bluuebunny/crossref_metadata_2025 huggingface dataset:
Effects of SGLT2 inhibitors on the onset of esophageal varices and extrahepatic cancer in type 2 diabetic patients with suspected MASLD: a nationwide database study in Japan
Authors: Kawaguchi Takumi , Fujishima Yoshiyuki , Wakasugi Daisuke , Io Fusayo , Sato Yuri , Uchida Saeko , Kitajima Yukiko
Published: October 2024

Background & aim

SGLT2 inhibitors (SGLT2i) improve hepatic steatosis in patients with type 2 diabetes mellitus (T2DM) and MASLD. We aimed to investigate the impact of SGLT2i on the incidence of liver-related events and extrahepatic cancer compared to DPP4 inhibitors (DPP4i) in patients with T2DM and suspected MASLD using a medical claims database in Japan.

Methods

We conducted a retrospective study using a Japanese medical claims database. Among patients with T2DM who were prescribed SGLT2i or DPP4i (n = 1,628,656), patients with suspected MASLD were classified into SGLT2i (n = 4204) and DPP4i (n = 4204) groups. Effects of SGLT2i on the following outcomes were compared to DPP4i: (1) changes in HbA1c and ALT levels after 6 months, (2) changes in hepatic fibrosis index, and (3) the incidence of liver-related events/extrahepatic cancer over 12 months.

Results

After 6 months, DPP4i significantly decreased HbA1c levels compared to SGLT2i. In contrast, SGLT2i significantly decreased ALT levels compared to DPP4i. SGLT2i significantly decreased FIB-4 index compared to DPP4i over 12 months. Although no significant difference was observed in the incidence of overall liver-related events between the two groups, SGLT2i significantly reduced the incidence of esophageal varices (HR 0.12, 95%CI 0.01–0.95, P = 0.044). Moreover, SGLT2i significantly suppressed the incidence of extrahepatic cancer (HR 0.50, 95%CI 0.30–0.84, P = 0.009) compared to DPP4i.

Conclusion

SGLT2i was more beneficial than DPP4i in improving the hepatic inflammation and fibrosis indices. Moreover, SGLT2i suppressed the incidence of esophageal varices and extrahepatic cancer compared to DPP4i. SGLT2i may suppress life-threatening events in patients with T2DM and suspected MASLD.
How much does an MRI change over a period of up to 2 years in patients with chronic low back pain? Is a repeated MRI really necessary in the follow-up of patients with chronic low back pain?
Authors: Tomé-Bermejo Félix , Otero-Romero Daniel , Javier-Martínez Elías , Sutil-Blanco Ángel , de la Rosa-Zabala Kelman Luis , Avilés-Morente Carmen , Oliveros-Escudero Beatriz , Núñez-Torrealba Alexa Anaís , Moreno-Mateo Fernando , Cervera-Irimia Javier , Mengis-Palleck Charles Louis , Garzón-Márquez Francisco , Plais Nicolas , Guerra-Gutiérrez Félix , Álvarez-Galovich Luis
Published: October 2024

Purpose

Clinical practices vary between healthcare providers when it comes to asking for a Magnetic Resonance Imaging (MRI) during follow-up for chronic low-back pain (LBP). The association between progressive changes on the MRI and the clinical relevance of these findings is not clearly defined. The objective of our study is to investigate to what extent do MRI findings change during a period less than or equal to two years in patients with chronic LBP. We question the efficacy of its routinary use as a tool for follow-up and we also study the correlation between new changes on MRI and modifications in therapeutic attitude.

Methods

Data was collected from 468 lumbar spine MRIs from 209 patients undergoing two or more MRIs between January 2015 and December 2019 with a mean of 2.24 MRIs per patient. The evaluated data included diagnosis, reason for request, MRI findings and treatment offered post-MRI. MRIs were assessed according to a standardized scoring system from 0 to 14 points according to the severity in findings (modified Babinska Score). Radiological changes were defined as increased severity of findings in the most affected segment.

Results

51.06% of MRI requests had no documented reason to be asked for. The average score of the findings on the first MRI was 5,733 (SD 2,462) and 6,131 (SD 2,376) on the second, not reaching a statistically significant difference (p = 0.062). There was no difference on the findings between the first and the second MRI in 40, 15% (n = 104) and up to 89, 96% with only mild changes (−1/ + 2 points over 14 possibles). After repeating the MRI, no modification to the treatment plan was made in 44, 79% of patients (n = 116) and only in 11.58% (n = 30) was surgical treatment indicated.

Conclusion

The rate of lumbar MRI has risen to an alarming pace without evidence of consequent improvements in patient outcomes. A significant number of repeated MRIs did not show radiological changes, nor did they give rise to further surgical treatment after obtaining these images. This study should help to review the real applications of clinical guides on the appropriate use for image tests.
Early mortality in STXBP1-related disorders
Authors: Furia Francesca , Rigby Charlene Son , Scheffer Ingrid E. , Allen Nicholas , Baker Kate , Hengsbach Christian , Kegele Josua , Goss James , Gorman Kathleen , Mala Misra-Isrie , Nicita Francesco , Allan Talia , Spalice Alberto , Weber Yvonne ,   European STXBP1 consortium (ESCO), Balagura Ganna , Benzeev Bruria , Bruining Hilgo , Darling Alejandra , Furia Francesca , Cazorla Ángeles García , Mala Misra-Isrie , Milh Mathieu , Møller Rikke Steensbjerre , Stamberger Hannah , Striano Pasquale , Syrbe Steffen , Thalwitzer Kim Marie , Verhage Matthijs , Weckhuysen Sarah ,   STXBP1 foundation, Rubboli Guido , Møller Rikke S. , Gardella Elena
Published: October 2024

Introduction

Pathogenic variants in STXBP1 cause a spectrum of disorders mainly consisting of developmental and epileptic encephalopathy (DEE), often featuring drug-resistant epilepsy. An increased mortality risk occurs in individuals with drug-resistant epilepsy and DEE, with sudden unexpected death in epilepsy (SUDEP) often the major cause of death. This study aimed to identify the rate and causes of mortality in STXBP1-related disorders.

Methods

Through an international call, we analyzed data on individuals with STXBP1 pathogenic variants, who passed away from causes related to their disease.

Results

We estimated a mortality rate of 3.2% (31/966), based on the STXBP1 Foundation and the STXBP1 Global Connect registry. In total, we analyzed data on 40 individuals (23 males) harboring pathogenic STXBP1 variants, collected from different centers worldwide. They died at a median age of 13 years (range: 11 months—46 years). The most common cause of death was SUDEP (36%), followed by pulmonary infections and respiratory complications (33%). The incidence of SUDEP peaked in mid-childhood, while non-SUDEP causes were more frequent in early childhood or adulthood (p = 0.006). In the most severe phenotypes, death was related to non-SUDEP causes (p = 0.018).

Conclusion

We found a mortality rate in STXBP1-related disorders similar to other DEEs, with an early age at death and SUDEP as well as pulmonary infections as the main cause of death. These findings assist in prognostic evaluation and genetic counseling for the families. They help to define the mortality risk of STXBP1-related disorders and implement preventative strategies.
Neoadjuvant chemotherapy in relation to long-term mortality in individuals cured of gastric adenocarcinoma
Authors: Leijonmarck Wilhelm , Mattsson Fredrik , Lagergren Jesper
Published: October 2024

Background

Late effects of chemotherapy could affect mortality amongst cancer survivors. This study aimed to clarify if neoadjuvant chemotherapy for gastric adenocarcinoma influences the long-term survival in individuals cured of this tumour.

Methods

This was a nationwide and population-based cohort study that included all individuals who underwent gastrectomy for gastric adenocarcinoma in Sweden between 2006 and 2015 and survived for ≥ 5 years after surgery. The cohort was followed up until death or end of study period (31 December 2020). Multivariable Cox proportional hazards regression was used to provide hazard ratios (HR) with 95% confidence intervals (CI). The HR were adjusted for age, sex, comorbidity, education, calendar year, tumour sub-location, in-hospital complications, and splenectomy. Data came from medical records and nationwide registers.

Results

Amongst 613 gastric adenocarcinoma survivors, neoadjuvant chemotherapy (used in 269 patients; 43.9%) was associated with a decreased crude mortality rate (HR 0.66, 95% CI 0.46–0.96). However, the association attenuated and became statistically non-significant after adjustment for all confounders (HR 0.83, 95% CI 0.56–1.23) and after adjustments solely for age and comorbidity (HR 0.82, 95% CI 0.56–1.20). Stratified analyses did not reveal any statistically significant associations between neoadjuvant chemotherapy and long-term mortality in categories of age, sex, comorbidity, calendar year and tumour sub-location.

Conclusion

Neoadjuvant chemotherapy did not decrease the long-term survival amongst gastric adenocarcinoma survivors. Patients who received neoadjuvant chemotherapy were a selected group characterised by younger age and fewer severe comorbidities and therefore with better chances of long-term survival.
Associations between loot box purchasing and gambling behaviours, financial problems, and low mental wellbeing in a household sample from a British island, a cross-sectional study
Authors: Wilson Charley , Butler Nadia , Quigg Zara , Sumnall Harry
Published: October 2024

Aim

This study estimated the prevalence of loot box purchasing and associated sociodemographic factors in a general population of a British island, and explored relationships between loot box purchasing and gambling behaviours, financial problems, and mental wellbeing.

Subject and methods

A cross-sectional survey was undertaken using representative household and supplementary convenience samples with (n = 1,234) residents of a British island aged 16 + years. The Problem Gambling Severity Index (PGSI) was used to assess gambling harm. Financial problems in the past year were defined as having been behind with payments for expenses. The Short Warwick Edinburgh Mental Wellbeing Scale was used to measure mental wellbeing. Purchasing loot boxes in the past year was measured via self-report as: ‘In the last 12 months, have you purchased in-game loot boxes (e.g. weapons, armour, players for a virtual sports team)?’. Analyses were performed using χ2 and binary logistic regressions.

Results

5.9% of participants purchased loot boxes in the past year. There was no significant association between purchasing loot boxes and PGSI score. After controlling for sociodemographics and PGSI score, those who purchased loot boxes in the past year were 3.39 (1.42–8.11; p < 0.01) times more likely to experience financial problems, and 2.99 times (1.46–6.13; p < 0.01) more likely to have low mental wellbeing, compared to those who didn’t purchase loot boxes.

Conclusion

Findings in the current study suggest that purchasing loot boxes is associated with increased odds of experiencing financial problems and low mental wellbeing, independently of gambling behaviours.
BRCA promoter methylation in triple-negative breast cancer is preserved in xenograft models and represents a potential therapeutic marker for PARP inhibitors
Authors: Däster Kavitha , Hench Jürgen , Diepenbruck Maren , Volkmann Katrin , Rouchon Adelin , Palafox Marta , Miragaya Jorge Gomez , Preca Bogdan Tiberius , Kurzeder Christian , Weber Walter Paul , Bentires-Alj Mohamed , Soysal Savas Deniz , Muenst Simone
Published: October 2024

Purpose

Most triple-negative breast cancers (TNBC) are sporadic in nature and often associated with dysfunction of the BRCA1 or BRCA2 genes. Since somatic BRCA mutations are rare in breast cancer (BC), this dysfunction frequently is the result of BRCA promoter methylation. Despite the phenotypic similarities of these tumors to those with germline or somatic BRCA mutation, the evidence of response to PARP inhibitors is unclear.

Methods

We analyzed the prevalence of BRCA promoter methylation in 29 BC metastases through the well-established Illumina Infinium EPIC Human Methylation Bead Chip. In cases with BRCA methylation, the xenograft of the same tumor was tested. Additionally, we compared BC xenografts with an identified BRCA methylation to their matched primary tumors and subsequently investigated the efficacy of PARP inhibitors on tumor organoids from a BRCA2 promoter-methylated BC.

Results

BRCA2 promotor hypermethylation was identified in one pleural metastasis of a young patient as well as in the xenograft tissue. We also identified five more xenograft models with BRCA2 promotor hypermethylation. Analysis of one matched primary tumor confirmed the same BRCA2 methylation. PARP inhibitor treatment of tumor organoids derived from the BRCA2 methylated xenograft tumor tissue of the young patient showed a significant decline in cell viability, similar to organoids with somatic BRCA1 mutation, while having no effect on organoids with BRCA1 wildtype.

Conclusion

BRCA promotor hypermethylation seems to be a rare event in metastatic BC but is preserved in subsequent xenograft models and might represent an attractive therapeutic marker for PARP inhibitors.
Relationship between social media use and critical thinking in university students
Authors: Galindo-Domínguez Héctor , Bezanilla María José , Campo Lucía
Published: October 2024

Although part of their use is intended for leisure, social networks could be a useful tool for developing students’ critical thinking. Nevertheless, this relationship could also be influenced by our competence in learning to learn, that is to say, our knowledge, skills, and attitudes associated with self-regulation, metacognition, use of learning strategies, and problem-solving. To test this hypothesis, 301 university students participated (M = 19.83; SD = 3.17). The results showed which functions of social media related to information, content creation, and problem-solving were associated with a higher level of Learning to Learn competence and of Critical Thinking. However, the different functions of social media use were poor predictors of Critical Thinking, with the best predictor of critical thinking being the competence of learning to learn. Finally, in students with a low competence in learning to learn, a greater interaction with their immediate environment (e.g. friends, family…) or with their teachers or peers through social media was associated with a higher development of critical thinking. Moreover, in students with a high competence in learning to learn, a greater use of social media to solve academic problems was associated with a higher development of critical thinking. These results shed some light on the potential benefits that the use of social media could bring in both formal and informal settings, as well as the need to work among university students on some of the main aspects of the learning to learn competence, like metacognition, self-regulation or problem-solving, to develop critical thinking.
The Effect of a training program based on the (TAWOCK) model for teaching computational thinking skills on teaching self- efficacy among female computer teachers
Authors: Alqahtani Remsh Nasser , Almassaad Ahmad Zaid
Published: October 2024

The aim of research is to reveal the effect of a training program based on the TAWOCK model for teaching computational thinking skills on teaching self-efficacy among computer teachers. It used the quasi-experimental approach, with a pre-test and post-test design with a control group. An electronic training program based on the TAWOCK model was designed, and prepared (teaching self-efficacy scale). The research sample included (42) female teachers in the experimental group, and (39) female teachers in the control group. The research reached: There was a statistically significant difference at the level (α ≤ 0.05) between the mean scores of computer teachers in the experimental and control groups in the post application; In favor of the experimental group, the value of the ETA square for the total scale of teaching self-efficacy was (0.613); Which indicates the size of significant impact on the self-teaching effectiveness of female computer teachers. There was also a statistically significant difference at the level (α ≤ 0.05) between the mean scores of computer teachers in the experimental group in the pre and post applications; In favor of the post application, the value of Cohen’s coefficient for the total scale of teaching self-efficacy was (1.26).
Development of an e-governance system to support cooperative environmental policy actions
Authors: Princz-Jakovics Tibor , Szemenyei Márton
Published: October 2024

The quality of the digital infrastructure supporting decisions is an important factor in the preparation phase of any environmental policy action, and this quality can greatly reduce the level of transaction costs. However, the development of a solution for Coaseian bargaining raises several unsolved technical problems to be able to efficiently decrease external costs. Here, we show the recommended structure of an information and communication technology (ICT)-based software infrastructure that aims to guide relevant stakeholders to achieve environmental deals and enhance green innovations. After reviewing the existing methods, practical solutions, and economics of transaction costs, we selected the design process of a new platform. We identified the functionality modules of the ICT infrastructure with descriptions of the features. Our results demonstrated that the establishment of an ICT-based e-governance system featuring participatory modeling could efficiently reduce transaction costs based on the widely used typology of them. We found that our platform could improve the involvement of any group of stakeholders through collaboration. Furthermore, we elaborate on the assessment of risks and evaluate the potential to avoid serious risks during the implementation or operation of the system. We anticipate our paper to be an initial step in the implementation of an innovative platform for the interested parties of environmental policy actions.
Fast Track Intervention Effects and Mechanisms of Action Through Established Adulthood
Authors: McCabe George , Godwin Jennifer W. , Rothenberg W. Andrew , Goulter Natalie , Lansford Jennifer E. ,   Conduct Problems Prevention Research Group, Bierman Karen L. , Coie John D. , Crowley D. Max , Dodge Kenneth A. , Greenberg Mark T. , Lochman John E. , McMahon Robert J. , Pinderhughes Ellen E.
Published: October 2024

Early preventive interventions can improve outcomes in childhood, but the most effective interventions can continue to deliver benefits through the life course. The Fast Track intervention, a randomized controlled trial for children at risk of conduct problems, has lowered psychopathology, substance use problems, and criminality and elevated happiness at age 25. However, research has not studied whether the intervention’s effects continue further into established adulthood. In addition, little is known about the mechanisms through which the intervention may affect adult outcomes. We attempted to answer both questions by simultaneously estimating the intervention’s direct effect on adult outcomes at age 31 and the intervention’s indirect effects on those outcomes via interpersonal, intrapersonal, and academic competencies gained through the intervention. Participants included the Fast Track intervention (n = 445; 72.4% male) and high-risk control samples (n = 446; 66.4% male). Direct and total effects of random assignment to Fast Track on age 31 outcomes were not significant. However, our analyses showed that Fast Track’s improvements to interpersonal and intrapersonal skills in childhood served as catalysts for better life outcomes at age 31. Higher interpersonal skills led to fewer externalizing, internalizing, and substance use problems, reduced criminality and sexual partners, in addition to increased general health and full-time employment. Improved intrapersonal skills led to greater strength. There were no significant indirect pathways via academic skills. Our findings inform understanding of how a childhood preventive intervention can improve adjustment and behaviors into established adulthood.
Assessing transparency and methodological precision in variable measurement within organizational research: implications for validity
Authors: Øby Elise
Published: October 2024

This study addresses the call for enhanced transparency in methodological reporting by critically assessing methodological rigor and transparency, particularly in variable measurement, within primary cross-sectional survey-based research in organizational studies. Through a combined approach of scoping review for systematic literature identification and qualitative analysis, instances of inadequate reporting transparency and lack of methodological rigor are revealed. Analyzing data from 68 published studies, the findings highlight unclear construct definitions and a consistent absence of theoretical limitations when presenting study findings, pointing to a need for better reporting transparency. Additionally, the study uncovers the presence of elusive links between variable constructs and measures, and misplaced claims of prior validation for measurement instruments, indicating a lack of methodological rigor. Collectively, these findings challenge the interpretation and validity of research results, potentially leading to misconceptions and misinterpretations about what is known about the variable(s) in question. In turn, this may lead to researchers and practitioners basing their research or practice on flawed assumptions about what a group of studies is saying or indicating. While acknowledging prior recommendations on variable measurement and transparency, this study brings renewed focus to these areas. It also explores the role of measurement proficiency, debating whether the observed limitations reflect ethical concerns or are indicative of researchers’ capabilities in variable measurement, validity assessment, and reporting.
Using a Feminist Approach to Classify Women and Girls’ Charitable Organisations
Authors: Dowrick Lorna
Published: October 2024

Women and girls’ organisations (WGOs) are a fundamental part of the voluntary and community sector (VCS) and wider society. They have a unique history and development as a sub-set of the wider VCS and have been pivotal in meeting important needs for women and girls, yet existing analysis of the VCS using data from the Charity Commission for England and Wales (CCEW) has not previously focused on WGOs. The purpose of this paper is to present a feminist approach to identifying and classifying WGOs utilising data from the CCEW register. The paper provides a detailed exploration of the methodological approach and argues that such an approach to compiling and analysing datasets is both necessary and advantageous in exposing areas of power and contestation. The paper provides an original overview of the scope of WGOs in England and Wales between 2008 and 2018 and also demonstrates benefits that can be applied in other classification work within the field.
Creating respiratory pathogen-free environments in healthcare and nursing-care settings: a comprehensive review
Authors: Nagy Attila , Czitrovszky Aladár , Lehoczki Andrea , Farkas Árpád , Füri Péter , Osán János , Groma Veronika , Kugler Szilvia , Micsinai Adrienn , Horváth Alpár , Ungvári Zoltán , Müller Veronika
Published: October 2024

Hospital- and nursing-care-acquired infections are a growing problem worldwide, especially during epidemics, posing a significant threat to older adults in geriatric settings. Intense research during the COVID-19 pandemic highlighted the prominent role of aerosol transmission of pathogens. Aerosol particles can easily adsorb different airborne pathogens, carrying them for a long time. Understanding the dynamics of airborne pathogen transmission is essential for controlling the spread of many well-known pathogens, like the influenza virus, and emerging ones like SARS-CoV-2. Particles smaller than 50 to 100 µm remain airborne and significantly contribute to pathogen transmission. This review explores the journey of pathogen-carrying particles from formation in the airways, through airborne travel, to deposition in the lungs. The physicochemical properties of emitted particles depend on health status and emission modes, such as breathing, speaking, singing, coughing, sneezing, playing wind instruments, and medical interventions. After emission, sedimentation and evaporation primarily determine particle fate. Lung deposition of inhaled aerosol particles can be studied through in vivo, in vitro, or in silico methods. We discuss several numerical lung models, such as the Human Respiratory Tract Model, the LUng Dose Evaluation Program software (LUDEP), the Stochastic Lung Model, and the Computational Fluid Dynamics (CFD) techniques, and real-time or post-evaluation methods for detecting and characterizing these particles. Various air purification methods, particularly filtration, are reviewed for their effectiveness in healthcare settings. In the discussion, we analyze how this knowledge can help create environments with reduced PM2.5 and pathogen levels, enhancing safety in healthcare and nursing-care settings. This is particularly crucial for protecting older adults, who are more vulnerable to infections due to weaker immune systems and the higher prevalence of chronic conditions. By implementing effective airborne pathogen control measures, we can significantly improve health outcomes in geriatric settings.
Generation of a virtual cohort of TAVI patients for in silico trials: a statistical shape and machine learning analysis
Authors: Scuoppo Roberta , Castelbuono Salvatore , Cannata Stefano , Gentile Giovanni , Agnese Valentina , Bellavia Diego , Gandolfo Caterina , Pasta Salvatore
Published: October 2024

Purpose

In silico trials using computational modeling and simulations can complement clinical trials to improve the time-to-market of complex cardiovascular devices in humans. This study aims to investigate the significance of synthetic data in developing in silico trials for assessing the safety and efficacy of cardiovascular devices, focusing on bioprostheses designed for transcatheter aortic valve implantation (TAVI).

Methods

A statistical shape model (SSM) was employed to extract uncorrelated shape features from TAVI patients, enabling the augmentation of the original patient population into a clinically validated synthetic cohort. Machine learning techniques were utilized not only for risk stratification and classification but also for predicting the physiological variability within the original patient population.

Results

By randomly varying the statistical shape modes within a range of ± 2σ, a hundred virtual patients were generated, forming the synthetic cohort. Validation against the original patient population was conducted using morphological measurements. Support vector machine regression, based on selected shape modes (principal component scores), effectively predicted the peak pressure gradient across the stenosis (R-squared of 0.551 and RMSE of 11.67 mmHg). Multilayer perceptron neural network accurately predicted the optimal device size for implantation with high sensitivity and specificity (AUC = 0.98).

Conclusion

The study highlights the potential of integrating computational predictions, advanced machine learning techniques, and synthetic data generation to improve predictive accuracy and assess TAVI-related outcomes through in silico trials.

Graphical Abstract
Studies on the Corrosion Performance of CP-Ti and Zr-4 in Hot Nitric Acid with Formaldehyde for Aqueous Reprocessing Applications
Authors: Vanithakumari S. C. , Nandakumar T. , Thinaharan C. , Shankar A. Ravi , Ningshen S.
Published: October 2024

The robust performance of components within nuclear fuel reprocessing plants, especially in environments characterized by hostility, corrosion, and radioactivity, is imperative for ensuring seamless plant operations. Nitric acid serves as the primary process medium in the complex chemical processes involved in reprocessing spent fuel. While 304L SS is conventionally employed for nitric acid service in these plants, there is an ongoing exploration of alternative candidates such as titanium (Ti), zirconium (Zr) and their alloys. This study focuses on assessing the performance of commercially pure titanium (CP-Ti) and zirconium alloy (Zr-4) in nitric acid with formaldehyde at 80 °C. The corrosion rate of the Zr-4 sample, immersed in nitric acid with formaldehyde for two weeks at 80 °C, was negligible when compared to the commercially pure titanium (CP-Ti) sample under the same conditions. Comprehensive characterization of the oxide film formed on the surface of CP-Ti and Zr-4 samples was achieved through field emission scanning electron microscopy (FE-SEM) coupled with energy dispersive x-ray spectroscopy (EDS), as well as x-ray photoelectron spectroscopy (XPS). The corrosion behavior of both Ti and Zr-4 samples in nitric acid containing formaldehyde was systematically evaluated using potentiodynamic polarization (PDP) and electrochemical impedance spectroscopy (EIS). The results revealed enhanced corrosion resistance for both CP-Ti and Zr-4 samples. Consequently, this study suggests that titanium and zirconium may be considered as suitable candidates for the process equipments handling hot nitric acid with formaldehyde in the aqueous reprocessing of spent fuel.
High-Grade Progression, Sarcomatous Transformation, and/or Metastasis of Pituitary Neuroendocrine Neoplasms (PitNENs): The UCSF Experience
Authors: Terry Merryl , Nguyen Minh P. , Tang Vivian , Guney Ekin , Bharani Krishna L. , Dahiya Sonika , Choutka Ondrej , Borys Ewa , Reis Gerald , Blevins Lewis , Aghi Manish K. , Kunwar Sandeep , DeGroot John , Raleigh David R. , Pekmezci Melike , Bollen Andrew W. , Cha Soonmee , Joseph Nancy M. , Perry Arie
Published: October 2024

Pituitary neuroendocrine tumors (PitNET) that metastasize comprise ~ 0.2% of adenohypophyseal tumors are aggressive and are challenging to treat. However, many non-metastatic tumors are also aggressive. Herein, we review 21 specimens from 13 patients at UCSF with metastatic PitNETs (CSF or systemic, N = 7 patients), high-grade pituitary neuroendocrine neoplasms (HG-PitNEN, N = 4 patients), and/or PitNETs with sarcomatous transformation (PitNET-ST, N = 5 patients). We subtyped cases using the World Health Organization (WHO) and International Agency for Research on Cancer (IARC) criteria for neuroendocrine neoplasms (NENs). Lineage subtypes included acidophil stem cell, null cell, thyrotroph, corticotroph, lactotroph, and gonadotroph tumors. The median Ki-67 labeling index was 25% (range 5–70%). Lack of p16 was seen in 3 cases, with overexpression in 2. Strong diffuse p53 immunopositivity was present in 3 specimens from 2 patients. Loss of Rb expression was seen in 2 cases, with ATRX loss in one. Molecular analysis in 4 tumors variably revealed TERT alterations, homozygous CDKN2A deletion, aneuploidy, and mutations in PTEN, TP53, PDGFRB, and/or PIK3CA. Eight patients (62%) died of disease, 4 were alive at the last follow-up, and 1 was lost to the follow-up. All primary tumors had worrisome features, including aggressive lineage subtype, high mitotic count, and/or high Ki-67 indices. Additional evidence of high-grade progression included immunohistochemical loss of neuroendocrine, transcription factor, and/or hormone markers. We conclude that metastatic PitNET is not the only high-grade form of pituitary NEN. If further confirmed, these histopathologic and/or molecular features could provide advanced warning of biological aggressiveness and be applied towards a future grading scheme.
Validation of the Parent-report Pandemic Anxiety Scale (PAS-P) in the context of COVID-19
Authors: Robertson Olly , Skripkauskaite Simona , Creswell Cathy , McElroy Eoin , Waite Polly
Published: October 2024

To be able to develop effective policy and targeted support for children and young people, it is vital to develop and validate measures that enable us to understand what aspects of pandemics are associated with anxiety and stress across a wide age range. We examined the psychometric properties of the Pandemic Anxiety Scale– Parent-report (PAS-P), which measures levels of child and adolescent pandemic-related anxieties. Factor structure, reliability, and convergent and discriminant validity of the PAS-P was assessed in a convenience sample of parents/carers (N­ = 8410) over at three time points in 2020 when COVID-19 case rates and restrictions varied. Factor structure was identified via two exploratory factor analyses (EFAs; n = 5601 and n = 1005) and then tested using confirmatory factor analysis (CFA; n = 800), measurement invariance tests, and a longitudinal CFA (n = 1651). Two factors structure for disease and consequence anxiety were observed across both EFAs and were found to have good fit in the CFAs. The PAS-P demonstrated good internal consistency and discriminant validity, as well as partial scalar invariance in latent construct measurement across child age, gender, and time. The PAS-P is a robust parent-report measure of two distinct forms of pandemic-related anxiety, suitable for reporting on children and adolescents aged 4-16 years. Although the scale has been validated in the context of the COVID-19 pandemic, it is not limited to this specific pandemic and, with minor wording modifications, may be a reliable tool in other health epidemic contexts.
Rational Design of HER2-Targeted Combination Therapies to Reverse Drug Resistance in Fibroblast-Protected HER2+ Breast Cancer Cells
Authors: Poskus Matthew D. , McDonald Jacob , Laird Matthew , Li Ruxuan , Norcoss Kyle , Zervantonakis Ioannis K.
Published: October 2024

Introduction

Fibroblasts, an abundant cell type in the breast tumor microenvironment, interact with cancer cells and orchestrate tumor progression and drug resistance. However, the mechanisms by which fibroblast-derived factors impact drug sensitivity remain poorly understood. Here, we develop rational combination therapies that are informed by proteomic profiling to overcome fibroblast-mediated therapeutic resistance in HER2+ breast cancer cells.

Methods

Drug sensitivity to the HER2 kinase inhibitor lapatinib was characterized under conditions of monoculture and exposure to breast fibroblast-conditioned medium. Protein expression was measured using reverse phase protein arrays. Candidate targets for combination therapy were identified using differential expression and multivariate regression modeling. Follow-up experiments were performed to evaluate the effects of HER2 kinase combination therapies in fibroblast-protected cancer cell lines and fibroblasts.

Results

Compared to monoculture, fibroblast-conditioned medium increased the expression of plasminogen activator inhibitor-1 (PAI1) and cell cycle regulator polo like kinase 1 (PLK1) in lapatinib-treated breast cancer cells. Combination therapy of lapatinib with inhibitors targeting either PAI1 or PLK1, eliminated fibroblast-protected cancer cells, under both conditions of direct coculture with fibroblasts and protection by fibroblast-conditioned medium. Analysis of publicly available, clinical transcriptomic datasets revealed that HER2-targeted therapy fails to suppress PLK1 expression in stroma-rich HER2+ breast tumors and that high PAI1 gene expression associates with high stroma density. Furthermore, we showed that an epigenetics-directed approach using a bromodomain and extraterminal inhibitor to globally target fibroblast-induced proteomic adaptions in cancer cells, also restored lapatinib sensitivity.

Conclusions

Our data-driven framework of proteomic profiling in breast cancer cells identified the proteolytic degradation regulator PAI1 and the cell cycle regulator PLK1 as predictors of fibroblast-mediated treatment resistance. Combination therapies targeting HER2 kinase and these fibroblast-induced signaling adaptations eliminates fibroblast-protected HER2+ breast cancer cells.
On Non-visibility of Kobayashi Geodesics and the Geometry of the Boundary
Authors: Ökten Ahmed Yekta
Published: October 2024

We show that on convex domains with

$$\mathcal {C}^{1,\alpha }$$

C

1
,
α

-smooth boundary the limit set of non-visible Kobayashi geodesics are contained in a complex face. In

$$\mathbb {C}^2$$

C

2

this implies the existence of a complex tangential line segment of non-Goldilocks point in the boundary. Conversely, we construct sequences of non-visible almost-geodesics on (

$$\mathbb {C}$$

C

-)convex domains whose boundary contains a complex tangential line segment of non-Goldilocks points in a specific direction.
Quantitative Estimates on the Singular Set of Minimal Hypersurfaces with Bounded Index
Authors: Aiex Nicolau S. , McCurdy Sean , Minter Paul
Published: October 2024

We prove local measure bounds on the tubular neighbourhood of the singular set of codimension one stationary integral n-varifolds V in Riemannian manifolds which have both: (i) finite index on their smoothly embedded part; and (ii)

$$\mathcal {H}^{n-1}$$

H

n
-
1

-null singular set. A direct consequence of such a bound is a bound on the upper Minkowski content of the singular set of such a varifold in terms of its total mass and its index. Such a result improves on known bounds, namely the corresponding bound on the

$$\mathcal {H}^{n-7}$$

H

n
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7

-measure of the singular set established by Song (Duke Math J 172(11):2073–2147, 2023), as well as the same bounds established by Naber and Valtorta (J Eur Math Soc 22(10):3305–3382, 2020) for codimension one area minimising currents. Our results also provide more structural information on the singular set for codimension one integral varifolds with finite index (on the regular part) and no classical singularities established by Wickramasekera (Ann Math 179:843–1007, 2014).
ER-Phagie und Neurodegeneration
Authors: Hübner Christian A. , Ðikić Ivan
Published: October 2024

Autophagy is a process to target substrates for lysosomal degradation, which starts with the enclosure of the substrate by the LC3-labelled isolation membrane and the subsequent fusion with lysosomes. Selectivity of this process can be achieved via autophagy receptors. In recent years, several receptors which target ER subdomains for degradation via autophagy (reticulophagy or ER-phagy) have been described. Some of which are associated with neurodegenerative disorders.
How Many Jews of Color Are There? Recognizing Jewish Diversity: Science and Controversy
Authors: Sheskin Ira M. , Dashefsky Arnold
Published: October 2024

First, this paper contends that, in 2013, the best estimate of the percentage of Jews who are Jews of Color (JoC) was about 6%, and in 2020, it was about 8%. We rely on two sources to support this conclusion: national Jewish population studies and local Jewish community studies. This paper also presents evidence that members of some groups (Hispanic Jews in particular) may not consider themselves to be “of color,” and Black, Hispanic, Asian, and “other” Jews differ from one another in significant ways. Treating these different groups under one umbrella may not lead to the best policy decisions. Second, we published a short piece on Jews of Color in the 2019 American Jewish Year Book to bring attention to the increasing diversity of American Jews. This was followed by a column in eJewishPhilanthropy. A controversy ensued upon publication of this column. In this paper, we respond to some of these charges and talk about the lessons we learned from this experience.
Myocardial Scar Imaging: Viability Beyond REVIVED
Authors: Kiberu Yusuf , Jathanna Nikesh , Narayanan Nithin , Vanezis Andrew P , Erhayiem Bara , Graham Adam , Jamil-Copley Shahnaz
Published: October 2024

Purpose of Review

It was previously believed that the presence of myocardial viability in patients with significant coronary artery disease improved outcomes following revascularisation, but the landmark STITCH trial found no significant correlation between viability and overall survival. However, the study used single photon emission contrast tomography or dobutamine stress echocardiography for viability assessment, but late gadolinium enhanced cardiac magnetic resonance imaging (LGE-CMR) has since become the gold standard for viability assessment. Additionally, there has been significant progress in heart failure pharmacotherapy. Leveraging these advances, the REVIVED study authors revisited the role of revascularisation on heart failure patient clinical outcomes. Similar to the STITCH study, REVIVED also identified a lack of correlation between viability and outcomes, confirming its limited role in revascularisation decision making. The purpose of this review is to discuss the advances in myocardial viability imaging and the role of LGE-CMR scar assessment beyond the REVIVED study.

Recent Findings

Myocardial scar predisposes to ventricular arrythmias and sudden cardiac death (SCD). It is the authors’ opinion that beyond REVIVED, focus should be placed on optimising the management of ventricular arrhythmias through visualisation and characterisation of cardiac scar to improve clinical outcomes. A significant proportion of SCDs occur in patients who remain unprotected if guided by current recommendations. Several studies have confirmed the presence and burden of scar as a better predictor of clinical outcomes in comparison to the current gold standard of left ventricular ejection fraction (LVEF).

The potential of machine learning and radiomics to visualise cardiac anatomy and characterise scar, leveraged with the ability to integrate segmented CMR and clinical electroanatomic maps intraoperatively shows promise in improving outcomes in VT ablations and delivering precision treatment based on individual risk.
Prognostic risk model of LIHC T-cells based on scRNA-seq and RNA-seq and the regulation of the tumor immune microenvironment
Authors: Ding Shoupeng , Yi Xiaomei , Gao Jinghua , Huang Chunxiao , Zheng Shouzhao , Wu Lixian , Cai Zihan
Published: October 2024

Background

T-cell-related genes play a crucial role in LIHC development. However, a reliable prognostic profile based on risk models of these genes has yet to be identified.

Methods

Single-cell datasets from both tumor and normal tissue samples were obtained from the GEO database. We identified T-cell marker genes and developed a genetic risk model using the TCGA-LIHC dataset, which was subsequently validated with an independent GEO dataset. We also explored the relationship between risk model predictions and immune responses.

Results

We constructed a prognostic risk model using eight gene features identified through screening 860 T-cell marker genes via scRNA-seq and RNA-seq, which was subsequently integrated with the TCGA dataset. Its validity was independently confirmed using GEO and ICGC datasets. The TCGA dataset was stratified into high-risk and low-risk groups based on the risk model. Multivariate Cox regression analysis confirmed the risk score as an independent prognostic factor. GSEA indicated ribosomal transporter metabolism enrichment in the high-risk group and significant transcriptional activation in the low-risk group. ESTIMATE analysis showed higher ESTIMATE, immune, and stromal scores in the low-risk group, which also exhibited lower tumor purity than the high-risk group. Immunophenotyping revealed distinct patterns of immune cell infiltration and an immunosuppressive environment in the high-risk group.

Conclusions

This study introduces a T-cell marker-based prognostic risk model for LIHC patients. This model effectively predicted survival outcomes and immunotherapy effectiveness in LIHC patients, aligning with diverse immune responses and the distinct immunological profiles observed in the high-risk group.
Pure wild forest reindeer (Rangifer tarandus fennicus) or hybrids? A whole-genome sequencing approach to solve the taxonomical status
Authors: Weldenegodguad Melak , Niemi Milla , Mykrä-Pohja Sakari , Pokharel Kisun , Hamama Tuula-Marjatta , Paasivaara Antti , Kantanen Juha
Published: October 2024

In Finland, the geographic distribution of domestic reindeer (Rangifer tarandus tarandus) and Finnish wild forest reindeer (Rangifer tarandus fennicus) partly overlap in the vicinity of the southern border of the reindeer herding area. Additionally, domestic reindeer are occasionally kept as pets within the distribution range of the wild forest reindeer. Hybridisation of these two subspecies is one of the major threats for the wild forest reindeer population. Concerns about potential hybridisation served as the catalyst also for this study, which we aimed to clarify the taxonomic status of presumed wild forest reindeer individuals intended as founder individuals for a reintroduction project. To do this, we resequenced genomes of four Rangifer tarandus individuals with unknown taxonomical status and investigated their ancestries by comparing the genomic data with the existing resequenced data of the Finnish domestic reindeer and Finnish wild forest reindeer. The genetic relationship investigations indicated that all individuals we analysed were pure wild forest reindeer, making them suitable as founder individuals for the reintroduction project. Thus, our study provided critical knowledge for practical conservation action, where it was essential to recognise each individual’s origin. In the future, it will also offer novel insights into the spread of native wild forest reindeer to new geographic regions in Finland. For subsequent studies, additional resequenced genomic data of Rangifer individuals will be needed to develop an ancestry information marker panel of single nucleotide polymorphisms for rapid and cost-effective identification of hybrid individuals of these subspecies.
Surface Roughness Evaluation of Blast-Cleaned Structural Steel Plates Considering Measurement Deviation
Authors: Takai Toshikazu , Morimoto Kenta
Published: October 2024

Surface roughness is an important characteristic of blast-cleaned structural steel plates. This is because the adhesion of the coating and the frictional grip of the bolted connections are related to surface roughness. Surface roughness is usually measured using a surface roughness meter. Because the roughness of blast-cleaned surfaces is not uniform, it varies from position to position. The surface roughness test results obtained from a broad area are more valuable than those obtained from a narrow area. Because the measured values contain deviations, they are measured multiple times and averaged to reduce the influence of deviations. However, to evaluate roughness, it is necessary to clarify the measurement conditions to obtain accurate results. Consider combining these sentences as follows: In this study, the surface roughness of the blast-cleaned structural steel sample was measured at multiple locations to obtain its distribution characteristics. During each sample measurement, the detection sensor of the surface roughness meter was lifted and placed on the steel sample to determine deviations from the actual results. The surface roughness distributions of five blast-cleaned samples were the same under the identical measurement conditions. This indicates that accurate results can be obtained by measuring representative samples, without the need for measuring all samples; actually, 17 measurements were adequate to obtain a mean surface roughness value with a 95% confidence level and a 5% acceptable error rate.