bluuebunny/crossref_metadata_2025 huggingface dataset:
Increased type-I interferon level is associated with liver damage and fibrosis in primary sclerosing cholangitis
Authors: Salzmann Rebekka J.S. , Krötz Christina , Mocan Tudor , Mocan Lavinia P. , Grapa Cristiana , Rottmann Sophia , Reichelt Ramona , Keller Cindy M. , Langhans Bettina , Schünemann Frederik , Pohl Alexander , Böhler Thomas , Bersiner Käthe , Krawczyk Marcin , Milkiewicz Piotr , Sparchez Zeno , Lammert Frank , Gehlert Sebastian , Gonzalez-Carmona Maria A. , Willms Arnulf , Strassburg Christian P. , Kornek Miroslaw T. , Dold Leona , Lukacs-Kornek Veronika
Published: February 2024

Background:

The level of type-I interferons (IFNs) in primary sclerosing cholangitis (PSC) was investigated to evaluate its association with disease activity and progression.

Methods:

Bioactive type-I IFNs were evaluated in a murine model of PSC and human patients’ sera using a cell-based reporter assay and ELISA techniques. In total, 57 healthy participants, 71 PSC, and 38 patients with primary biliary cholangitis were enrolled in this study.

Results:

Bioactive type-I IFNs were elevated in the liver and serum of multidrug resistance protein 2–deficient animals and showed a correlation with the presence of CD45+ immune cells and serum alanine transaminase levels. Concordantly, bioactive type-I IFNs were elevated in the sera of patients with PSC as compared to healthy controls (sensitivity of 84.51%, specificity of 63.16%, and AUROC value of 0.8267). Bioactive IFNs highly correlated with alkaline phosphatase (r=0.4179, p<0.001), alanine transaminase (r=0.4704, p<0.0001), and gamma-glutamyl transpeptidase activities (r=0.6629, p<0.0001) but not with serum bilirubin. In addition, patients with PSC with advanced fibrosis demonstrated significantly higher type-I IFN values. Among the type-I IFN subtypes IFNα, β and IFNω could be detected in patients with PSC with IFNω showing the highest concentration among the subtypes and being the most abundant among patients with PSC.

Conclusions:

The selectively elevated bioactive type-I IFNs specifically the dominating IFNω could suggest a novel inflammatory pathway that might also have a hitherto unrecognized role in the pathomechanism of PSC.
HBV DNA polymerase regulates tumor cell glycogen to enhance the malignancy of HCC cells
Authors: Zhao Xiaoqing , Wang Chunqing , Zhao Liqing , Tian Zhongzheng
Published: February 2024

Background:

The essential function of HBV DNA polymerase (HBV-DNA-Pol) is to initiate viral replication by reverse transcription; however, the role of HBV-DNA-Pol in HBV-associated HCC has not been clarified. Glycogen phosphorylase L (PYGL) is a critical regulator of glycogenolysis and is involved in tumorigenesis, including HCC. However, it is unknown whether HBV-DNA-Pol regulates PYGL to contribute to HCC tumorigenesis.

Methods:

Bioinformatic analysis, real-time quantitative PCR, western blotting, and oncology functional assays were performed to determine the contribution of HBV-DNA-Pol and PYGL to HCC development and glycolysis. The mechanisms of co-immunoprecipitation and ubiquitination were employed to ascertain how HBV-DNA-Pol upregulated PYGL.

Results:

Overexpression of HBV-DNA-Pol enhanced HCC progression in vitro and in vivo. Mechanistically, HBV-DNA-Pol interacted with PYGL and increased PYGL protein levels by inhibiting PYGL ubiquitination, which was mediated by the E3 ligase TRIM21. HBV-DNA-Pol competitively impaired the binding of PYGL to TRIM21 due to its stronger binding affinity to TRIM21, suppressing the ubiquitination of PYGL. Moreover, HBV-DNA-Pol promoted glycogen decomposition by upregulating PYGL, which led to an increased flow of glucose into glycolysis, thereby promoting HCC development.

Conclusions:

Our study reveals a novel mechanism by which HBV-DNA-Pol promotes HCC by controlling glycogen metabolism in HCC, establishing a direct link between HBV-DNA-Pol and the Warburg effect, thereby providing novel targets for HCC treatment and drug development.
Multisystem Inflammatory Syndrome in Children and Cardiac Involvement: A Quaternary Center Experience
Authors: Cruz Vidal Diego , Lee Simon , Ardoin Stacy P. , Dalmacy Djhenne , Chaparro Juan , Blaney Cristin , Rodriguez Vilmarie , Sankar Amanda , Akoghlanian Shoghik , Lisciandro Richard , Washam Matthew , Abraham Roshini S. , Leber Amy , Eby Meika , Bennett Berkeley , Erdem Guliz
Published: February 2024

We prospectively analyzed clinical and laboratory characteristics associated with cardiac involvement and severe presentation in multisystem inflammatory syndrome in children. Of 146 patients, 66 (45.2%) had cardiac dysfunction and 26 (17.8%) had coronary artery abnormalities. Lower serum albumin levels, absolute lymphocyte and platelet counts, and elevated ferritin, fibrinogen, d-dimer and interleukin-6 levels were associated with cardiac dysfunction. Possible treatment complications were identified.
Improving Management: Novel Guidelines for Diagnosing Urinary Tract Infection in Infants
Authors: Khoury Lana , Schnapp Zeev , Konopnicki Muriel
Published: February 2024

Background:

The diagnosis of urinary tract infection (UTI) in the pediatric field remains a topic of debate. In 2011, the American Academy of Pediatrics (AAP) introduced new guidelines for the diagnosis of UTI in patients 2–24 months old. However, concerns were raised regarding these guidelines.

Methods:

This is a retrospective data extraction study that included patients 0–6 months of age who were examined in the pediatric emergency department between 2016 and 2021 and had a urine culture. For each patient, we recorded the diagnosis documented in the medical records, the diagnosis based on the AAP and Israeli guidelines, and the diagnosis according to our 2 proposed protocols. We then compared the percentage of UTI diagnoses according to each diagnostic guideline.

Results:

A total of 1432 patients under the age of 6 months underwent urine culture testing during the study period. A total of 83 (5.81%) of these patients were diagnosed with UTI according to the AAP guidelines, 184 of the patients (12.8%) were diagnosed with UTI according to the Israeli guidelines, 102 (7.1%) and 109 (7.6%) of the patients were diagnosed with UTI according to our first and second proposed guidelines, respectively.

Conclusions:

We propose a new diagnostic method (guidelines II) that is suitable for patients older than 2 months, with obligatory criteria of abnormal urine test and a lower threshold for the colony count required for diagnosis compared to the AAP guidelines. Further research is required to examine the sensitivity and specificity of our proposed guidelines, so it may replace the current diverse guidelines.
Acquired factor V and factor X Deficiency coexisting with acquired dysfibrinogenaemia in a patient with light chain myeloma
Authors: Jeffrey Susan , Hamilton Craig , Ames Paul R.J.
Published: February 2024

An elderly woman with light chain myeloma presented with prolonged epistaxis and extensive cutaneous haematomas: her kappa/lambda ratio was high at 395, her coagulation screen, thrombin and reptilase times were abnormal, her FV and FX were in the low range in the absence of specific inhibitors, her Clauss fibrinogen was low at 0.95 g/l but antigenic FNG was 1.58 g/l. The patient denied treatment and died of progressive renal failure. We wish to describe the unusual association of FX and FV deficiency co-existing with an acquired dysfibrinogenaemia.
Real-world comparative effectiveness of dalteparin and enoxaparin for venous thromboembolism prophylaxis
Authors: Di Mauro Anna L. , Austin Lewis J. , Zande Jasmine , Winckel Karl , Neale Rodney , De Guzman Keshia R.
Published: February 2024

Venous thromboembolism (VTE) is a preventable cause of significant morbidity and mortality in hospitalized patients world-wide. In Australia, the low-molecular weight heparins (LMWHs) enoxaparin or dalteparin are usually used as first-line prophylaxis for VTE, though there is uncertainty whether dalteparin has the same effectiveness as enoxaparin in real-world settings. This is relevant because dalteparin is less renally cleared and may be more cost effective than enoxaparin. The aim of this study was to explore VTE event incidence in a general cohort of hospitalized adult inpatients who were prescribed enoxaparin or dalteparin for VTE prophylaxis. A retrospective observational study was conducted at a quaternary hospital in Brisbane, Australia, of patients who had experienced a hospital-acquired VTE from 1 September 2021 to 1 March 2023. Patients were identified from routinely collected data following an in-hospital VTE event, and further data was retrieved retrospectively from the integrated electronic Medical Record (ieMR). Incidence and type of VTE events, LMWH-prescribing patterns, and risk factors were assessed. The incidence of VTE events were similar across the dalteparin and enoxaparin cohorts (42.1 events/10 000 patients vs. 34.4 events/10 000 patients, respectively), although patients prescribed enoxaparin had a higher number of risk factors, particularly obesity and active cancer. Our research indicates comparable incidence of VTE in patients prescribed dalteparin compared with enoxaparin in an Australian hospital general cohort of adult inpatients. Dalteparin may be as effective as enoxaparin for VTE prophylaxis in a real-world cohort of patients, and as such dalteparin may be considered a suitable alternative to enoxaparin for VTE prophylaxis. Further research including large randomized controlled trials are required to confirm these results.
Bleeding disorders in Saudi Arabia, causes and prevalence: a review
Authors: Belali Tareg M.
Published: February 2024

As bleeding disorders are a worldwide health concern, Saudi Arabia is experiencing a notable prevalence of such disorders. Studying the frequency and cause of hemostatic disorders is the key to successful clinical interventions and instigating effective public policies that limit the spread of such disorders. The current review aims to highlight the major findings of the body of literature that has investigated the causes, prevalence, and major challenges associated with bleeding disorders in the country. The current review summarizes the major findings of different studies that have been conducted in Saudi Arabia regarding different bleeding disorders.

Multiple causes and symptoms of bleeding disorders have been reported by different studies. Some studies investigated the genetic aspect of bleeding disorders and revealed specific mutations in coagulation factor genes influencing the symptoms of different bleeding disorders. Moreover, rare bleeding disorders such as Glanzmann thrombasthenia and Henoch–Schönlein purpura, have been reported in different regions of Saudi Arabia. Combining clinical presentations, genetic factors, and epidemiological data, the current review of the literature provides a comprehensive insight into bleeding disorders in the kingdom. This will help in advancing the diagnostic capabilities and genetic counseling enhancing management strategies and therapeutic interventions benefiting bleeding disorder patients and the kingdom.
In vitro differential inhibition of the factor XI activity assay in the setting of a lupus anticoagulant
Authors: Rabichow Laura , Dinh Janet , Nguyen Lila , Qiao Jesse
Published: February 2024

Acquired factor XI deficiencies due to factor-specific inhibitors are rare and may be associated with lupus anticoagulant. We report a 63-year-old male with suspected postsurgical bleeding, prior surgical site infection, an isolated prolonged activated partial thromboplastin time, and a positive lupus anticoagulant. Although the factor II assay was normal, factor VIII and IX assays initially demonstrated nonparallelism with factor activity that consistently increased to normal reference ranges with serial dilutions. A discrepancy in factor XI activity results was discovered when the in-house method demonstrated undetectable activity (<3%); send-out testing using different instrument/reagent combinations revealed the presence of factor XI activity between 70% and 76%. The patient received surgical follow-up and was subsequently discharged home. Given the differential in vitro inhibition of factor XI activity on our initial in-house testing, this case highlights the importance of recognizing factor assay interference in the presence of a known lupus anticoagulant inhibitor, with strategies to mitigate potentially erroneous results.
A role of platelet C-type lectin-like receptor-2 and its ligand podoplanin in vascular biology
Authors: Suzuki-Inoue Katsue , Tsukiji Nagaharu
Published: February 2024

Purpose of review

Platelets are essential for hemostasis and are also vital in lymphatic and lung development and the maintenance of vascular integrity. Platelet activation receptor C-type lectin-like receptor 2 (CLEC-2) and its endogenous ligand podoplanin (PDPN) in lymphatic endothelial cells (LECs) and other cells regulate these processes. This review aims to comprehensively summarize the roles of platelet CLEC-2 and PDPN. This review also focuses on discussing the underlying mechanisms by which platelet CLEC-2 and PDPN mediate blood/lymphatic separation.

Findings

CLEC-2/PDPN-induced platelet activation in the primary lymph sacs, developmental lymphovenous junctions, neonatal mesentery, and the site of tumor lymphangiogenesis prevents blood/lymphatic vessel misconnection. Further, CLEC-2/PDPN-induced platelet activation is essential for lung development. Mice deficient in CLEC-2 or PDPN show blood-filled lymphatics, lung malformations, and cerebrovascular abnormalities. CLEC-2 deletion in steady-state adult mice did not result in blood/lymphatic vessel mixing. In adulthood, CLEC-2 maintains vascular integrity and that of high endothelial venules in lymph nodes. CLEC-2 deletion in adulthood results in hemorrhage under inflammatory conditions, and hemolymph nodes.

The platelet CLEC-2/LEC PDPN interaction prevents blood/lymphatic vessel mixing at active remodeling sites of the blood/lymphatic system, but not in steady-state adult mice. This interaction also regulates vascular integrity when vascular permeability increases before and after birth.
Costochondritis syndrome and thoracic-chest related pain: a scoping review
Authors: Bolandrini Andrea , Totti Vittoria , Segat Marco , Zaninetti Martina , Fascia Matteo , Segat Andrea , Minetti Federico , Margelli Michele , Maselli Filippo , Galeoto Giovanni
Published: February 2024

Background

Costochondritis is a frequent diagnosis related to chest pain but the etiology, treatment, and evolution of the disease are poorly documented.

Clinical examination lacks specificity and most treatment recommendations are conservative in nature and have been traditionally accepted, perhaps because of the self-limited nature of the condition.

However, costochondritis that does not self-resolve is referred to as atypical costochondritis and is associated with high medical expenses and psychological burden on the patient.

This scoping review will aim to provide a clear overview about costochondritis, including definitions and terms, signs and symptoms, causes, diagnosis, treatment and prognosis. This work will also aim to propose shareable terms to describe this condition.

Inclusion Criteria

Every study describing a condition of non-cardiac musculoskeletal chest pain due to inflammation of the costochondral junctions of ribs or costosternal joints where the areas of tenderness are not generally accompanied by heat, erythema or localized swelling (e.g.,Tietze syndrome). This scoping review will consider studies conducted in any context. Articles in English or Italian will be considered.

Methods

The proposed scoping review will be conducted in accordance with the Joanna Briggs Institute methodology (JBI) for scoping reviews.

The search will be carried out on 5 databases: MEDLINE, Embase, Cochrane Library, CENTRAL and CINAHL. Addictionally, research protocols will be searched on PROSPERO and ClinicalTrials.gov. Further research of grey literature will be carried out through OpenGrey and Google Scholar.

Selection and data extraction will be conducted by two blind independent researchers and inconsistencies will be resolved by a third reviewer.

The results will be presented in a schematic, tabular and descriptive format that will line up with the objectives and scope of the review.

Conclusions

This scoping review will aim to provide a comprehensive overview of the topic. The results will add meaningful information for clinicians. Furthermore, any knowledge gaps of the topic will be identified.
Disrupting CD38-driven T cell dysfunction restores sensitivity to cancer immunotherapy
Authors: Revach Or-Yam , Cicerchia Angelina M. , Shorer Ofir , Petrova Boryana , Anderson Seth , Park Joshua , Chen Lee , Mehta Arnav , Wright Samuel J. , McNamee Niamh , Tal-Mason Aya , Cattaneo Giulia , Tiwari Payal , Xie Hongyan , Sweere Johanna M. , Cheng Li-Chun , Sigal Natalia , Enrico Elizabeth , Miljkovic Marisa , Evans Shane A. , Nguyen Ngan , Whidden Mark E. , Srinivasan Ramji , Spitzer Matthew H. , Sun Yi , Sharova Tatyana , Lawless Aleigha R. , Michaud William A. , Rasmussen Martin Q. , Fang Jacy , Palin Claire A. , Chen Feng , Wang Xinhui , Ferrone Cristina R. , Lawrence Donald P. , Sullivan Ryan J. , Liu David , Sachdeva Uma M. , Sen Debattama R. , Flaherty Keith T. , Manguso Robert T. , Bod Lloyd , Kellis Manolis , Boland Genevieve M. , Yizhak Keren , Yang Jiekun , Kanarek Naama , Sade-Feldman Moshe , Hacohen Nir , Jenkins Russell W.
Published: February 2024

A central problem in cancer immunotherapy with immune checkpoint blockade (ICB) is the development of resistance, which affects 50% of patients with metastatic melanoma1,2. T cell exhaustion, resulting from chronic antigen exposure in the tumour microenvironment, is a major driver of ICB resistance3. Here, we show that CD38, an ecto-enzyme involved in nicotinamide adenine dinucleotide (NAD+) catabolism, is highly expressed in exhausted CD8+T cells in melanoma and is associated with ICB resistance. Tumour-derived CD38hiCD8+T cells are dysfunctional, characterised by impaired proliferative capacity, effector function, and dysregulated mitochondrial bioenergetics. Genetic and pharmacological blockade of CD38 in murine and patient-derived organotypic tumour models (MDOTS/PDOTS) enhanced tumour immunity and overcame ICB resistance. Mechanistically, disrupting CD38 activity in T cells restored cellular NAD+pools, improved mitochondrial function, increased proliferation, augmented effector function, and restored ICB sensitivity. Taken together, these data demonstrate a role for the CD38-NAD+axis in promoting T cell exhaustion and ICB resistance, and establish the efficacy of CD38 directed therapeutic strategies to overcome ICB resistance using clinically relevant, patient-derived 3D tumour models.
Quantitative genetics of naturalS. cerevisiaestrains upon sexual mating reveals heritable determinants of cellular fitness
Authors: Strauss Sivan Kaminski , Golomb Ruthie , Sheykhkarimli Dayag , Liti Gianni , Dahan Orna , Pilpel Yitzhak
Published: February 2024

Quantitative genetics requires large datasets of diverse phenotyped-genotyped strains from the same species. A special need is for such archived biological material and computerized data in sexually reproducing individuals from a species. Here we leverage sexual mating among close to 100 diverse natural isolates of the yeastS. cerevisiaethat form about 4,000 offspring combinations in several ecologically relevant growth conditions. In a first genetic study of this new resource we focus on fitness measurements and its modes of inheritance as a quantitative trait from parents to offspring. We employ genomic barcoding of all strains and a barcode recombination technique to follow offspring of each successful mate combination. For all parents, and separately for all offspring we measure fitness under each condition. We focus on the inheritance of fitness, the ultimate evolutionary trait, and its inheritance as a quantitative trait upon sexual mating. Predicting offspring fitness given parental parameters is a major challenge as it is likely multi-factorial. We find that offspring fitness in fermentable carbon source correlates positively, yet modestly, with parental fitness, while on non-fermentable carbon, offspring fitness shows no detectable correlation with parental fitness. Instead, the non-fermentable condition, fitness of offspring increases sharply with genetic distance between their parents, suggesting that outbreeding maximizes offspring fitness irrespective of parental fitness at that condition. The number of minor alleles in the genome of each offspring, analogous to polygenic risk score in classical genetics, negatively correlates with offspring fitness in both conditions. Modeling of fitness inheritance shows that modes of inheritance are explained by either a dominance or a co-dominance models, in the fermentable and non-fermentable conditions respectively. Our newly suggested biological resource and data provide new foundations for a quantitative research in genetics and evolution upon sexual mating. Furthermore, our barcoded strains and mating tracking method provide an important research resource for the yeast community.
Discovery of a newMyristicaswamp in the Northern Western Ghats of India
Authors: Desai Pravin , Sadekar Vishal , Desai Shital
Published: February 2024

Myristicaswamps are one of the world’s unique freshwater ecosystems. In recent years there has been an increase in the number of reports about their distribution along the western Ghats. In the current paper, we report a new distribution record for the occurrence ofMyristicaSwamp from the northern part of the western Ghats of Maharastra. TheMyristicaswamp is located within the Bhalandeshwar Sacred Grove of Kumbral Bagwadi, Dodamarg Maharastra, India. This forms a second report from the state of Maharastra. Frequent field visits were made to study and document the floral assemblage and biodiversity in the swamp from, November 2023 to January 2024. The swamp is dominated byMyristica magnificaBedd. The swamp is a part of a sacred grove and it is protected by Villagers due to religious beliefs. The discovery of this swamp points towards the possibility of the occurrence of more swamps in this region. Hence there is a need for a systematic survey for documenting swamps in the different areas.
Mapping Cell Fate Transition in Space and Time
Authors: Gu Yichen , Liu Jialin , Li Chen , Welch Joshua D.
Published: February 2024

Cell fate transition is fundamentally a spatiotemporal process, but previous work has largely neglected the spatial dimension. Incorporating both space and time into models of cell fate transition would be a key step toward characterizing how interactions among neighboring cells, the presence of local niche factors, and physical migration of cells contribute to tissue development. To realize this potential, we propose topological velocity inference (TopoVelo), a model for jointly inferring spatial and temporal dynamics of cell fate transition from spatial transcriptomic data. TopoVelo extends the RNA velocity framework to model single-cell gene expression dynamics of an entire tissue with spatially coupled differential equations. Our principled probabilistic approach enables the incorporation of time point labels and multiple slices. We further introduce the idea of cell velocity, which is defined as the physical direction of cell maturation and migration. Simulated data analysis indicates that incorporating spatial coordinates significantly improves the accuracy of velocity and time inference. When evaluated on real Slide-Seq and Stereo-Seq data, TopoVelo significantly improves the spatial coherence of inferred cell ordering compared to previous methods. Furthermore, TopoVelo accurately recovers the expected directions of cell differentiation and migration in the embryonic mouse cerebral cortex, gut, and lung. Our work introduces a new dimension into the study of cell fate transitions and lays a foundation for modeling the collective dynamics of cells comprising an entire tissue.
Skin Sensitisation Case Study: Comparison of Defined Approaches including OECD 497 Guidance
Authors: Ankli Pascal P. , Parween Shaheena , Lopez Béatrice , Daligaux Pierre , Mohorič Tomaž , Darde Thomas , Chesné Christophe , Stockman Nathan , Boglári Csaba , Poon Amanda Y. , Hardy Barry
Published: February 2024

Characterising known and new chemical compounds for skin sensitisation provides a basis for the development of safer products where ingredients are exposed to skin. By including new approaches, such as tiered testing strategies and integrated data analysis, it is possible to develop next generation products adhering to emerging regulations, scientific evidence and animal welfare principles. To ensure data integrity during such assessment the OECD provides characterisation guidelines and Defined Approaches (DAs) to uniform work-flows. In this study we developed and applied the integrated characterisation tool called «SaferSkin™» to compare the results of different DAs for eight compounds and included results obtained from current OECD guidance and emerging methods. We tested two compounds with unclear or indeterminate results with the SENS-IS assay to explore the value of the experiment in strengthening the weight of evidence and arriving at a clearer conclusion.
Mastication while rested does not improve sustained attention in healthy participants conducting short-duration cognitive tasks
Authors: Hansen Devon , Maislin Greg , Day Jon E. L.
Published: February 2024

Sustained attention is important for optimal neurobehavioral performance, but many biological and environmental factors (e.g., circadian rhythm, distraction, etc.) may cause sustained attention deficits. It has been suggested that mastication (chewing) may ameliorate such deficits. As part of a continuing program to study the effects of mastication under varying conditions of fatigue and cognitive demand, this trial used a randomized, within-subjects, cross-over design to investigate the effect of mastication (gum chewing) on levels of sustained attention. To initially provide data that was ecologically valid for the average person, participants were not sleep deprived or otherwise challenged. Fifty-eight healthy adults (aged 18 – 45 years; 38 females) completed a 5 h in-laboratory daytime study during which time they completed two, 40 min test bouts. Participants completed the Psychomotor Vigilance Test (PVT), the Sustained Attention to Response Task (SART), the Karolinska Sleepiness Scale (KSS) and the Positive and Negative Affect Schedule (PANAS). During one of the two test bouts, participants were instructed to chew a piece of gum at a steady, comfortable rate. The statistical analyses were conducted blind. The primary outcome variable used for analyses was PVT lapses using the transformation square root of lapses plus square root of lapses plus 1 in addition to PVT mean reciprocal response time. Secondary outcome variables were PVT time-on-task slope and SART error score. Using rested participants and moderately fatiguing tasks, we were unable to detect any significant improvement in PVT or SART performance, or in KSS or PANAS ratings. A follow-up study under conditions of sleep deprivation and/or with longer task duration may provide further insight into the countermeasure potential of mastication.
Brain eQTLs of European, African American, and Asian ancestry improve interpretation of schizophrenia GWAS
Authors: Chen Yu , Liu Sihan , Ren Zongyao , Wang Feiran , Jiang Yi , Dai Rujia , Duan Fangyuan , Han Cong , Ning Zhilin , Xia Yan , Li Miao , Yuan Kai , Qiu Wenying , Yan Xiao-Xin , Dai Jiapei , Kopp Richard F. , Huang Jufang , Xu Shuhua , Tang Beisha , Gamazon Eric R. , Bigdeli Tim , Gershon Elliot , Huang Hailiang , Ma Chao , Liu Chunyu , Chen Chao
Published: February 2024

Research on brain expression quantitative trait loci (eQTLs) has illuminated the genetic underpinnings of schizophrenia (SCZ). Yet, the majority of these studies have been centered on European populations, leading to a constrained understanding of population diversities and disease risks. To address this gap, we examined genotype and RNA-seq data from African Americans (AA, n=158), Europeans (EUR, n=408), and East Asians (EAS, n=217). When comparing eQTLs between EUR and non-EUR populations, we observed concordant patterns of genetic regulatory effect, particularly in terms of the effect sizes of the eQTLs. However, 343,737 cis-eQTLs (representing ∼17% of all eQTLs pairs) linked to 1,276 genes (about 10% of all eGenes) and 198,769 SNPs (approximately 16% of all eSNPs) were identified only in the non-EUR populations. Over 90% of observed population differences in eQTLs could be traced back to differences in allele frequency. Furthermore, 35% of these eQTLs were notably rare (MAF < 0.05) in the EUR population. Integrating brain eQTLs with SCZ signals from diverse populations, we observed a higher disease heritability enrichment of brain eQTLs in matched populations compared to mismatched ones. Prioritization analysis identified seven new risk genes (SFXN2,RP11-282018.3,CYP17A1,VPS37B,DENR,FTCDNL1, andNT5DC2), and three potential novel regulatory variants in known risk genes (CNNM2,C12orf65, andMPHOSPH9) that were missed in the EUR dataset. Our findings underscore that increasing genetic ancestral diversity is more efficient for power improvement than merely increasing the sample size within single-ancestry eQTLs datasets. Such a strategy will not only improve our understanding of the biological underpinnings of population structures but also pave the way for the identification of novel risk genes in SCZ.
Gemykibivirus detection in acute encephalitis patients from Nepal
Authors: Tuladhar Eans Tara , Shrestha Smita , Vernon Susan , Droit Lindsay , Mihindukulasuriya Kathie A. , Tamang Mamta , Karki Lata , Ngono Annie Elong , Jha Bimlesh , Awal Bal Krishna , Chalise Bimal Sharma , Jha Runa , Shresta Sujan , Wang David , Manandhar Krishna Das
Published: February 2024

Acute Encephalitis Syndrome (AES) causes significant morbidity and mortality worldwide. In Nepal, Japanese encephalitis virus (JEV) accounts for ∼ 5-20% of AES cases, but ∼75% of AES cases are of unknown etiology. We identified a gemykibivirus in CSF collected in 2020 from a male child with AES using metagenomic next-generation sequencing. Gemykibiviruses are single stranded, circular DNA viruses in the familyGenomoviridae. The complete genome of 2211 nucleotides was sequenced which shared 98.69% nucleotide identity to its closest relative, Human associated gemykibivirus 2 isolate SAfia-449D. Two real-time PCR assays were designed, and screening of 337 CSF and 164 serum samples from AES patients in Nepal collected in 2020 and 2022 yielded 11 CSF and 1 serum sample that were positive in both PCR assays. Complete genomes of 7 of the positives were sequenced. These results identify a candidate etiologic agent of encephalitis in Nepal.
Relationship between temporal projections and cognition in patients with putaminal hemorrhage
Authors: Jang Sung Ho , Kwon Hyeok Gyu
Published: February 2024

Background

The cognitive function is a complex mental process involving the temporal projections (cingulum, superior longitudinal fasciculus[SLF], inferior longitudinal fasciculus[ILF], and uncinate fasciculus[UF]). Therefore, a brain injury involving the temporal projections results in cognitive impairment. However, few studies have reported the pathophysiological mechanisms associated with cognitive impairment in patients with putaminal hemorrhage(PH). In this study, using diffusion tensor tractography(DTT), the relationship between the temporal projections and cognition was analyzed in patients with PH.

Methods

25 patients with PH were recruited for this study. A Mini-Mental State Examination(MMSE) was conducted twice to evaluate their cognitive function(within one month and six months after onset). The temporal projections(cingulum, SLF, ILF, and UF) were reconstructed and the values of DTT parameters were measured. Pearson correlation and multiple regression analyses were also performed to determine the relationship between the DTT parameters of the temporal projections and the MMSE.

Results

An analysis of the correlations showed that the fractional anisotropy and fiber number ratio of the UF were correlated with the MMSE performed within one month and six months after onset. In addition, the fiber number of the UF on the MMSE at six months from the onset had an explanatory power of 33% and showed the 0.064 for unstandardized coefficients.

Conclusions

Using DTT, this study demonstrated that among the temporal projections, the state of the UF in patients with PH could be the most significant indicator of cognitive function. Our results suggested that evaluation of the UF using DTT could be useful in predicting the cognitive function following PH.
The Northern Colours: Isolation and Characterisation of 4 Pigment-Producing Bacteria from the Arctic
Authors: Das Jenifar , Singh Ashish Kumar
Published: February 2024

Due to the adverse effects of synthetic colours on human health and the environment, there is a rapid shift towards the use of colours from natural sources like plants and microorganisms. Many pigment-producing microorganisms are identified and isolated from extreme environments like glaciers, ice cores, marine surface waters, etc. In this study, we have isolated 4 distinct pigment-producing bacterial strains from an Arctic stone sample collected from the vicinity of the Indian Research StationHimadri(78°55′N11°56′E), located at the International Arctic Research Base, NyÅlesund, Svalbard, Norway. Pigment production was optimised by identifying the right growth medium, temperature, pH, and incubation period. The morphological, cultural, and biochemical characteristics were identified using several experiments like Gram Staining, Catalase Test, Oxydative-Fermentative Test, etc. The objective of this study is to identify novel bacterial strains capable of producing distinct pigments for pharmaceutical and industrial applications.
Differentiation smelling footprints of the Chagas disease vector using an electronic nose based on artificial intelligence algorithms
Authors: Ruiz-Jiménez Luisa F. , Sierra Daniel A. , Ortega B Homero , Rincon-Orozco Bladimiro , Duque Jonny E.
Published: February 2024

The present study aims to present the design of an electronic nose capable of learning and differentiating semiochemical signals emitted by insects usable to identify species that transmit Chagas disease. The proposed device used different non-specific resistor gas sensors integrated into a system of artificial intelligence models. To validate the nose, we used eight insect species of the Triatominae subfamily and one population that was a natural carrier of the parasiteTrypanosoma cruzi. Also, the discriminatory capacity of distant species was tested with other insects likeAedes aegypti(arbovirus vector) andSitophilus oryzae(stored grains plague). As a result, the electronic nose was able to differentiate up to gender level with an accuracy of 89.64% and to differentiateRhodnius pallenscesnaturally infected withT. cruziwith less than 1% of error in classification. These results show that our designed device can detect particular smelling footprints, and one electronic nose like that could be a tool to discriminate against insects in the future.
A Workflow for Improved Analysis of Cross-linking Mass Spectrometry Data Integrating Parallel Accumulation-Serial Fragmentation with MeroX and Skyline
Authors: Rojas Echeverri Juan Camilo , Hause Frank , Iacobucci Claudio , Ihling Christian H. , Tänzler Dirk , Shulman Nicholas , Riffle Michael , MacLean Brendan , Sinz Andrea
Published: February 2024

Cross-linking mass spectrometry (XL-MS) has evolved into a pivotal technique for probing protein interactions. This study describes the implementation of Parallel Accumulation-Serial Fragmentation (PASEF) on timsTOF instruments, enhancing the detection and analysis of protein interactions by XL-MS. Addressing the challenges in XL-MS, such as the interpretation of complex spectra, low abundant cross-linked peptides, and a data acquisition bias, our current study integrates a peptide-centric approach for the analysis of XL-MS data and presents the foundation for integrating data-independent acquisition (DIA) in XL-MS with a vendor-neutral and open-source platform. A novel workflow is described for processing data-dependent analysis (DDA) of PASEF-derived information. For this, software by Bruker Daltonics is used, enabling the conversion of these data into a format that is compatible with MeroX and Skyline software tools. Our approach significantly improves the identification of cross-linked products from complex mixtures, allowing the XL-MS community to overcome current analytical limitations.
Matching dynamically varying forces with multi-motor-unit muscle models: A simulation study
Authors: Murtola T. , Richards C.
Published: February 2024

Human muscles exhibit great versatility, not only generating forces for demanding athleticism, but also for fine motor tasks. While standard musculoskeletal models may reproduce this versatility, they often lack multiple motor units (MUs) and rate-coded control. To investigate how these features affect a muscle’s ability to generate desired force profiles, we performed simulations with nine alternative MU pool models for two cases: 1) a tibialis anterior muscle generating an isometric trapezoidal force profile, and 2) a generic shoulder muscle generating force for a reaching movement whilst undergoing predetermined length changes. We implemented two control strategies, pure feedforward and combined feedforward-feedback, each parameterised using elementary tasks. The results suggest that the characteristics of MU pools have relatively little impact on the pools’ overall ability to match forces across all tasks, although performances for individual tasks varied. Feedback improved performance for nearly all MU pools and tasks, but the physiologically more relevant MU pool types were more responsive to feedback particularly during reaching. While all MU pool models performed well in the conditions tested, we highlight the need to consider the functional characteristics of the control of rate-coded MU pools given the vast repertoire of dynamic tasks performed by muscles.
Predictive simulation of human movement in OpenSim using floating-base task space control
Authors: Pickle Nathaniel T. , Sundararajan Aravind
Published: February 2024

Task space control, also known as operational space control, is a useful paradigm for investigating neural control of human movement using predictive simulations. While some efforts have been made to implement task space control in the widely used open-source platform OpenSim, existing implementations do not support floating base kinematics, which is necessary for simulating gait and other types of human movement. Our aim in this work is to fill that gap. In this paper, we describe the theory and implementation of a floating base kinematics task space framework for torque- and muscle-driven simulations in OpenSim. Our framework builds on previous work that was limited to models with a base (i.e., root) segment fixed to ground. In addition, we integrate various algorithms from robotics in order to handle dynamically changing contacts and task prioritization. The framework can be used to generate realistic walking gaits by prescribing a small set of controller gains and gait parameters such as step length, step width and center of mass velocity. Task can be specified as desired positions, rotations, or higher-order feature such as base of support and whole-body angular momentum. We provide several examples to demonstrate how framework is successful in orchestrating a complex hierarchy of tasks that work in concert to perform both balance control and gait generation. The implementation is freely available for roboticists and biomechanists to use with OpenSim.

Author summary

Recent advances in computational biomechanics have provided researchers with tools capable of predicting human movement. Previous approaches to simulating human movement required experimental data as input and the simulation would replicate the experimental motion. This conventional approach limited the scientific insights to the specific movement recorded in the laboratory. With predictive approaches, researchers can investigate how a person might respond to various factors, such as reduced muscle strength or an assistive device such as a robotic exoskeleton. Existing approaches for generating predictive simulations utilize optimization-based approaches, which can be time-consuming and difficult to troubleshoot. Task space control is an alternative approach which is widely used in robotics. Conceptually, task space control aims to generate a simulation by specifying “tasks”, such as moving a hand or foot to a desired position, and computing the joint angles required to achieve the task. Here we aim to outline the mathematics behind task space control and demonstrate how task space control can be used to generate simulations of movements such as walking.
Cytometry Masked Autoencoder: An Accurate and Interpretable Automated Immunophenotyper
Authors: Kim Jaesik , Ionita Matei , Lee Matthew , McKeague Michelle L. , Pattekar Ajinkya , Painter Mark M. , Wagenaar Joost , Truong Van , Norton Dylan T. , Mathew Divij , Nam Yonghyun , Apostolidis Sokratis A. , Clendenin Cynthia , Orzechowski Patryk , Jung Sang-Hyuk , Woerner Jakob , Ittner Caroline A.G. , Turner Alexandra P. , Esperanza Mika , Dunn Thomas G. , Mangalmurti Nilam S. , Reilly John P. , Meyer Nuala J. , Calfee Carolyn S. , Liu Kathleen D. , Matthy Michael A. , Swigart Lamorna Brown , Burnham Ellen L. , McKeehan Jeffrey , Gandotra Sheetal , Russel Derek W. , Gibbs Kevin W. , Thomas Karl W. , Barot Harsh , Greenplate Allison R. , Wherry E. John , Kim Dokyoon
Published: February 2024

High-throughput single-cell cytometry data are crucial for understanding involvement of immune system in diseases and responses to treatment. Traditional methods for annotating cytometry data, specifically manual gating and clustering, face challenges in scalability, robustness, and accuracy. In this study, we propose a cytometry masked autoencoder (cyMAE), which offers an automated solution for immunophenotyping tasks including cell type annotation. The cyMAE model is designed to uphold user-defined cell type definitions, thereby facilitating easier interpretation and cross-study comparisons. The cyMAE model operates on a pre-train and fine-tune approach. In the pre-training phase, cyMAE employsMasked Cytometry Modelling (MCM)to learn relationships between protein markers in immune cells solely based on protein expression, without relying on prior information such as cell identity and cell type-specific marker proteins. Subsequently, the pre-trained cyMAE is fine-tuned on multiple specialized tasks via task-specific supervised learning. The pre-trained cyMAE addresses the shortcomings of manual gating and clustering methods by providing accurate and interpretable predictions. Through validation across multiple cohorts, we demonstrate that cyMAE effectively identifies co-occurrence patterns of bound labeled antibodies, delivers accurate and interpretable cellular immunophenotyping, and improves the prediction of subject metadata status. Specifically, we evaluated cyMAE for cell type annotation and imputation at the cellular-level and SARS-CoV-2 infection prediction, secondary immune response prediction against COVID-19, and prediction of the infection stage in COVID-19 progression at the subject-level. The introduction of cyMAE marks a significant step forward in immunology research, particularly in large-scale and high-throughput human immune profiling. This approach offers new possibilities for predicting and interpreting cellular-level and subject-level phenotypes in both health and disease.
Pooled PPIseq: screening the SARS-CoV-2 and human interface with a scalable multiplexed protein-protein interaction assay platform
Authors: Miller Darach , Dziulko Adam , Levy Sasha
Published: February 2024

Protein-ProteinInteractions (PPIs) are a key interface between virus and host, and these interactions are important to both viral reprogramming of the host and to host restriction of viral infection. In particular, viral-host PPI networks can be used to further our understanding of the molecular mechanisms of tissue specificity, host range, and virulence. At higher scales, viral-host PPI screening could also be used to screen for small-molecule antivirals that interfere with essential viral-host interactions, or to explore how the PPI networks between interacting viral and host genomes co-evolve. Current high-throughput PPI assays have screened entire viral-host PPI networks. However, these studies are time consuming, often require specialized equipment, and are difficult to further scale. Here, we develop methods that make larger-scale viral-host PPI screening more accessible. This approach combines the mDHFR split-tag reporter with the iSeq2 interaction-barcoding system to permit massively-multiplexed PPI quantification by simple pooled engineering of barcoded constructs, integration of these constructs into budding yeast, and fitness measurements by pooled cell competitions and barcode-sequencing. We applied this method to screen for PPIs between SARS-CoV-2 proteins and human proteins, screening in triplicate >180,000 ORF-ORF combinations represented by >1,000,000 barcoded lineages. Our results complement previous screens by identifying 74 putative PPIs, including interactions between ORF7A with the taste receptors TAS2R41 and TAS2R7, and between NSP4 with the transmembrane KDELR2 and KDELR3. We show that this PPI screening method is highly scalable, enabling larger studies aimed at generating a broad understanding of how viral effector proteins converge on cellular targets to effect replication.
Current Research On Epigenetic Age and Cellular Senescence: A Bibliometric and Visual Analysis
Authors: Mureti kahaer M.M , Wang Hao B.M , Zhi-Guo Sun M.M , Kuo Xu M.M , Dilimulati Aikeremu M.M
Published: February 2024

The aim of this study is to summarize and visualize the current state of research on epigenetic age and cellular senescence over the last two decades using bibliometric methods and to explore the current research priorities and future development directions. Relevant literature on the topic Epigenetic age and cellular senescence data published between January 2000 and January 2024 were searched in the Web of Science core database and three bibliometric mapping tools (Biblimetrix R Package, VOS Viewer and CiteSpace) were used to provide an overview of the Literature to give and analyze keywords, the co-occurrence of reference citations, authors and institutions, to analyze the current status of epigenetic aging research and hot changes in recent years. A total of 2,193 relevant studies were included, and the co-occurrence network identified seven clusters of associations between epigenetic age and cellular senescence, including effects on human tissues, genetic clock analyses, the relationship of age-related diseases, precise genetic changes and accelerated cellular senescence, localized cellular transformations, and genetic immune regulation. The analysis shows that research in this area has shifted from disease-level studies to mechanism-based studies, with cancer being the main disease and the main pathogenic mechanism being related to DNA methylation. The research direction in recent years has focused on the mechanism study of epigenetic age and cellular senescence as well as target therapy. The bibliometric and visualization analyzes provide a comprehensive understanding of the research progress and the role between epigenetic age and human cellular senescence and enrich the review literature in this field.