bluuebunny/crossref_metadata_2025 huggingface dataset:
Generation Scotland: an update on Scotland’s longitudinal family health study
Authors: Milbourn Hannah , McCartney Daniel , Richmond Anne , Campbell Archie , Flaig Robin , Robertson Sarah , Fawns-Ritchie Chloe , Hayward Caroline , Marioni Riccardo E , McIntosh Andrew M , Porteous David J , Whalley Heather C , Sudlow Cathie
Published: June 2024

Purpose

Generation Scotland (GS) is a large family-based cohort study established as a longitudinal resource for research into the genetic, lifestyle and environmental determinants of physical and mental health. It comprises extensive genetic, sociodemographic and clinical data from volunteers in Scotland.

Participants

A total of 24 084 adult participants, including 5501 families, were recruited between 2006 and 2011. Within the cohort, 59% (approximately 14 209) are women, with an average age at recruitment of 49 years. Participants completed a health questionnaire and attended an in-person clinic visit, where detailed baseline data were collected on lifestyle information, cognitive function, personality traits and mental and physical health. Genotype array data are available for 20 026 (83%) participants, and blood-based DNA methylation (DNAm) data for 18 869 (78%) participants. Linkage to routine National Health Service datasets has been possible for 93% (n=22 402) of the cohort, creating a longitudinal resource that includes primary care, hospital attendance, prescription and mortality records. Multimodal brain imaging is available in 1069 individuals.

Findings to date

GS has been widely used by researchers across the world to study the genetic and environmental basis of common complex diseases. Over 350 peer-reviewed papers have been published using GS data, contributing to research areas such as ageing, cancer, cardiovascular disease and mental health. Recontact studies have built on the GS cohort to collect additional prospective data to study chronic pain, major depressive disorder and COVID-19.

Future plans

To create a larger, richer, longitudinal resource, ‘Next Generation Scotland’ launched in May 2022 to expand the existing cohort by a target of 20 000 additional volunteers, now including anyone aged 12+ years. New participants complete online consent and questionnaires and provide postal saliva samples, from which genotype and salivary DNAm array data will be generated. The latest cohort information and how to access data can be found on the GS website (www.generationscotland.org).
Incidence and predictors of diabetic foot ulcer among patients with diabetes mellitus in a diabetic follow-up clinic in Central Ethiopia: a retrospective follow-up study
Authors: Negussie Yohannes Mekuria , Komicha Meyrema Abdo , Abebe Tilaye Workneh
Published: June 2024

Background

Diabetic foot ulcer is a major medical, social, and economic problem, and a leading cause of hospitalisations, increased morbidity, and mortality. Despite a rising occurrence, there is a dearth of data on the incidence and its predictors.

Objective

To assess the incidence and predictors of diabetic foot ulcers among patients with diabetes mellitus in a diabetic follow-up clinic in Central Ethiopia.

Design

Retrospective follow-up study design.

Participants

A total of 418 newly diagnosed diabetes mellitus patients from 1 January 2012 to 31 December 2022. A computer-generated simple random sampling method was used to select the study participants. Data were collected using a structured data extraction checklist. The collected data were entered into Epi Info V.7.2 and exported to STATA V.14 for analysis. To estimate survival time, the Kaplan-Meier method was used, and the survival difference was tested using a log-rank test.

Outcome measures

The Cox proportional hazard model was fitted to identify the predictors of diabetic foot ulcer development. The strength of the association was estimated using an adjusted hazard ratio (AHR) with a 95% confidence interval (CI), and statistical significance was proclaimed at a p<0.05.

Result

The overall incidence of diabetic foot ulcer was 1.51 cases (95% CI 1.03 to 2.22) per 100 person-years of observation. The cumulative incidence was 6.2% (95% CI 4.1% to 8.6%) over 10 years. The median time of follow-up was 45 months (IQR 21–73). Diastolic blood pressure of 90 mm Hg or above (AHR 2.91, 95% CI 1.25 to 6.77), taking combined medication (AHR 3.24, 95% CI 1.14 to 9.19) and having a peripheral arterial disease (AHR 5.26, 95% CI 1.61 to 17.18) were statistically significant predictors of diabetic foot ulcer development.

Conclusion

The risk of occurrence of diabetic foot ulcer was relatively high. Diastolic blood pressure level, combined medication and peripheral arterial disease were independent predictors of diabetic foot ulcer development. Hence, close monitoring and proper interventions are essential.
Addressing the unmet needs of women with breast cancer in Mexico: a non-randomised pilot study of the digital ePRO intervention
Authors: Contreras Sánchez Saúl Eduardo , Doubova Svetlana V , Martinez Vega Ingrid Patricia , Grajales Álvarez Rocío , Villalobos Valencia Ricardo , Dip Borunda Abdel Karim , Lio Mondragón Lorena , Martínez Pineda Wendy Jazmín , Nuñez Cerrillo Jose Gustavo , Huerta López Alma Diana , Zalapa Velázquez Rita , Mendoza Ortiz Valeria , Vázquez Zamora Víctor Javier , Montiel Jarquín Álvaro José , García Galicia Arturo , Talamantes Gómez Enrique Isay , Sánchez Reyes Roberto , Aguirre Gómez Jaqueline , Ayala Anzures María Eugenia , Zapata Tarrés Marta , Monroy Adriana , Leslie Hannah H.
Published: June 2024

Objectives

This study aimed to explore the acceptability, feasibility, usability, and preliminary effect of an electronic patient-reported outcome (ePRO) intervention for patients with breast cancer in Mexico.

Design

We conducted a multimethod non-randomised pilot study. We used a pre-test/post-test design for quantitative assessment of the intervention’s effect on patients’ supportive care needs and quality of life. We conducted in-depth interviews (IDIs) with participants and healthcare workers to explore the intervention’s benefits and barriers and understand its feasibility.

Participants

50 women aged 20–75 diagnosed with stage I–III breast cancer were enrolled within 2 weeks of starting neoadjuvant or adjuvant treatment with chemotherapy or radiotherapy. We excluded illiterate women and those with visual impairment, cognitive disability or severe depression. IDIs were conducted with 18 participants and 10 healthcare providers.

Setting

Oncology services in three public hospitals of the Mexican Social Security Institute.

Intervention

The ePRO intervention consisted of a responsive web application for weekly symptom reporting combined with proactive follow-up by nurses guided by predefined clinical algorithms for 6 weeks.

Results

50 women were enrolled out of 66 eligible patients approached (75.8%). All 50 completed the 4-week follow-up assessment (100% retention). Completion of the symptom registry declined from 100% in week 1 to 66% in week 6. Participants experienced decreases in supportive care needs and increased quality of life. The ePRO application was rated highly usable. Participants and health professionals both perceived intervention benefits. Drawbacks included poor fit for women receiving radiotherapy and challenges using the application for women with low digital literacy or experiencing severe symptoms.

Conclusions

This pilot study provided evidence of the high usability and potential efficacy of a web-based ePRO intervention. We revised recruitment during the pilot to include multiple facilities, and we will further revise for the randomised trial to address barriers to successful ePRO implementation.

Trial registration number

ClinicalTrials.gov ID:NCT05925257.
Single-arm study of camrelizumab plus apatinib for patients with advanced mucosal melanoma
Authors: Zhao Lianjun , Ren Yu , Zhang Guiying , Zheng Kelin , Wang Jiayu , Sha Huizi , Zhao Mengke , Huang Rong , Kang Donglin , Su Xinyu , Wu Yirong , Zhang Wangling , Lai Ruihe , Li Lin , Mei Rui , Wang Yitao , Tian You , Wang Fufeng , Liu Baorui , Zou Zhengyun
Published: June 2024

Background

Previous studies have suggested the potential synergistic antitumor activity when combining immune checkpoint inhibitors with anti-angiogenic agents in various solid tumors. We aimed to assess the efficacy and safety of camrelizumab (a humanized programmed cell death-1 antibody) plus apatinib (a vascular endothelial growth factor receptor tyrosine kinase inhibitor) for patients with advanced mucosal melanoma (MM), and explore-related biomarkers.

Methods

We conducted a single-center, open-label, single-arm, phase II study. Patients with unresectable or recurrent/metastatic MM received camrelizumab and apatinib. The primary endpoint was the confirmed objective response rate (ORR).

Results

Between April 2019 and June 2022, 32 patients were enrolled, with 50.0% previously received systemic therapy. Among 28 patients with evaluable response, the confirmed ORR was 42.9%, the disease control rate was 82.1%, and the median progression-free survival (PFS) was 8.05 months. The confirmed ORR was 42.9% (6/14) in both treatment-naïve and previously treated patients. Notably, treatment-naïve patients had a median PFS of 11.89 months, and those with prior treatment had a median PFS of 6.47 months. Grade 3 treatment-related adverse events were transaminase elevation, rash, hyperbilirubinemia, proteinuria, hypertension, thrombocytopenia, hand-foot syndrome and diarrhea. No treatment-related deaths were observed. Higher tumor mutation burden (TMB), increased T-cell receptor (TCR) diversity, and altered receptor tyrosine kinase (RTK)/RAS pathway correlated with better tumor response.

Conclusion

Camrelizumab plus apatinib provided promising antitumor activity with acceptable toxicity in patients with advanced MM. TMB, TCR diversity and RTK/RAS pathway genes were identified as potential predictive biomarkers and warrant further validation.

Trial registration number

Chinese Clinical Trial Registry, ChiCTR1900023277.
Integrated analysis of tertiary lymphoid structures and immune infiltration in ccRCC microenvironment revealed their clinical significances: a multicenter cohort study
Authors: Wang Yu-Qi , Chen Wen-Jin , Zhou Wang , Dong Ke-Qin , Zuo Li , Xu Da , Chen Jia-Xin , Chen Wei-Jie , Li Wen-Yan , Liu Zi-Chang , Jiang Zheng-Yu , Tang Yi-Fan , Qin Yu-Xuan , Wang Lin-Hui , Pan Xiu-Wu , Cui Xin-Gang
Published: June 2024

Background

Tertiary lymphoid structures (TLSs) serve as organized lymphoid aggregates that influence immune responses within the tumor microenvironment. This study aims to investigate the characteristics and clinical significance of TLSs and tumor-infiltrating lymphocytes (TILs) in clear cell renal cell carcinoma (ccRCC).

Methods

TLSs and TILs were analyzed comprehensively in 754 ccRCC patients from 6 academic centers and 532 patients from The Cancer Genome Atlas. Integrated analysis was performed based on single-cell RNA-sequencing datasets from 21 ccRCC patients to investigate TLS heterogeneity in ccRCC. Immunohistochemistry and multiplex immunofluorescence were applied. Cox regression and Kaplan-Meier analyses were used to reveal the prognostic significance.

Results

The study demonstrated the existence of TLSs and TILs heterogeneities in the ccRCC microenvironment. TLSs were identified in 16% of the tumor tissues in 113 patients. High density (>0.6/mm2) and maturation of TLSs predicted good overall survival (OS) (p<0.01) in ccRCC patients. However, high infiltration (>151) of scattered TILs was an independent risk factor of poor ccRCC prognosis (HR=14.818, p<0.001). The presence of TLSs was correlated with improved progression-free survival (p=0.002) and responsiveness to therapy (p<0.001). Interestingly, the combination of age and TLSs abundance had an impact on OS (p<0.001). Higher senescence scores were detected in individuals with immature TLSs (p=0.003).

Conclusions

The study revealed the contradictory features of intratumoral TLSs and TILs in the ccRCC microenvironment and their impact on clinical prognosis, suggesting that abundant and mature intratumoral TLSs were associated with decreased risks of postoperative ccRCC relapse and death as well as favorable therapeutic response. Distinct spatial distributions of immune infiltration could reflect effective antitumor or protumor immunity in ccRCC.
Stroke as a career option for neurologists
Authors: Pereira Anthony C , Alakbarzade Vafa , Shribman Samuel , Crossingham Ginette , Moullaali Tom , Werring David
Published: June 2024

Stroke is one of the most common acute neurological disorders and a leading cause of disability worldwide. Evidence-based treatments over the last two decades have driven a revolution in the clinical management and design of stroke services. We need a highly skilled, multidisciplinary workforce that includes neurologists as core members to deliver modern stroke care. In the UK, the dedicated subspecialty training programme for stroke medicine has recently been integrated into the neurology curriculum. All neurologists will be trained to contribute to each aspect of the stroke care pathway. We discuss how training in stroke medicine is evolving for neurologists and the opportunities and challenges around practising stroke medicine in the UK and beyond.
Investigation on evolution law of frozen wall thickness in artificial ground freezing under seepage conditions
Authors: Li Kai-Qi , Yin Zhen-Yu , Jin Yin-Fu , Liu Yong
Published: June 2024

Frozen wall thickness ( E) is an important index that reflects the freezing performance of artificial ground freezing (AGF). In previous design and numerical studies, the inherent spatial variability of soil properties is often neglected. Moreover, groundwater seepage can remarkably affect the freezing performance in the AGF system, while the specific relations between seepage and E remain unclear. Accordingly, this study aims to explore the evolution of frozen wall thickness under seepage conditions via a numerical model that considers the coupled thermo-hydraulic process and variations in hydrothermal properties. As two vital soil properties, spatial variability of thermal conductivity and intrinsic permeability is simulated by random field combined with Monte Carlo simulations. Based on the coupled model, the effects of seepage velocity, direction, and pipe spacing are examined by sensitivity analysis. Two indicators are introduced to quantify the influences of uncertainty in hydrothermal properties and seepage. The unfavourable scenarios (i.e., lower bound) of E from random models are tabulated and formulated via evolutionary polynomial regression for practical references. These findings contribute to an enhanced understanding of the freezing behaviours of AGF and provide a rule of thumb for predicting frozen wall thickness under complex seepage conditions and design parameters.
Sprinting performance and behavior of adult shortnose sturgeon (Acipenser brevirostrum)
Authors: Castro-Santos Theodore , Kieffer Micah , Goerig Elsa
Published: June 2024

Swimming ability and performance are central to the ecology of aquatic species and to the design of structures intended to promote access to habitat. This is particularly important for migratory species traveling over significant distances. Here, we present results of a study of swimming behaviors of adult shortnose sturgeon ( Acipenser brevirostrum). Sturgeon were presented with velocity challenges of 0.5–2.5 m·s‒1 in a 35 m long flume that they were allowed to enter and ascend volitionally. Attempt rate was greatest among large sturgeon, at warm temperatures, and at low flow velocities. Sturgeon swam for shorter distances and durations against high-velocity flows; larger sturgeon had greater overall performance and endurance, but when velocities were standardized to body lengths the relative performance was reduced with increased body size. Overall, however, sturgeon were able to swim at much greater speeds than previously predicted, consistent with other studies showing that volitional performance exceeds that of data collected in common laboratory apparatus.
Cosmic microwave background in a non-Archimedean world
Authors: Postavaru Octavian
Published: June 2024

The universe begins its expansion from dimensions below the Planck scale, where the uncertainty principle reigns. If at these dimensions the Archimedean geometry is useless, the p-adic non-Archimedean world creates an environment conducive to phenomenological modeling. The standard description of the cosmological density contrast is made by the Fourier decomposition of plane waves in the field of p-adic numbers $$\mathbb {Q}_p$$

Q
p

. The coupling of the primordial perturbations is done by coupling the phases. Since the phases are the stars of this article, we represent them in the hue-saturation-brightness color space both in $$\mathbb {R}$$
R
and in $$\mathbb {Q}_p$$

Q
p

. If the primordial perturbations interact weakly with each other, with their growth they become important enough from an energetic point of view to gravitationally interact with each other. We identify the coupling using the phase gradient operator, and extract the coupled points from the spectrum. We use pseudoentropy for the quantitative analysis of the information generated by the phases.
An Integrated Approach for the Assessment of Hydrocarbon Potential in Carbonate Reservoirs: Potwar Plateau, Pakistan
Authors: Ehsan Muhsan , Munir Raja Waqas , Latif Muhammad Ali Umair
Published: June 2024

The Potwar Plateau region of the Upper Indus Basin in Pakistan is known for its complex carbonate reservoirs, which pose significant challenges for hydrocarbon exploration and production. The integrated reservoir simulation study can help mitigate these challenges by better understanding the reservoir behavior and optimizing production strategies. The reservoir characterization of this region has essential importance in Pakistan because tight limestone and fractures (with vugs and leached features) may provide a zone of high porosity, permeability, and reservoir properties with isolated distribution in tight carbonates. The seismic and well log data were integrated to get the reservoir characterization and mark targeted reservoirs (Chorgali and Sakesar Formations) in Balkassar Oil Field. The study utilized 3D seismic interpretation, petrophysics analysis, rock physics analysis, and seismic inversion techniques to evaluate the subsurface properties of the carbonate reservoir. The time grid and depth contour map generation for Chorgali and Sakesar Formations show less time, about 1.2–1.3 s for Chorgali and 1.32–1.488 s for Sakesar which reveal clearly that the central part between the two faults is a shallow portion which is the crest of Balkassar anticline forming the suitable structural trap for hydrocarbon accumulation. Three reservoir zones with certain depths are marked based on petrophysics and rock physics analysis. The cross‐plot between mu–rho versus lambda–rho value indicates a high porosity value at 2,460–2,580 m. From seismic inversion, low impedance values are observed in that reservoir zone (2,400–2,500 m).
Structural Response of a Large Transmission Tower to a Tornado in East China
Authors: Zhang Nai-Long , Qiu Gang , Tan Xiao , Chen Jie , Sun Rong , Wu Bai-Jian , Cheng Xiao-Xiang
Published: June 2024

Structural analyses of transmission towers against tornados, which are of vital practical significance in design and maintenance of the structures in regions suffering from the convective weather, were rarely reported by the wind engineering community up to today. To balance the computing efficiency and the simulation accuracy, numerical calculations based on Wen’s tornadic velocity model are employed to analyze the tornado‐induced structural responses of a 131‐meter‐high free‐standing transmission tower in east China in this article. Results suggest that both the tornadic load and the structural response are noticeably greater in the lateral direction than in the longitudinal direction, and they are found to be highly nonstationary due to the traveling nature of the tornado. In addition, according to the present study, the transmission tower is not prone to the strength failure during the tornadic event and slight fatigue damages are accumulated on the tower body due to the tornadic action which can be timely warned using the structural health monitoring strategy based on field measurements of low‐order structural natural frequencies. Besides the points mentioned above, the innovations of the present research additionally include the following: (1) tornado‐induced structural responses and atmospheric boundary layer wind‐induced structural behaviors have been compared to provide conclusions of theoretical significance; (2) a novel fatigue damage assessment method based on the high‐circle fatigue damage accumulation theory has been applied to the analysis of tornado‐induced structural damage; (3) the structural configuration of a key joint on a main chord has been optimized against the tornado based on the advanced response surface optimization method.
Biallelic Recessive Mutations in TLE6 and NLRP5 Cause Female Infertility Characterized by Human Early Embryonic Arrest
Authors: Li Ruiqi , Mei Mei , Zhou Ling , Zhao Haijing , Yang Min , Li Yingshi , Chen Xiaoli , Wang Wenjun , Yuan Ping
Published: June 2024

Preimplantation embryonic developmental arrest (EDA) is a common cause of unexplained female infertility. Genetic factors are believed to be one of the primary causes contributing to EDA. In this study, we identify four novel compound heterozygous mutations in TLE6 and NLRP5, in two infertile female patients experiencing recurrent EDA, using whole‐exome sequencing. Functional analysis revealed that the two splicing mutations in TLE6 (c.541+2dupT) and NLRP5 (c.2957+4A>G) resulted in aberrant RNA splicing, leading to abnormal truncations of the corresponding proteins. In vitro experiments further validated that a missense mutation in NLRP5 led to increased mRNA and protein expression levels compared to wild type, when transfected into HEK293T cells. Immunofluorescence analysis confirmed the decay of the expression of TLE6 protein. Additionally, RNA sequencing results revealed significantly higher expression levels of some maternal genes in mutated embryos with TLE6 mutations, possibly suggesting the disrupted clearance of maternal mRNA and the failure of embryo genome activation. These results highlight the role of biallelic recessive effects associated with TLE6 and NLRP5 variants in embryonic development, thereby widening the scope of the genetic landscape.
Discovery of Monovalent Direct Degraders of BRD4 that Act via the Recruitment of DCAF11
Authors: Parker Gregory S. , Toth Julia I. , Fish Sarah , Blanco Gabrielle , Kampert Taylor , Li Xiaoming , Yang Linette , Stumpf Craig R. , Steadman Kenneth , Jamborcic Aleksandar , Chien Stephen , Daniele Elizabeth , Dearie Alejandro , Leriche Geoffray , Bailey Simon , Thompson Peggy A.
Published: June 2024

Targeted protein degradation (TPD) using the ubiquitin proteasome system (UPS) is a rapidly growing drug discovery modality to eliminate pathogenic proteins. Strategies for TPD have focused on heterobifunctional degraders that often suffer from poor drug-like properties, and molecular glues that rely on serendipitous discovery. Monovalent “direct” degraders represent an alternative approach, in which small molecules bind to a target protein and induce degradation of that protein through the recruitment of an E3 ligase complex. Using an ultra-high throughput cell-based screening platform, degraders of the bromodomain extraterminal protein BRD4 were identified and optimized to yield a lead compound, PLX-3618. In this paper, we demonstrate that PLX-3618 elicited UPS-mediated selective degradation of BRD4, resulting in potent antitumor activity in vitro and in vivo. Characterization of the degradation mechanism identified DCAF11 as the E3 ligase required for PLX-3618-mediated degradation of BRD4. Protein–protein interaction studies verified a BRD4:PLX-3618:DCAF11 ternary complex, and mutational studies provided further insights into the DCAF11-mediated degradation mechanism. Collectively, these results demonstrate the discovery and characterization of a novel small molecule that selectively degrades BRD4 through the recruitment of the E3 substrate receptor, DCAF11, and promotes potent antitumor activity in vivo.
Designing and Implementing Experiments within Local Bureaucratic Systems: A Cautionary Tale from an Educator Incentive Program
Authors: Asad Saher , Habib Masooma , Karachiwalla Naureen , Kosec Katrina , Leaver Clare , ur Rehman Attique
Published: June 2024

Partnering with governments to co-design pilot interventions and embed them in local bureaucratic systems is increasingly seen as “best practice” on grounds of scalability and sustainability. This paper reports on a pilot program that was co-designed with, and embedded within, the Elementary and Secondary Education Department in Pakistan's Khyber Pakhtunkhwa province that offers a cautionary tale. The over-arching desire to work within existing bureaucratic systems, while laudable, constrained the design of the randomized controlled trial. This paper presents findings on some of the institutional factors which resulted in failed implementation of the randomized controlled trial and a lost opportunity to learn about the efficacy of key design features. The paper briefly outlines the design of the pilot—promotion-based incentives for educators—and summarizes the largely null results. It then turns to implementation, discussing what went wrong, how this was uncovered, and lessons learned for co-designing and embedding future pilot studies with(in) government.
Rare coincidence: Macro-thyroid-stimulating hormone and multiple manufacturer-specific interferences in thyroid hormone immunoassays
Authors: Mrosewski Ingo , Dannheim Viola , Klett Robert , Urbank Matthias , Stobbe Silvia , Ittner Jochen R , Bidlingmaier Martin
Published: June 2024

Immunoassays are widely used for laboratory assessment of endocrine functions including thyroid hormones. While usually adequate for patient evaluation, they are known to potentially suffer from interference from a variety of factors. We report the case of a 44 year-old male patient without clinical symptoms of thyroid disease who presented for specialist evaluation after pathological thyroid function tests prompted a transferal by his primary care practitioner. Thyroid function tests showed discrepant results across immunoassays and platforms of different manufacturers. Polyethylene glycol precipitation prompted the diagnosis of macro-thyroid-stimulating hormone, while heterophilic and non-specific antibody blocking reagents proved ineffective in eliminating the interference in thyroid-stimulating hormone, free triiodothyronine and free thyroxine measurements. Further assessment ruled out a diagnosis of familial dysalbuminemic hyperthyroxinemia, leaving an exclusion diagnosis of manufacturer-specific interference in free triiodothyronine and free thyroxine assays due to unknown factors. Both clinicians and laboratory specialists must be aware of potential interference in immunoassays which otherwise might be misleading, potentially triggering unnecessary (invasive) follow-up procedures or therapeutic interventions. Close communication is required for successful troubleshooting. To our knowledge, no other case of both macro-thyroid-stimulating hormone and manufacturer-specific interference in a single patient has been documented thus far.
Supporting Bereaved Family Members: A Qualitative Interview Study on the Experience of Bereavement Counselling by the Bereavement Network Lower Saxony (BNLS) in Germany for Parents Who Have Lost Children or Teenagers
Authors: Kruse Rebecca F. , Stiel Stephanie , Schwabe Sven
Published: June 2024

The “Trauer Netzwerk Niedersachsen” („Bereavement Network Lower Saxony“ (BNLS)) aims at supporting families after the loss of a child or teenager due to various causes. This study aims to describe the experiences of bereaved family members with the BNLS counsellors. 12 semi-structured interviews were conducted with parents who had received or were currently receiving BNLS counselling. The interviews revealed the vital role counselling played aiding individuals cope with their grief. Participants valued the bereavement support, which was often lacking in their personal support networks. Counselling assisted parents in returning to daily life and caring for loved ones. Discussing “death” and “dying” helped participants find peace with their loss. Our findings suggest that bereavement counselling should be considered an essential component of healthcare for family members dealing with the loss of a child. Additionally, there is need for awareness and publicity for both the BNLS and its bereavement counselling services.
Examining the Mediating Role of Resilience and Life Satisfaction in the Relationship Between Anxiety Sensitivity and Perceived Stress
Authors: Batmaz Hasan , Çelik Eyüp
Published: June 2024

This study examines the mediation role of life satisfaction and resilience variables in the relationships between anxiety sensitivity and perceived stress. The data was collected with the Anxiety Sensitivity Index-3, Life Satisfaction Scale, Perceived Stress Scale, and Brief Psychological Resilience Scale from 347 university students (Mage = 23.15, SD = 5.15; 70% girls, 30% boys). The analyses were examined by structural equation modeling using AMOS 24. The findings suggest that students with high anxiety sensitivity and perceived stress have low resilience and life satisfaction levels. More importantly, resilience and life satisfaction were found to have partial mediation. As a result, it is seen that anxiety sensitivity has a significant effect on reducing perceived stress by increasing students’ resilience and life satisfaction. Therefore, this situation facilitates decreased anxiety levels, greater satisfaction with life, and more robust mental health.
Le bouddhisme à Taïwan : quelle influence après trois décennies de transition démocratique ?
Authors: LALIBERTÉ André
Published: June 2024

In this article, I will first describe the extent of the influence of Buddhism in Taiwan, presenting some data on the demographic importance of this religion in terms of people who identify with it, but also in terms of associations that claim to do so. I will then introduce the positions of the main masters of this tradition relevant to four kinds of political issues relevant to Taiwan: the democratic transition process itself, the development of Taiwan’s welfare regime, cross-strait relations with China, and the contribution of Buddhist associations to the international influence of Taiwan in the context of the latter’s diplomatic isolation.
The effect of nickel oxide nanoparticles on the structure and properties of nanocomposites based on high-pressure polyethylene containing multiwalled carbon nanotubes
Authors: Kurbanova Nushaba I. , Mirzoeva Nurlana A. , Zeynalov Eldar B. , Huseynov Asgar B. , Hajiyeva Flora V. , Muradov Mustafa B.
Published: June 2024

Due to the unique properties of modern nanomaterials, many companies design complex electronic devices that are used in the aviation and space spheres to assemble powerful computers, video equipment, help diagnose various diseases, as well as quickly transmit information. Such nanostructured materials are obtained by embedding nanoparticles into various polymer matrices. The effect of nickel oxide nanoparticles (NiONPs) stabilized by a matrix of high-pressure polyethylene (LDPE) obtained by the mechanochemical method on the structure and properties of nanocomposites based on high-pressure polyethylene (LDPE) containing multiwalled carbon nanotubes (MWCNT) has been studied. The physical-mechanical, thermophysical and thermal properties of the obtained composites were studied using DTA and AFM analysis methods. The optimal composition of components for obtaining nanocomposites with improved properties has been determined. Shown that small amounts of nanofillers introduced into the polymer play the role of structure formers - artificial crystallization nuclei, which contributes to the appearance of a fine spherulite structure in the polymer. AFM micrographs show the complex interweaving of nanoparticles with each other and the polymer matrix and the formation of a new fine-crystalline supramolecular structure related to the interfacial interaction of nickel-containing nanoparticles with multilayer carbon nanotubes, which contributes to the maximum increase in the physical-mechanical and thermal properties of the resulting nanocomposite.
Effectiveness and Safety of Superimposed High-Frequency Jet Ventilation in Rigid Bronchoscopy: A Single-Center, Retrospective Study
Authors: Li Jing , Xu Shixia , Yang Rongna , Ding Ming
Published: June 2024

Introduction: Superimposed high-frequency jet ventilation (SHFJV) is a new type of jet ventilation, but its safety and effectiveness in rigid bronchoscopy have not been fully verified, especially in patients with airway stenosis and preoperative cardiovascular disease. This study is intended to retrospectively analyze the effectiveness and safety of SHFJV in the endobronchial treatment under rigid bronchoscopy. Methods: A total of 363 patients were included in this study. They were divided into 2 groups: Group A (n = 176)—presence of airway stenosis; Group B (n = 187)—absence of airway stenosis. Mean arterial pressure, heart rate, and pulse oxygen saturation were recorded before anesthesia and during the procedure. Arterial blood gases was recorded before anesthesia, at the end of the procedure and second-day postoperation respectively. The duration of procedure, extubation time, length of stay in the postanesthesia care unit (PACU), length of postoperative hospitalization, incidence of intraoperative and postoperative complications as well as 30 day mortality were also recorded. Results: All the patients had stable circulation during the procedure, including that with preoperative cardiovascular and pulmonary diseases. There were no substantial differences observed in terms of extubation time, PACU stay, and postoperative hospital days. Patients with severe preoperative airway stenosis exhibited longer procedure duration compared to those with mild to moderate stenosis, but there was no difference noted in terms of the extubation and PACU time. Conclusion: SHFJV is effective and safe in the endobronchial treatment for patients with airway stenosis and preoperative cardiovascular disease. It can serve as an ideal airway management strategy for rigid bronchoscopy.
Pharmacological Interventions for Menière’s Disease: A Systematic Review and Network Meta-Analysis
Authors: Zheng Xian , Lin Rui
Published: June 2024

Objective: Evaluation of the effectiveness and posttreatment effects of intratympanic gentamicin and corticosteroids in treating patients with Ménière’s disease (MD). Methods: Based on PubMed and Embase databases, randomized controlled trials using intratympanic injections of 4 drugs (gentamicin, methylprednisolone, dexamethasone, and placebo) for the treatment of MD were searched from 1995 to October 2023, and the literature was screened according to inclusion and exclusion criteria, and data were netted for meta-analysis using Stata 17. Results: A total of 13 studies were selected, involving 559 participants, with follow-up time ranging from 3 to 28 months. Meta-analysis showed that there was no statistically significant difference in pure-tone average between gentamicin and dexamethasone [standardized mean difference (SMD) = 0.09, 95% confidence interval (CI) (−0.42, 0.24), P < .05]. Compared to placebo, intratympanic injection of gentamicin [risk ratio (RR) = 1.18, 95% CI (0.43, 1.93)], methylprednisolone [RR = 0.88, 95% CI (0.07, 1.70)], and dexamethasone [RR = 0.70, 95% CI (−0.01, 1.41)] all showed better efficacy in treating vertigo. For the treatment of tinnitus, the SUCRA ranking results showed that dexamethasone was the most effective, followed by methylprednisolone and gentamicin. Conclusion: Pharmacological intervention is more effective than placebo in treating MD. Although gentamicin treatment shows significant effects in treating vertigo, corticosteroid combination therapy is markedly superior to gentamicin in controlling hearing loss and vertigo symptoms.
The Effect of Using Ofloxacin Ear Drops in Traumatic Tympanic Membrane Healing: A Systematic Review and Meta-Analysis
Authors: Kutbi Abdullah H. , Malas Moayyad , Al-Talhi Atheer Ali , Noori Faisal , Amoodi Hosam A.
Published: June 2024

Objectives: To evaluate the effectiveness of ofloxacin ear drops versus no intervention in the repair of traumatic tympanic membrane (TM) perforations from randomized controlled trials (RCTs). Data Sources: Medline/PubMed, CENTRAL, Clinical Trials.Gov, and Google Scholar. Study Selection: Inclusion criteria: (1) English language; (2) RCT studies; (3) reported the outcomes on the application of ofloxacin and outcomes of spontaneous healing. Exclusion criteria: (1) studies without a control group; (2) patient with severe otologic disease such as chronic suppurative otitis media or ossicular disruption or patients with craniocerebral injury; (3) studies with no pretreatment values or single-arm clinical studies. Data Extraction: Country, year of publication, number of participants in each arm, patient characteristics such as age, sex, intervention details, laterality, cause of TM perforation, position of perforation, follow-up time, hearing gain, rate of TM closure, and closure time. Results: A total of 6 RCTs studies were analyzed. A total of 502 participants were included; the relative risk for closure rate of ofloxacin treatment was 1.18 [95% confidence interval (CI), 1.08 to 1.28, P < .001] and the mean difference (MD) for healing time was −18.4 (95% CI, −19.96 to −16.82, P < .001), suggesting ofloxacin has a significant effect on closure of TM perforations. However, no clinically significant effect in hearing (SMD: 0.21, 95% CI, 0.02 to 0.40, P = .03) was seen in ofloxacin group. Also, patients in the ofloxacin group were associated with a 13% reduction in the risk of infections compared to their observation-assigned counterparts, but this estimate was not statistically significant. Conclusion: Ofloxacin use in patients with traumatic TM perforation is effective in reducing healing time and increasing rate of TM perforation closure. No evidence of increased risk of hearing loss or infection rates are encountered when ofloxacin is prescribed to patients with traumatic TM perforation.
Inter-Rater and Intra-Rater Agreement in Scoring Severity of Rodent Cardiomyopathy and Relation to Artificial Intelligence–Based Scoring
Authors: Steinbach Thomas J. , Tokarz Debra A. , Co Caroll A. , Harris Shawn F. , McBride Sandra J. , Shockley Keith R. , Lokhande Avinash , Srivastava Gargi , Ugalmugle Rajesh , Kazi Arshad , Singletary Emily , Cesta Mark F. , Thomas Heath C. , Chen Vivian S. , Hobbie Kristen , Crabbs Torrie A.
Published: June 2024

We previously developed a computer-assisted image analysis algorithm to detect and quantify the microscopic features of rodent progressive cardiomyopathy (PCM) in rat heart histologic sections and validated the results with a panel of five veterinary toxicologic pathologists using a multinomial logistic model. In this study, we assessed both the inter-rater and intra-rater agreement of the pathologists and compared pathologists’ ratings to the artificial intelligence (AI)-predicted scores. Pathologists and the AI algorithm were presented with 500 slides of rodent heart. They quantified the amount of cardiomyopathy in each slide. A total of 200 of these slides were novel to this study, whereas 100 slides were intentionally selected for repetition from the previous study. After a washout period of more than six months, the repeated slides were examined to assess intra-rater agreement among pathologists. We found the intra-rater agreement to be substantial, with weighted Cohen’s kappa values ranging from k = 0.64 to 0.80. Intra-rater variability is not a concern for the deterministic AI. The inter-rater agreement across pathologists was moderate (Cohen’s kappa k = 0.56). These results demonstrate the utility of AI algorithms as a tool for pathologists to increase sensitivity and specificity for the histopathologic assessment of the heart in toxicology studies.
Early and enduring: Targeting the endothelium for blood-brain barrier protection
Authors: Wu Silin , Ren Xuefang Sophie , Shi Yejie
Published: June 2024

The disruption of the blood-brain barrier marks a pivotal early pathological event in ischemic stroke that significantly contributes to subsequent permanent damage. Here we delve into the ramifications of a study conducted by Xu and colleagues, which underscores the essential role of the protein peroxiredoxin-4 in cerebrovascular endothelial cells. Peroxiredoxin-4 was shown to preserve blood-brain barrier integrity during the early stages after cerebral ischemia and reperfusion, ultimately leading to improved long-term outcomes.
Cost-effectiveness Analysis of Colorectal Cancer Screening Strategies Using Active Learning and Monte Carlo Simulation
Authors: Fouladi Amirhossein , Asadi Amin , Sherer Eric A. , Madadi Mahboubeh
Published: June 2024

Introduction

Detection of colorectal cancer (CRC) in the early stages through available screening tests increases the patient’s survival chances. Multimodal screening policies can benefit patients by providing more diverse screening options and balancing the risks and benefits of screening tests. We investigate the cost-effectiveness of a wide variety of multimodal CRC screening policies.

Methods

We developed a Monte Carlo simulation framework to model CRC dynamics. We proposed an innovative calibration process using machine learning models to estimate age- and size-specific adenomatous polyps’ progression and regression rates. The proposed approach significantly expedites the model parameter space search.

Results

Two multimodal proposed policies (i.e., 1] colonoscopy at 50 y and fecal occult blood test annually between 60 and 75 y and 2] colonoscopy at 50 and 60 y and fecal immunochemical test annually between 70 and 75 y) are identified as efficient frontier policies. Both policies are cost-effective at a willingness to pay of $50,000. Sensitivity analyses were performed to assess the sensitivity of results to a change in screening test costs as well as adherence behavior. The sensitivity analysis results suggest that the proposed policies are mostly robust to the considered changes in screening test costs, as there is a significant overlap between the efficient frontier policies of the baseline and the sensitivity analysis cases. However, the efficient frontier policies were more sensitive to changes in adherence behavior.

Conclusion

Generally, combining stool-based tests with visual tests will benefit patients with higher life expectancy and a lower expected cost compared with unimodal screening policies. Colonoscopy at younger ages (when the colonoscopy complication risk is lower) and stool-based tests at older ages are shown to be more effective.

Highlights

We propose a detailed Markov model to capture the colorectal cancer (CRC) dynamics. The proposed Markov model presents the detailed dynamics of adenomas progression to CRC. We use more than 44,000 colonoscopy reports and available data in the literature to calibrate the proposed Markov model using an innovative approach that leverages machine learning models to expedite the calibration process. We investigate the cost-effectiveness of a wide variety of multimodal CRC screening policies and compare their performances with the current in-practice policies.
Can I See Your Answers? Applying the Fishbowl Method in Marketing Analytics Classes
Authors: Jiang Han-Ling , Lu Lin-Hua , Yuen Tsunwai Wesley , Liu Yu-Lun , Coelho Conrad
Published: June 2024

Data-driven marketing analytics courses are integral to modern business management degrees in universities, yet many graduates focus solely on single, separated data analysis techniques during their learning process, hindering effective integration and practical performance. This study proposes that employing the Fishbowl method, which divides students into “fish” or “observers” to facilitate active problem-solving and analytical reflection, can effectively empower students to augment their learning and performance in marketing analysis by strengthening their metacognition. This research also explores the moderating effects of task complexity and students’ divergent thinking. Two field experiments (41 Cohort 22/23 students in Study 1; 39 Cohort 23/24 students in Study 2) were implemented. The results revealed that the Fishbowl method significantly enhances students’ metacognition, which affects their task-solving performance. Furthermore, students with higher (lower) divergent thinking perform better and are better suited to the observer (fish) roles. This moderating effect was strengthened when the task complexity was high. This study bridges the use of the Fishbowl method with the enhancement of metacognition in the context of marketing analytics courses. Appropriate utilization of the Fishbowl method during marketing analytics courses, along with grouping students based on their thinking traits, can significantly enhance learning effectiveness and performance.
The role of geographic distance and technological complexity in U.S. interregional co-patenting over almost two centuries
Authors: Abbasiharofteh Milad , Broekel Tom , Mewes Lars
Published: June 2024

This paper examines how geographical proximity affected interregional co-patenting links in various technologies in the USA from 1836 to 2010. We classify technologies by their complexity and test whether it moderates the impact of distance on collaboration. Contrary to the ‘death of distance’ hypothesis, distance still matters for knowledge creation and exchange. Moreover, we show that the role of complexity has changed over time. In the 19th century, interregional collaborations within complex technologies were more sensitive to distance than within simple ones. This pattern reversed in the late 20th century, and such collaborative relations became more resilient to distance than simple ones.
Calendula officinalis extract-loaded conduits improved sciatic nerve injury repair through upregulation of BDNF and GFAP
Authors: Xu Feng , Su GuiBin
Published: June 2024

In the current research, the nanofibrous neural channels were produced by electrospinning of PCL/Gelatin solution loaded with Calendula officinalis extract. The produced scaffolds properties were studied using various in vitro characterization methods. Then, the conduits’ healing potential was investigated in a rat model of PNS injury. In vitro results showed that scaffolds were not toxic and quenched DPPH free radicals. In addition, the extract-loaded conduits exhibited significant anti-inflammatory activity. In vivo study showed that the regular treadmill exercise significantly improved the healing efficacy of the Calendula officinalis-delivering conduits by upregulating BDNF and GFAP proteins.