bluuebunny/crossref_metadata_2025 huggingface dataset:
Platelet Volume Parameters as Predictors of Valvular Thrombosis Risk in Patients with Aortic and Mitral Valve Replacement
Authors: Pourbashash Boshra , Eftekhar Seyed Parsa , Ahmadi Pooria , Jalali Arash , Hosseinsabet Ali , Badalabadi Reza Mohseni
Published: January 2025

Percutaneous valve implantation or surgical replacement with mechanical or biological valves are standard therapies for severe valvular heart diseases. Prosthetic valve thrombosis, though rare, is a serious complication, particularly with mechanical prostheses. This study aimed to investigate the predictive value of platelet volume parameters, including mean platelet volume (MPV), platelet distribution width (PDW), and platelet-large cell ratio (P-LCR), for valvular thrombosis risk in patients undergoing valve replacement therapy. A retrospective cross-sectional study was conducted from May 2002 to May 2020, involving 108 patients with a history of mitral or aortic valve replacement and valvular thrombosis, and 216 controls with a history of valve surgery without valvular malfunction. PDW was significantly associated with an increased risk of thrombosis after adjusting for confounders, while MPV showed a clinical difference but did not reach statistical significance. P-LCR did not exhibit a significant association. These findings suggest PDW as a potential predictor of valvular thrombosis in such patients. The ease of measuring platelet volume parameters suggests their utility in routine hematological analysis for identifying patients at higher risk of valvular thrombosis post-replacement surgery. Further studies are warranted to validate these findings and explore additional laboratory markers, such inflammatory markers, for thrombotic risk assessment in this population.
Disclination dipole-dislocation interaction in the interface of an elastically heterogeneous bilayer
Authors: Colin Jérôme
Published: January 2025

The equilibrium positions of an edge dislocation gliding in the interface between two solids of different elastic coefficients have been determined in the neighborhood of a disclination dipole lying in a boundary separating two grains located in the upper phase. From the study of the Peach–Koehler force applied on the dislocation, the effects of the shear moduli and Poisson ratios of the two phases on the stability of the dislocation have been characterized. It is found that the stable positions do not depend on the dipole strength and are observed only when the two solids are elastically heterogeneous. A condition on the elastic coefficients of both solids has been finally determined for which stable equilibrium positions exist in the interface.
A matched case-control study on polypharmacy and co-medications one year before drug treatment for Alzheimer's disease
Authors: Alghamdi Ali , de Vos Stijn , Bos Jens HJ , Schuiling-Veninga Catharina CM , van Munster Barbara C , Mubarik Sumaira , Luijendijk Hendrika J , Hak Eelko
Published: January 2025

Background

Alzheimer's disease (AD) is the most prevalent form of dementia, characterized by amyloid-β plaques and neurofibrillary tangles. With an aging population, both AD and comorbidities are increasingly common. Managing comorbidities often requires multiple medications, leading to polypharmacy, defined as the concurrent use of five or more medications.

Objective

This study aimed to estimate and compare the prevalence of polypharmacy one-year prior AD diagnosis compared to non-AD individuals. Methods: A matched cross-sectional design used data from the IADB.nl prescription database (1994–2021), including individuals aged 65 and older with at least one AD medication prescription within a year. Controls were matched by age and sex at a 9:1 ratio. Analyses were stratified by time period (≤2010 and >2010) and further by sex and age.

Results

4150 AD individuals were included and matched with 37,350 controls. AD individuals had a higher prevalence of polypharmacy compared to controls, ≤ 2010 (OR: 1.15, 95% CI: 1.03–1.29), > 2010 (OR: 1.25, 95% CI: 1.16–1.36). Females with AD had slightly higher odds of polypharmacy than males. The prevalence was consistent across different time periods and age groups, with the highest odds in individuals aged 65–74.

Conclusions

AD individuals in the Netherlands exhibit a significantly higher prevalence of polypharmacy in a year pre-AD diagnosis. The findings highlight the complexity of managing multiple comorbid conditions in AD individuals, emphasizing the need for regular review and optimization of medication regimens and the inclusion of non-pharmacological interventions to minimize adverse outcomes and improve quality of life.
Sex-specific association of comorbid heart failure on mortality after Alzheimer's disease diagnosis in older adults aged 75 years and above: A health insurance claims data analysis in Japan
Authors: Matsunaga Masaaki , Tanihara Shinichi , He Yupeng , Yatsuya Hiroshi , Ota Atsuhiko
Published: January 2025

Background

Research on the influence of heart failure on mortality after Alzheimer's disease diagnosis is limited.

Objective

To evaluate the association between comorbid heart failure and mortality following Alzheimer's disease diagnosis, particularly considering sex differences.

Methods

We analyzed administrative claims data from Japan, involving 32,363 individuals (11,064 men and 21,299 women) aged 75 or older newly diagnosed with Alzheimer's disease, with 7% having comorbid heart failure. Cox proportional hazard models and population attributable fractions (PAFs) were used to evaluate the association between comorbid heart failure and mortality within one year following Alzheimer's disease diagnosis.

Results

Individuals with Alzheimer's disease and heart failure had a multivariate-adjusted hazard ratio of 1.51 (95% confidence interval [CI], 1.32–1.73) for mortality during the one-year follow-up period compared to those with Alzheimer's disease and without heart failure. Subgroup analysis by sex revealed a higher mortality hazard ratio in women of 1.63 (95% CI, 1.36–1.95) than that in men of 1.39 (95% CI, 1.13–1.71). Further age and sex subgroup analysis indicated that women across all age brackets—75–79, 80–84, and ≥ 85 years—had higher mortality hazard ratios. The PAF for heart failure increased with age in both sexes, with women having higher PAFs than men, and the sex difference in PAF being most pronounced in the 75–79 age category (men: 1.4%, women: 4.0%).

Conclusions

Hazard ratios and PAFs for mortality associated with comorbid heart failure in newly diagnosed Alzheimer's disease are higher in women than in men, which persists across all age subgroups.
Structure-function coupling alterations in cognitively normal individuals with white matter hyperintensities
Authors: Du Junyong , Xu Shabei , Zhu Wenhao
Published: January 2025

Background

White matter hyperintensities (WMH) are prominent neuroimaging markers of cerebral small vessel disease (CSVD) linked to cognitive decline. Nevertheless, the pathophysiological mechanisms underlying WMH remain unclear.

Objective

This study aimed to assess the structural decoupling index (SDI) as a novel metric for quantifying the brain's hierarchical organization associated with WMH in cognitively normal older adults.

Methods

We analyzed data from 112 cognitively normal individuals with varying WMH burdens (43 high WMH burden and 69 low WMH burden). Neuroimaging data were used to calculate SDI, and gene enrichment analysis was conducted to explore related molecular pathways.

Results

An increased spatial gradient of SDI from the sensory-motor cortex to the associative cortex was observed. Compared to the low WMH burden group, the high WMH group exhibited elevated SDI in the right superior frontal gyrus, bilateral orbital gyrus, bilateral precentral gyrus, bilateral cingulate gyrus, bilateral thalamus, and bilateral striatum. In the high WMH burden group, SDI in the left thalamus and right cingulate gyrus negatively correlated with memory, while SDI in the right orbital gyrus and left precentral gyrus positively correlated with processing speed. Gene enrichment analysis highlighted associations with pathways involved in neural system function, potassium ion transmembrane transport, synaptic signaling, neuron projection development, and cell secretion regulation.

Conclusions

The findings suggest SDI alterations as a potential mechanistic pathway in WMH, which is associated with significant molecular pathways and cognitive impairments. This study provides a theoretical framework for understanding the pathophysiology of WMH progression and subsequent cognitive deficits.
When Girl Drama Goes Viral: A Case Study in Freedom of Speech
Authors: Balkcom Connie , Faaborg Ashley , Graham Fallon , McClure Amy , Terwilliger Sarah
Published: January 2025

This case explores the challenges faced by educational leaders at Maple Middle School, a rural school in a diverse community, involving a physical altercation between two students, subsequent student protests, and an investigation by Child Protective Services. Amid growing community unrest, a divided school board must address student discipline issues, restraint policies, and the balance between maintaining a safe environment and respecting students’ rights. As tensions escalate, the Deputy Superintendent’s office faces pressure to take action, requiring careful investigation, policy revisions, and conflict resolution strategies to navigate the complexities of a deeply divided community. The case highlights the importance of communication, transparency, and unbiased decision-making in addressing sensitive issues.
Using One-Shot Prompting of Non-Fine-Tuned Commercial Artificial Intelligence to Assess Nutrients from Photographs of Japanese Meals
Authors: Ji Yuexiang , Waki Kayo , Yamauchi Toshimasa , Nangaku Masaomi , Ohe Kazuhiko
Published: January 2025

Background:

Diet interventions often have poor adherence due to burdensome food logging. Approaches using photographs assessed by artificial intelligence (AI) may make food logging easier, if they are adequately accurate.

Method:

We used OpenAI’s GPT-4o model with one-shot prompts and no fine-tuning to assess energy, fat, protein, carbohydrate, fiber, and salt through photographs of 22 meals, comparing assessments to weighed food records for each meal and to assessments of dieticians.

Results:

The model had poor performance overall. For fiber, though, the model achieved an intraclass correlation coefficient of 0.71 (0.67-0.74 95% CI), well above the dietician performance of 0.57.

Conclusions:

The simplest use of current AI via one-shot prompting and no fine-tuning accurately assesses fiber content in meals but is inaccurate for other nutritional parameters.
Authoritarians Do It Better? Belief in Misinformation in Turkey
Authors: Andı Simge , Çarkoğlu Ali , Baruh Lemi , Bocskay Zsofia
Published: January 2025

Misinformation poses a significant threat to the integrity of political systems, particularly in competitive authoritarian regimes (CARs), where it can distort public perception and undermine democratic processes. This study focuses on the 2023 Turkish general elections—a context characterized by widespread misinformation. While extensive research has been conducted on misinformation in democratic systems, where press freedom and digitalization foster a mix of reliable and misleading information, this investigation targets the unique challenges and media consumption patterns in CARs. Utilizing a nationally representative survey after the 2023 elections, we examine the association between media consumption (traditional and online) and susceptibility to misinformation among government and opposition voters. Our findings reveal that partisan news consumption significantly influences belief in misinformation, with individuals tending to believe claims aligning with their political affiliations while rejecting opposing claims. Moreover, television remains a dominant source of information in Turkey, unlike social media, which shows a limited impact on misinformation beliefs but possesses a conditional corrective potential for certain electorate segments. This study underscores the enduring influence of traditional media in CARs and suggests that while the theory of selective exposure and partisanship is applicable, the constrained information environment significantly shapes public perceptions and misinformation dynamics.
Associated Anatomic Abnormalities in Patients Undergoing Rotational Tibial Osteotomies for Patellofemoral Pathology and Implications for the Level of Correction
Authors: Haikal Mohammad , Singh Nishant , Issac Renjit , Silk Gwithyen , Snow Martyn
Published: January 2025

Purpose

Tibial rotational deformity is a known risk factor for patellofemoral joint (PFJ) disorders. However, it is commonly associated with other abnormalities which affect the PFJ. The purpose of this study was to describe the prevalence of associated factors known to affect PFJ in patients undergoing rotational tibial osteotomy and their implication for the correction level.

Methods

All patients with PFJ disorder, who underwent rotational tibial osteotomy between July 2009 and February 2020, were included. Patients were excluded if there were no preoperative computed tomography (CT)/magnetic resonance imaging (MRI). Scans were analyzed by 2 observers. Parameters of interest were femoral version, tibial torsion, trochlear dysplasia, lateral trochlear inclination (LTI), tibial tuberosity–trochlear groove (TT-TG) distance, Insall-Salvati (IS), and Caton Deschamps Index (CDI).

Results

The search resulted in 80 knees, which had a mean femoral version of 21.0 ± 11.7, tibial torsion of 45.9 ± 9.1, TT-TG of 18.3 ± 5.5, and LTI of 11.4 ± 14.7. In total, 42.5% had TT-TG value of ≥ 20 mm. Patella alta/baja was found in 54% based on CDI or IS >1.2 and <0.8. High-grade trochlear dysplasia was found in 25%. In total, 29% had a tibial torsion abnormality but normal TT-TG and patella height. In total, 18% had abnormal TT-TG but normal patellar height.

Conclusion

Based on the associated abnormalities of patella height and tubercle lateralization, 18% of the population were suitable for supratubercle osteotomy, and 29% of patients were suitable for diaphyseal or distal tibial osteotomy. A tibial tubercle osteotomy was required in 54% of patients, making a through-tubercle approach the most appropriate option for most patients.

Level of evidence:

Radiological cross-sectional study.
Uncommon presentation of a chronic recurrent symptomatic encapsulated calcified postoperative paraspinal lumbar hematoma: A case report
Authors: Edwards Timothy , Sadhwani Shaan , Sweeney Brendan , Almeda-Lopez Antonio , Peppelman Walter C , Beutler William J
Published: January 2025

Paraspinal hematomas are common complications following spine surgery. In general, these hematomas are asymptomatic and resolve without issue. Unfortunately, there is a paucity of literature that describes the recurrence of these hematomas in a chronic setting. This case report describes a patient with a chronic recurrent calcified paraspinal hematoma that first developed over 4 years and then reoccurred 11 years later at the same site. The case features a 53-year-old female presented with severe lumbar back pain and right lower extremity radiculopathy in which she underwent a lumbar decompression posterior spinal fusion from L3 to L5 in 2008. Postoperatively, she developed a lumbar paraspinal hematoma which was treated with aspiration followed by conservative management. Four years later, the patient had a large paraspinal mass removed from a similar location in an outside medical facility. The procedure required the assistance of plastic surgery for flap closure and a pathologic review of the mass revealed a calcified hematoma. Ten years later, the patient sought treatment from her index surgeon for a recurrence of the lumbar mass with new onset radicular symptoms. Magnetic resonance imaging of the lumbar spine confirmed the presence of a large paraspinal mass. The patient proceeded with the removal of hardware, revision of laminectomy, revision of posterior instrumentation from L2 to L5, and removal of the lumbar mass. The pathology report classified the mass as a chronic calcified hematoma. The patient remains symptom-free for 1 year following the revision procedure. This case demonstrates an extremely rare presentation, ill-described in the existing literature, of a recurrent symptomatic calcified lumbar paraspinal hematoma requiring repeat operative intervention.
Case report: Diagnostic challenges of papulonodular mucinosis in a 67-year-old female
Authors: Zahary Loreman Holly E , Holfeld Karen I
Published: January 2025

Papulonodular mucinosis is a rare dermatological condition characterized by mucin deposition in the dermis, leading to the formation of papules and nodules that can occur with, or antedate, autoimmune connective tissue diseases. This case report presents a 67-year-old female with a chronic history of cutaneous mucinosis, which posed significant diagnostic challenges. Despite various treatments and extensive diagnostic workup, her condition evolved, highlighting the difficulties in diagnosing papulonodular mucinosis, especially in the absence of systemic lupus erythematosus and antinuclear antibody positivity. The unusual presentation and diagnostic complexity underscore the need for awareness and thorough investigation in similar cases.
Public opinion and the news: Polls and journalists’ perceptions of issue importance
Authors: Hassell Hans J.G. , Wlezien Christopher
Published: January 2025

Most work on the media and the public starts from the premise that coverage influences opinion and behavior. We report results of a field experiment attempting to identify whether the reverse is true. Specifically, we examine the effects of providing public opinion information to journalists on their perceptions of the newsworthiness of different topics. We randomly assigned journalists to receive results of a survey of Americans about the importance of different political issues, and followed up with a survey of those journalists (from a different source) asking about the newsworthiness of stories about those issues. The results provide some support for the hypothesis that public opinion influences journalists’ perceptions of topical newsworthiness, particularly on low salience issues, and also allow us to rule out large opinion effects on journalists’ perceptions of the newsworthiness of certain issues. The effects appear to be more pronounced for those journalists with less experience in the communities in which they currently work. Overall, we see the research as both offering insight into the nature of the effects that public opinion has on news coverage and helping guide future research, which we consider in the concluding section.
Pulmonary Atresia with Ventricular Septal Defect without Major Aorto-Pulmonary Collateral Arteries: Echocardiography and the Role of Computed Tomography and Magnetic Resonance Imaging
Authors: Gurson Sarah Chambers
Published: January 2025

Pulmonary atresia with ventricular septal defect (PA-VSD) is usually diagnosed by transthoracic or fetal echocardiography, with the prenatal diagnosis being feasible and accurate if fetal cardiology services are available. The limitations of transthoracic echocardiography (TTE) in the evaluation of PA-VSD include the complete evaluation of the pulmonary arteries and patent ductus arteriosus, quantitative evaluation of the right ventricle size and function, and delineation of associated cardiac anomalies such as coronary artery anomalies, anomalies of systemic or pulmonary venous return, and complex arch anomalies. Echocardiography also has limitations in evaluating hemodynamics such as flow volumes, shunts, and regurgitant fraction. Despite these limitations, TTE remains the most widely available and the most cost-effective cardiac imaging modality for patients with PA-VSD and its accuracy in evaluating the sources of pulmonary blood flow and in selecting patients for systemic-to-pulmonary artery shunt palliation is well established. Cardiac computed tomography (CT) can answer many of the questions not answered by TTE, including demonstrating the PA anatomy and defining coronary artery, systemic and pulmonary venous, and aortic arch anatomies. The short acquisition time allows for the study to be performed without sedation/anesthesia in most patients. Cardiac CT is also useful in defining postoperative anatomy when there are non-magnetic resonance imaging (MRI) compatible devices or even MRI-compatible devices that cause a significant MRI artifact. Cardiac MRI/magnetic resonance angiography has emerged as an ideal modality to evaluate patients with PA-VSD as it allows for anatomic, functional, and hemodynamic assessment without exposure to ionizing radiation or iodinated contrast material. Both cardiac CT and cardiac MRI can be used to generate 3D imaging of the heart.
Endometriosis management in a low/middle income country – Integration of a multidisciplinary medical team and patient social support group
Authors: Muteshi Charles , Mwaka Gilbert , Duncan Andrew , Gitau Samuel , Kathiresan Prabu , Bwika Jumaa , Yousef Ahmed , Wandera Elsie
Published: January 2025

Endometriosis is a chronic condition that causes significant pain, subfertility and impairs the quality of life of affected women and girls. There is no known cure and management is tailored to specific individual circumstances. International best practice recommendation advocates managing severe endometriosis within centres of excellence with multidisciplinary team (MDT) of specialists. This type of care should focus on the chronic disease and biopsychosocial models. We describe a first and unique endometriosis MDT that incorporates patient social support group in a low and middle income country.
La Gallera: Los Zetas’ extermination camp in northern Veracruz, Mexico
Authors: Melenotte Sabrina
Published: January 2025

Since 2006 and the official fight against drug trafficking in Mexico which has left at least 116,000 people missing and 500,000 people dead, clandestine spaces and traces of violence left by mass disappearances have multiplied and with them the searches for missing persons. I describe here a specific clandestine space of disappearance in the north of Veracruz, called “La Gallera,” which was an “extermination camp” of the cruelest kind, created by Los Zetas Cartel. In February 2020, I joined the 5th National Brigade for the Search for Missing Persons with many collectives of family members from many states. But this “clandestine cemetery” saw multiple exhumation processes before we arrived in February 2020. I will cross-reference my ethnographic observations of these searches with journalistic and documentary sources, as well as elements from an interview with Maricel Torres, representative of the collective Familiares en Búsqueda María Herrera Poza Rica, to show the complexity of exhumations and the forensic, analytical and sensitive challenges. Then I will make a historical reconstruction of Los Zetas that expanded in northern Veracruz in order to propose a contextual analysis necessary to understand the criminal logics of the perpetrators and the repressive logics behind the human remains.
Unveiling a Diagnostic Enigma: A Rare Case Report of Abdominal Sarcoidosis
Authors: Dutta Debayan , Shrivastava Pushpendra
Published: January 2025

Sarcoidosis is an idiopathic inflammatory granulomatous disorder that primarily affects the lungs. Abdominal manifestations without pulmonary involvement are infrequent. We present an atypical case of sarcoidosis in an elderly lady who presented with symptomatic hypercalcemia with computed tomography (CT) revealing multiple hepatosplenic hypodense granulomatous lesions with raised angiotensin-converting enzyme (ACE) levels. She had a good response to immunosuppressants. There is a rare possibility of isolated organ involvement without any pulmonary manifestation. Hence, ruling out other differentials and starting appropriate immunosuppressive treatment is necessary.
Leisure travel and life satisfaction in a Dutch sample
Authors: Nissen Adam T , Bleidorn Wiebke , Lenhausen Madeline R , Hopwood Christopher J
Published: January 2025

People generally go on vacation to improve their life satisfaction. However, the association between life satisfaction and leisure travel is poorly understood, partly because of methodological limitations in previous research. In the present study, we examined the longitudinal association between life satisfaction and leisure travel using data from a representative Dutch sample ( N = 12,027) gathered annually over 8 years. We specifically compared travelers and non-travelers on their levels and growth in life satisfaction over time using a growth model framework. We also examined whether more frequent and international (vs. domestic) travel was associated with life satisfaction among travelers. Travelers and non-travelers were similar in levels and changes in life satisfaction. Traveling more frequently and internationally was related to greater life satisfaction during the year of travel, but not stable levels or long-term trajectories. Our findings suggest that vacations are only positively linked to life satisfaction in the short term.
Site-response high-frequency frontiers and the added value of site-specific earthquake record-based measurements of velocity and attenuation
Authors: Pilz Marco , Cotton Fabrice , Zhu Chuanbin
Published: January 2025

One-dimensional (1D) ground-response analysis based on 1D velocity profiles and generic relationships between damping and velocity is frequently employed under the assumption that it can provide a reliable assessment of site effects. According to this hypothesis, epistemic uncertainty in site response primarily stems from inaccurately determined soil parameters. As shown by the recent development of ground-motion models in the Fourier domain, the underlying site-to-site variability of site response rises sharply at intermediate to high frequencies (>3 Hz), and this increase cannot be compensated for when relying on coarse velocity profiles and generic relationships between damping and velocity. In order to solve this high-frequency frontier in site response, we invert the spectral ratio of the horizontal-to-vertical components of strong motions based on the diffuse field concept for obtaining refined 1D velocity profiles and site-specific damping profiles. These updated equivalent structures of both velocity and damping significantly improve the performance of 1D ground-response analyses. This effect is particularly strong at intermediate frequencies (3–10 Hz), where both the deep sedimentary structure and the damping profile above the seismological bedrock have a strong influence on site response. While the use of refined 1D velocity and generic damping profiles for test sites of the Japanese KiK-net already provides a reduction of the intermediate-to-high-frequency residual and corrected site-to-site variability (and then an increase in the precision of predictions), the inclusion of site-specific damping allows this value almost to be halved. The results show that many sites are indeed too complex to be modeled by classical 1D ground-response analysis relying on generic damping relationships, while only site-specific record-based models allow a significant reduction in the bias.
Targeting DOT1L and EZH2 synergizes in breaking the germinal center identity of Diffuse Large B-cell Lymphoma
Authors: Göbel Camiel , Niccolai Rachele , de Groot Marnix Hugo Philip , Jayachandran Jayashree , Traets Joleen , Kloosterman Daan Juri , Gregoricchio Sebastian , Morris Ben , Kreft Maaike , Song Ji-Ying , Azarang Leyla , Kasa Eirini , Oskam Nienke , de Groot Daniel , Hoekman Liesbeth , Bleijerveld Onno , Kersten Marie José , Aslam Muhammad Assad , van Leeuwen Fred , Jacobs Heinz
Published: January 2025

Differentiation of antigen-activated B cells into pro-proliferative germinal center (GC) B cells depends on the activity of the transcription factors MYC and BCL6, and the epigenetic writers DOT1L and EZH2. GCB-like Diffuse Large B Cell Lymphomas (GCB-DLBCLs) arise from GCB cells and closely resemble their cell of origin. Given the dependency of GCB cells on DOT1L and EZH2, we investigated the role of these epigenetic regulators in GCB-DLBCLs and observed that GCB-DLBCLs synergistically depend on the combined activity of DOT1L and EZH2. Mechanistically, inhibiting both enzymes led to enhanced derepression of PRC2 target genes compared to EZH2 single treatment, along with the upregulation of BCL6 target genes and suppression of MYC target genes. The sum of all these alterations results in a 'cell identity crisis', wherein GCB-DLBCLs lose their pro-proliferative GC identity and partially undergo PC differentiation, a state associated with poor survival. In support of this model, combined epi-drugging of DOT1L and EZH2 prohibited the outgrowth of human GCB-DLBCL xenografts in vivo. We conclude that the malignant behavior of GCB-DLBCLs strongly depends on DOT1L and EZH2 and that combined targeting of both epigenetic writers may provide an alternative differentiation-based treatment modality for GCB-DLBCL.
Donor Regulatory T-Cell Therapy to Prevent Graft-Versus-Host Disease
Authors: Meyer Everett , Pavlova Anna , Villar-Prados Alejandro , Bader Cameron S , Xie Bryan , Muffly Lori , Kim Paige , Sutherland Katherine C. , Bharadwaj Sushma , Dahiya Saurabh , Frank Matthew J , Arai Sally , Johnston Laura , Miklos David B , Rezvani Andrew R. , Shiraz Parveen , Sidana Surbhi , Shizuru Judith A. , Weng Wen-Kai , Agrawal Vaibhav , Putnam Amy , Fernhoff Nathanial B , Tamaresis John , Lu Ying , Pawar Rahul D , McClellan J Scott , Lowsky Robert , Negrin Robert S.
Published: January 2025

Allogeneic hematopoietic cell transplantation (HCT) is a curative therapy limited by graft-versus-host disease (GVHD). In preclinical studies and early-phase clinical studies enrichment of donor regulatory T cells (Tregs) appears to prevent GVHD and promote healthy immunity.We enrolled 44 patients on an open-label, single-center, phase 2 efficacy study investigating if a precision selected and highly purified Treg cell therapy manufactured from donor mobilized peripheral blood improves one-year GVHD-free relapse free survival (GRFS) after myeloablative conditioning (trial NCT 01660607). We compared this study arm to a concomitant standard of care (SOC) cohort. All donor Treg cell products were successfully manufactured and administered without cryopreservation within 72 hours. Participants had a one-year incidence of acute grade III-IV GVHD of 7%, moderate to severe chronic GVHD of 11% and non-relapse mortality rate of 4.5%. The primary endpoint of significantly improved one-year GRFS was achieved at 64% evaluated against a predicted incidence of 40% (p = 0.002) with a realized incidence of 36% in the SOC comparitor. For those trial patients whow developed grade II-IV acute GVHD, 91% responded to front-line steroid therapy wheras 50% responded in the SOC comparator group. Trial participants had a reduced incidence and burden of GVHD and improved GRFS, as compared to rates common to highly variable unmanipulated donor grafts and multi-agent immune suppression.
Physical activity and the outcome of cognitive trajectory: a machine learning approach
Authors: Barisch-Fritz Bettina , Shah Jay , Krafft Jelena , Geda Yonas E. , Wu Teresa , Woll Alexander , Krell-Roesch Janina
Published: January 2025

Background

Physical activity (PA) may have an impact on cognitive function. Machine learning (ML) techniques are increasingly used in dementia research, e.g., for diagnosis and risk stratification. Less is known about the value of ML for predicting cognitive decline in people with dementia (PwD). The aim of this study was to use an ML approach to identify variables associated with a multimodal PA intervention that may impact cognitive changes in PwD, i.e., by distinguishing between cognitive decliners and non-decliners.

Methods

This is a secondary, exploratory analysis using data from a Randomized Controlled Trial that included a 16-week multimodal PA intervention for the intervention group (IG) and treatment as usual for the control group (CG) in nursing homes. Predictors included in the ML models were related to the intervention (e.g., adherence), physical performance (e.g., mobility, balance), and pertinent health-related variables (e.g., health status, dementia form and severity). Primary outcomes were global and domain-specific cognitive performance (i.e., attention/ executive function, language, visuospatial skills, memory) assessed by standardized tests. A Support Vector Machine model was used to perform the classification of each primary outcome into the two classes of decline and non-decline. GridSearchCV with fivefold cross-validation was used for model training, and area under the ROC curve (AUC) and accuracy were calculated to assess model performance.

Results

The study sample consisted of 319 PwD (IG, N = 161; CG, N = 158). The proportion of PwD experiencing cognitive decline, in the different domains measured, ranged from 27–48% in CG, and from 23–49% in IG, with no statistically significant differences and no time*group effects. ML models showed accuracy and AUC values ranging from 40.6–75.6. The strongest predictors of cognitive decline or non-decline were performance of activities of daily living in IG and CG, and adherence and mobility in IG.

Conclusions

ML models showed moderate performance, suggesting that the selected variables only had limited value for classification, with adherence and performance of activities of daily living appearing to be predictors of cognitive decline. While the study provides preliminary evidence of the potential use of ML approaches, larger studies are needed to confirm our observations and to include other variables in the prediction of cognitive decline, such as emotional health or biomarker abnormalities.
Integrated metabolomic and transcriptomic analysis of anthocyanin metabolism in wheat pericarp
Authors: Wang Jiao , Sun Lei , Jiao Bo , Zhao Pu , Xu Tianyun , Gu Sa , Huo Chenmin , Pang Jianzhou , Zhou Shuo
Published: January 2025

Background

Wheat seeds display different colors due to the types and contents of anthocyanins, which is closely related to anthocyanin metabolism. In this study, a transcriptomic and metabolomic analysis between white and purple color wheat pericarp aimed to explore some key genes and metabolites involved in anthocyanin metabolism.

Results

Two wheat cultivars, a white seed cultivar Shiluan02-1 and purple seed cultivar Hengzi151 were used to identify the variations in differentially expressed genes (DEGs) and differentially accumulated flavonoids (DAFs). Based on metabolomic data, 314 metabolites and 191 DAFs were identified. Chalcone, flavonol, pro-anthocyanidin and anthocyanidin were the most differentially accumulated flavonoid compounds in Hengzi151. 2610 up-regulated and 2668 down-regulated DEGs were identified according to transcriptomic data. The results showed that some structural genes in anthocyanin synthesis pathway were prominently activated in Hengzi151, such as PAL, CAD, CHS and so on. Transcription factors (TFs) of MYB, bHLH, WD40 and some other TFs probably involved in regulating anthocyanin biosynthesis were identified. Some genes from hormone synthetic and signaling pathways that may participate in regulating anthocyanin biosynthesis also have been identified.

Conclusions

Our results provide valuable information on the candidate genes and metabolites involved in the anthocyanin metabolism in wheat pericarp.
Understanding and measuring workplace violence in healthcare: a Canadian systematic framework to address a global healthcare phenomenon
Authors: Schulz-Quach Christian , Lyver Brendan , Reynolds Charlene , Hanagan Trevor , Haines Jennifer , Shannon John , Pozzobon Laura Danielle , Sarraf Yasemin , Sabbah Sam , Ensafi Sahand , Bloomberg Natasha , Gorla Jaswanth , Singh Brendan , Chartier Lucas B. , Escaf Marnie , Elder Diana , Toppings Marc , Hodges Brian , Sethi Rickinder
Published: January 2025

Background

Globally, healthcare institutions have seen a marked rise in workplace violence (WPV), especially since the Covid-19 pandemic began, affecting primarily acute care and emergency departments (EDs). At the University Health Network (UHN) in Toronto, Canada, WPV incidents in EDs jumped 169% from 0.43 to 1.15 events per 1000 visits (p < 0.0001). In response, UHN launched a comprehensive, systems-based quality improvement (QI) project to ameliorate WPV. This study details the development of the project’s design and key takeaways, with a focus on presenting trauma-informed strategies for addressing WPV in healthcare through the lens of health systems innovation.

Methods

Our multi-intervention QI initiative was guided by the Systems Engineering Initiative for Patient Safety (SEIPS) 3.0 framework. We utilized the SEIPS 101 tools to aid in crafting each QI intervention.

Results

Using the SEIPS 3.0 framework and SEIPS 101 tools, we gained a comprehensive understanding of organizational processes, patient experiences, and the needs of HCPs and patient-facing staff at UHN. This information allowed us to identify areas for improvement and develop a large-scale QI initiative comprising 12 distinct subprojects to address WPV at UHN.

Conclusions

Our QI team successfully developed a comprehensive QI project tailored to our organization’s needs. To support healthcare institutions in addressing WPV, we created a 12-step framework designed to assist in developing a systemic QI approach tailored to their unique requirements. This framework offers actionable strategies for addressing WPV in healthcare settings, derived from the successes and challenges encountered during our QI project. By applying a systems-based approach that incorporates trauma-informed strategies and fosters a culture of mutual respect, institutions can develop strategies to minimize WPV and promote a safer work environment for patients, families, staff, and HCPs.
Optimizing hip MRI: enhancing image quality and elevating inter-observer consistency using deep learning-powered reconstruction
Authors: Kang Yimeng , Li Wenjing , Lv Qingqing , Tao Qiuying , Sun Jieping , Dang Jinghan , Niu Xiaoyu , Liu Zijun , Li Shujian , Zhang Zanxia , Wang Kaiyu , Wen Baohong , Cheng Jingliang , Zhang Yong , Wang Weijian
Published: January 2025

Background

Conventional hip joint MRI scans necessitate lengthy scan durations, posing challenges for patient comfort and clinical efficiency. Previously, accelerated imaging techniques were constrained by a trade-off between noise and resolution. Leveraging deep learning-based reconstruction (DLR) holds the potential to mitigate scan time without compromising image quality.

Methods

We enrolled a cohort of sixty patients who underwent DL-MRI, conventional MRI, and No-DL MRI examinations to evaluate image quality. Key metrics considered in the assessment included scan duration, overall image quality, quantitative assessments of Relative Signal-to-Noise Ratio (rSNR), Relative Contrast-to-Noise Ratio (rCNR), and diagnostic efficacy. Two experienced radiologists independently assessed image quality using a 5-point scale (5 indicating the highest quality). To gauge interobserver agreement for the assessed pathologies across image sets, we employed weighted kappa statistics. Additionally, the Wilcoxon signed rank test was employed to compare image quality and quantitative rSNR and rCNR measurements.

Results

Scan time was significantly reduced with DL-MRI and represented an approximate 66.5% reduction. DL-MRI consistently exhibited superior image quality in both coronal T2WI and axial T2WI when compared to both conventional MRI (p < 0.01) and No-DL-MRI (p < 0.01). Interobserver agreement was robust, with kappa values exceeding 0.735. For rSNR data, coronal fat-saturated(FS) T2WI and axial FS T2WI in DL-MRI consistently outperformed No-DL-MRI, with statistical significance (p < 0.01) observed in all cases. Similarly, rCNR data revealed significant improvements (p < 0.01) in coronal FS T2WI of DL-MRI when compared to No-DL-MRI. Importantly, our findings indicated that DL-MRI demonstrated diagnostic performance comparable to conventional MRI.

Conclusion

Integrating deep learning-based reconstruction methods into standard clinical workflows has the potential to the promise of accelerating image acquisition, enhancing image clarity, and increasing patient throughput, thereby optimizing diagnostic efficiency.

Trial registration

Retrospectively registered.
Quality assessment of fish vaccine data in the Norwegian Veterinary Prescription Register (VetReg)
Authors: Udhwani Trishang , Dean Katharine R. , Sommerset Ingunn , Helgesen Kari Olli
Published: January 2025

Background

Vaccination of farmed salmonids has been an integral part of preventing infectious diseases in Norway’s aquaculture industry. In Norway, vaccine usage is regulated by the government. There is a need to monitor vaccine usage for both regulatory and research purposes, at local and national scales. The Norwegian Veterinary Prescription Register (VetReg) is a national database that includes all prescriptions of medicines to animals dispensed by pharmacies and all medicines used for food producing animals by veterinarians. This study aimed to evaluate the quality of fish vaccination data reported to VetReg in 2016–2022. We considered the following attributes: completeness, validity, and timeliness. For external validation, we compared the data in VetReg to wholesaler statistics.

Results

Pharmacies reported fish vaccines to VetReg in a variety of quantity units, including doses and volumes, which required us to harmonize the data to a single unit. It was not possible to harmonize the quantity units for nine percent of the records, which were mainly bath vaccines reported in doses. We identified specific issues that required manual editing of the units of 1 percent of the records. We validated individual variables such as product codes and location identifiers using external registers. The ‘number of animals’ variable was inconsistent for 31 percent of the records. The coverage of vaccine data in VetReg ranged from 81 to 113 percent for the ten most sold vaccines in 2020–2022, as compared to wholesales statistics. For the timeliness, we found that 75 percent of the records were submitted within 25 days for all years.

Conclusions

Overall, we found that the fish vaccination data in VetReg was of sufficient quality to monitor injectable vaccine usage at hatcheries after 2020. We identified issues at the product level, with bath vaccines, and with single variables (number of animals, weight, and species). We recommend that quality can be improved by reporting all vaccines in volume rather than doses, reporting a single vaccine prescription per report, and including a deadline for pharmacies to report in the legislation.
Therapeutic development to accelerate malaria control through intentional intervention layering
Authors: Braunack-Mayer Lydia , Nekkab Narimane , Malinga Josephine , Kelly Sherrie L. , Ansah Evelyn , Moehrle Joerg J. , Penny Melissa A.
Published: January 2025

The clinical development of novel vaccines, injectable therapeutics, and oral chemoprevention drugs has the potential to deliver significant advancements in the prevention of Plasmodium falciparum malaria. These innovations could support regions in accelerating malaria control, transforming existing intervention packages by supplementing interventions with imperfect effectiveness or offering an entirely new tool. However, to layer new medical tools as part of an existing programme, malaria researchers must come to an agreement on the gaps that currently limit the effectiveness of medical interventions for moderate to low transmission settings. In this perspective, three crucial gaps that may prevent new therapeutics from being used to their fullest extent are presented. First, do burden reduction outcomes, which are typically monitored in studies of new medical products, sufficiently capture the broader goal of accelerating malaria control? Layering novel malaria products requires monitoring health outcomes that reflect the novel product’s targeted stage of the parasite life cycle, in addition to all-infection and prevalence-based outcomes. Second, what public health outcome does a novel medical prevention tool provide that existing malaria interventions cannot fully deliver? Novel medical tools should be developed not just for an incremental improvement in preventive efficacy over an existing product, but also to meet a gap in protection. Specifically, this means designing products with components that target parts of the parasite life cycle beyond the scope of existing therapeutics, and better addressing populations and settings not well covered by existing tools. Finally, when do the population-level benefits of a multi-tool prevention programme justify the individual-level outcomes from receiving multiple interventions? An individual-level perspective should be key for exploring when and how layering a novel prevention intervention can accelerate efforts towards P. falciparum malaria control.
Understanding the clinical and molecular epidemiological characteristics of carbapenem-resistant Acinetobacter baumannii infections within intensive care units of three teaching hospitals
Authors: Zhang Pengyu , Hao Jingchen , Zhang Yafen , Su Junfeng , Sun Guozhuang , Xie Jun , Hu Jian , Li Guocai
Published: January 2025

Background

Carbapenem-resistant Acinetobacter baumannii (CRAB) is recognized as a common clinical conditional pathogen with bla
OXA−23 gene-mediated multidrug-resistance that is a significant threat to public health safety. Timely and effective infection control measures are needed to prevent their spread.

Methods

We conducted a retrospective study of CRAB patients at three teaching hospitals from 2019 to 2022. We identified bacterial isolates, collected clinical data, and performed antimicrobial susceptibility testing. Genome characteristics of isolates were investigated by whole genome sequencing. Multilocus sequence typing and phylogenetic trees were used to assess the genetic similarity of isolates. Acquired antimicrobial resistance genes and virulence factors carried in the isolated group genome were analyzed by ResFinder, PubMLST and VFDB. Sequence alignment was used to analyze genetic environment around bla
OXA−23. Phylogenetic tree was constructed to analyze the genetic relationship of isolates.

Results

A total of 92 non-repetitive CRAB isolates were collected, with sputum samples accounting for the majority (94.57%, n = 87) of samples. These were distributed into ST2, with ST2 identified to have the highest prevalence of infection, accounting for 99.99% (n = 91) of all isolates. The major resistance genes identified were bla
OXA−23, bla
OXA−66, bla
OXA−51, and bla
ADC. Also, 92 CRAB strains showed high levels of resistance to common clinical antibiotics, but not minocycline. Meanwhile, most of the isolates carried virulence genes such as various ompA, csuA, csuB, csuC, csuD, abaI, abaR, lpxC, lpxA, and bmfRS. Single nucleotide polymorphism (SNP) analyses further indicated that the bacterial genome was progressively polymorphic with time. We analyzed the environment of the bla
OXA−23 gene and found that CRAB accumulated in the context of prominent environmental antibiotic exposure and had longer survival times in the antibiotic environment, resulting in the tendency of bacteria to develop greater antibiotic resistance.

Conclusions

We find that CRAB is prevalent within the ICU and is progressively resistant to antibiotics over time. Enhanced clinical understanding and timely management of CRAB infections will be crucial to minimize or even eliminate the spread of CRAB within the ICU setting.