June 2023 were extracted from the Referral Management System (RMS) and analyzed. The study focused on newly referred patients, excluding those previously seen or awaiting procedures. Clinical efficacy was determined through sensitivity, specificity, and predictive values, with a receiver operating characteristic (ROC) curve assessing the TH method’s discrimination threshold.

Results: Of the 239 patients, 131 met the inclusion criteria, with a compliance rate of 96%. The TH clinic demonstrated a sensitivity of 75.76% and specificity of 52.46% in distinguishing between colorectal and anal pathologies. The average time from referral to a diagnostic procedure was 9.75 weeks, with a reduction in median wait time for first appointments from 19 weeks prepandemic to 3.6 weeks. A cost–benefit analysis highlighted TH clinics’ ability to reduce overhead costs and maintain a revenue stream despite reduced face‐to‐face consultations.

Conclusion: Our study concludes that the telecare service model serves as an effective complementary approach for managing new LGI bleeding referrals. Further research on long‐term outcomes and cost‐effectiveness is necessary to fully assess telecare as a potentially sustainable hybrid model.
Effect of Pressure on MHD Flow of Blood‐Based Hybrid Nanofluid Through an Inclined Stenotic–Aneurysmal Artery
Authors: Imoro Issah , Etwire Christian John , Musah Rabiu
Published: January 2025

Pressure gradient influence on magnetohydrodynamic (MHD) flow of blood‐based hybrid nanofluid containing gold and copper nanoparticles is investigated in the present study. We adopted Caputo’s definition of fractional derivative to transform time‐varying terms in governing equations after being appropriately normalized. Partial‐analytical solutions of these equations are then numerically sought via the concentrated matrix exponential (CME) method, since complex forms of modified Bessel functions are contained in the normalized equations whose inverse Laplace transforms cannot easily be accomplished using known analytical schemes, which is the overriding novelty of this study. Results for velocity, temperature, and concentration profiles are analyzed graphically. Numerical results for skin friction, Nusselt, and Sherwood numbers are also presented in a table. Our results revealed that the fractional‐order derivative increases velocity, temperature, skin friction, and Sherwood’s number, while concentration and Nusselt’s number decrease, accounting for its memory effects in the behavior of the fluid. Additionally, we observed that blood velocity declines with magnetic parameter values, while temperature distribution increases with Eckert’s number values. The study also shows fluctuations in flow motion, temperature, concentration, skin friction, and Nusselt’s number with the stenosis/aneurysmal height. Overall, our findings have significant implications for targeted drug delivery in the arterial system, especially concerning the treatment of atherosclerosis, aneurysms, and other cardiovascular diseases.
High Frequency of Detection of NDM‐Producing Enterobacterales Among Companion Animals Hospitalized in an Italian Veterinary Teaching Hospital
Authors: Scarpellini R. , Pulido-Vadillo M. , Serna C. , Gonzalez-Zorn B. , Blanco J. L. , Delgado-Blas J. F. , Giunti M. , Piva S.
Published: January 2025

Carbapenems are considered one of the most important last‐resort classes of antibiotics, and the spread of carbapenem‐resistant Enterobacterales (CRE) is a serious concern worldwide. From a One Health point of view, reports on CRE in companion animals are increasing, requiring attention regarding their role in maintenance and direct transmission to humans. The aim of this study was to assess the frequency of detection at admission and the in‐hospital acquisition of CRE from perirectal swabs in dogs and cats hospitalized in an Italian Veterinary Teaching Hospital (VTH). Of the 150 patients sampled, 11.3% (n = 17) were CRE carriers at admission, 25.6% (n = 34) acquired CRE in their commensal microbiota during their hospital stay, and 2% (n = 3) developed an infection caused by CRE. Genotypical analysis showed that in 100% (78/78) of the CRE isolates (44 Escherichia coli, 33 Klebsiella pneumoniae, and 1 Klebsiella aerogenes) carbapenem resistance was conferred by the carbapenemase gene blaNDM, suggesting an endemic presence of such gene within the hospital. Co‐occurrent β‐lactamase‐encoding genes were found in most of the isolates. Risk factors associated with CRE acquisition were length of hospitalization (p = 0.0002) and treatment with piperacillin–tazobactam (PTZ; p = 0.0380), indicating potential cross‐selection of CRE. These results reinforce the suspicion that companion animals could silently contribute to the maintenance and dissemination of CRE in the local community, posing a threat to global health.
Evaluating YouTube Videos With Prophylactic Mastectomy Content in Terms of Their Quality and Reliability
Authors: Altintas Tansu , Bilgi Kirmaci Mehlika
Published: January 2025

Aim: Purpose of this study is to investigate the quality and reliability of YouTube video contents on prophylactic mastectomy.

Material and Methods: The search terms “prophylactic mastectomy,” “prophylactic mastectomy surgery,” “preventive surgery for breast cancer,” “risk‐reducing mastectomy,” and “prophylactic mastectomy and breast reconstruction” were searched on YouTube. The uploader, video content, length (seconds), upload date, number of days since upload date, number of views, number of comments, and likes were recorded and evaluated. Finally, the videos included in the study were evaluated using modified Quality Criteria for Consumer Health Information (DISCERN) and Global Quality Scale (GQS).

Results: The total number of views of the 50 videos reviewed in the study was found as 3.674.469. The mean DISCERN score of the two observers was calculated as 3.35 ± 1, and the videos were found to be of medium reliability. The mean GQS score of all videos was 3.39 ± 0.9 and the videos were of medium quality. The researchers gave 1‐2 points (misleading) to 7 (14%) videos, 3 points (somewhat helpful) to 20 (40%) videos, 4 points (beneficial) to 16 (32%) videos, and 5 points (excellent) to 7 (14%) videos.

Conclusion: In our study, we found that the videos uploaded by doctors were of good quality, the videos uploaded by health channels were of medium quality, and the videos uploaded by patients were of poor quality and misleading. The videos with health contents should be evaluated by the relevant specialists, and only useful videos should be broadcast.
Assessing the Threshold of Need for Supplemental Damping in Seismic Base Isolation of Multistory Buildings
Authors: Amini Ali Reza Babaeian , Narjabadifam Peyman , Asl Gholam Reza Ostadi , Emamverdi Samad , Derogar Shahram , Ozarisoy Bertug
Published: January 2025

The comprehension of the threshold for the need of supplemental dampers in the base isolation of multistory buildings could be beneficial in the advancement of the application of base isolation to achieve seismic safety. In this study, stick models of 1‐, 4‐, 7‐, 10‐, 13‐, 16‐, and 19‐story buildings were designed in fixed‐base, simply base‐isolated, and damping‐assisted base‐isolated scenarios. The isolation system considered is the well‐known friction pendulum system, with supplemental damping provided by widely used viscous dampers. Time history analyses were conducted using seven far‐fault accelerograms and seven near‐fault accelerograms. Seismic performances were evaluated in terms of base shear values, story accelerations, interstory drifts, and story shears. The results indicate that base isolation is highly effective in controlling seismic responses in both far‐fault and near‐fault earthquakes, with average base shear values in the base‐isolated models reduced by approximately 60%–75% compared with the fixed‐base models. Displacements, accelerations, drifts, and story shears were also decreased by more than 50% compared with the fixed‐base models. Base isolation demonstrated acceptable performance in the 4‐, 7‐, and 10‐story models, but supplemental damping was necessary for effective structural control of the 13‐story model in near‐fault earthquakes, as well as the 16‐story and 19‐story models in both far‐fault and near‐fault earthquakes. The incorporation of supplemental damping significantly enhances structural control by further mitigating displacements, shears, and accelerations.
Supplemental Table 4 from Validating Wave 1 (2014) Urinary Cotinine and TNE-2 Cut-points for Differentiating Wave 4 (2017) Cigarette Use from Non-use in the United States Using Data from the PATH Study
Authors: Edwards Kathryn C. , Khan Asia , Sharma Eva , Wang Lanqing , Feng June , Blount Benjamin C. , Sosnoff Connie S. , Smith Danielle M. , Goniewicz Maciej L. , Pearson Jennifer , Villanti Andrea C. , Delnevo Cristine D. , Bover-Manderski Michelle T. , Hatsukami Dorothy K. , Niaura Raymond , Everard Colm , Kimmel Heather L. , Duffy Kara , Rostron Brian L. , Del Valle-Pinero Arseima Y. , van Bemmel Dana M. , Stanton Cassandra A. , Hyland Andrew
Published: January 2025

Supplemental Table 4 provides prevalence rates of any tobacco use using TNE-2 cut-points.
Supplemental Table 2 from Validating Wave 1 (2014) Urinary Cotinine and TNE-2 Cut-points for Differentiating Wave 4 (2017) Cigarette Use from Non-use in the United States Using Data from the PATH Study
Authors: Edwards Kathryn C. , Khan Asia , Sharma Eva , Wang Lanqing , Feng June , Blount Benjamin C. , Sosnoff Connie S. , Smith Danielle M. , Goniewicz Maciej L. , Pearson Jennifer , Villanti Andrea C. , Delnevo Cristine D. , Bover-Manderski Michelle T. , Hatsukami Dorothy K. , Niaura Raymond , Everard Colm , Kimmel Heather L. , Duffy Kara , Rostron Brian L. , Del Valle-Pinero Arseima Y. , van Bemmel Dana M. , Stanton Cassandra A. , Hyland Andrew
Published: January 2025

Supplemental Table 2 provides demographic and tobacco use characteristics of any tobacco users.
NXP800 Activates the Unfolded Protein Response, Altering AR and E2F Function to Impact Castration-Resistant Prostate Cancer Growth
Authors: Welti Jonathan , Bogdan Denisa , Figueiredo Ines , Coleman Ilsa , Jiménez Vacas Juan , Liodaki Kate , Weigl Franziska , Buroni Lorenzo , Zeng Wanting , Bernett Ilona , Bertan Claudia , Roumeliotis Theodoros I. , Bhamra Amandeep , Rekowski Jan , Gurel Bora , Neeb Antje J. , Ning Jian , Li Dapei , Gil Veronica S. , Riisnaes Ruth , Miranda Susana , Crespo Mateus , Ferreira Ana , Tunariu Nina , Pasqua Elisa , Chessum Nicola , Cheeseman Matthew , te Poele Robert , Powers Marissa , Carreira Suzanne , Choudhary Jyoti , Clarke Paul , Banerji Udai , Swain Amanda , Jones Keith , Yuan Wei , Workman Paul , Nelson Peter S. , de Bono Johann S. , Sharp Adam
Published: January 2025

Purpose:

Advanced prostate cancer is invariably fatal, with the androgen receptor (AR) being a major therapeutic target. AR signaling inhibitors have improved overall survival for men with advanced prostate cancer, but treatment resistance is inevitable and includes reactivation of AR signaling. Novel therapeutic approaches targeting these mechanisms to block tumor growth is an urgent unmet clinical need. One attractive strategy is to target heat shock proteins (HSP) critical to AR functional activity.

Experimental Design:

We first did transcriptome analysis on multiple castration-resistant prostate cancer (CRPC) cohorts to correlate the association between the Gene Ontology cellular response to heat gene expression signature and overall survival. Next, we analyzed the impact of targeting the heat shock factor 1 (HSF1) pathway, with an inhibitor in clinical development, namely, NXP800 (formerly CCT361814), in models of treatment-resistant prostate cancer. Finally, we confirmed our mechanistic and phenotypic findings using an NXP800-resistant model and an in vivo model of CRPC.

Results:

We report that in multiple CRPC transcriptome cohorts, the Gene Ontology cellular response to heat gene expression signature associates with AR signaling and worse clinical outcome. We demonstrate the effects of targeting the HSF1 pathway, central to cellular stress, with an inhibitor in clinical development, namely, NXP800, in prostate cancer. Targeting the HSF1 pathway with the inhibitor NXP800 decreases HSP72 expression, activates the unfolded protein response, and inhibits AR- and E2F-mediated activity, inhibiting the growth of treatment-resistant prostate cancer models.

Conclusions:

Overall, NXP800 has antitumor activity against treatment-resistant prostate cancer models, including molecular subtypes with limited treatment options, supporting its consideration for prostate cancer–specific clinical development.
Targeting Pancreatic Cancer Cell Stemness by Blocking Fibronectin-Binding Integrins on Cancer-Associated Fibroblasts
Authors: Wu Chengsheng , Von Schalscha Tami , Sansanwal Diva , Qian Chen , Jiang Qinlin , Shepard Ryan M. , Wettersten Hiromi I. , McCormack Stephen J. , Weis Sara M. , Cheresh David A.
Published: January 2025

Cancer-associated fibroblasts (CAF) generate an extracellular matrix (ECM) which provides a repository for factors that promote pancreatic cancer progression. In this study, we establish that CAF contribution to pancreatic tumor initiation, i.e., stemness, depends on fibronectin (FN) as a scaffold required for assembly of a collagen-containing fibrotic ECM with a critical dependence on the FN-binding integrins, α5β1 and αvβ3. CAF matrix assembly can be prevented by knockdown of FN, integrin α5, or integrin β3 or by a bispecific antibody with dual recognition of α5β1 and αvβ3 that can also destabilize a preexisting matrix. In mice, the ability of CAFs to produce a stiff collagenous matrix and accelerate tumor initiation can be blocked by knockdown of FN or FN-binding integrins or systemic treatment with the α5β1/αvβ3 bispecific antibody. Together, these results reveal that dual targeting of the FN-binding integrins, α5β1 and αvβ3, can block the ability of CAFs and their matrix to enhance pancreatic cancer stemness and progression.

Significance:

Simultaneous targeting of two integrins that function as receptors for FN, a protumor ECM protein, can prevent fibroblasts from supporting the malignant behavior of pancreatic cancer cells.
Congenital Hyperinsulinism and Long QT Syndrome Attributable to a Variant in KCNE1
Authors: Sigal Winifred , Boodhansingh Kara E. , Ganguly Arupa , Mitteer Lauren M. , Stanley Charles A. , De León Diva D.
Published: January 2025

Introduction: This is a report of a child with congenital hyperinsulinism associated with a loss-of-function variant in KCNE1. KCNE1 encodes a human potassium channel accessory (beta) subunit that modulates potassium channel Kv7.1 (encoded by KCNQ1). Loss-of-function pathogenic variants in either the KCNQ1 or KCNE1 genes result in long QT syndrome by causing prolongation in the action potential duration at the cellular level. In addition to long QT syndrome, the phenotype associated with loss-of-function pathogenic variants in KCNQ1 is characterized by post-prandial hyperinsulinemic hypoglycemia.
Case Presentation: Clinical data for the proband was extracted from the medical records. The proband presented with fasting hypoglycemia due to hyperinsulinism in early childhood as well as post-prandial hypoglycemia triggered by carbohydrates and by protein. Whole exome sequencing was undertaken in genomic DNA isolated from proband and both parents. Whole exome sequencing revealed a variant in KCNE1 inherited from the father, who also has a history of hyperinsulinism. Both the patient and father were subsequently diagnosed with long QT syndrome. The proband and father underwent phenotype testing including fasting test, oral glucose tolerance test, oral protein tolerance test, and exercise tolerance test.
Conclusions: This case illustrates that loss-of-function variants in KCNE1, similar to KCNQ1, are associated with a cardiac and a beta cell phenotype, and thus, this patient population should be screened for hypoglycemia, particularly in the postprandial state.
Clinical values of serum platelet-activating factor in hypertensive disorders complicating pregnancy
Authors: Liu Shasha , Lan Qianyu , Li Weiling , Zhang Jiefang , Fu Liman , Xu Yanlei , Li Yuan
Published: January 2025

Introduction: Serum platelet-activating factor (PAF) was proven to be associated with gestational hypertension. However, the predictive value of serum PAF at early pregnancy for the occurrence and outcomes of hypertensive disorders complicating pregnancy (HDCP) remained unclear.
Methods: The demographic and clinical characteristics of patients were compared among the different subgroups. The serum PAF level was determined using an enzyme-linked immunosorbent assay. The predictive value of serum PAF for the occurrence and outcomes of HDCP was evaluated using receiver operating characteristic curve analysis. The correlation of serum PAF with blood pressure was assessed using Spearman analysis.
Results: Both systolic blood pressure and diastolic blood pressure were significantly higher in HDCP patients, as well as the serum levels of TNF-α and IL-1β at diagnosis/enrollment, while serum levels of IL-10 showed the opposite trend. Serum PAF levels were significantly higher in patients with HDCP compared to normal pregnant women. Furthermore, serum PAF levels were higher in HDCP patients with mild preeclampsia compared to those with gestational hypertension and even more elevated in HDCP patients with severe preeclampsia at the early pregnancy stage and at diagnosis. In HDCP patients, increased serum PAF levels at early pregnancy and at diagnosis were associated with poor outcomes. Additionally, serum PAF levels could predict the occurrence of HDCP and poor outcomes.
Conclusion: Serum PAF from HDCP patients at both the early pregnancy and diagnosis stages could effectively predict the occurrence and outcome of HDCP.
Patient Preferences for HR+/HER2− Early Breast Cancer Adjuvant Treatment: A Multicountry Discrete Choice Experiment
Authors: Harmer Victoria , Ammendolea Cathy , Ryan Mandy , Boyle Frances , Werutsky Gustavo , El Mouzain Dina , Marshall Deborah A. , Thomas Caitlin , Heidenreich Sebastian , Lu Hui , Krucien Nicolas , Payan Juan Mora , Aubel Dawn , Danyliv Andriy , Pathak Purnima , Harbeck Nadia
Published: January 2025

Introduction: More adjuvant treatment options are becoming available for hormone receptor-positive/human epidermal growth factor receptor 2-negative (HR+/HER2−) early breast cancer (EBC) based on results of clinical trials. This study quantified the importance of different attributes of EBC adjuvant therapies to patients and the benefit-risk tradeoffs patients were willing to make. Methods: Women with HR+/HER2− EBC completed an online discrete choice experiment (DCE) survey; the design was informed by clinical data, qualitative interviews (n = 40), and pre-testing interviews (n = 40). Participants (pts) made 10 choices between pairs of hypothetical treatments described by varying levels of 6 attributes. DCE data were analyzed using a correlated mixed logit model. Relative attribute importance scores captured the impact of each attribute across clinically relevant ranges. Benefit-risk tradeoffs were captured as the minimum improvements in 5-year invasive disease-free survival (iDFS) that pts would require to tolerate increases in therapy-associated adverse event (AE) risks. Results: A total of 866 patients from the USA, France, Spain, Canada, the UK, Germany, South Korea, and Australia completed the DCE (mean age: 57.7 years; 76% postmenopausal; 29% stage I disease, 55% stage II, 16% stage III). Improved 5-year iDFS (75.4–82.7% range; associated with combination regimens [CRs] vs. endocrine therapy [ET] alone) contributed the most to treatment preferences (clinically relevant relative attribute importance: 38.4%), followed by reduced risks of venous thromboembolic events (VTEs) (20.4%), neutropenia (20.3%), and diarrhea (15.0%). Treatment type + duration (3.7%) and fatigue (2.3%) were less important. Pts required the largest improvement in 5-year iDFS (3.9%) to tolerate increased risks of VTE (0.7%–2.5%) or neutropenia (5.6%–46%); willingness to accept tradeoffs depended on the AE. Preference heterogeneity was observed across subgroups, but 5-year iDFS improvement was consistently the most impactful on treatment choice in all subgroups. Conclusion: A multicountry sample of patients most valued adjuvant therapies with higher 5-year iDFS and may therefore prefer CRs over ET alone. The value of CRs depends on their specific safety profiles, and shared decision-making should consider this to select treatment options that align with individual preferences.
Cardiorenal disease and heart failure with preserved ejection fraction: Two sides of the same coin
Authors: Núñez-Marína Gonzalo , Santas Enrique
Published: January 2025

Background: Heart failure with preserved ejection fraction (HFpEF) and chronic kidney disease (CKD) have a strong pathophysiological interrelationship, and their combination worsens prognosis.
Summary: This article briefly reviews the bidirectional epidemiological burden and the pathophysiological interplay between HFpEF and CKD. It also discusses some of the controversial aspects regarding the diagnosis and screening of HFpEF in CKD patients and focuses on the most effective therapeutic approaches to improve symptoms and prognosis in this high-risk population.
Key Messages: Due to its prevalence and prognostic significance, HFpEF screening should be considered in patients with CKD, with careful use of traditional diagnostic tools in this population. Optimal medical therapy has seen major recent advances in patients with both HFpEF and CKD. SGLT2 inhibitors, finerenone, and semaglutide have consistently demonstrated cardio- and renoprotective effects in both conditions.
Stroke Epidemiology in Asia
Authors: Venketasubramanian Narayanaswamy
Published: January 2025

Background: Stroke is a major cause of death and disability globally, with different stroke burdens in different regions. This paper reviews the epidemiology of stroke in Asia. Summary: There is a wide range in age- and sex-standardised stroke incidence, highest in China, lowest in Bhutan. Geographically, incidence is highest in East Asia, lowest in South Asia. Stroke mortality is highest in Papua New Guinea, lowest in Singapore. There are variations in mortality within regions – in East Asia, it is higher in Mongolia and North Korea, lowest in Japan; in South Asia, it is higher in Bangladesh and Pakistan, lowest in Sri Lanka; in Southeast Asia, it is higher in Papua New Guinea and Indonesia, lowest in Singapore. Stroke disability-adjusted life years (DALYs) lost is highest in Papua New Guinea, lowest in Singapore. There is intra-regional variation – in East Asia, it is higher in Mongolia and North Korea, lowest in Japan; in South Asia, higher in Bangladesh and Pakistan, lowest in Sri Lanka; in Southeast Asia, it is highest in Papua New Guinea, lowest in Singapore. Among the stroke subtypes, ischaemic stroke (IS) has the highest incidence, intracerebral haemorrhage (ICH) is second, subarachnoid haemorrhage (SAH) is third. IS incidence is highest in China, lowest in Bhutan. The burden due to ICH is highest in Mongolia; ICH incidence is lowest in Sri Lanka, mortality and DALYs are lowest in Japan. SAH has a high incidence in Japan, Singapore, Brunei, and Republic of Korea. In hospital-based registries, the frequency of ICH was highest in Myanmar, low in Mongolia. Among IS, based on the Trial of Org 10,172 in Acute Stroke Treatment classification, large artery atherosclerosis (LAA) is more frequent in some countries (e.g., China, India, Indonesia, Japan, Pakistan, and Republic of Korea), but small artery occlusion (SAO) in most others (Bangladesh, Nepal, Singapore, Sri Lanka, Taiwan, Thailand, and Vietnam); cardioembolism is third. Of the stroke risk factors, hypertension is the most frequent, diabetes mellitus (DM) is usually second, with varying positions for hyperlipidaemia, smoking, and prior stroke or transient ischaemic attacks, obesity, and insufficient physical activity. Key Messages: Asia carries a particularly heavy burden of stroke, higher in some countries. IS is the most common subtype. Among IS, the more common mechanisms are LAA and SAO. Hypertension and DM are the more common risk factors. A greater understanding of stroke epidemiology and risk factors will help in healthcare planning for the prevention and management of stroke.
Temozolomide treatment in refractory pituitary adenomas and pituitary carcinomas
Authors: Deng Congcong , Yang Shuangjian , Pu Changqin , Bai Xuexue , Tian Chenxin , Feng Ming
Published: January 2025

Background: Temozolomide (TMZ), a non-classical alkylating agent, possesses lipophilic properties that allow it to cross the blood-brain barrier, making it active within the central nervous system. Furthermore, the adverse reactions of the TMZ are relatively mild, which is why it is currently recommended as a first-line chemotherapy drug for refractory pituitary adenomas (RPAs) and pituitary carcinomas (PCs).
Summary: Systematic evaluations indicate a radiological response rate of 41% and a hormonal response rate of 53%, underscoring TMZ clinical efficacy, particularly when combined with radiotherapy. Functional tumors demonstrate a higher response rate compared to non-functional tumors. While the optimal duration of TMZ treatment remains undetermined, studies suggest that longer therapy durations may lead to better prognoses. Additionally, prior to TMZ administration, it is advisable to conduct immunohistochemical analysis of O6-methylguanine-DNA methyltransferase (MGMT), MSH2, MSH6, MLH1, PMS2, and N-methylpurine DNA glycosylase (MPG) to assess the potential impact of repair mechanisms such as direct repair (DR), mismatch repair pathway (MMR), and base excision repair (BER) on TMZ treatment. The efficacy of TMZ analogs, combined TMZ therapies, and TMZ with nanomaterials following TMZ treatment failure remains uncertain.
Key Messages: The involvement of experienced multidisciplinary pituitary teams in all management decisions for RPAs/PCs patients is essential.
Association between the Achievement of Textbook Outcomes in Liver Surgery (TOLS) and Overall Survival in Perihilar Cholangiocarcinoma Patients Following Major Hepatectomy: A Multicenter Study
Authors: Zhong Shi-Yun , Gao Shu-Yang , Jiang Yan , Luo Yu-Le , Gong Yi , Yu Ting , Liu Xing-Chao , Fan Hai-Ning , Pang Shu-Jie , Bai Jie , Dai Hai-Su , Chen Zhi-Yu , Zhang Yan-Qi , Liu Zhi-Peng , Wang Hua-Qiang
Published: January 2025

Introduction
Major hepatectomy is the mainstay of curative-intent resection for perihilar cholangiocarcinoma (pCCA) patients. Textbook Outcomes in Liver Surgery (TOLS) are a new composite parameter for evaluating the short-term outcomes of surgery; however, their association with overall survival (OS) is unknown. Therefore, this study aimed to investigate the association between TOLS and OS in pCCA patients following major hepatectomy.
Methods
Consecutive pCCA patients who underwent major hepatectomy between 2014 and 2020 at 5 hospitals were included in this analysis. TOLS were defined as no intraoperative grade ≥ 2 incidents, no postoperative grade B/C bile leakage, no postoperative grade B/C liver failure, no postoperative major morbidity, no readmission within 90 days due to surgery-related major morbidity, no mortality within 90 days after hospital discharge, and R0 resection. The Kaplan‒Meier method was used to compare OS rates between patients who achieved TOLS and those who did not. Cox regression analysis was used to identify independent risk factors for poor OS.
Results
In total, 399 patients were included in this study, 214 (53.6%) of whom achieved TOLS. After excluding patients who died within 90 days, the 5-year OS rate of patients who achieved TOLS were significantly greater than that of patients who did not achieve TOLS (5-year OS rate: 26.2% vs. 17.3%, P=0.001). TOLS were independently associated with OS for pCCA patients following major hepatectomy.
Conclusions
TOLS were achieved in approximately half of the pCCA patients following major hepatectomy, and the patients who achieved TOLS had better survival.
Performance of the High-STEACS Early Rule Out Pathway Using hs-cTnT at 30 Days in a Multisite US Cohort
Authors: Ashburn Nicklaus P. , Snavely Anna C. , Supples Michael W. , Millard Marissa J. , Allen Brandon R. , Christenson Robert H. , Madsen Troy , Mumma Bryn E. , Hashemian Tara , Wilkerson R. Gentry , Mahler Simon A.
Published: January 2025

BACKGROUND:

The High-STEACS (High-Sensitivity Troponin in the Evaluation of Patients With Acute Coronary Syndrome) pathway risk stratifies emergency department patients with possible acute coronary syndrome. This study aims to determine if the High-STEACS hs-cTnT (high-sensitivity cardiac troponin T) pathway can achieve the ≥99% negative predictive value (NPV) safety threshold for 30-day cardiac death or myocardial infarction (CDMI) in a multisite US cohort of patients with and without known coronary artery disease (CAD).

METHODS:

A secondary analysis of the STOP-CP (High-Sensitivity Cardiac Troponin T [Gen 5 STAT Assay] to Optimize Chest Pain Risk Stratification) cohort, which enrolled adult emergency department patients with possible acute coronary syndrome at 8 US sites (January 25, 2017–September 6, 2018). Participants were classified into outpatient and admission dispositions using the High-STEACS hs-cTnT pathway. Known CAD was defined as prior MI, coronary revascularization, or ≥70% coronary stenosis. Outcomes included 30-day CDMI and efficacy, defined as the proportion identified for outpatient disposition. NPVs and negative likelihood ratios for 30-day CDMI were calculated. NPVs were compared between CAD subgroups using a Fisher exact test.

RESULTS:

Among 1351 patients, 53.2% (719/1351) were male, 31.4% (424/1351) had known CAD, and the mean age was 57.4±12.8 years. At 30 days, CDMI occurred in 13.8% (187/1351). High-STEACS classified 63.4% (857/1351) to outpatient disposition, of which 2.0% (17/857) had 30-day CDMI, corresponding to an NPV of 98.0% (95% CI, 96.8–98.8) and negative likelihood ratio of 0.13 (95% CI, 0.08–0.20). In patients with CAD, 46.9% (199/424) were classified to outpatient disposition, of which 4.0% (8/199) had 30-day CDMI. Among patients without CAD, 71.0% (658/927) were classified to outpatient disposition with 1.4% (9/658) having 30-day CDMI. The NPV for 30-day CDMI was 96.0% (95% CI, 92.2–98.2) in patients with CAD versus 98.6% (95% CI, 97.4–99.4) among patients without CAD (
P
=0.04). The negative likelihood ratio for 30-day CDMI among patients with CAD was 0.16 (95% CI, 0.08–0.31) and 0.12 (95% CI, 0.06–0.22) among patients without CAD.

CONCLUSIONS:

The High-STEACS hs-cTnT pathway had high efficacy but was unable to achieve the ≥99% NPV safety threshold for 30-day CDMI.

REGISTRATION:

URL:
https://www.clinicaltrials.gov
; Unique identifier: NCT02984436.
Comparison of Associations of Food Security Instruments and Mediators With Premature All-Cause and Cardiovascular Disease Death in US Adults
Authors: Tian Ling , Jaeger Byron C. , Marshall Allison N. , Dorans Kirsten S. , Bell Caryn N. , Theall Katherine P. , Chen Jing , He Jiang , Bundy Joshua D.
Published: January 2025

BACKGROUND:

Food insecurity is associated with high morbidity and mortality and is typically measured with the 10-item US Adult Food Security Survey Module. Shorter instruments may capture similar information, but this has not been validated against mortality in general populations.

METHODS:

A nationally representative sample of individuals aged 20 to 74 years from the US National Health Interview Survey 2011 to 2018 was included, with deaths linked to the National Death Index through 2019. Cardiovascular disease deaths were ascertained by
International Classification of Diseases-Tenth Revision
codes for heart disease or stroke. Standard 10-, 6-, and 2-item food security instruments were compared for associations with premature all-cause and cardiovascular disease deaths occurring before age 75 years using Cox regression adjusted for demographics and social determinants of health and C statistics. Findings were replicated in the National Health and Nutrition Examination Survey 2004 to 2018, and differences were explored using mediation analysis.

RESULTS:

We included 218 136 National Health Interview Survey participants (mean age, 45.3 years; 50.8% women). Over a mean 5.0-year follow-up, 7025 premature deaths were observed (1711 from cardiovascular disease). In multivariable-adjusted models, hazard ratios (95% CIs) for all-cause death were similar among food security instruments (10-item, 1.22 [1.13, 1.32]; 6-item, 1.23 [1.13, 1.34]; and 2-item, 1.23 [1.14, 1.32]), and C statistics were identical (0.823). Hazard ratios (95% CIs) for cardiovascular disease deaths were also similar among food security instruments (10-item, 1.38 [1.17, 1.62]; 6-item, 1.27 [1.07, 1.51]; and 2-item, 1.41 [1.20, 1.66]), and C statistics ranged from 0.852 to 0.853. In the National Health and Nutrition Examination Survey replication (n=37 027, mean 7.8-year follow-up), associations were attenuated and became not statistically significant after adjustment for several cardiometabolic intermediates, particularly enrollment in food assistance programs, diabetes, low diet quality, inadequate or excessive sleep, and depression.

CONCLUSIONS:

A 2-item food security instrument captures similar mortality risk information compared with 10- and 6-item instruments. Furthermore, potential intermediate cardiometabolic factors may explain associations between food insecurity and mortality.
Combination Antithrombotic Therapy for Reduction of Recurrent Ischemic Stroke in Intracranial Atherosclerotic Disease
Authors: Perera Kanjana S. , Sharma Mukul A. , Eikelboom John W. , Ng Kelvin Kuan Huei , Field Thalia S. , Buck Brian H. , Hill Michael D. , Stotts Grant , Casaubon Leanne K. , Mandzia Jennifer , Katsanos Aristeidis H. , Yip Samuel , Shoamanesh Ashkan , Young G. Bryan , Appireddy Ramana , Nayar Sumiti , Swartz Rick , Taylor Amanda , Carrier Alexandra , Srivastava Abhilekh , Deshmukh Aviraj S. , Zhao Robin , Hart Robert G. ,   on behalf of the CATIS-ICAD Investigators
Published: January 2025

BACKGROUND:

Stroke secondary to intracranial atherosclerotic disease (ICAD) is associated with high recurrence risk despite currently available secondary prevention strategies. In patients with systemic atherosclerosis, a significant reduction of stroke risk with no increase in intracranial or fatal hemorrhage was seen when rivaroxaban 2.5 mg twice daily was added to aspirin. However, there are no trials in ICAD using this combination. To facilitate the design of future ICAD trials, the CATIS-ICAD study (Combination Antithrombotic Treatment for Prevention of Recurrent Ischemic Stroke in Intracranial Atherosclerotic Disease) assessed (1) the feasibility of recruitment, (2) the safety of low-dose rivaroxaban plus aspirin compared with standard-of-care antiplatelet therapy, and (3) trends toward efficacy.

METHODS:

This was a prospective, randomized, open-label, blinded end point pilot trial conducted in 10 Canadian centers. Eligible participants aged ≥40 years, with acute ischemic stroke or high-risk transient ischemic attack, were randomly assigned in a 1:1 ratio to receive low-dose rivaroxaban plus aspirin or aspirin alone within 7 to 100 days of their index event. The primary safety outcome was hemorrhagic stroke. The main efficacy end point was the composite of ischemic stroke or covert brain infarct on magnetic resonance imaging at the end of the study.

RESULTS:

A total of 101 participants were randomized. Average enrollment was 10 participants/site per year. Average follow-up was 20 months. Median time from index stroke to randomization was 67 days. The median age of participants was 67 years (±10.94), and 29% of participants were women. There was no hemorrhagic stroke in either arm. The composite efficacy outcome was less frequent in the combination arm (15.7%) compared with the aspirin arm (24.0%), with a hazard ratio of 0.78 ([95% CI, 0.32–1.93];
P
=0.59) favoring the intervention.

CONCLUSIONS:

A multicenter randomized trial comparing the combination of low-dose rivaroxaban and aspirin in patients with recent ischemic stroke or transient ischemic attack due to ICAD is feasible and appears safe without an increased risk of hemorrhagic stroke. A numerical trend toward efficacy for the composite primary end point of symptomatic ischemic stroke and covert infarcts was observed. These findings will inform the design of a phase III trial.

REGISTRATION:

URL:
https://www.clinicaltrials.gov
; Unique identifier: NCT04142125.
Debunking the Myth of Excitatory and Inhibitory Repetitive Transcranial Magnetic Stimulation in Cognitive Neuroscience Research
Authors: Hussain Sara J. , Freedberg Michael V.
Published: January 2025

Repetitive TMS (rTMS) is a powerful neuroscientific tool with the potential to noninvasively identify brain–behavior relationships in humans. Early work suggested that certain rTMS protocols (e.g., continuous theta-burst stimulation, intermittent theta-burst stimulation, high-frequency rTMS, low-frequency rTMS) predictably alter the probability that cortical neurons will fire action potentials (i.e., change cortical excitability). However, despite significant methodological, conceptual, and technical advances in rTMS research over the past few decades, overgeneralization of early rTMS findings has led to a stubbornly persistent assumption that rTMS protocols by their nature induce behavioral and/or physiological inhibition or facilitation, even when they are applied to nonmotor cortical sites or under untested circumstances. In this Perspectives article, we offer a “public service announcement” that summarizes the origins of this problematic assumption, highlighting limitations of seminal studies that inspired them and results of contemporary studies that violate them. Next, we discuss problems associated with holding this assumption, including making brain–behavior inferences without confirming the locality and directionality of neurophysiological changes. Finally, we provide recommendations for researchers to eliminate this misguided assumption when designing and interpreting their own work, emphasizing results of recent studies showing that the effects of rTMS on neurophysiological metrics and their associated behaviors can be caused by mechanisms other than binary changes in excitability of the stimulated brain region or network. Collectively, we contend that no rTMS protocol is by its nature either excitatory or inhibitory, and that researchers must use caution with these terms when forming experimental hypotheses and testing brain–behavior relationships.
Monkey Lateral Prefrontal Cortex Subregions Differentiate between Perceptual Exposure to Visual Stimuli
Authors: Leaman Kyoko , Rodriguez Nadira Yusif , Ahuja Aarit , Basu Debaleena , McKim Theresa H. , Desrochers Theresa M.
Published: January 2025

Each day, humans must parse visual stimuli with varying amounts of perceptual experience, ranging from incredibly familiar to entirely new. Even when choosing a novel to buy at a bookstore, one sees covers they have repeatedly experienced intermixed with recently released titles. Visual exposure to stimuli has distinct neural correlates in the lateral prefrontal cortex (LPFC) of nonhuman primates. However, it is currently unknown if this function may be localized to specific subregions within LPFC. Specifically, we aimed to determine whether the posterior fundus of Area 46 (p46f), an area that responds to deviations from learned sequences, also responds to less frequently presented stimuli outside of the sequential context. We compare responses in p46f to the adjacent subregion, posterior ventral area 46 (p46v), which we propose may be more likely to show exposure-dependent responses due to its proximity to novelty-responsive regions. To test whether p46f or p46v represent perceptual exposure, we performed awake fMRI on three male monkeys as they observed visual stimuli that varied in their number of daily presentations. Here, we show that p46v, but not p46f, shows preferential activation to stimuli with low perceptual exposure, further localizing exposure-dependent effects in monkey LPFC. These results align with previous research that has found novelty responses in ventral LPFC and are consistent with the proposal that p46f performs a sequence-specific function. Furthermore, they expand on our knowledge of the specific role of LPFC subregions and localize perceptual exposure processing within this broader brain region.