bluuebunny/crossref_metadata_2025 huggingface dataset:
Incidence and predictors of hyperglycemic emergencies among adult diabetic patients at public hospitals of Sidama Region and Gedeo Zone, Southern Ethiopia: a survival analysis
Authors: Tiruneh Kasie Gebeyehu , Mekonnen Migbar Sibhat , Getnet Zemeskel Addisu , Ayehu Akele Mequanint , Meno Abose Abinet , Zewde Wendimu Ashenafi
Published: December 2024

Background:

Hyperglycemic emergencies (HGEs) are the major deadliest acute complications of diabetes. HGEs have reached an alarming stage and increased year-to-year leading to increased morbidity, hospitalization, and mortality. Despite HGEs causing this increased healthcare, psychological, social, and economic burden, studies conducted to address this burden and its predictive factors remain limited. Thus, this study aimed to investigate the incidence and predictors of HGEs among adult diabetic patients.

Methods:

An institution-based retrospective follow-up study was employed on 538 systematically selected adult diabetic patients who had diabetic follow-up in Sidama region and Gedeo zone public hospitals from September 1, 2018, to September 1, 2022. The sample size was determined using STATA V-14. Data were collected using an extraction checklist, entered into EPI data version 4.4.2.2, and analyzed using STATA version 14. The Kaplan–Meier curve and log-rank test were used to determine the survival probabilities and to compare the survival status. The Cox proportional hazard regression model was used to determine the association and identify the predictor variables. A statistical significance was declared at a p-value of <0.05 in line with a 95% confidence interval (CI) and hazard ratios.

Results:

The study was conducted on 538 diabetic adult patients with a response rate of 100%. The mean age of study participants was 44.5 years, and more than 66.7% were males. The incidence rate of HGEs was found to be 29 (95% CI: 25.3–33.2) per 1000 person-months with a total of 7176.5 person-month observations. Being farmer (adjusted hazard ratio (AHR) = 6.47; 95% CI: 2.61–16.04), poor glycemic control (AHR = 6.84; 95% CI: 3.47–13.49), less frequent diabetic follow-up (AHR = 4.00; 95% CI: 1.02–15.57), and having hypertension (HTN) (AHR = 2.94; 95% CI: 1.62–5.34) were significantly associated with increased hazard of acquiring HGEs among adult diabetic patients. Conversely, the hazard of experiencing HGE was 63% lower among patients who had diabetic nephropathy relative to those without diabetic nephropathy (AHR = 0.35; 95% CI: 0.15–0.83). Hence, setting and strengthening specific diabetic management strategies focused on the identified predictors could be paramount to reducing HGEs and their unwanted effects. Moreover, it’s better to consider more frequent diabetic follow-up visits for all patients regardless of other complications.
Formation of creative thinking among students in the digital educational environment
Authors: Motukeeva Alina , Azhibaeva Ainura , Kulbachaev Daniar , Abdyrakunova Zhyldyz , Toloev Maksatbek
Published: December 2024

The study aims to address the processes and methods for the development of creative thinking among students in the context of using digital educational tools and technologies. During the research, a survey was conducted with the participation of students of the Kyrgyz State University named after I. Arabaev to study their experience of using digital educational materials. The survey of students revealed the importance of creative thinking in the context of the educational environment, as well as its relationship with other cognitive skills, such as logical thinking and analytical abilities. The study highlighted that these interrelationships complement each other, enriching the educational process and contributing to the formation of complex thinking in students. However, the results of group surveys showed that the use of digital educational resources led to a significant increase in the proportion of students with high and medium levels of creativity, as well as a decrease in the proportion of students with low levels of creativity. This indicates the positive impact of digital technologies on the development of creativity among students. Logical thinking, which aims to systematise and analyse information for consistent solutions, and creative thinking, which generates new ideas and non-standard approaches for problem-solving, and synergistic interactions to ensure the development of critical thinking and intellectual growth. Analytical skills are substantial in the successful implementation of creative ideas, ensuring their structuring, evaluation and analysis. The use of digital technologies in the educational process has a significant positive impact on the development of students’ creativity. These technologies not only stimulate creative thinking but also enrich the learning process, making it more interesting and attractive to students.
Riverine writing: Ecopedagogical explorations with Australian river ecologies
Authors: Duhn Iris , Morse Marcus
Published: December 2024

This article traverses the confluence of ecopedagogies and river ecologies, employing a unique methodological approach that intertwines canoeing with academic inquiry to explore riverscape learning and its potential for becoming ecoliterate with the river. Drawing on wild pedagogies and outdoor education expertise alongside feminist new materialist eco-thinking, the text explores themes of environmental education, critical pedagogy, ecofeminism and place-based learning by playing with river-writing as an ecopedagogical methodological experiment. River-writing as ecopedagogy is responsive to the complexities of ecological systems and the challenges posed by the climate crisis. By engaging with the material and metaphorical currents of rivers, the text underscores the importance of experiential learning and the potential of natural landscapes as educational spaces that can inspire critical reflection, environmental stewardship and a deeper connection with the more-than-human world. The integration of theoretical perspectives from environmental philosophy and the practical insights gained from canoeing provide a rich narrative that contributes to the evolving discourse on ecopedagogies, offering insights for educators, environmentalists, researchers and policy-makers interested in advancing sustainable and inclusive educational practices.
Anti-tumor necrosis factor-alpha inhibitor-induced linear psoriasis: A case report
Authors: MacIntyre Olivia C. , Purdy Kerri
Published: December 2024

A 56-year-old male presented to the clinic for follow-up of severe, longstanding hidradenitis suppurativa. On physical examination, there was a linear Blaschkoid distribution of erythematous scaly papules extending from the left upper arm toward the scapular mid-back region. A clinical diagnosis of linear psoriasis was made, and the patient’s dosage interval of infliximab was decreased to every 6 weeks. The patient was offered Betamethasone diproprionate/calcipotriol (Enstilar) topical foam to use daily which demonstrated efficacy in clearing 90% of the affected areas. This case illustrates the potential for Betamethasone diproprionate/calcipotriol (Enstilar) topical foam use as a treatment approach for anti-tumor necrosis factor-alpha inhibitor-induced linear psoriasis. At present there is no consensus on linear psoriasis pathogenesis or best treatment approach, therefore, more research is needed to understand its pathogenesis and establish management guidelines.
Incidence and Risk Factors of Recurrent Proximal Junctional Failure in Adult Spinal Deformity Surgery
Authors: Park Se-Jun , Park Jin-Sung , Kang Dong-Ho , Lee Chong-Suh , Kim Hyun-Jun
Published: December 2024

Study Design

Retrospective cohort study.

Objectives

This study aimed to examine the incidence and risk factors for recurrent proximal junctional failure (R-PJF) in adult spinal deformity (ASD) surgery.

Methods

Among 482 patients receiving ≥ five-level fusion to the pelvis for ASD, 60 patients who underwent fusion extension surgery for PJF were included in the study cohort. R-PJF was defined as the performance of re-revision surgery after revision surgery for PJF. Various clinical and radiographic variables were compared between no R-PJF and R-PJF groups. Stepwise multivariate logistic analysis was performed to identify the risk factors for R-PJF.

Results

Of the 60 patients, there were 51 women (85.0%) and 9 men (15.0%) with a mean age of 72.4 ± 6.7 years. The mean fusion length at the index surgery was 7.3 ± 1.6 levels and an average of 4.1 ± 1.3 levels was extended during the revision surgery. Among them, R-PJF developed in 17 patients (28.3%). Multivariate analysis revealed that overcorrection relative to age-adjusted pelvic incidence (PI) – lumbar lordosis (LL) at the index surgery and high total sum of proximal junctional kyphosis severity scale (PJKSS) at the revision surgery were significant risk factors for R-PJF development. The cutoff value for the PJKSS sum was calculated as 8.5 points.

Conclusions

R-PJF was developed in 17 patients (28.3%). PI–LL overcorrection should be avoided during the index surgery to mitigate the R-PJF. In addition, timely surgical intervention is required in patients with PJF, considering that the PJF severity tends to increase over time.
Purchase Intention of Green Financial Products: Application of Behavioral Reasoning Theory
Authors: Pokhrel Laxman , Dangi Bhaskar Bahadur , Chaudhary Manoj Kumar , Giri Bishnu
Published: December 2024

The concept of green financial products, such as green bonds and green equity, has attracted academic attention as an intervention to safeguard institutions and society from unforeseen economic challenges in the future. Since it is incomplete to introduce green financial products without understanding the purchase intention of green financial products, this article investigated purchase intention of green financial products drawing from behavioral reasoning theory (BRT) and perceived risk theory. This study employed a purposive sampling technique and a cross-sectional survey research design to gather data from 297 investors. Data were gathered using structured questionnaires, and the suggested model was tested using partial least square structural equation modeling. The article found that reasons for, reasons against, and attitudes are significant predictors of purchasing green financial products. Moreover, values and beliefs can develop attitudes, reasons for, and reasons against green financial products. Finally, attitudes toward financial products are developed from reasons for, reasons against, and perceived financial risk of green financial products. This article validated the BRT model with new variables of perceived risk in the context of green financial products. These results could offer unique theoretical and managerial contributions to researchers and practitioners.
Referral patterns for the interdisciplinary care of chronic pelvic pain
Authors: Roversi Gustavo A , Strasburg Jessica , Genco Lauren , Ferrando Cecile A
Published: December 2024

Objective:

The primary objective of this study was to describe referral patterns to an interdisciplinary CPP clinic at a tertiary care center.

Study design:

This was a retrospective cohort study of female patients assigned an ICD-10 code diagnosis related to chronic pelvic pain at a tertiary care referral center between January 2017 and December 2019. Electronic medical records were queried for patient and clinician characteristics. The rate of referral to this clinic was determined based on the data collected, and patient and provider factors associated with referral were assessed using logistic regression analyses.

Results:

Of the 732 patients identified, 25.9% ( n = 190, 95% CI = [22.9%,29.3%]) received a referral to an interdisciplinary CPP clinic. Logistic regression analyses significantly revealed multiple factors associated with referral: number of previous treatment modalities used (adjusted OR [aOR] = 1.76 per treatment 95% CI = [1.48, 2.10], p < 0.001), distance to the treatment center (aOR = 0.48 [0–25 miles vs 25–60 miles] 95% CI = [0.31, 0.74], p < 0.001), IBS diagnosis (aOR = 1.67 95% CI = [1.02, 2.74], p = 0.044), endometriosis diagnosis (aOR = 1.63 95% CI = [1.06, 2.52], p = 0.026), as well as a psychiatric diagnosis (aOR = 1.46 95% CI = [1.00, 2.12], p = 0.048). Physicians were less likely to make a referral compared to Advanced Practice Providers (aOR = 0.38 95% CI = [0.22, 0.65], p < 0.001).

Conclusion:

Approximately one in four patients with a diagnosis of CPP were referred to our interdisciplinary clinic. Several patient factors were associated with referral. These data show a need for education about the existence of this type of center.
Multidisciplinary management of primary umbilical endometriosis (Villar’s nodule) with coexistent uterine leiomyomata: A case report
Authors: Gang’ombe Rukia Swaleh , Mutiso Stephen , Damtew Eyosias , Walong Edwin , Kiriga Maroa Fred , Wabwire Benjamin , Mecha Ezekiel
Published: December 2024

Introduction:

Primary umbilical endometriosis, also known as Villar’s nodule, is a rare manifestation of endometriosis within the umbilicus.

Case description:

A 41-year-old female who presented with a 4-year history of umbilical swelling associated with cyclic umbilical bleeding, dysmenorrhoea and heavy menstrual bleeding is herewith reported. Imaging procedures revealed an umbilical mass and uterine leiomyomas. The patient underwent combined surgery by the gynaecology and plastic surgery teams where an open myomectomy followed by omphalectomy, mesh repair of the rectus sheath and panniculectomy was done. Histopathological examination confirmed the presence of estrogen and progesterone receptor-positive endometrial glands and stroma in the umbilicus consistent with primary umbilical endometriosis and coexistent uterine leiomyomas. Clinical improvement was demonstrated 3 months following the surgery.

Conclusion:

Umbilical swelling associated with catamenial symptoms should raise suspicion for primary umbilical endometriosis. Inter-specialty approach is key in the management of primary umbilical endometriosis.
Comparison of Revision and Redislocation Rates After First-Time Anterior Shoulder Instability Between Subluxators and Dislocators: A Midterm Outcome Study
Authors: Nazzal Ehab M. , Herman Zachary J. , Engler Ian D. , Kaarre Janina , Tisherman Robert T. , Gibbs Christopher M. , Greiner Justin J. , Rai Ajinkya , Hughes Jonathan D. , Lesniak Bryson P. , Lin Albert
Published: December 2024

Background:

Anterior shoulder instability is a common pathology seen especially in young men and highly active patient populations. Subluxation is a commonly encountered clinical issue, yet little is known about the effects of first-time subluxation compared with dislocation on shoulder stability and clinical outcomes after surgical stabilization.

Purpose:

To compare revision and redislocation rates as well as patient-reported outcomes (PROs) between subluxators and dislocators after a first-time anterior shoulder instability event.

Study Design:

Cohort study; Level of evidence, 3.

Methods:

Included were patients who underwent operative intervention for a first-time anterior instability event between 2013 and 2020 at a single institution. Exclusion criteria were posterior/multidirectional instability, revision surgery, and recurrent instability. The main outcomes of interest were the rates of redislocation and revision. Demographics and surgical details were retrospectively collected. Instability was categorized as subluxation (no documentation of formal shoulder reduction) or dislocation (documented formal shoulder reduction). Labral tear location and size were determined from preoperative magnetic resonance imaging scans. PROs and return-to-sport, redislocation, and revision rates were collected from prospective survey data.

Results:

A total of 256 patients (141 subluxators and 115 dislocators) were available for analysis. There were no significant differences in baseline demographics or preoperative physical examination findings. Rates of bony Bankart lesions were comparable, but Hill-Sachs lesions were more commonly present in dislocators compared with subluxators (88.7% vs 53.9%; P < .01). There were no group differences in labral tear size, incidence of concomitant posterior or superior labrum anterior-posterior tears, or number of anchors used. Rates of remplissage were comparable between groups. Prospectively collected survey data of 60 patients (35 subluxators, 25 dislocators) were collected at 6.4 and 7.1 years of follow-up, respectively. Rates of recurrent dislocation (11.8% vs 20.0%) and revision (8.8% vs 16.0%) were comparable between subluxators and dislocators, respectively. All PROs and return-to-sport rates were comparable between groups.

Conclusion:

Subluxators and dislocators may present with comparable rates of redislocation and revision surgery even at midterm follow-up. Both cohorts may further present with comparable injury characteristics and PROs. Given the findings, future prospective studies comparing outcomes of first-time instability events are needed.
Evaluating Performance Among National Basketball Association Players After Jones Fractures: A Retrospective Cohort Study
Authors: Kim Andrew H. , Cha Myung-Jin , Pan Alvina , Dafflisio Gianna , Cartagena-Reyes Miguel A. , Mun Frederick , Kaplan Jonathan R. , Aiyer Amiethab A.
Published: December 2024

Background:

In professional basketball, Jones fractures are among the most common cause of lower extremity stress injury. Despite its prevalence, there is a paucity of research on the impact of Jones fractures on athletic performance in the National Basketball Association (NBA).

Purpose:

To determine the impact of Jones fractures on return to play and performance among NBA players when compared with preinjury values and healthy matched controls.

Study Design:

Cohort study; Level of evidence, 3.

Methods:

NBA injury reports were analyzed to identify 18 players who sustained a Jones fracture between 2011 and 2022. Reports were verified through public press releases, social media accounts, and player profiles. A publicly available database was used to collect player data including position, age, and years of NBA experience. Performance and advanced statistics were collected for seasons pre- and postinjury. Players were 1:1 matched with healthy controls based on age, player position, and career performance. Univariate and multivariable regression analyses were performed to compare advanced and per-game performance statistics between injured and healthy control players.

Results:

NBA players who sustained a Jones fracture had a mean age of 23.9 ± 2.31 years at the time of injury. The mean NBA experience was 3.00 ± 2.35 years and mean preinjury minutes played per game was 19.64 ± 11.24. All players (18/18) were able to return to NBA-level competition the year following the injury. There was no change in player efficiency rating (PER), value added, and estimated wins added metrics when comparing pre- and postinjury performances among injured players. Injured players missed more games ( P < .001) postinjury compared with the matched controls. Multivariate analysis revealed that for players with a height of <2 m, every additional centimeter of height significantly decreased postinjury PER by 1.08 (95% CI, 0.35-1.80; P < .01).

Conclusion:

Despite its severity, most NBA players who sustain Jones fractures can return to preinjury performance and level of competition. There was no statistically significant decline in advanced statistics in the following season after injury, with a significant decrease in games played when comparing injured players with their healthy controls.
Kosovo’s multilateral engagement: A strategy for international legitimacy
Authors: Krasniqi Valon , Mexhuani Burim
Published: December 2024

This study examines the ways in which Kosovo strategically uses multilateral diplomacy to navigate challenges and improve its international standing, despite the significant geopolitical constraints facing it. Regardless of opposition from influential states such as Serbia and Russia, Kosovo has been able to make incremental progress in gaining international recognition and legitimacy through its proactive participation in multilateral forums. Kosovo participates in different International and Regional Organisations, Treaties, and Conventions where it has a member/observer/participant/beneficiary and contracting party status. Using these platforms, Kosovo has effectively constructed a narrative of responsible statehood, positioning itself as a credible and constructive participant in global diplomacy. This approach yielded immediate diplomatic gains and has also contributed to a sustained trajectory towards broader acceptance and recognition. The study concludes that Kosovo’s strategic use of multilateral diplomacy has led to both short-term diplomatic successes and long-term progress towards achieving broader international integration and acceptance. This illustrates the continued relevance of multilateralism for small states seeking to assert their sovereignty in the international arena.
Adapting to the Unsanctioned Use of AI-Supported Technologies in Student Assessments
Authors: Landers Matthew
Published: December 2024

This article presents a brief overview of the state-of-the-art in large language models (LLMs) like ChatGPT and discusses the difficulties that these technologies create for educators with regard to assessment. Making use of the ‘arms race’ metaphor, this article argues that there are no simple solutions to the ‘AI problem’. Rather, this author shows that educators and universities will need to adopt a complex strategy consisting of solutions at four different levels of vulnerability: Ethical, pedagogic/didactic, technological and policy. Lastly, the article presents general recommendations for addressing vulnerabilities at each of these levels.
Persecution, a Church Council and the Shaping of the Church of Uganda, ca. 1884 - 1888
Authors: Teketwe Kimeze
Published: December 2024

In July 1885, the Church Missionary Society (CMS) mission in Uganda formed a church council comprised of twelve baptized Ugandans as an organizational response to persecution. Faced with a reign of terror that had begun with the enthronement of a new king following the death of the one who had invited them, English missionaries believed that the council was the only way their work would continue if the new king expelled them. In this paper, I argue that although formed as a response to persecution, the council had a far greater impact on the emergence of the Church of Uganda.
A New Clinical Test to Evaluate Intrinsic Foot Muscle Function
Authors: Panchbhavi Megna , Poliner Michael C. , Finegan Patrick M. , Jupiter Daniel C.
Published: December 2024

Background:

Intrinsic foot muscle weakness has been implicated in a wide range of forefoot conditions and is typically measured by the paper grip test. The proposed “knuckle test” is intended to evaluate intrinsic foot muscle function, in which active flexion of toes makes the metatarsal heads (“knuckles”) prominent in the forefoot. This study seeks to compare prevalence of negative knuckle test results and intrinsic muscle weakness in patients, primarily by association with a positive paper grip test result and secondarily with presence of toe deformities.

Methods:

Ninety-eight patients, 55 with toe deformity and 43 without, were evaluated for ability to flex their toes to the extent of knuckle prominence (knuckle test) and grip paper on the ground with their toes (paper grip test). Variables were compared between those with positive and negative knuckle test results.

Results:

A negative knuckle test result is significantly associated with the inability to grip a paper strip ( P < .05).

Conclusion:

Given that the paper grip test outcomes are a well-established sign of intrinsic muscle weakness, the significant association between knuckle and paper grip test outcomes substantiates the use of the knuckle test to detect intrinsic muscle weakness. The knuckle test is a potentially quick, simple, and cost-effective clinical maneuver to indicate intrinsic foot muscle weakness in a patient.

Level of Evidence:

Level III, diagnostic test development.
Some Truths About Engagement
Authors: Chella Ganesh
Published: December 2024

History tells us that some problems are admired so deeply that we forget to solve them. But then, there are also times when we move to solve them too quickly, without having admired them enough.

So, what about employee engagement?

For several decades motivational theorists admired the problem with great fascination and offered the world a whole host of theories that we continue to fall back on. Then in the last few decades, consulting companies have offered the world their own models of motivation under the umbrella of engagement.

Given that the context has changed so enormously and so much water has flown under the bridge, I believe it is time to step back and admire the problem once again. That is the purpose of my article.
India’s Engagement Imperative
Authors: Singh Puneet Pratap , Singh Rashi
Published: December 2024

Employee engagement is a leading indicator of business performance. Improving engagement must therefore be a leadership priority to unleash employee potential. Gallup’s latest measure of global engagement shows that less than a third (32%) of India’s workforce is engaged, and only 14% of employees are ‘thriving’, based on Gallup’s Life Evaluation Index. Challenges that impede the effectiveness of engagement initiatives include conflating ‘agree’ and ‘strongly agree’ responses to artificially boost positive engagement survey results, implementing tactical interventions based on data that are either erroneous or of poor quality, over-reliance on pulse surveys with little or no follow-up, and a perception that engagement programmes are ‘an HR thing’ rather than the responsibility of leaders. Employees need a workplace environment in which they feel valued and can contribute to the organisation’s mission or purpose, and a manager who coaches and inspires them.
“People Need to Know; We’re Part of the Community. We’re Here.”: Examining Experiences of Sharing Demographic Information for a Community-Based Diabetes Prevention Program
Authors: Craven Sarah A. , Sim Jenna A. P. , Cranston Kaela D. , Jung Mary E.
Published: December 2024

Background

Collecting demographic data is critical for identifying inequities in healthcare services and delivery. Inaccurate collection of demographic data can make developing equitable health interventions and improving reach of existing interventions difficult. This study aimed to (a) examine experiences in completing a community-based type 2 diabetes prevention program Small Steps for Big Changes (SSBC) demographic questionnaire (SSBC-DQ) among adults from equity-owed groups, and (b) assess recommendations for improvement to the questionnaire.

Methods

Adults with no prior involvement in SSBC were recruited. Participants completed the SSBC-DQ online and then engaged in one-on-one structured interviews. Interview data was analyzed using interpretive description and coded using the APEASE criteria.

Results

Twelve participant interviews were included in analysis. Five principle themes were developed to capture the experiences of completing the SSBC-DQ: representation, comprehension, demographics are an emotional experience, the role that privilege plays, and beliefs about demographic data. Sixty suggested changes were coded using the APEASE criteria; six suggestions met the criteria for implementation, 20 did not meet the criteria, and 34 required further discussion with the research team.

Conclusions

Results from this study illustrate that people’s lived experiences can drive their reactions and interpretations to demographic questionnaires. Based on end-user suggestions, SSBC made changes to its demographic questionnaire to be more inclusive. Having a demographic questionnaire that is more inclusive can help SSBC better understand what populations it is and is not reaching in an acceptable and inclusive manner. This will help inform future directions regarding evaluating program reach and equity.
Parasocial media: The mass production of intimacy on a Chinese pop idol mobile application
Authors: Shen Xinyue , Hallinan Blake
Published: December 2024

With the spread of monetization features like tipping and paid subscriptions, social media increasingly incorporates financial transactions and blurs the boundaries between social and parasocial relationships. While research documents how creators and audiences navigate economic interactions, there has been little attention to the role of platforms, particularly outside of Western contexts. We leverage the case of Pocket48, the custom mobile application for Chinese pop idol girl group SNH48, to investigate how platforms infrastructure asymmetrical relationships and the implications for both cultural production and online sociality. Based on an ethnographically-informed walkthrough analysis, we argue that the app employs two primary strategies for channeling fan-idol relationships: underclassifying interactions and invoking the aesthetics of intimacy. To do so, we first expose how Pocket48's policies ambivalently construct the user and the relationship between idols and fans. Next, we show how the app's design cultivates an intimate environment and unobtrusively incorporates transactions. Finally, we discuss how idols customize app infrastructure and moderate transactional functions to guide fans toward desired affective states. We conclude by introducing the concept of parasocial media, defined as platforms that feature (1) asymmetrical relationships between different classes of users, (2) tiered access to content and/or communication, and (3) tools to directly monetize relationships. Parasocial media platforms infrastructure relational work, helping media personas facilitate and financially exploit intimacy with their fans. Yet, as the case of Pocket48 attests, monetizing fan support is compatible with and can even strengthen the position of traditional industry actors.
A Fault Displacement Model Based on the FDHI Database
Authors: Kuehn Nicolas M , Kottke Albert R , Sarmiento Alexandra C , Madugo Christopher M , Bozorgnia Yousef
Published: December 2024

Fault displacement models are a key component of probabilistic fault displacement hazard analysis (PFDHA), providing the displacement probability density function. We present a new fault displacement model developed using the comprehensive database compiled for the Fault Displacement Hazard Initiative (FDHI) project. The model predicts the total net displacement across multi-stranded surface ruptures as a function of moment magnitude and position along the rupture length. We provide separate models for strike-slip, reverse, and normal faulting. A bilinear magnitude scaling is used to capture the steeper magnitude scaling for smaller magnitudes observed in the data for strike-slip and normal faulting. The scaling for reverse faulting approaches log-linear but still uses a bilinear form. Our flexible location scaling functional form captures the asymmetric profile shapes common in the data for dip-slip events and more symmetrical elliptical profiles in the strike-slip data. We applied a Box-Cox transformation to the displacement dataset so that the data resemble a normal distribution, which allows the transformed displacement to be conveniently modeled as normally distributed. Between- and within-event aleatory variability are modeled separately. All model parameters are estimated using Bayesian regression, which allows within-model epistemic uncertainty to be quantified. Compared with earlier models, the new model produces less aleatory variability and smaller upper-tail displacements for magnitudes greater than about 6.5 for all styles of faulting and all locations along the rupture. Data dispersion at the rupture end-points in the strike-slip and reverse faulting resulted in large aleatory variability. Large aleatory variability for smaller magnitude strike-slip and normal events is driven by a lack of data at smaller magnitudes. The use of a large, high-quality database and advanced statistical modeling techniques in our new model provides improved predictions of fault displacement compared with earlier models.
Single-cell epigenetic and clonal analysis decodes disease progression in pediatric acute myeloid leukemia
Authors: Cui Boyu , Ai Lanlan , Lei Minghui , Duan Yongjuan , Tang Chao , Zhang Jingliao , Gao Yan , Li Xuan , Zhu Caiying , Zhang Yingchi , Zhu Xiaofan , Isobe Tomoya , Yang Wenyu , Gottgens Berthold , Zhu Ping
Published: December 2024

Pediatric acute myeloid leukemia (pAML) is a clonal disease with recurrent genetic alterations that affect epigenetic states. However, the implications of epigenetic dysregulation in disease progression remain unclear. Here, we interrogated single-cell and clonal level chromatin accessibility of bone marrow samples from 28 pAML patients representing multiple subtypes using mtscATAC-seq, which revealed distinct differentiation hierarchies and abnormal chromatin accessibility in a subtype-specific manner. Innate immune signaling was commonly enhanced across subtypes and related to improved advantage of clonal competition and unfavorable prognosis, with further reinforcement in a relapse-associated leukemia stem cell-like population. We identified a panel of 31 innate immunity related genes to improve the risk classification of pAML patients. By comparing paired diagnosis and post-chemotherapy relapse samples, we showed that primitive cells significantly reduced MHC class II signaling, suggesting an immune evasion mechanism to facilitate their expansion at relapse. Key regulators orchestrating cell cycle dysregulation were identified to contribute to pAML relapse in drug-resistant clones. Our work establishes the single-cell chromatin accessibility landscape at clonal resolution and reveals the critical involvement of epigenetic disruption, offering insights into classification and targeted therapies of pAML patients.
Empirical prediction intervals applied to short term mortality forecasts and excess deaths
Authors: Duerst Ricarda , Schöley Jonas
Published: December 2024

Background

In the winter of 2022/2023, excess death estimates for Germany indicated a 10% elevation, which has led to questions about the significance of this increase in mortality. Given the inherent errors in demographic forecasting, the reliability of estimating a 10% deviation is questionable. This research addresses this issue by analyzing the error distribution in forecasts of weekly deaths. By deriving empirical prediction intervals, we provide a more accurate probabilistic study of weekly expected and excess deaths compared to the use of conventional parametric intervals.

Methods

Using weekly death data from the Short-term Mortality Database (STMF) for 23 countries, we propose empirical prediction intervals based on the distribution of past out-of-sample forecasting errors for the study of weekly expected and excess deaths. Instead of relying on the suitability of parametric assumptions or the magnitude of errors over the fitting period, empirical prediction intervals reflect the intuitive notion that a forecast is only as precise as similar forecasts in the past turned out to be. We compare the probabilistic calibration of empirical skew-normal prediction intervals with conventional parametric prediction intervals from a negative-binomial GAM in an out-of-sample setting. Further, we use the empirical prediction intervals to quantify the probability of detecting 10% excess deaths in a given week, given pre-pandemic mortality trends.

Results

The cross-country analysis shows that the empirical skew-normal prediction intervals are overall better calibrated than the conventional parametric prediction intervals. Further, the choice of prediction interval significantly affects the severity of an excess death estimate. The empirical prediction intervals reveal that the likelihood of exceeding a 10% threshold of excess deaths varies by season. Across the 23 countries studied, finding at least 10% weekly excess deaths in a single week during summer or winter is not very unusual under non-pandemic conditions. These results contrast sharply with those derived using a standard negative-binomial GAM.

Conclusion

Our results highlight the importance of well-calibrated prediction intervals that account for the naturally occurring seasonal uncertainty in mortality forecasting. Empirical prediction intervals provide a better performing solution for estimating forecast uncertainty in the analyses of excess deaths compared to conventional parametric intervals.
Clonal T cell populations scarcely impair patients with rheumatic diseases: a prospective long-term follow up study
Authors: Gernert Michael , Müller Tobias , Schweiker Lukas , Schmalzing Marc , Fröhlich Matthias , Nagler Lea-Kristin , Strunz Patrick-Pascal , Labinsky Hannah , Schwaneck Eva Christina
Published: December 2024

Background

Clonal T cell populations are frequently detected in patients with rheumatic diseases. The relevance of this finding is often uncertain, as the clinical spectrum can range from being asymptomatic to T cell leukemia. Former studies suggested that certain anti-rheumatic drugs might influence the course of the clonal T cell populations.

Methods

A prospective long-term follow up study was performed including patients with rheumatic diseases and clonal T cell populations. Clinical features, adverse events, especially infections and cytopenias, and immunosuppressive medication were assessed. T cell populations were characterized by polymerase chain reaction, flow cytometry and stimulated cell cultures.

Results

28 Patients with rheumatoid arthritis, spondyloarthritis, or giant cell arteritis were prospectively followed for up to 7.6 years. Severe infections or cytopenias (10.7% autoimmune neutropenias) were rare. The clonal T cell populations mostly persisted over time, the tumor burden decreased in the long-term. The cytokine secretion in stimulated T cell cultures did not differ in the subgroup of RA patients with versus without clonal T cells.

Conclusion

Clonal T cell populations in patients with rheumatic diseases are common, but are rarely harmful. Feared neutropenia, infections or progression into T cell leukemia could not be detected in the long-term in our cohort.
DNA methylation-based analysis reveals accelerated epigenetic aging in giant cell-enriched adult-type glioblastoma
Authors: Cakmak Pinar , Jurmeister Philipp , Divé Iris , Zeiner Pia S. , Steinbach Joachim P. , Fenton Tim R. , Plate Karl H. , Czabanka Marcus , Harter Patrick N. , Weber Katharina J.
Published: December 2024

Background

Giant cell (gc)-enriched glioblastoma (gcGB) represents a distinct histological variant of isocitrate dehydrogenase wild-type adult-type glioblastoma with notable enlarged mono- or multinuclear tumor cells. While some studies suggest a survival advantage for gcGB patients, the underlying causes remain elusive. GcGBs are associated with TP53 mutations, and gcs were shown to accumulate DNA double-strand breaks and show deficient mitosis, potentially triggering cellular senescence programs. Epigenetic clocks have emerged as valuable tools for assessing tumor-induced age acceleration (DNAMethAgeAcc), which has lately proved itself as prognostic biomarker in glioblastoma. Our study aimed to comprehensively analyze the methylome and key metabolic proteins of gcGBs, hypothesizing that they undergo cellular aging programs compared to non-gcGBs.

Results

A total of 310 epigenetically classified GBs, including 26 gcGBs, and nine adults with malignant gliomas allocating to pediatric high-grade glioma molecular subclasses (summarized as “pediatric GB”) were included. DNAMethAgeAcc was computed by subtraction of chronological patient ages from DNA methylome-derived age estimations and its increase was associated with better survival within gcGB and non-gcGB. GcGBs were significantly more often allocated to the subgroup with increased DNAMethAgeAcc and demonstrated the highest DNAMethAgeAcc. Hypothetical senescence/aging-induced changes of the tumor microenvironment were addressed by tumor deconvolution, which was able to identify a cluster enriched for tumors with increased DNAMethAgeAcc. Key metabolic protein expression did not differ between gcGB and non-gcGB and tumor with versus without increased DNAMethAgeAcc but for elevated levels of one single mitochondrial marker, anti-mitochondrial protein MT-C02, in gcGBs.

Conclusions

With its sped-up epigenetic aging, gcGB presented as the epigenetic oldest GB variant in our cohort. Whereas the correlation between accelerated tumor-intrinsic epigenetic aging and cellular senescence in gcGB stays elusive, fostering epigenetic aging programs in GB might be of interest for future exploration of alternative treatment options in GB patients.
Nano-fluorescence imaging: advancing lymphatic disease diagnosis and monitoring
Authors: Han Chae Yeon , Choi Sang-Hun , Chi Soo-Hyang , Hong Ji Hyun , Cho Young-Eun , Kim Jihoon
Published: December 2024

The lymphatic system plays a crucial role in maintaining physiological homeostasis and regulating immune responses. Traditional imaging modalities such as magnetic resonance imaging, computerized tomography, and positron emission tomography have been widely used to diagnose disorders in the lymphatic system, including lymphedema, lymphangioma, lymphatic metastasis, and Castleman disease. Nano-fluorescence technology has distinct advantages—including naked-eye visibility, operational simplicity, portability of the laser, and real-time visibility—and serves as an innovative alternative to traditional imaging techniques. This review explores recent advancements in nano-fluorescence imaging aimed at enhancing the resolution of lymphatic structure, function, and immunity. After delineating the fundamental characteristics of lymphatic systems, it elaborates on the development of various nano-fluorescence systems (including nanoparticles incorporating fluorescent dyes and those with intrinsic fluorescence) while addressing key challenges such as photobleaching, limited tissue penetration, biocompatibility, and signal interference from biomolecules. Furthermore, this review highlights the clinical applications of nano-fluorescence and its potential integration into standard diagnostic protocols. Ongoing advancements in nanoparticle technology underscore the potential of nano-fluorescence to revolutionize the diagnosis and treatment of lymphatic disease.

Graphical abstract
Systolic blood pressure, mean arterial pressure and incident mortality in heart failure in a West-African cohort: the blood pressure paradox revisited
Authors: Oguntade Ayodipupo S. , Ogah Okechukwu S. , Adebiyi Adewole A. , Aje Akinyemi
Published: December 2024

Background

The prognostic relevance of blood pressure in Africans with heart failure (HF) has not been well investigated despite the different trajectories of HF in Africans compared to other ethnicities. We investigated the shape and strength of associations of systolic blood pressure (SBP) and mean arterial pressure (MAP) with incident death in Nigerian Africans with hypertensive HF.

Results

Present analyses include 118 participants (mean age 57.6 years, 55% men) with ambulatory hypertensive HF. Over a median 2.2 years of follow-up, there were 74 incident deaths. There was an inverse log-linear association between each of SBP and MAP, and incident death throughout the distribution of blood pressure studied and no J-shape effect was seen. Individuals in the bottom distribution of SBP (mean 100 mmHg) and MAP (mean 77 mmHg) had the highest cumulative incident death. Each 10 mmHg higher SBP and MAP was associated with lower risk of incident death (aHR 0.80 [95% CI: 0.70–0.91, p < 0.001] and aHR 0.78 [95% CI: 0.66–0.92, p < 0.01] respectively) which persisted despite adjustment for NHYA class, left ventricular function and systolic pulmonary artery pressure. The blood pressure paradox was partially explained by haematocrit, serum sodium, chloride and renal function (aHR SBP: 0.86 [95% CI: 0.73–1.00, p = 0.05] and aHR MAP: 0.88 [95% CI: 0.72–1.08, p = 0.22]).

Conclusions

There was a graded inverse dose−response association between each of SBP, MAP and incident death in hypertensive HF which was not fully explained by haemodynamic and clinical factors.
Mindfulness-based relapse prevention for drug addiction in Nepal: impact and implications of an initial 2-day training of trainers
Authors: Jha Arun , Goit Bharat , Jha Robin , Jha Prerna , Pradhan Prabhat Kiran , Acharya Achyut
Published: December 2024

Drug addiction is rife in Nepal, with a high relapse rate following treatment. Apart from basic psychosocial support, there are no evidence-based aftercare services for individuals in recovery. Recently, mindfulness-based interventions have shown promising results in preventing relapse. We discuss the context, challenges and opportunities of organising a 2-day intensive face-to-face mindfulness-based training for Nepalese mental health professionals to facilitate 8-week mindfulness-based relapse prevention (MBRP). Altogether, 24 participants completed the feedback questionnaire. Most were rehabilitation staff, along with a few psychologists and psychiatrists. Feedback suggested a high degree of satisfaction and provided comments to improve the programme. It has prompted us to design online MBRP training and set up a feasibility study for an MBRP programme in Nepal. If successful, this may help a huge number of individuals in recovery.
Effect of Vitamin D3, Omega-3 Fatty Acids, and Exercise on Serum Sclerostin Levels and Bone Turnover Markers
Authors: Tsourdi Elena , Gängler Stephanie , Kistler-Fischbacher Melanie , Rauner Martina , Dawson-Hughes Bess , Orav E John , Tsai Li-Tang , Lang Wei , Kanis John A , Theiler Robert , Egli Andreas , Bischoff-Ferrari Heike A , Hofbauer Lorenz C
Published: December 2024

Context

Sclerostin inhibits canonical Wnt signaling, a pathway promoting bone formation. The effects of vitamin D3, omega-3 fatty acids (omega-3s), and exercise on serum sclerostin levels and bone metabolism are unclear.

Objective

To investigate the effects of 2000 IU/day vitamin D3, 1 g/day omega-3s, and a simple home-based strength exercise program (SHEP), alone or in combination, on serum sclerostin and bone turnover marker levels.

Methods

Sclerostin, procollagen type 1 N propeptide (P1NP) and C-terminal telopeptide (β-CTx) levels were predefined secondary outcomes of DO-HEALTH, a double blind, randomized controlled trial in healthy physically active older adults in 5 European countries. Outcome measures were changes in yearly serum sclerostin, P1NP, and β-CTx levels over 3 years, adjusted for age, sex, prior falls, study site, baseline body mass index, and baseline level of the respective outcome.

Results

A total of 1848 participants were included (mean age 74.8 ± 4.4 years, 58.9% women, 41.4% 25(OH)D < 20 ng/mL, 83.9% at least moderately physically active at baseline). Vitamin D3 and omega-3s supplementation alone did not change sclerostin levels significantly, while SHEP compared with control exercise (joint mobility) led to greater decrease in sclerostin levels (−1.56 pmol/L [−2.54, −0.58], P = .002). Omega-3s plus SHEP led to a greater decrease in sclerostin levels than no omega-3s/control exercise (−1.93 pmol/L [−3.31, −0.54], P = .007). For P1NP and β-CTx there were no significant effects for any of the individual treatments and treatment combinations.

Conclusion

In this 3-year prevention trial among largely vitamin D replete adults age 70 and older, SHEP alone or in combination with omega-3s reduced serum sclerostin levels, while vitamin D3 and omega-3s alone did not affect serum sclerostin levels.