bluuebunny/crossref_metadata_2025 huggingface dataset:
Clinical and Histopathologic Characteristics of Acute Severe Hepatitis Associated With Human Herpesvirus 6 Infection
Authors: Wang Huiying , Vannilam Annette , Hafberg Einar T. , Gillis Lynette A. , Kassardjian Ari , Naini Bita V. , Prasad Vinay , Kelly David R. , Mroczek-Musulman Elizabeth C. , Knox Konstance , Correa Hernan , Liang Jiancong
Published: June 2024

Acute severe hepatitis associated with active human herpesvirus 6 (HHV-6) infection is a rare life-threatening condition with unclear clinical course and histopathology. In this study, we retrospectively analyzed 5 patients with indeterminate acute severe hepatitis found to have active hepatic HHV-6 infection during care. All patients were previously healthy children presenting with a nonspecific prodrome. Four developed acute liver failure (ALF) and 3 received liver transplantation. The explanted livers and biopsies demonstrated a centrilobular pattern of necroinflammation characterized by moderate to marked central perivenulitis and confluent centrilobular to panlobular necrosis in 4 cases, accompanied by marked hepatocellular swelling and milder portal inflammation in 3. Central perivenulitis was more prominent in comparison to a control of group of ALF without HHV-6 (P=0.01). When compared with the children with acute severe hepatitis associated with adenovirus encountered in the recent outbreak, both central perivenulitis and centrilobular necrosis were significant predictors for association with HHV-6 (P<0.01). Liver immunohistochemistry detected HHV-6 structural protein in biliary epithelium in all cases and a predominance of CD8+ T cells in the perivenular inflammatory infiltrate. Among the 4 patients with ALF, one received early anti-HHV-6 therapy and had transplant-free survival, while the other 3 received either general prophylactic antiviral treatment only (n=2) or late anti-HHV-6 therapy (n=1) and needed liver transplantation. Our findings were similar to those in previously reported cases. In summary, acute severe hepatitis associated with HHV-6 tends to affect children, progress to ALF, and exhibit characteristic centrilobular necroinflammation which likely represents an immune-mediated process.
Histopathologic and Clinical Characterization of Brentuximab Vedotin-associated Rash
Authors: Narala Saisindhu , Saleem Atif , Brown Ryanne A. , Novoa Roberto A. , Kim Youn H. , Rieger Kerri E.
Published: June 2024

Rash is one of the commonly observed adverse events with brentuximab vedotin (BV), a CD30-targeted antibody-drug conjugate used to treat cutaneous T-cell lymphoma (CTCL). However, clinical and histopathologic characterization of BV-associated rash (BVAR) is limited. Distinguishing BVAR from a patient’s underlying CTCL can be challenging and can lead to treatment interruptions or even premature drug discontinuation. We performed a thorough clinical and histopathologic retrospective characterization of BVAR from a single institution. Utilizing polymerase chain reaction (PCR) and T-cell receptor high-throughput sequencing (TCR-HTS), we were able to isolate skin biopsy specimens from rash clinically suggestive of BVAR that also lacked a dominant TCR clone. A retrospective evaluation was performed of 26 biopsy specimens from 14 patients. Clinical features of BVAR included predominantly morbilliform or maculopapular morphology, delayed onset, and the trend toward moderate to severe classification, often requiring oral steroids. Most histopathologic specimens (25/26) showed spongiotic dermatitis as the primary reaction pattern. Many cases showed subtle findings to support a background interface or lichenoid eruption. Langerhans cell microabscesses were seen in one-fourth of specimens, and eosinophils were present in over one-half of the specimens. There were focal features mimicking CTCL, but these were not prominent. In 17 specimens with immunohistochemistry, the CD4:CD8 ratio in intraepidermal lymphocytes was relatively normal (1-6:1) in 65% (11/17) and 1:1 in 35% (6/17), demonstrating a trend toward increased CD8-positive cells compared with baseline CTCL. We have identified features that can help distinguish BVAR from a patient’s CTCL, which can, in turn, help guide appropriate clinical management.
Stage III Melanoma
Authors: Balaban Alexandra , McCollum Kasey J. , Al-Rohil Rami N.
Published: June 2024

National Comprehensive Cancer Network guidelines state that clinical stage III melanoma patients may undergo ultrasound surveillance of the nodal basin in lieu of complete lymph node dissection (CLND). This has led to an inability to accurately classify patients according to the American Joint Committee on Cancer (AJCC) eighth edition staging system because it uses the total number of positive lymph nodes from the CLND to assign a pathologic N stage. We propose a new model for clinical stage III melanoma patients that does not rely on the total number of positive lymph nodes. Instead, it uses Breslow depth, ulceration status, sentinel lymph node metastasis size, and extracapsular extension to stratify patients into groups 1 to 4. We compared our model’s ability to predict melanoma-specific survival (MSS), distant metastasis–free survival (DMFS) and locoregional recurrence, and distant metastasis–free survival (DMFS-LRFS) to the current AJCC system with and without CLND-data using a Cox proportional hazards model and Akaike Information Criteria weights. Although not reaching our predetermined level of statistical significance of 95%, our model was 5 times more likely to better predict MSS compared with the AJCC model with CLND. In addition, our model was significantly better than the AJCC model without CLND in predicting MSS. Our model performed significantly better than the AJCC model in predicting DMFS and DMFS-LRFS regardless of whether data from CLND were included.
Convective forces contribute to post-traumatic degeneration after spinal cord injury
Authors: Kwon Hoi Y , Streilein Christopher , Chase Cornelison R.
Published: June 2024

Spinal cord injury (SCI) initiates a complex cascade of chemical and biophysical phenomena that result in tissue swelling, progressive neural degeneration, and formation of a fluid-filled cavity. Previous studies show fluid pressure above the spinal cord (supraspinal) is elevated for at least three days after injury and contributes to a phase of damage called secondary injury. Currently, it is unknown how fluid forces within the spinal cord itself (interstitial) are affected by SCI and if they contribute to secondary injury. We find spinal interstitial pressure increases from -3 mmHg in the naive cord to a peak of 13 mmHg at 3 days post-injury (DPI) but relatively normalizes to 2 mmHg by 7 DPI. A computational fluid dynamics model predicts interstitial flow velocities up to 0.9 μm/s at 3 DPI, returning to near baseline by 7 DPI. By quantifying vascular leakage of Evans Blue dye after a cervical hemi-contusion in rats, we confirm an increase in dye infiltration at 3 DPI compared to 7 DPI, suggestive of higher fluid velocities at the time of peak fluid pressure.In vivoexpression of the apoptosis marker caspase-3 is strongly correlated with regions of interstitial flow at 3 DPI, and exogenously enhancing interstitial flow exacerbates tissue damage.In vitro, we show overnight exposure of neuronal cells to low pathological shear stress (0.1 dynes/cm2) significantly reduces cell count and neurite length. Collectively, these results indicate that interstitial fluid flow and shear stress may play a detrimental role in post-traumatic neural degeneration.

Translational Impact Statement

Trauma to the central nervous system induces neural tissue degeneration, resulting in permanent disability and loss of function. A better understanding of this degenerative process is needed, towards developing new clinical treatments that effectively minimize tissue damage and preserve neural function after injury. The present study identifies a potential role for altered fluid transport within the injured spinal cord. These results provide new insight into basic pathophysiology and may inform therapeutic development for neuroprotection.
Genome-wide Mapping of Topoisomerase Binding Sites Suggests Topoisomerase 3α (TOP3A) as a Reader of Transcription-Replication Conflicts (TRC)
Authors: Zhang Hongliang , Sun Yilun , Saha Sourav , Saha Liton Kumar , Pongor Lorinc S. , Dhall Anjali , Pommier Yves
Published: June 2024

Both transcription and replication can take place simultaneously on the same DNA template, potentially leading to transcription-replication conflicts (TRCs) and topological problems. Here we asked which topoisomerase(s) is/are the best candidate(s) for sensing TRC. Genome-wide topoisomerase binding sites were mapped in parallel for all the nuclear topoisomerases (TOP1, TOP2A, TOP2B, TOP3A and TOP3B). To increase the signal to noise ratio (SNR), we used ectopic expression of those topoisomerases in H293 cells followed by a modified CUT&Tag method. Although each topoisomerase showed distinct binding patterns, all topoisomerase binding signals positively correlated with gene transcription. TOP3A binding signals were suppressed by DNA replication inhibition. This was also observed but to a lesser extent for TOP2A and TOP2B. Hence, we propose the involvement of TOP3A in sensing both head-on TRCs (HO-TRCs) and codirectional TRCs (CD-TRCs). In which case, the TOP3A signals appear concentrated within the promoters and first 20 kb regions of the 5’ -end of genes, suggesting the prevalence of TRCs and the recruitment of TOP3A in the 5’-regions of transcribed and replicated genes.

GRAPHICAL ABSTRACT
Phyloformer: Fast, accurate and versatile phylogenetic reconstruction with deep neural networks
Authors: Nesterenko Luca , Blassel Luc , Veber Philippe , Boussau Bastien , Jacob Laurent
Published: June 2024

Phylogenetic inference aims at reconstructing the tree describing the evolution of a set of sequences descending from a common ancestor. The high computational cost of state-of-the-art Maximum likelihood and Bayesian inference methods limits their usability under realistic evolutionary models. Harnessing recent advances in likelihood-free inference and geometric deep learning, we introduce Phyloformer, a fast and accurate method for evolutionary distance estimation and phylogenetic reconstruction. Sampling many trees and sequences under an evolutionary model, we train the network to learn a function that enables predicting the former from the latter. Under a commonly used model of protein sequence evolution and exploiting GPU acceleration, it outpaces fast distance methods while matching maximum likelihood accuracy on simulated and empirical data. Under more complex models, some of which include dependencies between sites, it outperforms other methods. Our results pave the way for the adoption of sophisticated realistic models for phylogenetic inference.
Gut-immune reactivity underlies sex differences in the maternal immune activation preclinical model of autism
Authors: Salia Stephanie , Burke Francine F , Hinks Meagan Elizabeth , Randell Alison M , Matheson Mairead Anna , Walling Susan G , Swift-Gallant Ashlyn
Published: June 2024

The gut microbiome plays a vital role in health and disease, including neurodevelopmental disorders like autism spectrum disorder (ASD). ASD affects 4:1 males-to-females, and sex differences are apparent in gut microbiota composition among ASD individuals and in animal models of this condition, such as the maternal immune activation (MIA) mouse model. However, few studies have included sex as a biological variable when assessing the role of gut microbiota in mediating ASD symptoms. Using the MIA model of ASD, we assessed whether gut microbiota contributes to the sex differences in the presentation of ASD-like behaviors. Gut microbiota transplantation from MIA or vehicle/control male and female mice into healthy, otherwise unmanipulated, 4-week-old C57Bl/6 mice was performed for 6 treatments over 12 days. Colonization with male, but not female, MIA microbiota was sufficient to reduce sociability, increase repetitive burying behavior, decrease microbiota diversity and increase neuroinflammation with more pronounced deficits in male recipients. Colonization with both male and female donor microbiota altered juvenile ultrasonic vocalizations and anxiety-like behavior in recipients of both sexes, and there was an accompanied change in the gut microbiota and serum cytokine IL-4 and IL-7 levels of all recipients of MIA gut microbiota. In addition to the increases in gut microbes associated with pathological states, the female donor microbiota profile also had increases in gut microbes with known neural protective effects (e.g., Lactobacillus and Rikenella). These results suggest that gut reactivity to environmental insults, such as in the MIA model, plays a pivotal role in shaping the sex disparity observed in ASD development.
A Multi-Country Evaluation of Patient Preferences for Tuberculosis Diagnostics: A Discrete Choice Experiment to Inform WHO Target Product Profiles
Authors: Shah Kinari , Nalugwa Talemwa , Marcelo Danaida , Nakawunde Robinah , Trinh Trang , Shankar Deepa , Nakaweesa Annet , Schraufnagel Ann , Andama Alfred , Christopher DJ , Van Luong Dinh , Theron Grant , Worodria William , del Mar Castro Maria , Nahid Payam , Denkinger Claudia M. , Cattamanchi Adithya , Yu Charles , Kerkhoff Andrew D.
Published: June 2024

Background

Recognizing new and improved diagnostics as a key step to reducing the global tuberculosis (TB) burden, the World Health Organization (WHO) publishes target product profiles (TPPs) to guide development of novel TB diagnostics; however, TPPs have not included the preferences of people undergoing TB testing. Understanding their preferences is crucial for optimizing the acceptability and uptake of TB diagnostic services.

Design/methods

We conducted a discrete choice experiment (DCE) among adults with presumptive or microbiologically confirmed TB in 5 countries (Philippines, Vietnam, South Africa, Uganda, and India). The DCE evaluated preferences for 5 TB diagnostic test attributes (sample type, accuracy, cost, location, time to result) with 3-4 levels per attribute. We estimated mean preference weights for attribute levels using Hierarchical Bayesian models and conducted willingness-to-trade analyses for preferred test features.

Results

Among 1,033 participants (median age 43 years, Interquartile Range: 30-55), 52% were female, 10% had HIV, 14% had diabetes, 36% had current or prior TB), the most strongly valued test features were free cost, high diagnostic accuracy, and rapid (within 15 minutes) result availability. Among less valued attributes, facility-based testing (location) and sputum (sample type) were most preferred. The relative importance of attributes and their levels differed by country. In willingness-to-trade simulations, participants in each country were willing to trade 10-20% lower accuracy for the availability of rapid tests but were unwilling to trade accuracy for alternative sample types (e.g., tongue-swab, urine, blood) or testing locations (e.g., home- or community-based); participants in India and Vietnam were willing to pay $3.20 and $4.00 USD, respectively, for tests with rapid results.

Conclusions

Persons accessing TB services in five high-burden countries universally value free cost, high diagnostic accuracy, and rapid result availability. However, many were willing to accept lower test accuracy and some were willing to incur small out-of-pocket costs to access rapid tests. To align with preferences of TB-affected communities, future TPP updates and new test development should prioritize rapid results while maintaining high accuracy and minimizing costs.
Single-cell multi-omics analysis reveals cooperative transcription factors for gene regulation in oligodendrocytes
Authors: Choi Jerome J. , Svaren John , Wang Daifeng
Published: June 2024

Oligodendrocytes are the myelinating cells within the central nervous system. Many oligodendrocyte genes have been associated with brain disorders. However, how transcription factors (TFs) cooperate for gene regulation in oligodendrocytes remains largely uncharacterized. To address this, we integrated scRNA-seq and scATAC-seq data to identify the cooperative TFs that co-regulate the target gene (TG) expression in oligodendrocytes. First, we identified co- binding TF pairs whose binding sites overlapped in oligodendrocyte-specific regulatory regions. Second, we trained a deep learning model to predict the expression level of each TG using the expression levels of co-binding TFs. Third, using the trained models, we computed the TF importance and TF-TF interaction scores for predicting TG expression by the Shapley interaction scores. We found that the co-binding TF pairs involving known important TF pairs for oligodendrocyte differentiation, such as SOX10-TCF12, SOX10-MYRF, and SOX10-OLIG2, exhibited significantly higher Shapley scores than others (t-test, p-value < 1e-4). Furthermore, we identified 153 oligodendrocyte-associated eQTLs that reside in oligodendrocyte-specific enhancers or promoters where their eGenes (TGs) are regulated by cooperative TFs, suggesting potential novel regulatory roles from genetic variants. We also experimentally validated some identified TF pairs such as SOX10-OLIG2 and SOX10-NKX2.2 by co-enrichment analysis, using ChIP-seq data from rat peripheral nerve.
Optimal processing of tongue swab samples for Mycobacterium tuberculosis detection by the Xpert MTB/RIF Ultra assay
Authors: Chilambi Gayatri Shankar , Reiss Robert , Daivaa Naranjargal , Banada Padmapriya , De Vos Margaretha , Penn-Nicholson Adam , Alland David
Published: June 2024

Tongue swabs represent a potential alternative to sputum as a sample type for detecting pulmonary tuberculosis (TB) using molecular diagnostic tests. The methods used to process tongue swabs for testing in the WHO-recommended Xpert MTB/RIF Ultra (Xpert Ultra) assay vary greatly. We aimed to identify the optimal method for processing diagnostic tongue swabs for subsequent testing by Xpert Ultra. We compared four methods for treating dry tongue swabs with Xpert Ultra sample reagent (SR) mixed with various concentrations of Tris-EDTA-Tween (TET), to treatment with SR alone or to a commonly used SR-free heat-inactivation protocol. In each condition, swabs obtained from volunteers without TB were placed into test buffer spiked with known amounts ofMycobacterium tuberculosis(Mtb) strain H37Rv-mc26230. Swabs processed with 1:1 diluted SR buffer had the lowestMtblimit of detection (LOD) at 22.7 CFU/700 µl (95% CI 14.2-31.2), followed by 2:1 diluted SR buffer at 30.3 CFU/700 µl (95% CI 19.9-40.7), neat SR at 30.9 CFU/700 µl (95% CI 21.5-40.3) and SR prefilled in the Xpert Ultra at 57.1 CFU/700 µl (95% CI 42.4-71.7). Swabs processed using the heat-based protocol had the highest LOD (77.6 CFU/700 µl; 95% CI 51.2–104.0). Similar findings were observed for LOD of RIF-susceptibility. Assay sensitivity using the 2:1 diluted SR buffer did not vary considerably in the presence of sputum matrix or phosphate buffer saline. Further studies are needed to assess the performance of this processing protocol in a clinical setting.

Importance

Xpert MTB/RIF Ultra (Xpert Ultra) is approved by the World Health Organization for the diagnosis of tuberculosis (TB). This test is typically performed using sputum specimens obtained from people with presumptive TB. In order to inactivateMtband aid liquefaction, sputum must be mixed with Xpert SR prior to transfer into the Xpert Ultra. However, some people under evaluation for TB are unable to produce sputum. Alternative sample types for TB diagnosis would therefore be of value. Oral-swabs, including tongue-swabs have shown promise, but there are technical challenges associated with sample processing. In this study, several new tongue swab processing conditions were evaluated, utilizing SR, either neat or diluted in buffer. The ability of Xpert Ultra to detect TB was improved under these conditions compared with the previously published heat-processing method (1–3), processing steps were simplified, and technical challenges were overcome.
Neural tube organoid generation: a robust and reproducible protocol from single mouse embryonic stem cells
Authors: Krammer Teresa , Tanaka Elly M.
Published: June 2024

The development of mammals is a highly complex process, characterized by the necessity for precise concentration- and time-dependent signaling for correct pattern formation and morphogenesis. Despite considerable technological advancements and knowledge gathered, numerous aspects of mammalian development remain elusive. When examining the entire organism, it becomes challenging to disentangle the effects of individual pathways or the mechanism by which external stimuli guide the interference of surrounding tissues and factors. In addressing this complexity, three-dimensional (3D)in vitromodels such as organoids have emerged as valuable tools. Organoids, derived from embryonic stem cells (ESCs) or induced pluripotent stem cells (iPSCs), exhibit tissue-like features that closely resemble theirin vivocounterparts in terms of expression patterns and functionality. Importantly, they offer accessibility for manipulation and extensive biological studies within a controlled experimental setting. Despite originating from pluripotent cultures, organoid systems often exhibit heterogeneity and substantial variability, limiting their utility when studying complex and intricate biological questions. Therefore, there is a pressing need for detailed protocols aimed at harmonizing procedures that result in high-quality reproducible data, reduction of materials used and which importantly permit the investigation of convoluted phenomena. In this context, we present an optimized protocol for the cultivation of neural tube organoids (NTOs)in vitro. By producing stable culture conditions and offering comprehensive troubleshooting strategies, this protocol enables the reliable and reproducible generation of NTOs which serve as an adequate model to study relevant scientific questions.

Three-dimensional neural tube organoids (NTOs) derived from mouse embryonic stem cells are valuable tools to study the central nervous system during early development. Here, we present a step-by-step demonstration of an optimized protocol for cultivating NTOsin vitro, providing stable culture conditions and troubleshooting strategies for reliable and reproducible NTO generation.
Alzheimer’s disease-like features in resting state EEG/fMRI of cognitively intact and healthy middle-agedAPOE/PICALMrisk carriers
Authors: Dzianok Patrycja , Wojciechowski Jakub , Wolak Tomasz , Kublik Ewa
Published: June 2024

Introduction

Genetic susceptibility is a primary factor contributing to etiology of late-onset Alzheimer’s disease (LOAD). The exact mechanisms and timeline through whichAPOE/PICALMinfluence brain functions and contribute to LOAD remain unidentified. This includes their effects on individuals prior to the development of the disease.

Methods

APOE/PICALMalleles were assessed to determine the genetic risk of LOAD in 79 healthy, middle-aged participants who underwent EEG and fMRI recordings. The resting-state signal was analyzed to estimate relative spectral power, complexity (Higuchi’s algorithm), and connectivity (coherence in EEG and ICA-based connectivity in fMRI).

Results

The main findings indicated that individuals at risk for LOAD exhibited reduced signal complexity and the so-called “slowing of EEG” which are well-known EEG markers of AD. Additionally, these individuals showed altered functional connectivity in fMRI (within attention related areas).

Discussion

Risk alleles ofAPOE/PICALMmay affect brain integrity and function prior to the onset of the disease
DeEPsnap: human essential gene prediction by integrating multi-omics data
Authors: Zhang Xue , Xiao Weijia , Cochran Brent , Xiao Wangxin
Published: June 2024

Essential genes are necessary for the survival or reproduction of a living organism. The prediction and analysis of gene essentiality can advance our understanding of basic life and human diseases, and further boost the development of new drugs. Wet lab methods for identifying cell essential genes are often costly, time-consuming, and laborious. As a complement, computational methods have been proposed to predict essential genes by integrating multiple biological data sources. Most of these methods are evaluated on model organisms. However, prediction methods for human essential genes are still limited and the relationship between human gene essentiality and different biological information still needs to be explored. In addition, exploring suitable deep learning techniques to overcome the limitations of traditional machine learning methods and improve prediction accuracy is also important and interesting. We propose a snapshot ensemble deep neural network method, DeEPsnap, to predict human essential genes. DeEPsnap integrates sequence features derived from DNA and protein sequence data with features extracted or learned from multiple types of functional data, such as gene ontology, protein complex, protein domain, and protein-protein interaction network. More than 200 features from these biological data are extracted/learned which are integrated together to train a series of cost-sensitive deep neural networks by utilizing multiple deep learning techniques. The proposed snapshot mechanism enables us to train multiple models without increasing extra training effort and cost. The experimental results of 10-fold cross-validation show that DeEPsnap can accurately predict human gene essentiality with an average AUROC (Area Under the Receiver Operating Characteristic curve) of 96.1%, the average AUPRC (Area under the Precision-Recall curve) of 93.82%, the average accuracy of 92.21%, and the average F1 measure about 80.62%. In addition, the comparison of experimental results shows that DeEPsnap outperforms several popular traditional machine learning models and deep learning models. We have demonstrated that the proposed method, DeEPsnap, is effective for predicting human essential genes.
EngineeringRhodosporidium toruloidesfor sustainable production of value-added punicic acid from glucose and wood residues
Authors: Wang Juli , Haddis Dagem Zekaryas , Xiao Qiong , Bressler David C , Chen Guanqun
Published: June 2024

Rhodosporidium toruloideshas emerged as a prominent candidate for producing single-cell oil from cost-effective feedstocks. In this study, the capability ofR. toruloidesto produce punicic acid (PuA), a representative plant unusual fatty acid, was investigated. The introduction of acyl lipid desaturase and conjugase (PgFADX) allowedR. toruloidesto accumulate 3.7% of total fatty acids as PuA. Delta-12 acyl lipid desaturase (PgFAD2) and diacylglycerol acyltransferase 2 were shown to benefit PuA production. The strain withPgFADXandPgFAD2coexpression accumulated 12% of its lipids as PuA from glucose, which translated into a PuA titer of 451.6 mg/L in shake flask condition. Utilizing wood hydrolysate as the feedstock, this strain produced 6.4% PuA with a titer of 310 mg/L. Taken together, the results demonstrated thatR. toruloidescould serve as an ideal platform for the production of plant-derived high-value conjugated fatty acid using agricultural and forestry waste as feedstock.
Using Photovoice to explore HIV self-testing and secondary distribution of HIV self-testing among gay, bisexual and other men who have sex with men in China
Authors: Wang Qianyun , Lu Ying , Ni Yuxin , Yan Xumeng , Jin Tan Rayner Kay , Wu Dan , Tucker Joseph D , Ong Jason J , Tang Weiming
Published: June 2024

Background

Human immunodeficiency virus self-testing (HIVST) has been globally recognized as a useful and reliable strategy to promote HIV testing, especially among marginalized populations. In order to improve the understanding of HIVST uptake of the test users, notably gay, bisexual and other men who have sex with men (GBMSM) in China, this study aims to qualitatively explore the HIVST uptake experiences among this population.

Methods

The study employed Photovoice methodology, theoretically built on documentary photography and critical consciousness, to explore the experiences of HIVST and secondary distribution among GBMSM in China. Participants created photos and citations and shared and discussed them in the group. Three focus groups and one follow-up interview were held virtually for each participant who were self-identified as gay or bisexual and used a self-test kit before.

Results

This program recruited 22 participants from all throughout China. The findings revealed that systemic discrimination based on gay identification and AIDS-phobia both inside and outside the gay community, affected participants’ decision to take HIVST and to pass HIVST kits on to others. Participants utilized HIVST on a routine basis, citing sexual health concerns, psychological comfort, and a responsibility to their significant others as reasons for doing so.

HIVST kitdistribution within intimacy,andthe significant role of gay-led community-based organizationswere found as characteristics of interactions between participants and those who they passed HIVST kit(s) on to. There were observed both facilitators and barriers to HIVST uptake and/or secondary distribution in this demographic.

Conclusion

In the study, images and narratives were acquired through empowering GBMSM and promoting their community engagement to underline the necessity for measures and policies on promoting HIVST among this population. Findings also entailed the need to create a more inclusive society for sexual minorities and people living with HIV. Implications for promoting HIVST secondary distribution and limitations and strengths of the pioneer photovoice study among GBMSM in China were also listed.
Health status and care utilization among Afghan refugees newly resettled in Calgary, Canada between 2011-2020
Authors: Smati Hannah , Hassan Nour , Essar Mohammad Yasir , Abdaly Fawzia , Noori Shayesta , Grewal Rabina , Norrie Eric , Talavlikar Rachel , Bietz Julia , Kimball Sarah L. , Coakley Annalee , Chatterjee Avik , Fabreau Gabriel E.
Published: June 2024

Background

The United States and Canada have resettled over 120,000 Afghan refugees since August 2021, but sociodemographic and health status data remains sparse with investigations often limited to refugee entrance exams, standardized health screenings, or acute health settings.

Methods

This retrospective community-engaged cohort study investigated Afghan patients who received care between January 1, 2011 and December 31, 2020 at an interdisciplinary specialized refugee clinic in Calgary, Canada that provides care to newly arrived refugees. Two reviewers independently extracted and manually verified sociodemographic factors, medical diagnoses, and clinic utilization variables from patients’ electronic medical records, then coded patient diagnoses into ICD-10 codes and chapter groups. Diagnosis frequencies were calculated and stratified by age group and sex. We corroborated these findings with Afghan refugee co-investigators.

Findings

Among 402 Afghan refugee patients, 228 were adults (mean age 34·2 [SD 13] years), and 174 were children (mean age 7·5 [SD 5·4] years). We identified 1535 total individual diagnoses and classified them into 382 unique ICD-10 codes. Patients had a median 2 diagnoses each [IQR 0-6], 4 clinic visits across primary, specialty and multidisciplinary care annually, and an 11% appointment no-show rate. Among adults, the most frequent diagnoses were abdominal pain (26·3%, 60/228), mechanical back pain (20·2%, 46/228), and H. pylori infection (19·3%, 44/228). Among children, the most frequent diagnoses were upper respiratory tract infection (12·1%, 21/174),Giardia(10·3%, 18/174), and short stature (7·5%, 13/174).

Interpretation

Recently resettled Afghan refugees in Canada were relatively young, experienced diverse health characteristics, and had multi-specialty care engagement in their first two years after arrival. These findings may guide specialized healthcare provision to this inadequately characterized but growing population of refugee arrivals in North America and elsewhere.

Funding

Research grants from the M.S.I. Foundation and University of Calgary O’Brien Institute for Public Health
Subthreshold intracortical microstimulation of human somatosensory cortex enhances tactile sensitivity
Authors: Osborn Luke E. , Christie Breanne , McMullen David P. , Arriola Victoria , Thomas Tessy M. , Pawar Ambarish S. , Nickl Robert W. , Anaya Manuel A. , Wester Brock A. , Greenspon Charles M. , Cantarero Gabriela L. , Celnik Pablo A. , Bensmaia Sliman J. , Yau Jeffrey M. , Fifer Matthew S. , Tenore Francesco V.
Published: June 2024

Intracortical microstimulation (ICMS) of the somatosensory cortex activates neurons around the stimulating electrodes and can elicit tactile sensations. However, it is not clear how the direct activation of cortical neurons influences their ability to process additional tactile inputs originating from the skin. In a human implanted with chronic microelectrode arrays in both left and right somatosensory cortices, we presented mechanical vibration to the skin while simultaneously delivering ICMS and quantified the effects of combined mechanical and electrical stimulation on tactile perception. We found that subthreshold ICMS enhanced sensitivity to touch on the skin, as evidenced by a reduction in vibrotactile detection thresholds (median: −1.5 dB), but subthreshold vibration did not systematically impact the detectability of ICMS. Suprathreshold vibration led to an increase in ICMS thresholds (median: 2.4 dB) but suprathreshold ICMS had little impact on vibrotactile thresholds. The ICMS-induced enhancement of vibrotactile sensitivity was location dependent with the effect size decreasing as the projected field of the stimulating electrode and the locus of vibratory stimulation became farther apart. These results demonstrate that targeted microstimulation of cortex alone can focally enhance tactile sensitivity, potentially enabling restoration or strengthening of retained tactile sensations after injury.
The association between rs6859 inNECTIN2gene and Alzheimer’s disease is partly mediated by pTau
Authors: Lathika Rajendrakumar Aravind , Arbeev Konstantin G. , Bagley Olivia , Yashin Anatoliy I. , Ukraintseva Svetlana
Published: June 2024

Introduction

Emerging evidence suggests a connection between vulnerability to infections and Alzheimer’s disease (AD). The nectin cell adhesion molecule 2(NECTIN2)gene coding for a membrane component of adherens junctions is involved in response to infection, and its single nucleotide polymorphism (SNP) rs6859 was significantly associated with AD risk in several human cohorts. It is unclear, however, how exactly rs6859 influences the development of AD pathology. The aggregation of hyperphosphorylated tau protein (pTau) is a key pathological feature of neurodegeneration in AD, which may be induced by infections, among other factors, and potentially influenced by genes involved in both AD and vulnerability to infections, such asNECTIN2.

Materials and methods

We conducted a causal mediation analysis (CMA) on a sample of 708 participants in the Alzheimer’s Disease Neuroimaging Initiative (ADNI). The relationship between rs6859 and Alzheimer’s disease (AD), with AD (yes/no) as the outcome and pTau-181 levels in the cerebrospinal fluid (CSF) acting as a mediator in this association, was assessed. Adjusted estimates from the probit and linear regression models were used in the CMA model, where an additive model considered an increase in dosage of the rs6859 A allele (AD risk factor).

Results

The increase in dose of allele A of the SNP rs6859 resulted in about 0.144 increase per standard deviation (SD) of pTau-181 (95% CI: 0.041, 0.248, p<0.01). When included together in the probit model, the change in A allele dose and each standard deviation change in pTau-181 predicted 6.84% and 9.79% higher probabilities for AD, respectively. In the CMA, the proportion of the average mediated effect was 17.05% and was higher for the risk allele homozygotes (AA), at 19.40% (95% CI: 6.20%, 43.00%, p<0.01). The sensitivity analysis confirmed the evidence of a robust mediation effect.

Conclusion

This study reported a new causal relationship between pTau-181 and AD. We found that the association between rs6859 in theNECTIN2gene and AD is partly mediated by pTau-181 levels in CSF. The rest of this association may be mediated by other factors. Further research, using other biomarkers, is needed to uncover the remaining mechanisms of the association between theNECTIN2gene and AD.
Bayesian Estimation Improves Prediction of Outcomes after Epilepsy Surgery
Authors: Dickey Adam S. , Reddy Vineet , Pedersen Nigel P. , Krafty Robert T.
Published: June 2024

Low power is a problem in many fields, as underpowered studies that find a statistically significant result will exaggerate the magnitude of the observed effect size. We quantified the statistical power and magnitude error of studies of epilepsy surgery outcomes. The median power across all studies was 14%. Studies with a median sample size or less (n<=56) and a statistically significant result exaggerated the true effect size by a factor of 5.4 (median odds ratio 9.3 vs. median true odds ratio 1.7), while the Bayesian estimate of the odds ratio only exaggerated the true effect size by a factor of 1.6 (2.7 vs. 1.7). We conclude that Bayesian estimation of odds ratio attenuates the exaggeration of significant effect sizes in underpowered studies. This approach could help improve patient counseling about the chance of seizure freedom after epilepsy surgery.

SHORT SUMMARY

We estimated the statistical power of studies predicting seizure freedom after epilepsy surgery. We exacted data from a Cochrane meta-analysis. The median power across all studies was 14%. Studies with a median sample size or less (n<=56) and a statistically significant result exaggerated the true effect size by a factor of 5.4, while the Bayesian estimate of the odds ratio only exaggerated the true effect size by a factor of 1.6. We conclude that Bayesian estimation of odds ratios attenuates the exaggeration of significant effect sizes in underpowered studies. This result could improve patient counseling regarding epilepsy surgery.
Polygenic Risk Scores Provide Strong Evidence for the Biologic Relevance of Molecular Subtypes of Schizophrenia
Authors: Rhodes C. Harker , Granger Richard
Published: June 2024

We have previously described how the post-mortem DLPFC transcriptomes of schizophrenia patients can be used to define two patient groups: “Type 1” patients with a relatively normal DLPFC transcriptome and “Type 2” patients with hundreds of genes differentially expressed in the DLPFC at a statistical significance which survives Bonferroni correction. The biological significance of the distinction between Type 1 and Type 2 patients remains an open question. In the present report we examine the schizophrenia polygenic risk scores (PRS) in those two groups of schizophrenic patients and observe that PRS account for twice the variance in schizophrenia risk in the patients with a relatively normal DLPFC transcriptome (“Type 1”) compared to those with dramatically abnormal DLPFC transcriptomes (“Type 2”). That result supports the hypothesis that the DLPFC transcriptome-defined schizophrenia subtypes are biologically meaningful.

As important as that result is, a serendipitous observation involving patient ancestry is potentially more important because it suggests an approach which future studies might use to investigate the pathogenic pathways leading to these two distinct forms of schizophrenia. Summary statistics from the Psychiatric Genetics Consortium (PGC) wave 3 core cohort GWAS data were used to calculate schizophrenia PRS. That cohort is composed primarily of Caucasians with about 13% Asians. It contains no Africans or African Americans. However, the cohort we studied here (the NIMH Human Brain Collection Core, or HBCC cohort) is composed of roughly 50% Caucasians and 50% African Americans. When the HBCC cohort is stratified based on ancestry it becomes obvious that in African Americans the polygenic risk scores based on summary statistics from the (Caucasian) PGC core cohort capture the genetic risk associated with Type 1, but not Type 2 schizophrenia. Future work comparing summary statistics from schizophrenia GWAS studies of Caucasian and African American populations should reveal the genes and genetic pathways which are specifically involved in the pathogenesis of the two types of schizophrenia

Disclosures

The opinions expressed herein are those of the authors and not necessarily representative of those of the Uniformed Services University of the Health Sciences (USU), the Department of Defense (DOD), the United States Army, Navy, Air Force, VA, NIH or any other US federal agency.
Depressive Symptoms Are Associated With Reduced Unsupervised Training Participation in Inpatients With Subacute Stroke: A Secondary Data Analysis Study
Authors: Oyake Kazuaki , Takahashi Kaori , Arikawa Aiko , Abe Honoka , Kondo Kunitsugu , Otaka Yohei , Tanaka Satoshi
Published: June 2024

Objective: To investigate the association between depressive symptoms and time spent in unsupervised training among inpatients with subacute stroke. Design: This study was a secondary analysis of an unpublished dataset from 34 inpatients with subacute stroke (19 males; median age 65 [interquartile range, 55-75] years). Primary outcome was the median time spent in unsupervised training across three leg cycle sessions. Secondary outcomes included the Functional Independence Measure motor scores at discharge and the length of stay. Depressive symptoms were defined as the Japanese version of the Geriatric Depression Scale Short Form score of 7 or more. Results: Twelve participants (35.3%) had depressive symptoms. The median total time spent in unsupervised training was significantly lower in the group with depressive symptoms (367 [249-799] sec) than in the group without depressive symptoms (888 [579-901] sec), with a medium effect size (U = 57, p = 0.006, Cohen's r = 0.46). No significant differences were found in the secondary outcomes (p > 0.05). Conclusions: Depressive symptoms were associated with reduced participation in unsupervised training among inpatients after stroke. The findings highlight the importance of considering psychological factors in designing and implementing self-rehabilitation programs at the early stages of rehabilitation.
ViViEchoformer: Deep Video Regressor Predicting Ejection Fraction
Authors: Akan Taymaz , Alp Sait , Bhuiyan Md. Shenuarin , Helmy Tarek , Orr A. Wayne , Rahman Bhuiyan Md. Mostafizur , Conrad Steven A. , Vanchiere John A. , Kevil Christopher G. , Bhuiyan Mohammad A. N
Published: June 2024

Heart disease is the leading cause of death worldwide, and cardiac function as measured by ejection fraction (EF) is an important determinant of outcomes, making accurate measurement a critical parameter in PT evaluation. Echocardiograms are commonly used for measuring EF, but human interpretation has limitations in terms of intra- and inter-observer (or reader) variance. Deep learning (DL) has driven a resurgence in machine learning, leading to advancements in medical applications. We introduce the ViViEchoformer DL approach, which uses a video vision transformer to directly regress the left ventricular function (LVEF) from echocardiogram videos. The study used a dataset of 10,030 apical-4-chamber echocardiography videos from patients at Stanford University Hospital. The model accurately captures spatial information and preserves inter-frame relationships by extracting spatiotemporal tokens from video input, allowing for accurate, fully automatic EF predictions that aid human assessment and analysis. The ViViEchoformer’s prediction of ejection fraction has a mean absolute error of 6.14%, a root mean squared error of 8.4%, a mean squared log error of 0.04, and anR2of 0.55. ViViEchoformer predicted heart failure with reduced ejection fraction (HFrEF) with an area under the curve of 0.83 and a classification accuracy of 87 using a standard threshold of less than 50% ejection fraction. Our video-based method provides precise left ventricular function quantification, offering a reliable alternative to human evaluation and establishing a fundamental basis for echocardiogram interpretation.
Nationwide Study on Clinical Outcomes of Endovascular Interventions for Cerebral Venous Thrombosis in Japan
Authors: Senda Atsushi , Suginaka Hiroshi , Morishita Koji , Fushimi Kiyohide
Published: June 2024

Background

Cerebral venous thrombosis (CVT) is a rare but devastating disease, with some patients experiencing disease deterioration despite treatment. Endovascular treatment is an anticipated option, but its clinical relevance is yet to be determined. This observational study aimed to assess the clinical effects and identify patient populations that may benefit from treatment.

Methods

Patient data from April 2014 to March 2022 were extracted from a nationwide Japanese database. The primary outcome was in-hospital mortality, while secondary outcomes included modified Rankin Score (≥ 3) and posthospitalization complications. Severity adjustments were performed using a generalized linear mixed model and propensity score matching.

Results

The analysis included 2901 patients; 240 patients in the endovascular treatment group were matched with 240 patients in the standard treatment group. After adjusting for background factors, endovascular treatment did not improve in-hospital mortality (adjusted odds ratio 1.45 [95% CI: 0.74–2.16]) or the modified Rankin Score (adjusted odds ratio 0.89 [95% CI: 0.56–1.23]). No subpopulations that could benefit from endovascular treatment were identified. However, posthospitalization intracranial complications did not increase with endovascular treatment (0.8% vs. 1.2% in the standard treatment group).

Conclusions

Endovascular treatment did not show any clinical benefit in patients with CVT. These findings are crucial for guiding clinical decisions and suggest that further evidence is warranted.
Holistic Processing Strategy in Cross-Species Face Perception between Dogs and Humans
Authors: Park Soon Young , Niehorster Diederick C. , Huber Ludwig , Virányi Zsófia
Published: June 2024

Extensive studies have shown that humans process faces holistically, considering not only individual features but also the relationships among them. Knowing where humans and dogs fixate first and the longest when they view faces is highly informative, because the locations can be used to evaluate whether they use a holistic face processing strategy or not. However, the conclusions reported by previous eye-tracking studies appear inconclusive. To address this, we conducted an experiment with humans and dogs, employing experimental settings and analysis methods that can enable direct cross-species comparisons. Our findings reveal that humans, unlike dogs, preferentially fixated on the central region, surrounded by the inner facial features, for both human and dog faces. This pattern was consistent for initial and sustained fixations over seven seconds, indicating a clear tendency towards holistic processing. Although dogs did not show an initial preference for what to look at, their later fixations may suggest holistic processing when viewing faces of their own species. We discuss various potential factors influencing species differences in our results, as well as differences compared to the results of previous studies.