bluuebunny/crossref_metadata_2025 huggingface dataset:
Mental health disorders before, during and after the COVID-19 pandemic: a nationwide study
Authors: Grønkjær Clara S , Christensen Rune H B , Kondziella Daniel , Benros Michael E
Published: November 2024

The COVID-19 pandemic and lockdowns prompted a major concern for mental health effects. Comprehensive nationwide studies are lacking on the indirect effect of the COVID-19 pandemic on the population’s mental health. We aimed to determine whether the COVID-19 pandemic and lockdowns affected mental health service usage, suicide attempts, and suicides.

This comprehensive nationwide register-linked study followed all individuals in Denmark from 1990. The main outcomes were rates of psychiatric admissions, use of psychotropic medication, suicide attempts, suicides, patients in community-based private psychiatry or psychology practices, and referrals to psychiatric hospitals. The impact of the pandemic (March 11, 2020–June 30, 2023) and lockdowns was assessed with log-normal models adjusted for pre-pandemic trends (January 1, 2017–March 10, 2020). We reported Rate Ratios (RR) of the observed and counterfactual rates.

We identified the 5 807 714 (50.3% females) individuals living in Denmark on March 1, 2020. The rates of psychiatric admissions (RR: 0.95, 95% Confidence Interval (CI): 0.91 to 0.99, p-value: 0.017) and suicide attempts (RR: 0.85, 95% CI: 0.76 to 0.95, p-value: 0.007) were lower during the pandemic compared to the pre-pandemic trend. The rates of suicides (RR: 0.89, 95% CI: 0.75-1.05, p-value: 0.173), patients in private practices (RR: 1.00, 95% CI: 0.96-1.04, p-value: 0.986), and referrals (RR: 1.06, 95% CI: 0.95-1.18, p-value: 0.307) were not significantly different during the pandemic compared to the pre-pandemic trend. During the first lockdown, rates were lower for psychiatric admissions (RR: 0.85, 95% CI: 0.80 to 0.90, p-value <0.001), suicide attempts (RR: 0.80, 95% CI: 0.69 to 0.94, p-value: 0.007), suicides (RR: 0.67, 95% CI: 0.52 to 0.86, p-value: 0.002), patients in private practices (RR: 0.88, 95% CI: 0.82 to 0.93, p-value <0.001), and referrals (RR: 0.69, 95% CI: 0.60 to 0.81, p-value < 0.001) compared to the pre-pandemic trend. However, during the pandemic, the rate of psychotropic medication users increased by 6% compared to the pre-pandemic trend (RR: 1.06, 95% CI: 1.05 to 1.06, p-value < 0.001).

The COVID-19 pandemic and lockdowns did not severely influence pre-pandemic trends of the mental health burden in Denmark’s population on a nationwide level.
Functional and connectivity correlates associated with Parkinson’s disease psychosis: a systematic review
Authors: Pisani Sara , Gunasekera Brandon , Lu Yining , Vignando Miriam , Ffytche Dominic , Aarsland Dag , Chaudhuri K R , Ballard Clive , Lee Jee-Young , Kim Yu Kyeong , Velayudhan Latha , Bhattacharyya Sagnik
Published: November 2024

Neural underpinnings of Parkinson’s disease psychosis remain unclear to this day with relatively few studies and reviews available. Using a systematic review approach, here, we aimed to qualitatively synthesize evidence from studies investigating Parkinson’s psychosis-specific alterations in brain structure, function or chemistry using different neuroimaging modalities. PubMed, Web of Science and Embase databases were searched for functional MRI (task-based and resting state), diffusion tensor imaging, PET and single-photon emission computed tomography studies comparing Parkinson’s disease psychosis patients with Parkinson’s patients without psychosis. We report findings from 29 studies (514 Parkinson’s psychosis patients, mean age ± SD = 67.92 ± 4.37 years; 51.36% males; 853 Parkinson’s patients, mean age ± SD = 66.75 ± 4.19 years; 55.81% males). Qualitative synthesis revealed widespread patterns of altered brain function across task-based and resting-state functional MRI studies in Parkinson’s psychosis patients compared with Parkinson’s patients without psychosis. Similarly, white matter abnormalities were reported in parietal, temporal and occipital regions. Hypo-metabolism and reduced dopamine transporter binding were also reported whole brain and in sub-cortical areas. This suggests extensive alterations affecting regions involved in high-order visual processing and attentional networks.
Spinal cord evaluation in multiple sclerosis: clinical and radiological associations, present and future
Authors: Keegan B Mark , Absinta Martina , Cohen-Adad Julien , Flanagan Eoin P , Henry Roland G , Klawiter Eric C , Kolind Shannon , Krieger Stephen , Laule Cornelia , Lincoln John A , Messina Steven , Oh Jiwon , Papinutto Nico , Smith Seth Aaron , Traboulsee Anthony
Published: November 2024

Spinal cord disease is important in most people with multiple sclerosis, but assessment remains less emphasized in patient care, basic and clinical research and therapeutic trials. The North American Imaging in Multiple Sclerosis Spinal Cord Interest Group was formed to determine and present the contemporary landscape of multiple sclerosis spinal cord evaluation, further existing and advanced spinal cord imaging techniques, and foster collaborative work. Important themes arose: (i) multiple sclerosis spinal cord lesions (differential diagnosis, association with clinical course); (ii) spinal cord radiological–pathological associations; (iii) ‘critical’ spinal cord lesions; (iv) multiple sclerosis topographical model; (v) spinal cord atrophy; and (vi) automated and special imaging techniques. Distinguishing multiple sclerosis from other myelopathic aetiology is increasingly refined by imaging and serological studies. Post-mortem spinal cord findings and MRI pathological correlative studies demonstrate MRI’s high sensitivity in detecting microstructural demyelination and axonal loss. Spinal leptomeninges include immune inflammatory infiltrates, some in B-cell lymphoid-like structures. ‘Critical’ demyelinating lesions along spinal cord corticospinal tracts are anatomically consistent with and may be disproportionately associated with motor progression. Multiple sclerosis topographical model implicates the spinal cord as an area where threshold impairment associates with multiple sclerosis disability. Progressive spinal cord atrophy and ‘silent’ multiple sclerosis progression may be emerging as an important multiple sclerosis prognostic biomarker. Manual atrophy assessment is complicated by rater bias, while automation (e.g. Spinal Cord Toolbox), and artificial intelligence may reduce this. Collaborative research by the North American Imaging in Multiple Sclerosis and similar groups with experts combining distinct strengths is key to advancing assessment and treatment of people with multiple sclerosis spinal cord disease.
Glial fibrillary acidic protein in Alzheimer’s disease: a narrative review
Authors: Leipp Florine , Vialaret Jérôme , Mohaupt Pablo , Coppens Salomé , Jaffuel Aurore , Niehoff Ann-Christin , Lehmann Sylvain , Hirtz Christophe
Published: November 2024

Astrocytes are fundamental in neural functioning and homeostasis in the central nervous system. These cells respond to injuries and pathological conditions through astrogliosis, a reactive process associated with neurodegenerative diseases such as Alzheimer’s disease. This process is thought to begin in the early stages of these conditions. Glial fibrillary acidic protein (GFAP), a type III intermediate filament protein predominantly expressed in astrocytes, has emerged as a key biomarker for monitoring this response. During astrogliosis, GFAP is released into biofluids, making it a candidate for non-invasive diagnosis and tracking of neurodegenerative diseases. Growing evidence positions GFAP as a biomarker for Alzheimer’s disease with specificity and disease-correlation characteristics comparable to established clinical markers, such as Aβ peptides and phosphorylated tau protein. To improve diagnostic accuracy, particularly in the presence of confounders and comorbidities, incorporating a panel of biomarkers may be advantageous. This review will explore the potential of GFAP within such a panel, examining its role in early diagnosis, disease progression monitoring and its integration into clinical practice for Alzheimer’s disease management.
Feature attributions for water–solubility predictions obtained via artificial intelligence methods and chemists
Authors: Sadakane Teruhisa , Nakata Koki , Suda Kayo , Yokogawa Daisuke
Published: November 2024

The field of explainable artificial intelligence has garnered significant research interest. In particular, “feature attribution” in the field of chemistry has been focused upon. However, studies on comparisons of the relationship between artificial intelligence–based and human-based feature attributions when predicting the same outcome are scarce. Thus, this study aimed to investigate this relationship by comparing machine learning–based feature attributions (graph neural networks and integrated gradients) with those of chemists (Hansch–Fujita method) considering the case of predicting water–solubility. The artificial intelligence–based attributions were found to be similar to those of chemists despite their distinct origins.
Enhancing perceptual, attentional, and working memory demands through variable practice schedules: insights from high-density EEG multi-scale analyses
Authors: Cretton Alexandre , Schipper Kate , Hassan Mahmoud , Ruggeri Paolo , Barral Jérôme
Published: November 2024

Contextual interference (CI) enhances learning by practicing motor tasks in a random order rather than a blocked order. One hypothesis suggests that the benefits arise from enhanced early perceptual/attentional processes, while another posits that better learning is due to highly activated mnemonic processes. We used high-density electroencephalography in a multi-scale analysis approach, including topographic analyses, source estimations, and functional connectivity, to examine the intertwined dynamics of attentional and mnemonic processes within short time windows. We recorded scalp activity from 35 participants as they performed an aiming task at three different distances, under both random and blocked conditions using a crossover design. Our results showed that topographies associated with processes related to perception/attention (N1, P3a) and working memory (P3b) were more pronounced in the random condition. Source estimation analyses supported these findings, revealing greater involvement of the perceptual ventral pathway, anterior cingulate and parietal cortices, along with increased functional connectivity in ventral alpha and frontoparietal theta band networks during random practice. Our results suggest that CI is driven, in the random compared to the blocked condition, by enhanced specific processes such as perceptual, attentional, and working memory processes, as well as large-scale functional networks sustaining more general attentional and executive processes.
Changes in resting-state functional connectivity of large-scale brain networks in bulimia nervosa: evidence from causal analysis
Authors: Wang Jiani , Wang Xinghao , Wang Yiling , Li Weihua , Li Zhanjiang , Tang Lirong , Huang Xinyu , Grzegorzek Marcin , Chen Qian , Wang Zhenchang , Zhang Peng
Published: November 2024

Bulimia nervosa (BN) has been observationally linked to the functional connectivity (FC) of large-scale brain networks, but the biological mechanisms remain unclear. This study used two-sample Mendelian randomization (MR) with genetic variations as instrumental variables (IVs) to explore potential causal relationships between FC and BN. Summary data from genome-wide association studies (GWAS) involving 2,564 individuals were analyzed to identify genetically predicted BN. Functional magnetic resonance imaging parameters and materials were sourced from the UK Biobank. The variables underwent independent component analysis processing by the database to generate the final GWAS dataset. Various methods, including MR Pleiotropy RESidual Sum and Outlier, MR Egger, and weighted median, were employed to detect heterogeneity and pleiotropy, with inverse variance weighting serving as the principal estimation method (P < 0.05). The FC imaging-derived phenotypes revealed that BN exerted a causal influence on the FC between large-scale networks, including the visual network, default mode network (DMN), frontoparietal network, somatosensory network (SSN), and ventral attention network. Additionally, BN had a causal impact on the within-network FC of both the DMN and SSN. The study provides evidence that BN leads to further changes in FC patterns within and between large-scale brain networks.
Causal relationship between cortical structural changes and onset of anxiety disorder: evidence from Mendelian randomization
Authors: Teng Fei , Wang Mengqi , Lu Zhangyu , Zhang Chunyu , Xiao Linglong , Chen ZhaoMing , Huang Mengshuang , Xie Linglin , Chen Zheyu , Wang Wei
Published: November 2024

Previous studies have reported a correlation between anxiety disorders and changes in brain structure, yet the specific alterations in brain region volumes remain unclear. This study aimed to infer the causal relationship between anxiety disorders and changes in brain structure volume through Mendelian Randomization analysis. We selected 63 cortical structure volumes from the GWAS database as exposure data and anxiety disorder data from the FinnGen and UK Biobank databases as outcomes. We found a significant correlation between atrophy in the Left precentral volume area (Odds Ratio [OR] = 0.935, 95% Confidence intervals [CI]: 0.891–0.981, P value, P = 0.007) and an increased risk of anxiety disorders. Additionally, changes identified in specific brain regions, such as atrophy in the Right rostral anterior cingulate area (OR = 0.993, 95% CI: 0.987–0.999, P = 0.025) and increased volume in the Left superior parietal area (OR = 1.001, 95% CI: 1.000–1.001, P = 0.028), may correlate with an increased risk of anxiety disorders. Furthermore, both phenotypes demonstrated directional consistency in their respective and overall meta-analyzed OR values pre- and post-merger, enhancing the reliability of the results. This study elucidates the causal relationship between anxiety disorders and specific brain structures, providing new insights for further research into psychiatric disorders.
Highly concentrated solution of lithium chloride in organic solvents with heteroditopic receptors
Authors: Kondo Shin-ichi , Mimuro Tsubasa , Yoshida Akihiro , Sugawara Reo , Hirasawa Manabu
Published: November 2024

The solubilization and selective extraction of lithium salts, in particular lithium chloride, in organic solvents have recently attracted attention due to the application in industry. A heteroditopic receptor 1b, which has ether oxygens and 2 urea moieties as cation and anion recognition sites, respectively, cooperatively associates with LiCl in organic solvents. The selective solid–liquid extraction of LiCl and LiBr was observed by 1H NMR in CDCl3 and MeCN-d3. It is possible to prepare highly concentrated solutions of 1b and LiCl in MeCN up to a concentration of 9.6 M, and these solutions exhibit properties similar to those of ionic liquids.
Global Trends in CD4 Count Measurement and Distribution at First Antiretroviral Treatment Initiation
Authors: de Waal Reneé , Wools-Kaloustian Kara , Brazier Ellen , Althoff Keri N , Jaquet Antoine , Duda Stephany N , Kumarasamy Nagalingeswaran , Savory Theodora , Byakwaga Helen , Murenzi Gad , Justice Amy , Ekouevi Didier K , Cesar Carina , Pasayan Mark K U , Thawani Agness , Kasozi Charles , Babakazo Pelagie , Karris Maile , Messou Eugene , Cortes Claudia P , Kunzekwenyika Cordelia , Choi Jun Yong , Owarwo Noela C , Niyongabo Annabelle , Marconi Vincent C , Ezechi Oliver , Castilho Jessica L , Petoumenos Kathy , Johnson Leigh F , Ford Nathan , Kassanjee Reshma
Published: November 2024

Background

While people with human immunodeficiency virus (PWH) start antiretroviral treatment (ART) regardless of CD4 count, CD4 measurement remains crucial for detecting advanced human immunodeficiency virus (HIV) disease and evaluating ART programs. We explored CD4 measurement (proportion of PWH with a CD4 result available) and prevalence of CD4 <200 cells/µL (hereafter “CD4 <200”) at ART initiation within the International epidemiology Databases to Evaluate AIDS (IeDEA) global collaboration.

Methods

We included PWH at participating ART programs who first initiated ART at age 15–80 years during 2005–2019. We described proportions of PWH with a CD4 result (measured within 6 months before to 2 weeks after ART initiation) and, among those with a CD4 result, with CD4 <200, by year of ART initiation and region.

Results

We included 1 355 104 PWH from 42 countries in 7 regions; 63% were female. The median (interquartile range) age at ART initiation was 37 (3144) years in males and 32 (26–39) years in females. CD4 measurement initially increased, or remained stable over time until around 2013, but then declined to low levels in some regions (Southern Africa, except South Africa: from 54% to 13%; East Africa: 85% to 31%; Central Africa: 72% to 20%; West Africa: 91% to 53%; and Latin America: 87% to 56%). Prevalence of CD4 <200 declined over time in all regions, but plateaued after 2015 at ≥30%.

Conclusions

CD4 measurement has declined sharply in recent years, especially in sub-Saharan Africa. Among those with a CD4 measurement, the prevalence of CD4 <200 remains concerningly high. Scaling up CD4 testing and securing adequate funding are urgent priorities.
Epigenetic biomarker for preeclampsia-associated preterm birth and potential preventative medicine
Authors: Nilsson Eric E , Winchester Paul , Proctor Cathy , Beck Daniel , Skinner Michael K
Published: November 2024

Preterm birth (PTB) has dramatically increased within the population (i.e. >10%) and preeclampsia is a significant sub-category of PTB. Currently, there are no practical clinical parameters or biomarkers which predict preeclampsia induced PTB. The current study investigates the potential use of epigenetic (DNA methylation) alterations as a maternal preeclampsia biomarker. Non-preeclampsia term births were compared to preeclampsia PTBs to identify DNA methylation differences (i.e. potential epigenetic biomarker). Maternal buccal cell cheek swabs were used as a marker cell for systemic epigenetic alterations in the individuals, which are primarily due to environmentally induced early life or previous generations impacts, and minimally impacted or associated with the disease etiology or gestation variables. A total of 389 differential DNA methylation regions (DMRs) were identified and associated with the presence of preeclampsia. The DMRs were genome-wide and were predominantly low CpG density (<2 CpG/100 bp). In comparison with a previous PTB buccal cell epigenetic biomarker there was a 15% (60 DMR) overlap, indicating that the majority of the DMRs are unique for preeclampsia. Few previously identified preeclampsia genes have been identified, however, the DMRs had gene associations in the P13 K-Akt signaling pathway and metabolic gene family, such as phospholipid signaling pathway. Preliminary validation of the DMR use as a potential maternal biomarker used a cross-validation analysis on the samples and provided 78% accuracy. Although prospective expanded clinical trials in first trimester pregnancies and clinical comparisons are required, the current study provides the potential proof of concept a preeclampsia epigenetic biomarker may exist. The availability of a preeclampsia PTB maternal susceptibility biomarker may facilitate clinical management and allow preventative medicine approaches to identify and treat the preeclampsia condition prior to its occurrence.
Short-term Frailty Index Fluctuations in Older Adults: Noise or Signal?
Authors: Stolz Erwin , Schultz Anna , Hoogendijk Emiel O , Theou Olga , Rockwood Kenneth
Published: November 2024

Background

Reversible short-term fluctuations in the frailty index (FI) are often thought of as representing only noise or error. Here, we assess (i) the size and source of short-term FI fluctuations, (ii) variation across sociodemographic characteristics, (iii) association with chronic diseases, (iv) correlation with age, frailty level, frailty change, and mortality, and (v) whether fluctuations reflect discrete health transitions.

Methods

Nationwide, biweekly longitudinal data from 426 community-dwelling older adults (70+) were collected in the FRequent health Assessment In Later life (FRAIL70+) study using a measurement burst design (5 122 repeated observations, median of 13 repeated observations per person). We calculated the intraindividual standard deviation of the FI and used location-scale mixed regression models.

Results

Mean intraindividual standard deviation was 0.04 (standard deviation = .03). Fluctuations were driven foremost by cognitive problems, somatic symptoms, and limitations in instrumental and mobility-related activities of daily living. Short-term fluctuations correlated with higher FI levels (r = 0.62), 1-year FI change (r = 0.26), and older age (+3% per year). Older adults who took to bed due to a health problem (+50%), those who had an overnight hospital stay (+50%), and those who died during follow-up (+44%) exhibited more FI fluctuations.

Conclusions

Short-term FI fluctuations were neither small nor random. Instead, as older adults become frailer, their measured health also becomes more unstable; hence, short-term fluctuations in overall health status can be seen as a concomitant phenomenon of the aging process. Researchers and clinicians should be aware of the existence of reversible fluctuations in the FI over weeks and months and its consequences for frailty monitoring.
Isomorphism Between Twisted q-Yangians and Affine ι Quantum Groups: Type AI
Authors: Lu Kang
Published: November 2024

By employing Gauss decomposition, we establish a direct and explicit isomorphism between the twisted $q$-Yangians (in R-matrix presentation) and affine $\imath $quantum groups (in current presentation) associated to symmetric pair of type AI introduced by Molev–Ragoucy–Sorba and Lu–Wang, respectively. As a corollary, we obtain a PBW-type basis for affine $\imath $quantum groups of type AI.
Characterization of blaNDM in two Escherichia coli ST1193 clinical isolates in the Gulf region
Authors: Tsui Clement Kin-Ming , Ben Abid Fatma , McElheny Christi Lee , Hamed Manal M , Perez-Lopez Andres , Omrani Ali S , Doi Yohei
Published: November 2024

Introduction

Escherichia coli ST1193 is an emerging high-risk clone associated with the production of plasmid-mediated CTX-type extended-spectrum β-lactamases. However, this clone has seldom been found to contain plasmids carrying carbapenemase genes. We report two epidemiologically unlinked multidrug-resistant (MDR) clinical isolates of E. coli ST1193 with plasmids harbouring NDM-type carbapenemase genes from the Gulf region.

Methods

The isolates were identified by MALDI-TOF MS and antibiotic susceptibility testing was performed using the VITEK 2/Phoenix system. A conjugation experiment was performed to assess the transferability of the resistance plasmids. Genomic DNA of both isolates was subject to Illumina sequencing; one isolate was also sequenced using Oxford Nanopore technology. Bioinformatics analyses were performed to detect antimicrobial resistance genes, and to annotate the genetic context of the NDM genes.

Results and Conclusions

Both isolates were resistant to carbapenems using phenotypic tests. Conjugation experiment confirmed that NDM-5-encoding plasmids of both strains could be transferred to the recipient cells. The completed NDM-5-encoding plasmid of E. coli isolate FQ71 was highly similar to several plasmids from ST410 isolates in the NCBI database. Genomic analysis revealed the presence of transposase genes and transposons in the flanking regions of the NDM genes in the plasmids. Since carbapenems constitute first-line agents for the treatment of serious infections caused by ESBL producers, E. coli ST1193 isolates co-producing ESBL and NDM-type carbapenemases represent a serious challenge for antimicrobial stewardship and infection control programmes.
Targetable molecular algorithm and training platform development for the treatment of non-small cell lung cancer
Authors: Bhuvaneshwar Krithika , Kim Chul , Parikh Kaushal , Reuss Joshua E , Bencheqroun Camelia , Agraharam Anvitha G , Munir Ayesha , Alaoui Adil , Gusev Yuriy , Veytsman Irina G
Published: November 2024

Background and Introduction

Over the last decade, treatment of patients with advanced non-small cell lung cancer (NSCLC) has become dependent on tissue and/or blood biomarkers to guide treatment decisions. Timely access to comprehensive biomarker and tumor signature information is crucial for diagnostic testing. With the rapid development and implementation of complex biomarker testing, comprehensive molecular profiling with in-depth analysis of DNA, RNA, and proteins can be easily performed. Initial data from the MedStar Health system showed considerable disparities in the use of next generation sequencing (NGS) between hospitals, and there is a clear need to improve education and understanding regarding which cases are appropriate for NGS, as well as the use of protocols to make those decisions in an expeditious manner.

Materials and Methods

Clinical pathways are systems-based tools that aim to create greater transparency around care decision making, therapeutic selection, and care delivery. They enhance quality and efficiency by reducing non-value-added intra-provider variability in care. We aimed to create a comprehensive clinical pathway system, the Targetable Molecular Algorithm (TMA), to increase the understanding and use of NGS in NSCLC by physicians in training, oncology nurse navigators, nurse practitioners, and general oncologists.

Discussion

We provide an overview of the implementation of the platform along with navigation guide. A realistic case study—a typical clinical workflow for a patient requiring NGS testing with an EGFR mutation—is also reviewed, demonstrating how the TMA platform can be applied. Additionally, we highlight the importance of the resource, and discuss its strengths, weaknesses, and potential future applications.

Results and Conclusion

This new and innovative pathway system will make decision-making easier for clinicians trying to understand the appropriate tests and treatment algorithms for their patients. Our aim is to increase the appropriate and timely use of NGS among health-system providers with the hope that this system will empower physicians to provide better care by providing a quick, simple, user-friendly tool for comprehensive patient care.
A landmark federal interagency collaboration to promote data science in health care: Million Veteran Program-Computational Health Analytics for Medical Precision to Improve Outcomes Now
Authors: Justice Amy C , McMahon Benjamin , Madduri Ravi , Crivelli Silvia , Damrauer Scott , Cho Kelly , Ramoni Rachel , Muralidhar Sumitra
Published: November 2024

Objectives

In 2016, the Department of Veterans Affairs (VA) and the Department of Energy (DOE) established an Interagency Agreement (IAA), the Million Veteran Program-Computational Health Analytics for Medical Precision to Improve Outcomes Now (MVP-CHAMPION) research collaboration.

Materials and Methods

Oversight fell under the VA Office of Research Development (VA ORD) and DOE headquarters. An Executive Committee and 2 senior scientific liaisons work with VA and DOE leadership to optimize efforts in the service of shared scientific goals. The program supported centralized data management and genomic analysis including creation of a scalable approach to cataloging phenotypes. Cross-cutting methods including natural language processing, image processing, and reusable code were developed.

Results

The 79.6 million dollar collaboration has supported centralized data management and genomic analysis including a scalable approach to cataloging phenotypes and launched over 10 collaborative scientific projects in health conditions highly prevalent in veterans. A ground-breaking analysis on the Summit and Andes supercomputers at the Oak Ridge National Laboratory (ORNL) of the genetic underpinnings of over 2000 health conditions across 44 million genetic variants which resulted in the identification of 38 270 independent genetic variants associating with one or more health traits. Of these, over 2000 identified associations were unique to non-European ancestry. Cross-cutting methods have advanced state-of-the-art artificial intelligence (AI) including large language natural language processing and a system biology study focused on opioid addiction awarded the 2018 Gordon Bell Prize for outstanding achievement in high-performance computing. The collaboration has completed work in prostate cancer, suicide prevention, and cardiovascular disease, and cross-cutting data science. Predictive models developed in these projects are being tested for application in clinical management.

Discussion

Eight new projects were launched in 2023, taking advantage of the momentum generated by the previous collaboration. A major challenge has been limitations in the scope of appropriated funds at DOE which cannot currently be used for health research.

Conclusion

Extensive multidisciplinary interactions take time to establish and are essential to continued progress. New funding models for maintaining high-performance computing infrastructure at the ORNL and for supporting continued collaboration by joint VA-DOE research teams are needed.
Exploring optimal folic acid supplementation levels for lactating-pregnant rabbit does with different litter size
Authors: Song Bing , Yu Lin , Liu Xiaoxiao , Goswami Naqash , Gong Ruiguang , Ren Zhanjun
Published: November 2024

The lactation-pregnancy overlap in the industrialized 49-d breeding model increases nutritional demands for lactating-pregnant rabbit does. This study examined the effects of folic acid (FA) on the production performance and intestinal microflora of does with different litter sizes (LS, or number of kits). A total of 144 third-parity Hyplus does, aged 11 mo and weighing approximately 5.00 ± 0.07 kg, were divided into 4 treatment groups: control group (basal diet) and FA groups (basal diet + 15, 30, and 45 mg/kg FA). Does with LS of 5, 7, and 9 were selected after weaning. Our findings revealed that 1) Increased FA supplementation initially increased and then decreased the pre-lactation body weight of 21-d-old kits and prolactin (PRL) level of lactating does, while showing an inverse trend for estrogen (E) level of does. Increased LS significantly (P < 0.05) correlated with reduced milk yield of does. There was a significant (P < 0.05) interaction between FA and LS affecting PRL, E, growth hormone levels of does, and the pre-lactation body weight of 21-d-old kits; 2) Increased FA supplementation initially increased and then decreased the post-lactation body weight of 21-d-old and 35-d-old kits, elevated plasma FA (PFA) level of lactating-pregnant does, and significantly (P < 0.05) impacted the pregnancy rate of does. Increased LS was associated with reduced post-lactation body weight in 21-d-old and 35-d-old kits (P < 0.05). There was a significant (P < 0.05) interaction between FA and LS affecting plasma insulin-like growth factor-1 (IGF-1), homocysteine (HCY), PFA levels of does, the post-lactation body weight of 21-d-old kits, and weaning body weight of 35-d-old kits; and 3) FA supplementation promoted the growth of Ruminococcaceae and Rikenellaceae_RC9_gut_group in the feces of lactating-pregnant does, as well as the proliferation of Lachnospiraceae_NK4A136_group in the feces of pregnant does, suggesting enhanced anti-inflammatory properties and improved crude fiber breakdown. In summary, FA supplementation improved conception rates, regulated lactation-related hormone synthesis and secretion, increased body weight of 21-d-old kits, and enhanced intestinal anti-inflammatory functions.
Cost-effectiveness of radiofrequency echographic multi-spectrometry for the diagnosis of osteoporosis in the United States
Authors: Reginster Jean-Yves , Silverman Stuart L , Alokail Majed , Al-Daghri Nasser , Hiligsmann Mickael
Published: November 2024

Radiofrequency echographic multi-spectrometry (REMS) is an innovative, non-ionizing diagnostic technique that has shown high accuracy and precision, making it a promising alternative to DXA for osteoporosis diagnosis in clinical settings. With economic considerations playing an increasingly crucial role in healthcare decisions, this study aims to evaluate the cost-effectiveness and economic impact of improved osteoporosis diagnosis using REMS followed by treatment in the United States. A microsimulation-based Markov model was constructed to estimate the cost per quality-adjusted life year (QALY) gained (in US$2022) for REMS followed by treatment vs no diagnosis and treatment in US women aged 50 yr and older with osteoporosis. Women were categorized as high risk (receiving alendronate monotherapy for 5 yr) or very high risk (receiving an 18-mo course of anabolic treatment, abaloparatide, followed by 5 yr of alendronate). The study evaluated 2 medication adherence scenarios: one assuming full adherence to treatment and the other reflecting real-world adherence. The results indicate that REMS followed by treatment is associated with improved health outcomes, including more QALYs and fewer fractures, and reduced fracture-related costs compared to no diagnosis and treatment. The incremental cost-effectiveness ratio of REMS was estimated at $33 891 and $49 198 per QALY gained, under the full adherence and real-world adherence scenarios, respectively. These values are below the US cost-effectiveness threshold of $100 000 per QALY. Moreover, a 5% increase in the diagnosis and treatment of women over 50 yr at high and very high risk of fractures using REMS is projected to save approximately 30 000 life yr, 43 500 QALYs, and prevent 100 000 fractures over a lifetime under real-world medication adherence. In conclusion, this study suggests that REMS is a cost-effective strategy for the diagnosis and management of osteoporosis in US women, offering substantial potential economic benefits and improved health outcomes.
Three-dimensional hullform reconstruction from two-dimensional drawings based on image processing techniques
Authors: Park Jun-Su , Ham Seung-Ho
Published: November 2024

Repair shipyards sometimes need three-dimensional geometry for repairs and retrofits. However, they often create models manually from two-dimensional drawings provided by ship owners. In this case, human error leads to inaccuracies, making the process time-consuming and laborious. Therefore, there is a need for research on efficient three-dimensional hullform reconstruction from two-dimensional drawings. This study proposed a method to automatically extract points from two-dimensional lines and visualize them in three dimensions. The proposed method consists of three steps. The first step is a point extraction through image processing, which uses a starting point search algorithm to access overlapping or intersection lines and extracts the points on the lines in the drawing by searching for paths between the starting point and the end point entered by the user. The second step is the transformation of the extracted data, which transforms the points based on pixel coordinate into 3D points through coordinate transformation and scaling by utilizing the stored line data and three-dimensional coordinate information. The last step is to visualize the transformed data as a real three-dimensional model with point visualization. This study demonstrates that the proposed method can be effectively utilized by detecting two-dimensional lines and reconstructing the hullform in three dimensions.
A genome assembly for the California endemic liverwort Calasterella californica
Authors: González-Ramírez Ixchel S , Escalona Merly , Miller Courtney , Chumchim Noravit , Marimuthu Mohan P A , Nguyen Oanh , Song Michael J , Mishler Brent D
Published: November 2024

Calasterella californica belongs to a monotypic genus of liverworts endemic to the west coast of North America, primarily distributed in California. This dioicous species occurs in a variety of ecosystems from deserts to redwood forests; little is known about how this species is adapted to live in those seemingly contrasting environments. In this paper, we report on the assembly of the nuclear genome of C. californica. As part of the California Conservation Genomics Project (CCGP), we used Pacific Biosciences HiFi long-read sequencing data to produce a de novo assembly that consists of 772 contigs, with a total length of 517 Mbp and a BUSCO complete score of 95%. Calasterella californica is only the sixth species of liverworts—a group with more than 7,200 described species—to have a nuclear reference genome. The availability of this reference genome will facilitate the study of the unique features of C. californica and other liverworts, pave the road towards a comparative understanding of liverwort genomes, and add an important starting point for studies of the geographic variation of this species within the CCGP project.
The invasive spongy moth, Lymantria dispar japonica (Lepidoptera: Erebidae) in South Korea
Authors: Jeong Na Ra , Inoue Maki N , Lee Sang-Bin , Nam Youngwoo , Lee Wonhoon
Published: November 2024

Lymantria dispar japonica (Lepidoptera: Erebidae), commonly known as the spongy moth, is predominant and widely distributed in Japan. However, between 2021 and 2023, L. d. japonica was simultaneously discovered in several regions of South Korea. Lymantria dispar japonica was distinguished from Lymantria dispar asiatica on the basis of adult forewing length and wing patterns and their genetic distance ranged from 0.065% to 0.588% in the COI gene. Here, we provide a description of this subspecies and details of its sampling locations. The discovery of L. d. japonica is of great importance to the forests of South Korea. Therefore, this study presents an opportunity to investigate new strategies for advancing the efforts to detect and eliminate threats related to this pest in the future.
Role of the basic leucine zipper transcription factor BATF2 in modulating immune responses and inflammation in health and disease
Authors: van der Geest Rick , Lee Janet S
Published: November 2024

BATF2 is a transcription factor known to exhibit tumor-suppressive activity in cancer cells. Within recent years, however, BATF2 has also emerged as an important transcriptional regulator of the immune system. Through its immunomodulatory function, BATF2 has been implicated in a variety of (patho)physiological processes, including host defense against infection, antitumor immunity, and maintenance of tissue inflammatory homeostasis. Below, we discuss recent literature that has provided insight into the role of BATF2 as a transcriptional regulator of immune responses in health and disease, including the cell types that express BATF2, the different diseases in which the immunomodulatory effects of BATF2 have been shown to play a role, and the molecular mechanisms through which BATF2 is thought to exert those effects. In doing so, we highlight that the immunological effects of BATF2 are highly context dependent, and we point out the overlap between the mechanisms of action of BATF2 in infectious and noninfectious diseases. We also discuss areas of interest for future research, the clinical relevance of better understanding BATF2 function, and potential strategies for therapeutic modulation of BATF2.
Development of a pharmacokinetic/pharmacodynamic evaluation model for osteomyelitis and usefulness of tedizolid as an alternative to vancomycin against MRSA osteomyelitis
Authors: Liu Xiaoxi , Enoki Yuki , Taguchi Kazuaki , Matsumoto Kazuaki
Published: November 2024

Objectives

This study aimed to develop a suitable osteomyelitis model for pharmacokinetic/pharmacodynamic (PK/PD) evaluation and to investigate the target PK/PD values of vancomycin and tedizolid against methicillin-resistant Staphylococcus aureus (MRSA) osteomyelitis.

Methods

An osteomyelitis model was established by implanting an MRSA-exposed sterilized suture in the tibia of normal mice and mice with cyclophosphamide-induced neutropenia. The suitability of the osteomyelitis mouse model for PK/PD evaluation was assessed using vancomycin as an indicator. The target PK/PD values for tedizolid were determined using this model.

Key findings

In neutropenic mice, to achieve a static effect and 1 log10 kill against MRSA, the ratios of the area under the free drug concentration–time curve for 24 h to the minimum inhibitory concentration (fAUC24/MIC) of vancomycin were 91.29 and 430.03, respectively, confirming the validity of the osteomyelitis model for PK/PD evaluation. In immunocompetent mice, the target fAUC24/MIC values of tedizolid for achieving a static effect and 1 log10 kill against MRSA were 2.40 and 49.20, respectively. Additionally, only a 0.28 log10 kill was achieved in neutropenic mice with 20 times the human equivalent dose of tedizolid.

Conclusions

In patients with restored immunity, tedizolid can potentially be used as an alternative to intravenous vancomycin therapy.
Atypical presentation of Wilms’ tumor in an adult: a case report and diagnostic considerations
Authors: Aaboudech Taha Yassine , Derqaoui Sabrine , Znati Kaoutar , Zouaidia Fouad , Ibrahimi Ahmed , Mzouri Khalid , Nouini Yassine , Bernoussi Zakia , Jahid Ahmed
Published: November 2024

Wilms’ tumor (WT), while common in pediatric populations, is exceedingly rare in adults, accounting for only 0.5% of renal neoplasms. This report describes a 44-year-old patient diagnosed with stage II WT in the left kidney who underwent a radical nephrectomy, illustrating the diagnostic challenges encountered in adult cases. The patient’s symptoms and radiological findings were non-specific, complicating early detection. Histopathological analysis revealed a mixed-type tumor with a 60% blastemal component. Accurate histopathological evaluation is crucial for determining prognosis and guiding treatment. This case is rare due to its early-stage (stage II) diagnosis in an adult, which is almost unheard of in the literature, where most adult WT are advanced. This highlights the critical need for heightened clinical suspicion, early diagnostic efforts, and pivotal surgery-based treatment to improve outcomes in such rare cases.
A novel, double Limberg flap repair for recurrent pilonidal sinus disease
Authors: Leung Emily , Finlayson Andrew
Published: November 2024

Pilonidal sinuses are chronic inflammation and/or infection of the intergluteal region. Recurrent disease is common and is a source of significant morbidity for affected patients. We present a case of an eighteen-year-old male with extensive recurrent pilonidal disease. A novel technique of a double Limberg flap repair was used, with the vertical axes of each flap positioned to optimise wound tension. The cranio-caudal length of the disease in the natal cleft would have resulted in a large amount of excised normal tissue laterally if a single Limberg flap was considered. To avoid this, we used two Limberg flaps over the craniocaudal length to minimise the laterally excised tissue. The patient made an uneventful recovery with no recurrence at 3 months follow-up. This technique demonstrates the flexibility of the Limberg flap, and that a double flap may be successfully used in extensive disease.
Squamous cell carcinoma arising from anal fistula in an HIV-positive individual: a case report
Authors: Yang Jie , Zhang Liman , Wang Qiang , Wang Lili
Published: November 2024

Chronic anal fistula represents a prevalent form of perianal disease that frequently originates from perianal infection. Specifically, perianal abscesses that are inadequately or improperly treated are susceptible to the development of chronic anal fistulas. In HIV-infected individuals, an impaired immune system significantly diminishes the body’s capacity to combat infections and inflammation, thereby complicating the healing process of anal fistulas. Moreover, the impact of HIV on tissue repair results in a markedly prolonged healing process for wounds and tissue damage in these patients, exacerbating the difficulty in anal fistula resolution. Chronic anal fistulas that remain untreated for extended periods not only severely impair the patient’s quality of life but also pose an increased risk of malignant transformation.
Magnitude and timescales of Ca isotope variability in human urine: implications for bone mass balance monitoring
Authors: Tissot François L H , Cleveland Dylan , Grigoryan Rosa , Kipp Michael A , Shafiee Roxana T , Miaou Emily , Chunduri Rithika , Melton Hayward , Tacail Theo , Razionale Dan
Published: November 2024

Calcium (Ca) isotopes in blood/urine are emerging biomarkers of bone mineral balance (BMB) in the human body. While multiple studies have investigated Ca isotopes in patients suffering from diseases affecting BMB, comparatively little effort has been devoted to understanding the homeostasis of Ca isotopes in healthy individuals. Here, we report on a longitudinal study of the urine Ca isotope composition (δ44/42CaUrine) from 22 healthy participants (age 19–60) over timescales ranging from days to months. Data from a single participant collected over a 30-day period show that morning urine is an excellent proxy for 24-h pooled urine fractions. Data from all participants reveal large inter-individual variability in δ44/42CaUrine (up to 2.2‰), which is partly due to anthropometric differences, as shown by a correlation between the participants’ body mass index (BMI) and δ44/42CaUrine values. In contrast, intra-individual data reveal encouraging stability (within ∼±0.2–0.3‰) over timescales >160 days, indicating that self-referencing approaches for BMB monitoring hold greater promise than cross-sectional ones. Our data confirm that intra-individual δ44/42CaUrine variations are mainly a function of Ca reabsorption in the kidney, but also reveal the impact of other (and at times equally important) drivers, such as diet, alcohol consumption, physical exercise, or fasting. We also find that a magnetic resonance imaging contrast agent (gadolinium) can lead to artifacts during Ca isotope analysis. Based on our results, a series of practical considerations for the use of Ca isotopes in urine as tracers of BMB are presented.
Current Status of Neonatal Music Therapy Services Within the US
Authors: Robertson Amy M , Evans Ellyn H
Published: November 2024

Over the past 30 years, music therapy services in the neonatal intensive care units (NICUs) have expanded, yet there is still limited literature available that captures current practice trends in this setting. The purpose of this paper was to obtain descriptive data about current demographics, consultation, and clinical practice trends in NICU music therapy clinical practice in the US. A questionnaire was sent to 9,222 Board-Certified Music Therapists. Those providing music therapy services in the NICU and choosing to participate (N = 87) completed the questionnaire. Results showed that a majority of music therapists working in the NICU who responded to the questionnaire have completed additional training to provide specialized services. Most NICU music therapists reported spending less than 20 hr a week on the unit and providing a variety of family-centered interventions to infants starting at 28 weeks postmenstrual age (PMA). Common diagnoses for referral besides prematurity were Neonatal Opioid Withdrawal Syndrome and Chronic Lung Disease. Music therapists are well integrated within treatment teams with a majority reporting collaborating and/or co–treating with other therapies and/or clinical staff.
A perspective on the fundamental theory of nonaqueous electrolytes for rechargeable batteries
Authors: Chen Xiang , Yao Nan , Zheng Zhao , Gao Yu-Chen , Zhang Qiang
Published: November 2024

The chemical origins of the major differences between nonaqueous electrolytes and classical solution models were delved to promote the future development of battery electrolyte theories.