bluuebunny/crossref_metadata_2025 huggingface dataset:
Effect of Tranexamic Acid on the Reduction of Blood Loss in Craniosynostosis Surgery: A Systematic Review and Meta-analysis
Authors: Alabdulkarim Abdulaziz , Al Qurashi Abdullah A. , Odeh Nour B. , Hashemi Ammar S.A. , Arbili Lana M. , AlSwealh Maab S. , Shakir Malak N. , Banser Sultan M. , Sharaf Lina A. , Alkhonizy Sarah W. , AlBattal Nouf Z.
Published: June 2023

Background:

Although many published studies have investigated the benefits of tranexamic acid (TXA) in reducing perioperative bleeding, no large meta-analysis has been conducted to demonstrate its overall benefit.

Methods:

A systematic review was performed by following the Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines. PubMed, Cochrane, Ovid, Embase, Web of Science, ClinicalTraisl.Gov, and Scopus databases were searched for articles reporting the benefit of TXA in reducing perioperative bleeding in craniosynostosis surgery from establishment through October 2022. The results of our meta-analysis were pooled across the studies using a random-effects model, and presented as a weighted mean difference with 95% confidence interval (95% CI).

Results:

The database search yielded 3207 articles, of which 27 studies with a corresponding number of 9696 operations were eligible. The meta-analysis included only 18 studies, accounting for 1564 operations. Of those operations, 882 patients received systemic TXA, whereas 682 patients received placebo (normal saline), no intervention, low dose TXA, or other control substances. This meta-analysis demonstrated a significant beneficial effect of TXA in reducing perioperative bleeding, particularly when compared with other controlled substances, with a weighted mean difference of −3.97 (95% CI = −5.29 to −2.28).

Conclusions:

To our knowledge, this is the largest meta-analysis in the literature investigating the benefit of TXA in reducing perioperative blood loss in craniosynostosis surgery. We encourage implementing TXA-protocol systems in hospitals after the appraisal of the data presented in this study.
Cutaneous nerve fiber and peripheral Nav1.7 assessment in a large cohort of patients with postherpetic neuralgia
Authors: Fetell Michael , Sendel Manon , Li Thomas , Marinelli Leslie , Vollert Jan , Ruggerio Elizaeth , Houk George , Dockum Marilyn , Albrecht Phillip J. , Rice Frank L. , Baron Ralf
Published: June 2023

The mechanisms of pain in postherpetic neuralgia (PHN) are still unclear, with some studies showing loss of cutaneous sensory nerve fibers that seemed to correlate with pain level. We report results of skin biopsies and correlations with baseline pain scores, mechanical hyperalgesia, and the Neuropathic Pain Symptom Inventory (NPSI) in 294 patients who participated in a clinical trial of TV-45070, a topical semiselective sodium 1.7 channel (Nav1.7) blocker. Intraepidermal nerve fibers and subepidermal Nav1.7 immunolabeled fibers were quantified in skin punch biopsies from the area of maximal PHN pain, as well as from the contralateral, homologous (mirror image) region. Across the entire study population, a 20% reduction in nerve fibers on the PHN-affected side compared with that in the contralateral side was noted; however, the reduction was much higher in older individuals, approaching 40% in those aged 70 years or older. There was a decrease in contralateral fiber counts as well, also noted in prior biopsy studies, the mechanism of which is not fully clear. Nav1.7-positive immunolabeling was present in approximately one-third of subepidermal nerve fibers and did not differ on the PHN-affected vs contralateral sides. Using cluster analysis, 2 groups could be identified, with the first cluster showing higher baseline pain, higher NPSI scores for squeezing and cold-induced pain, higher nerve fiber density, and higher Nav1.7 expression. While Nav1.7 varies from patient to patient, it does not seem to be a key pathophysiological driver of PHN pain. Individual differences in Nav1.7 expression, however, may determine the intensity and sensory aspects of pain.
Mechanisms of education and graded sensorimotor retraining in people with chronic low back pain: a mediation analysis
Authors: Cashin Aidan G. , Lee Hopin , Wand Benedict M. , Bagg Matthew K. , O'Hagan Edel T. , Rizzo Rodrigo R.N. , Stanton Tasha R. , Moseley G. Lorimer , McAuley James H.
Published: June 2023

An improved understanding of the biopsychosocial influences that contribute to and maintain pain has promoted the development of new efficacious treatments for chronic low back pain (CLBP). This study aimed to investigate the mechanisms of a new treatment—education and graded sensorimotor retraining—on pain and disability. We conducted a preplanned causal mediation analysis of a randomized clinical trial which allocated 276 participants with CLBP to 12 weekly clinical sessions of education and graded sensorimotor retraining (n = 138) or a sham and attention control (n = 138). Outcomes were pain intensity and disability, both assessed at 18 weeks. Hypothesized mediators included tactile acuity, motor coordination, back self-perception, beliefs about the consequences of back pain, kinesiophobia, pain self-efficacy, and pain catastrophizing, all assessed at the end of treatment (12 weeks). Four of 7 mechanisms (57%) mediated the intervention effect on pain; the largest mediated effects were for beliefs about back pain consequences (−0.96 [−1.47 to −0.64]), pain catastrophizing (−0.49 [−0.61 to −0.24]), and pain self-efficacy (−0.37 [−0.66 to −0.22]). Five of 7 mechanisms (71%) mediated the intervention effect on disability; the largest mediated effects were for beliefs about back pain consequences (−1.66 [−2.62 to −0.87]), pain catastrophizing (−1.06 [−1.79 to −0.53]), and pain self-efficacy (−0.84 [−1.89 to −0.45]). When all 7 mechanisms were considered simultaneously, the joint mediation effect explained most of the intervention effect for both pain and disability. Optimizing interventions to target beliefs about the consequences of back pain, pain catastrophizing, and pain self-efficacy is likely to lead to improved outcomes for people with CLBP.
Increased Mortality Associated With Disability Among Workers’ Compensation Claimants With Upper Extremity Neuropathy
Authors: Martin Christopher J. , Woods SueAnn , Bertke Stephen , Pinkerton Lynne , Jin Chuanfang
Published: June 2023

Objective

The aim of the study was to evaluate and compare mortality after disabling and nondisabling occupational injuries.

Methods

Vital status was ascertained through 2020 for 2077 individuals with a workers’ compensation claim for upper extremity neuropathy in West Virginia in 1998 or 1999. Standardized mortality ratios compared mortality to the West Virginia general population. Hazard ratios (HRs) obtained from Cox regression models compared mortality among those with and without lost work time or permanent disability.

Results

Overall, the standardized mortality ratio for accidental poisoning deaths was elevated (1.75, 95% confidence interval [CI]: 1.08–2.68). All-cause mortality HRs and cancer HRs were elevated for lost work time (HR = 1.09, 95% CI: 0.93–1.28; HR = 1.50, 95% CI: 1.09–2.08, respectively) and permanent disability (HR = 1.22, 95% CI: 1.04–1.44; HR = 1.78, 95% CI: 1.27–2.48, respectively).

Conclusions

Work-related disability was associated with broad elevations in mortality.
Building the Worksite Wellness Foundation Infrastructure
Authors: Honn Allison , Okut Hayrettin , Lu Kelsey (Liuqiang) , Bowen Cassidy , Chenault Melinda , Ablah Elizabeth
Published: June 2023

Objective

Workplace health programs can be ineffective, and changes are likely to be temporary without first establishing a wellness infrastructure. This study sought to determine whether attending a WorkWell KS Building the Worksite Wellness Foundation (Foundation) workshop enabled worksites to develop this infrastructure.

Methods

Survey data were collected from worksites before attending a workshop and approximately 1 year later. Survey items were designed to assess whether the worksite was implementing best practices.

Results

In total, 212 worksites participated in a workshop and completed both a baseline and follow-up assessments. At follow-up, more worksites reported having a wellness committee (89.6% vs 59.7%, P < 0.001) and having wellness committee duties included in position descriptions (26.2% vs 6.4%, P < 0.001).

Conclusions

This study suggests that Foundation workshops can support worksites’ implementation of best practices to establish worksite wellness infrastructure.
Role of Endoscopic Biopsies and Morphologic Features in Predicting Microsatellite Instability Status in Gastric Cancer
Authors: Silva João R. , Mascarenhas-Lemos Luís , Neto do Nascimento Catarina , Sousa Marques Diogo , Wen Xiaogang , Pinho Lídia , Maio Rui , Pontes Patrícia , Cirnes Luís , Cravo Marília , Carneiro Fátima , Gullo Irene
Published: June 2023

Evaluation of mismatch repair (MMR) protein and microsatellite instability (MSI) status plays a pivotal role in the management of gastric cancer (GC) patients. In this study, we aimed to evaluate the accuracy of gastric endoscopic biopsies (EBs) in predicting MMR/MSI status and to uncover histopathologic features associated with MSI. A multicentric series of 140 GCs was collected retrospectively, in which EB and matched surgical specimens (SSs) were available. Laurén and WHO classifications were applied and detailed morphologic characterization was performed. EB/SS were analyzed by immunohistochemistry (IHC) for MMR status and by multiplex polymerase chain reaction (mPCR) for MSI status. IHC allowed accurate evaluation of MMR status in EB (sensitivity: 97.3%; specificity: 98.0%) and high concordance rates between EB and SS (Cohen κ=94.5%). By contrast, mPCR (Idylla MSI Test) showed lower sensitivity in evaluating MSI status (91.3% vs. 97.3%), while maintaining maximal specificity (100.0%). These results suggest a role of IHC as a screening method for MMR status in EB and the use of mPCR as a confirmatory test. Although Laurén/WHO classifications were not able to discriminate GC cases with MSI, we identified specific histopathologic features that are significantly associated with MMR/MSI status in GC, despite the morphologic heterogeneity of GC cases harboring this molecular phenotype. In SS, these features included the presence of mucinous and/or solid components (P=0.034 and <0.001) and the presence of neutrophil-rich stroma, distant from tumor ulceration/perforation (P<0.001). In EB, both solid areas and extracellular mucin lakes were also discriminating features for the identification of MSI-high cases (P=0.002 and 0.045).
Understanding sports injury: A preliminary study
Authors: Pinheiro João P. , Branquinho Lurdes R. , Pinheiro Joana , Ramos Susana
Published: June 2023

Objective:

The aim of this study was to identify the awareness of residents from Physical Medicine and Rehabilitation, Orthopedics, and General Practice regarding the integration of biomedical and biopsychosocial models in the diagnosis and treatment of sports injuries.

Design:

A prospective, exploratory, preliminary descriptive study conducted with an anonymous online questionnaire.

Results:

Overall, it was attributed greater value to questions related to symptoms and signs. There were no significant differences in the perception of the 8 suggested questions, regarding residents of the 3 specialties mentioned above.

Conclusion:

This study suggests the need to reconsider medical training to be updated and become more centered on biopsychosocial models.
Effect of Truncal-Type Occlusion Based on Multiphase or Single-Phase Computed Tomographic Angiography in Predicting Intracranial Atherosclerotic Stenosis–Related Acute Middle Cerebral Artery Occlusion
Authors: Xu Zhi-Jia , Cao Yue-Zhou , Zhao Lin-Bo , Jia Zhen-Yu , Lu Shan-Shan , Xu Xiao-Quan , Shi Hai-Bin , Liu Sheng
Published: June 2023

Objective

To investigate whether truncal-type occlusion based on multiphase computed tomographic angiography (mpCTA) was more effective for predicting intracranial atherosclerotic stenosis–related occlusion (ICAS-O) than occlusion type based on single-phase computed tomographic angiography (spCTA) in patients with acute ischemic stroke with large-vessel occlusion (AIS-LVO) in the middle cerebral artery (MCA).

Methods

Data were retrospectively collected from 72 patients with AIS-LVO in the MCA between January 2018 and December 2019. The occlusion types included truncal-type and branching-site occlusions. The association between ICAS-O and occlusion type based on the 2 computed tomographic angiography patterns was analyzed, and receiver operating characteristic curves were plotted for assessment. The areas under the curve were compared to determine the difference between the predictive powers of truncal-type occlusion based on mpCTA and spCTA.

Results

Among the 72 patients, 16 were classified as having ICAS-O and 56 as having embolisms. In univariate analysis, truncal-type occlusion was significantly associated with ICAS-O (P < 0.001 for mpCTA and P = 0.001 for spCTA). After multivariable analysis, truncal-type occlusion based on both mpCTA and spCTA remained independently associated with ICAS-O (P = 0.002 for mpCTA and P = 0.029 for spCTA). The areas under the curve were 0.821 for mpCTA and 0.683 for spCTA; this difference was statistically significant (P = 0.024).

Conclusions

In patients with AIS-LVO in the MCA, truncal-type occlusion based on mpCTA enables more accurate detection of ICAS-O than that based on spCTA.
Parkinson's disease – current treatment
Authors: Wang Ryan , Shih Ludy C.
Published: June 2023

Purpose of Review

The purpose is to review the results and impact of recent studies for current and future treatment of both motor and non-motor symptoms in Parkinson's disease (PD).

Recent Findings

New formulations of levodopa further optimize motor fluctuations, allowing for more on-time and less dyskinesia. On demand apomorphine continues to showcase itself as an effective and tolerable tool for treating motor off-periods. Though there are no clear treatment guidelines for PD-related constipation and sleep related disorders, several new agents for these non-motor symptoms show promising preliminary data. Expiratory muscle strength training may represent a useful and cost-effective strategy to alleviate oropharyngeal dysphagia associated with PD. There is evidence to suggest that the use of shorter pulse width and directional deep brain stimulation leads can results in a greater therapeutic window.

Though no interventions currently exist to significantly modify the disease progression of PD, new studies continue to give insight into optimal symptomatic management. Clinicians should be familiar with expanding the repertoire of tools available to treat the diverse range of symptoms and challenges associated with PD.
Atypical forms of Alzheimer's disease: patients not to forget
Authors: Montembeault Maxime , Migliaccio Raffaella
Published: June 2023

Purpose of review

The aim of this paper is to summarize the latest work on neuroimaging in atypical Alzheimer's disease (AD) patients and to emphasize innovative aspects in the clinic and research. The paper will mostly cover language (logopenic variant of primary progressive aphasia; lvPPA), visual (posterior cortical atrophy; PCA), behavioral (bvAD) and dysexecutive (dAD) variants of AD.

Recent findings

MRI and PET can detect and differentiate typical and atypical AD variants, and novel imaging markers like brain iron deposition, white matter hyperintensities (WMH), cortical mean diffusivity, and brain total creatine can also contribute. Together, these approaches have helped to characterize variant-specific distinct imaging profiles. Even within each variant, various subtypes that capture the heterogeneity of cases have been revealed. Finally, in-vivo pathology markers have led to significant advances in the atypical AD neuroimaging field.

Overall, the recent neuroimaging literature on atypical AD variants contribute to increase knowledge of these lesser-known AD variants and are key to generate atypical variant-specific clinical trial endpoints, which are required for inclusion of these patients in clinical trials assessing treatments. In return, studying these patients can inform the neurobiology of various cognitive functions, such as language, executive, memory, and visuospatial abilities.
Sympathetic Organizations: body, mind, and society in Robert Whytt and David Hume
Authors: Demeter Tamás
Published: June 2023

This paper argues that Robert Whytt's concepts of ‘particular’ and ‘general sympathy’ in animate bodies are homologous with a less-discussed concept of sympathy in David Hume. There are at least three different concepts of sympathy in Hume's
Treatise of human nature.
 Hume is rather critical of alleged sympathies between different bodies, but he elaborates a much-discussed theory of sympathy explaining the interpersonal exchange of sentiments. He invokes a third concept to designate the phenomenon of mutual responsiveness between, and coordination for a common end among, the parts of the mind while suggesting that the mind's unity and identity is of the same kind as the unity of organized living bodies. Without deploying this concept explicitly, he speaks a remarkably identical language while discussing social coordination and convention. This third concept is congruent with the physiological sympathies that Whytt finds in animate bodies. According to the unfolding picture, Whytt and Hume provide conceptually highly integrated accounts of living bodies, minds, and societies inspired by an idea of vital matter.
Seroprevalence and risk factor analysis of Brucellosis among Dairy Farmers in Aligarh Region of North India: Creating awareness of a Neglected Disease
Authors: Alam Alveera , Sami Hiba , Hashmi S. Zeeshan Ahmad , Gururaj K , Khan Mohammad Azam , Khan Parvez A , Ahmad Haleema , Fatima Nazish , Khan Haris M
Published: June 2023

INTRODUCTION
Brucellosis, a worldwide spreading zoonotic disease, is caused by the Gram-negative bacteria known as Brucella. Humans acquire infection through direct contact with blood, urine, the placenta of animals, inhalation of dust or aerosol in infected animal farms, and raw milk and meat intake. This study aimed to assess the prevalence of brucellosis in dairy farmers in and around the Aligarh region of North India, to document various clinical signs and symptoms in Brucella-positive individuals, and to create awareness in dairy farmers aware about brucellosis and ways to prevent it.
METHODS
This was an observational study that comprised 125 dairy farmers in and around the Aligarh Region. Serum Samples were taken from this high-risk group after taking informed consent. Also, a pre-designed proforma was used to collect information about their knowledge, attitude, and practices (KAP) about brucellosis and assess the risk factors of the disease. Rose Bengal Test (RBT), Serum Agglutination Test (SAT), and Enzyme-Linked Immunosorbent Assay (ELISA) were done to detect the seroprevalence of brucellosis.
RESULT
Brucella infection was diagnosed in 65 (52%) cases by Indirect ELISA (IgM+ IgG), 41 (32.8%) by RBT, and 4 (3.2%) by SAT. Significant clustering of patients was seen in the 20-55 years age group. The most common symptom in ELISA IgM-positive patients was joint pain prevalent (16.07%), Fatigue (14.28%), Anorexia (12.50%), weight loss (8.92%), Malaise (5.35%), Undulant fever (3.57%), Night sweats (3.57%) and headache (1.78%). The findings of this study indicate that ELISA (IgM + IgG) exhibits great sensitivity as compared to SAT and RBT. KAP was very poor among dairy farmers.
CONCLUSION
In India, Brucella is a frequent but severely underreported illness. ELISA is the most sensitive serological test for diagnosing Brucellosis. No potential vaccine has yet been introduced for humans against Brucellosis. Thus, it is necessary to impart awareness and sensitize the high-risk groups about Brucellosis.
Research Letter: Therapeutic targets for haemorrhoidal disease: proteome-wide Mendelian randomisation and colocalization analyses
Authors: Li Shifang , Gong Meijiao
Published: June 2023

Human haemorrhoidal disease (HEM) is a common anorectal pathology. However, the etiology of HEM, as well as its molecular mechanism, remains largely unclear. In this study, we applied a two-sample bi-direction Mendelian randomisation (MR) analysis to estimate the causal effects of 4907 plasma proteins on HEM outcomes and investigated the mediating impacts of plasma proteins on HEM risk factors to uncover potential HEM treatment targets by integrating GWASs statistics of HEM and plasma protein levels. Following MR analysis, our study identified 5 probable causal proteins associated with HEM. ERLEC1 and ASPN levels were genetically predicted to be positively and inversely associated with HEM risk, respectively, with strong evidence of colocalization (H4>0.9). The findings of an independent cohort corroborate the causal relationship between these two proteins and HEM. Furthermore, gene expression analysis of haemorrhoidal tissue and normal specimens revealed that ERLEC1 but not ASPN were differentially expressed. By analyzing single-cell ERLEC1 expression in human rectum tissues, ERLEC1 was found to be highly expressed in transient-amplifying cells. Interestingly, a genetically greater risk of myxoedema was linked to an elevated risk of HEM. However, there was no evidence that dorsalgia, hernia, diverticular disease, and ankylosing spondylitis were causally associated with HEM. Furthermore, no association was found between myxoedema and the genetically predicted ERLEC1 and ASPN levels. Overall, this study identified some causal associations of circulating proteins and risk factors with HEM by integrating the largest-to-date plasma proteome and GWASs of HEM. The findings could provide further insight into understanding biological mechanisms for HEM.
VULNERABLE CAROTID PLAQUE: ROBUSTNESS AND CLASSIFICATION CAPABILITIES OF MRI RADIOMIC FEATURES
Authors: Meddings Zakaria , Rundo Leonardo , Sadat Umar , Zhao Xihai , Teng Zhongzhao , Graves Martin J.
Published: June 2023

Objectives

To assess how radiomic features may be combined with plaque morphological and compositional features identified by multi-contrast magnetic resonance imaging (MRI) to improve upon conventional risk assessment models in determining culprit lesions.

Methods

Fifty-five patients (mean age: 62.6; 35 males) with bilateral carotid stenosis who experienced transient ischaemic attack (TIA) or stroke were included from the CARE-II multi-centre carotid imaging trial (ClinicalTrials.govIdentifier:NCT02017756). They underwent MRI within 2 weeks of the event. Classification capability in distinguishing culprit lesions was assessed by machine learning. Repeatability and reproducibility of the results were investigated by assessing the robustness of the radiomic features.

Results

Radiomics combined with a relatively conventional plaque morphological and compositional metric-based model provided incremental value over a conventional model alone [area under curve (AUC), 0.819 ± 0.002 vs. 0.689 ± 0.019 respectively, p = 0.014]. The radiomic model alone also provided value over the conventional model [AUC, 0.805 ± 0.003 vs. 0.689 ± 0.019 respectively, p = 0.031]. T2-weighted imaging-based radiomic features had consistently higher robustness and classification capabilities compared with T1-weighted images. Higher-dimensional radiomic features outperformed first-order features. Grey Level Co-occurrence Matrix (GLCM), Grey Level Dependence Matrix (GLDM) and Grey Level Size Zone Matrix (GLSZM) sub-types were particularly useful in identifying textures which could detect vulnerable lesions.

Conclusions

The combination of MRI-based radiomic features and lesion morphological and compositional parameters provided added value to the reference-standard risk assessment for carotid atherosclerosis. This may improve future risk stratification for individuals at risk of major adverse ischemic cerebrovascular events.

Clinical Relevance

The clinical relevance of this work is that it addresses the need for a more comprehensive method of risk assessment for patients at risk of ischemic stroke, beyond conventional stenosis measurement. Radiomics provides a non-invasive means of assessing plaque vulnerability.

Key points

T2-weighted imaging-based radiomic features had consistently higher robustness and classification capabilities compared with T1-weighted images.

Higher dimensional radiomic features had better performance than first-order features in identifying textures which could detect vulnerable carotid lesions.

Radiomic features combined with MRI plaque features may improve atherosclerotic plaque risk stratification.
Adverse childhood experiences and recent negative events activate immune and growth factor pathways, which are associated with first episode major depression and suicidal behaviours
Authors: Almulla Abbas F. , Algon Ali Abbas Abo , Maes Michael
Published: June 2023

Background

Adverse Childhood Experiences (ACEs) and Negative Life Events (NLEs) may activate immune-inflammatory pathways, which play a role in the onset of Major Depressive Disorder and its severe phenotype Major Dysmood disorder (MDMD).

Objectives

To assess if elevated ACEs and NLEs in first episode (FE)-MDMD predict activation of the immune-inflammatory response system (IRS), chemokines, and growth factors that participate in the pathophysiology of MDMD.

Methods

This research assessed the effects of ACEs and NLEs on forty-eight cytokines/chemokines/growth factors, in 71 FE-MDMD patients and forty heathy controls.

Results

ACEs are highly significantly associated with the classical M1 macrophage, T helper (Th)-1, Th-1 polarization, IRS, and neurotoxicity immune profiles, and not with the alternative M2, and Th-2 immune profiles. There are highly significant correlations between ACEs and NLEs and different cytokines/chemokines/growth factors, especially with interleukin (IL)-16, CCL27, stem cell growth factor, and platelet-derived growth factor. Partial Least Squares analysis showed that 62.3% of the variance in the depression phenome (based on severity of depression, anxiety and suicidal behaviors) was explained by the regression on IL-4 (p=0.001, inversely), the sum of ACEs + NLEs (p<0.0001), and a vector extracted from 10 cytokines/chemokines/growth factors (p<0.0001; both positively associated). The latter partially mediated (p<0.0001) the effects of ACE + NLEs on the depression phenome.

Conclusions

Part of the effects of ACEs and NLEs on the depression phenome is mediated via activation of immune and growth factor networks. These pathways have a stronger impact in subjects with lowered activities of the compensatory immune-regulatory system.
Managing the Infodemic: Leveraging Deep Learning to Evaluate the Maturity Level of AI-Based COVID-19 Publications for Knowledge Surveillance and Decision Support
Authors: Awasthi Raghav , Nagori Aditya , Mishra Shreya , Mathur Anya , Mathur Piyush , Nasri Bouchra
Published: June 2023

COVID-19 pandemic has taught us many lessons, including the need to manage the exponential growth of knowledge, fast-paced development or modification of existing AI models, limited opportunities to conduct extensive validation studies, the need to understand bias and mitigate it, and lastly, implementation challenges related to AI in healthcare. While the nature of the dynamic pandemic, resource limitations, and evolving pathogens were key to some of the failures of AI to help manage the disease, the infodemic during the pandemic could be a key opportunity that we could manage better. We share our research related to the use of deep learning methods to quantitatively and qualitatively evaluate AI-based COVID-19 publications which provides a unique approach to identify “mature” publications using a validated model and how that can be leveraged further by focused human-in-loop analysis. The study utilized research articles in English that were human-based, extracted from PubMed spanning the years 2020 to 2022. The findings highlight notable patterns in publication maturity over the years, with consistent and significant contributions from China and the United States. The analysis also emphasizes the prevalence of image datasets and variations in employed AI model types. To manage an infodemic during a pandemic, we provide a specific knowledge surveillance method to identify key scientific publications in near real-time. We hope this will enable data-driven and evidence-based decisions that clinicians, data scientists, researchers, policymakers, and public health officials need to make with time sensitivity while keeping humans in the loop.
Association of Marital/Partner Status with Hospital Readmission Among Young Adults With Acute Myocardial Infarction
Authors: Zhu Cenjing , Dreyer Rachel P , Li Fan , Spatz Erica S , Caraballo César , Mahajan Shiwani , Raparelli Valeria , Leifheit Erica C , Lu Yuan , Krumholz Harlan M , Spertus John A , D’Onofrio Gail , Pilote Louise , Lichtman Judith H
Published: June 2023

Introduction

Despite evidence supporting the benefits of marriage on cardiovascular health, the impact of marital/partner status on the long-term readmission of young acute myocardial infarction (AMI) survivors is less clear. We aimed to examine the association between marital/partner status and 1-year all-cause readmission, and explore sex differences, among young AMI survivors.

Methods

Data were from the VIRGO study (Variation in Recovery: Role of Gender on Outcomes of Young AMI Patients), which enrolled young adults aged 18-55 years with AMI (2008-2012). The primary end point was all-cause readmission within 1 year of hospital discharge, obtained from medical record, patient interviews, and adjudicated by a physician panel. We performed Cox proportional hazards models with sequential adjustment for demographic, socioeconomic, clinical and psychosocial factors. Sex-marital/partner status interaction was also tested.

Results

Of the 2,979 adults with AMI (2002 women [67.2%]; mean age 48 [interquartile range, 44-52] years), unpartnered individuals were more likely to experience all-cause readmissions compared with married/partnered individuals within the first year after hospital discharge (34.6% versus 27.2%, hazard ratio [HR]=1.31; 95% confidence interval [CI], 1.15-1.49). The association attenuated but remained significant after adjustment for demographic and socioeconomic factors (adjusted HR, 1.16; 95%CI, 1.01-1.34), and was not significant after further adjusting for clinical factors and psychosocial factors (adjusted HR, 1.10; 95%CI, 0.94-1.28). Sex-marital/partner status interaction was not significant (p=0.69). Sensitivity analysis using data with multiple imputation, and restricting outcomes to cardiac readmission yielded comparable results.

Conclusions

In a cohort of young adults aged 18-55 years, unpartnered status was associated with 1.3-fold increased risk of all-cause readmission within 1 year of AMI discharge. Further adjustment for demographic, socioeconomic, clinical and psychosocial factors attenuated the association, suggesting that these factors may explain disparities in readmission between married/partnered versus unpartnered young adults. Whereas young women experienced more readmission compared to similar-aged men, the association between marital/partner status and 1-year readmission did not vary by sex.
Fidelity and adherence to a liquefied petroleum gas stove and fuel intervention: the multi-country Household Air Pollution Intervention Network (HAPIN) trial
Authors: Williams Kendra N. , Quinn Ashlinn , North Hayley , Wang Jiantong , Pillarisetti Ajay , Thompson Lisa M. , Díaz-Artiga Anaité , Balakrishnan Kalpana , Thangavel Gurusamy , Rosa Ghislaine , Ndagijimana Florien , Underhill Lindsay J. , Kirby Miles A. , Puzzolo Elisa , Hossen Shakir , Waller Lance A. , Peel Jennifer L. , Rosenthal Joshua P. , Clasen Thomas F. , Harvey Steven A. , Checkley William
Published: June 2023

ABSTRACT

Background

Reducing household air pollution (HAP) to levels associated with health benefits requires nearly exclusive use of clean cooking fuels and abandonment of traditional biomass fuels.

Methods

The Household Air Pollution Intervention Network (HAPIN) trial randomized 3,195 pregnant women in Guatemala, India, Peru, and Rwanda to receive a liquefied petroleum gas (LPG) stove intervention (n=1,590), with controls expected to continue cooking with biomass fuels (n=1,605). We assessed fidelity to intervention implementation and participant adherence to the intervention starting in pregnancy through the infant’s first birthday using fuel delivery and repair records, surveys, observations, and temperature-logging stove use monitors (SUMs).

Results

Fidelity and adherence to the HAPIN intervention were high. Median time required to refill LPG cylinders was 1 day (interquartile range 0-2). Although 26% (n=410) of intervention participants reported running out of LPG at some point, the number of times was low (median: 1 day [Q1, Q3: 1, 2]) and mostly limited to the first four months of the COVID-19 pandemic. Most repairs were completed on the same day as problems were reported. Traditional stove use was observed in only 3% of observation visits, and 89% of these observations were followed up with behavioral reinforcement. According to SUMs data, intervention households used their traditional stove a median of 0.4% of all monitored days, and 81% used the traditional stove <1 day per month. Traditional stove use was slightly higher post-COVID-19 (detected on a median [Q1, Q3] of 0.0% [0.0%, 3.4%] of days) than pre-COVID-19 (0.0% [0.0%, 1.6%] of days). There was no significant difference in intervention adherence pre– and post-birth.

Conclusion

Free stoves and an unlimited supply of LPG fuel delivered to participating homes combined with timely repairs, behavioral messaging, and comprehensive stove use monitoring contributed to high intervention fidelity and near-exclusive LPG use within the HAPIN trial.
A model-based hypothesis framework to define and estimate the diel niche via the ‘Diel.Niche’ R package
Authors: Gerber Brian D. , Devarajan Kadambari , Farris Zach J. , Fidino Mason
Published: June 2023

How animals use the diel period (24-hour light-dark cycle) is of fundamental importance to understand their niche. While ecological and evolutionary literature abound with discussion of diel phenotypes (e.g., diurnal, nocturnal, crepuscular, cathemeral), they lack clear and explicit quantitative definitions. As such, inference can be confounded when evaluating hypotheses of animal diel niche switching or plasticity across studies because researchers may be operating under different definitions of diel phenotypes.

We propose quantitative definitions of diel phenotypes using four alternative hypotheses sets (Maximizing, Traditional, General, and Selection) aimed at achieving different objectives. Each hypothesis set is composed of mutually exclusive hypotheses defined based on the activity probabilities in the three fundamental periods of light availability (twilight, daytime, and nighttime).

We develop a Bayesian modeling framework that compares diel phenotype hypotheses using Bayes factors and estimates model parameters using a multinomial model with linear inequality constraints. Model comparison, parameter estimation, and visualizing results can be done in the Diel.Niche R package. A simplified R Shiny web application is also available.

We provide extensive simulation results to guide researchers on the power to discriminate among hypotheses for a range of sample sizes (10 to 1280). We also work through several examples of using data to make inferences on diel activity, and include online vignettes on how to use the Diel.Niche package. We demonstrate how our modeling framework complements analyses that are commonly used to investigate diel activity, such as circular kernel density estimators.

Our aim is to encourage standardization of the language of diel activity and bridge conceptual frameworks and hypotheses in diel research with data and models. Lastly, we hope more research focuses on the ecological and conservation importance of understanding how animals use diel time.
Quantitative analysis of chest computed tomography of COVID-19 pneumonia using a software widely used in Japan
Authors: Suzuki Minako , Fujii Yoshimi , Nishimura Yurie , Yasui Kazuma , Fujisawa Hidefumi
Published: June 2023

This study aimed to determine the optimal conditions to measure the percentage of area considered as pneumonia (pneumonia volume ratio, PVR) and the computed tomography (CT) score due to coronavirus disease 2019 (COVID-19) using the Ziostation2 image analysis software (Z2; Ziosoft, Tokyo, Japan), which is popular in Japan, and to evaluate its usefulness in assessing the clinical severity. We included 53 patients (41 men and 12 women, mean age: 61.3 years) diagnosed with COVID-19 using the polymerase chain reaction who had undergone chest CT and were hospitalized between January 2020 and January 2021. Based on the COVID-19 infection severity, the patients were classified as mild (n=38) or severe (n=15). For 10 randomly selected samples, the PVR and CT scores by Z2 under different conditions and the visual simple PVR and CT scores were compared, and the conditions with the highest statistical agreement were determined. The usefulness of the clinical severity assessment based on PVR and CT scores using Z2 under the determined conditions was statistically evaluated. The best agreement with the visual measurement was achieved by the Z2 measurement condition of ≥ –600 HU. The areas under the receiver operating characteristic curves, the Youden index, and the sensitivity, specificity, and p-values of PVR and CT scores by Z2 were as follows: PVR; 0.881, 18.69, 66.7, 94.7, and <0.001, CT score; 0.77, 7.5, 40, 74, and 0.002, respectively. We determined the optimal condition for assessing the PVR of COVID-19 pneumonia using Z2 and demonstrated that the AUC of PVR was higher than that of the CT score in the assessment of clinical severity. The introduction of new technologies is time-consuming and expensive; our method has high clinical utility and can be promptly used in any facility where Z2 has been introduced.
The influence of the way of regression on the results obtained by the receptorial responsiveness method (RRM), a procedure to estimate a change in the concentration of a pharmacological agonist near the receptor
Authors: Ovari Ignac , Viczjan Gabor , Erdei Tamas , Takacs Barbara , Szekeres Reka , Lampe Nora , Zsuga Judit , Szucs Miklos , Szilvassy Zoltan , Juhasz Bela , Gesztelyi Rudolf
Published: June 2023

The receptorial responsiveness method (RRM) enables the estimation of a change in the concentration of a degradable agonist, near its receptor, by fitting its model to (at least) two concentration-effect (E/c) curves of a stable agonist of this receptor. One curve should be generated before this change in concentration, while the other one after this change, in the same (or in identical) biological system(s). It follows that RRM yields a surrogate parameter (“cx”), the concentration of the stable agonist that is equieffective with the change in the concentration of the degradable agonist. However, the curve fitting can be implemented several ways, which can affect accuracy, precision and convenience of use.

This study utilized data of previousex vivoinvestigations. Known concentrations of stable agonists were estimated with RRM by performing individual (local) or global fitting (with one or two model(s)), combined with the use of a logarithmic (logcx) or non-logarithmic parameter (cx), and with ordinary least-squares or robust regression.

We found that the individual regression, the most complicated option, was the most accurate, followed closely by the moderately complicated two-model global regression and then by the easy-to-perform one-model global regression. The two-model global fitting was the most precise, followed by the individual fitting (closely) and by the one-model global fitting (from afar). The use of cxand robust regression did not, whereas pairwise fitting (i.e. fitting only two E/c curves at once) did improve the quality of estimation. Thus, the two-model global fitting, performed pairwise, is recommended for RRM, but the individual fitting is a good alternative.
The European Reality Regarding ICU Follow–Up Clinics: A Systematic Review
Authors: Charalampopoulos Marios , Triantafyllaki Panagiota , Sampani Christina-Athanasia , Triantafyllou Christos , Papageorgiou Dimitrios
Published: June 2023

Introduction

The ICU Follow up Clinics support and treat adult patients in the community in order to cover the needs that occur after their discharge from the ICU at the hospital.

Aim

To study the effectiveness and the way of the ICU Follow up Clinic operation management for adult patients after their discharge from the hospital.

Methods

A search was performed on the Greek and international literature, as well as at the online Databases PubMed, Cochrane, EMBASE and Google Scholar. Exclusion and integration criteria were set for the studies found, and a flow chart was created for the studies included.

Results

Through the search, 30 articles were found matching the subject under study, and after further evaluation, seven articles were included. The majority of the articles highlight the importance of these services at the patients’ follow-up after discharge. More specifically, through these services, the mortality rate, the risk of recurrence, and the readmission risk are decreased as well as the patient’s mental health is improved.

Conclusions

The main aim of these Services is the follow-up of the adult patients after discharge, the consultation, and the application of therapeutic protocols in order to face the primary pathological cause, as well as matters that occurred as a result of the hospitalization. At the same time, they can help to detect the needs of the patients that occurred after the discharge so that finally, improve the care given and the patient’s outcome.
HPC-based genome variant calling workflow (HPC-GVCW)
Authors: Zhou Yong , Kathiresan Nagarajan , Yu Zhichao , Rivera Luis F. , Thimma Manjula , Manickam Keerthana , Chebotarov Dmytro , Mauleon Ramil , Chougule Kapeel , Wei Sharon , Gao Tingting , Green Carl D. , Zuccolo Andrea , Ware Doreen , Zhang Jianwei , McNally Kenneth L. , Wing Rod A.
Published: June 2023

A high-performance computing genome variant calling workflow was designed to run GATK on HPC platforms. This workflow efficiently called an average of 27.3 M, 32.6 M, 168.9 M, and 16.2 M SNPs for rice, sorghum, maize, and soybean, respectively, on the most recently released high-quality reference sequences. Analysis of a rice pan-genome reference panel revealed 2.1 M novel SNPs that have yet to be publicly released.
PepFlow: direct conformational sampling from peptide energy landscapes through hypernetwork-conditioned diffusion
Authors: Abdin Osama , Kim Philip M.
Published: June 2023

Deep learning approaches have spurred substantial advances in the single-state prediction of biomolecular structures. The function of biomolecules is, however, dependent on the range of conformations they can assume. This is especially true for peptides, a highly flexible class of molecules that are involved in numerous biological processes and are of high interest as therapeutics. Here, we introduce PepFlow, a generalized Boltzmann generator that enables direct all-atom sampling from the allowable conformational space of input peptides. We train the model in a diffusion framework and subsequently use an equivalent flow to perform conformational sampling. To overcome the prohibitive cost of generalized all-atom modelling, we modularize the generation process and integrate a hyper-network to predict sequence-specific network parameters. PepFlow accurately predicts peptide structures and effectively recapitulates experimental peptide ensembles at a fraction of the running time of traditional approaches. PepFlow can additionally be used to sample conformations that satisfy constraints such as macrocyclization.
Isolation of stage-specific spermatogenic cells by dynamic histone incorporation and removal in spermatogenesis
Authors: Fujiwara Yasuhiro , Hada Masashi , Fukuda Yuko , Koga Chizuko , Inoue Erina , Okada Yuki
Published: June 2023

Due to the lack of anin vitrospermatogenesis system, studies on mammalian spermatogenesis require the isolation of specific germ cell populations for further analyses. BSA gradient and elutriation have been used for several decades to purify testicular germ cells; more recently, fluorescence-activated cell sorting (FACS) has become popular. Although each method has its advantages and disadvantages and is used depending on the purpose of the experiment, reliance on FACS is expected to be more prevalent because fewer cells can be managed. However, the currently used FACS method for testicular germ cells relies on karyotypic differences via DNA staining. Thus, it remains challenging to separate post-meiotic haploid cells (spermatids) according to their differentiation stage despite significant variations in morphology and chromatin state. In this study, we developed a method for finely separating testicular germ cells using VC mice carrying fluorescently tagged histones. This method enables the separation of spermatogonia, spermatocytes, and spermatids based on the intensity of histone fluorescence and cell size. Combined with a DNA staining dye, this method separates spermatids after elongation according to each spermiogenic stage. Although the necessity for a specific transgenic mouse line is less versatile, this method is expected to be helpful for the isolation of testicular germ cell populations because it is highly reproducible and independent of complex cell sorter settings and staining conditions.
Saliva as an alternative sample type for detection of pneumococcal carriage in young children
Authors: Wyllie Anne L. , Rots Nynke Y. , Wijmenga-Monsuur Alienke J. , van Houten Marlies A. , Sanders Elisabeth A.M. , Trzciński Krzysztof
Published: June 2023

In children, the gold standard for the detection of pneumococcal carriage is conventional culture of a nasopharyngeal swab. Saliva, however, has a history as one of the most sensitive methods for surveillances on pneumococcal colonisation and has recently been shown to improve carriage detection in older age groups. Here, we compared the sensitivity of nasopharyngeal and saliva samples from PCV7-vaccinated 24-month-old children for pneumococcal carriage detection using conventional and molecular diagnostic methods.

Nasopharyngeal and saliva samples were collected from 288 24-month-old children during the autumn/winter, 2012/2013. All samples were first processed by conventional diagnostic techniques. Next, DNA extracted from all plate growth was tested by qPCR for the presence of pneumococcal genespiaBandlytAand a subset of serotypes.

By culture, 164/288 (57%) nasopharyngeal swabs tested positive for pneumococcus, but detection was not possible from saliva due to abundant polymicrobial growth on culture-plates. Molecular methods increased the number of children pneumococci-positive to 172/288 (60%) when testing culture-enriched saliva and to 212/288 (73%) when testing nasopharyngeal samples. Altogether, by molecular methods 239/288 (83%) infants were positive, with qPCR-based carriage detection of culture-enriched nasopharyngeal swabs significantly detecting more carriers compared to either conventional culture (p<0.001) or qPCR-detection of saliva (p<0.001). However, 27/240 (11%) carriers were positive only in saliva, significantly contributing to the overall number of carriers detected (p<0.01).

While testing nasopharyngeal swabs with qPCR proved most sensitive for pneumococcal detection in infants, saliva sampling could be considered as complementary to provide additional information on carriage and serotypes which may not be detected in the nasopharynx and may be particularly useful in longitudinal studies, requiring repeated sampling events.