bluuebunny/crossref_metadata_2025_split huggingface dataset:
Melanogenic Activity Facilitates Dendritic Cell Maturation via FMOD
Authors: Halasi Marianna , Adini Irit 
Published: May 2022

ABSTRACTAccording to epidemiological research, autoimmune diseases are more prevalent among African Americans, therefore we hypothesized that pigment production in the microenvironment contribute to local immune regulation. Here, in anin vitrosetting we examined the role for pigment production by murine epidermal melanocytes in immune and inflammatory responses via DC activation. Our results revealed that dark pigmented melanocytes increase the production of IL-3 and the pro-inflammatory cytokines IL-6 and TNF-a, and consequently they induce pDC maturation. Further, we found that low pigment associated FMOD interferes with cytokine secretion and subsequent pDC maturation. To the best of our knowledge, this is the first study to assess the effect of baseline pigmentation on epidermal melanocyte cytokine profile, and its impact on DCs.
Illustration of a Novel Gut-Brain Axis of Alcohol Withdrawal, Withdrawal-Associated Depression, Craving and Alcohol-Severity Index in Alcohol Use Disorder Patients
Authors: Vatsalya Vatsalya , Parthasarathy Ranganathan , Verster Joris , Royer Amor C. , Sagaram Manasa , Zamani Zarlakhta , Hu Huirong , Schwandt Melanie L. , Lorenzo Leggio , Kong Maiying , Ramchandani Vijay A , Feng Wenke , Zhang Xiang , McClain Craig J. 
Published: May 2022

AbstractPathways underlying the gut-brain axis and pro-inflammatory cytokine production influence brain functions and behavior. Alcohol use disorder (AUD) patients exhibit domains such as alcohol withdrawal, depression, and craving; and the gut-immune response may play a significant role in these domains of AUD. This study examined the role of intestinal permeability, pro-inflammatory cytokines, and hormones levels on the domains of AUD.Forty-eight AUD patients [male (n=34) and female (n=14)] aged 23-63 yrs. were grouped categorically using the Clinical Institute Withdrawal Assessment of alcohol scale (CIWA) as either clinically significant CIWA group (CS-CIWA [score>10] Gr.1 [n=22]), and clinically not-significant group (NCS-CIWA [score≤10] Gr.2 [n=26]). A sub-set of 13 AUD patient were also tested for reward response for drug-seeking using Penn-Alcohol Craving Score (PACS). Clinical data and blood samples were collected upon enrollment. Blood samples were analyzed for pro-inflammatory cytokines, and hormones, and markers of intestinal permeability. CIWA, 90-day timeline followback (TLFB90), and lifetime drinking history (LTDH) were also collected for comparison.As expected, recent and chronic heavy drinking were significantly higher in Gr.1: HDD90 (heavy drinking days), NDD90 (number of drinking days), as was LTDH, especially in Gr.1 females. Further, in Gr.1, adiponectin (associated with withdrawal) was significantly higher; and numerically higher levels of lipopolysaccharide (LPS) and LPS-binding protein (LBP) were also reported. Gr.1 patients exhibited higher effects of association on the withdrawal-associated depression domain for the parameters of LPS, sCD14, IL-6 and IL-8. Leptin also showed a significantly high effect of association with HDD90 in those AUD patients with craving. The craving domain (assessed by PACS, Penn-Alcohol Craving Scale) could be described as a gut-immune-brain model by the gut-dysregulation (LBP and Leptin) markers, and specific pro-inflammatory activity (IL-1β and TNF-α). Such pathway model describes the heavy drinking phenotype, HDD90 with even higher effects (R2=0.955, p=0.006) in the AUD patients who had higher ratings for craving (PACS>5).Interaction of gut-dysfunction, cytokines involved in both inflammation and in mediating-chemotactic activity constitute a novel pathophysiological gut-brain axis for withdrawal, and alcohol-associated depression and craving domains of AUD. AUD patient with higher craving show higher reinforcing effects of the gut-brain axis response for heavy drinking.
Population genomics of a threespine stickleback tapeworm in Vancouver Island
Authors: Shim Kum C. , Weber Jesse N. , Hernandez Catherine A. , Bolnick Daniel I. 
Published: May 2022

AbstractWe surveyed the genetic structuring of 12 Schistocephalus solidus tapeworm populations from Vancouver Island (BC, Canada) using ddRAD sequencing and compared it to that of their threespine stickleback fish hosts. There were small but mostly significant genetic differences among the tapeworm populations. PCA results separated the populations by watershed (from the lakes where the tapeworms were collected), but we could not determine if the genetic structures seen were due to discrete models (i.e. watershed) or to a continuous model (i.e. isolation by distance). However, the tapeworm genetic differences were significantly smaller (P < 0.001) than those of the fish, which indicates that the parasite disperses more readily than their fish hosts.
On the bacterial ancestry of mitochondria: new insights with triangulated approaches
Authors: Esposti Michelle Degli , Geiger Otto , Sanchez-Flores Alejandro , Esposti Mauro Degli 
Published: May 2022

ABSTRACTWe breathe at the molecular level when mitochondria in our cells consume oxygen to extract energy from nutrients. Mitochondria are characteristic cellular organelles that derive from aerobic bacteria similar to some of those thriving in the oceans nowadays. These organelles carry out most metabolic pathways in eukaryotic cells. The precise bacterial origin of mitochondria and, consequently, the metabolic ancestry of our cells remains controversial - despite the vast genomic information that is now available. Here we triangulate across multiple phylogenomic and molecular approaches to pinpoint the most likely living relatives of the ancestral bacteria from which mitochondria originated.
Senolytic Treatment Reduces Cell Senescence and Necroptosis in Sod1 Knockout Mice that is Associated with Reduced Inflammation and Hepatocellular Carcinoma
Authors: Thadathil Nidheesh , Selvarani Ramasamy , Mohammed Sabira , Nicklas Evan H. , Tran Albert L. , Kamal Maria , Luo Wenyi , Brown Jacob L. , Lawrence Marcus M. , Borowik Agnieszka K. , Miller Benjamin F. , Van Remmen Holly , Richardson Arlan , Deepa Sathyaseelan S. 
Published: May 2022

ABSTRACTThe goal of this study was to test the role cellular senescence plays in the increase in inflammation, chronic liver disease, and hepatocellular carcinoma, which are seen in mice null for Cu/Zn-Superoxide dismutase (Sod1KO). To inhibit senescence, six-month-old wildtype (WT) and Sod1KO mice were given the senolytics, dasatinib and quercetin (D+Q) for seven months. D+Q treatment reduced the expression of p16 in the livers of Sod1KO mice to WT levels as well as the expression of several SASP (senescence associated secretory phenotype) factors (IL-6, IL-1β, CXCL-1, and GDF-15). D+Q treatment also reduced markers of inflammation in livers of the Sod1KO mice, e.g., cytokines, chemokines, macropthage levels, and Kupffer cell clusters. D+Q treatment had no effect on various markers of liver fibrosis in the Sod1KO mice but reduced the expression of genes involved in liver cancer (Myc, Tgfbr2, Socs3, and Cdkn2a) as well as dramatically reducing the incidence of hepatocellular carcinoma. Surprisingly, D+Q also reduced markers of necroptosis (phosphorylated and oligomerized MLKL) in the Sod1KO mice to WT levels. We also found that inhibiting necroptosis in the Sod1KO mice with necrostatin-1s reduced the markers of cellular senescence (p16, p21, and p53). The data from our study suggest that an interaction occurs between cellular senescence and necroptosis in the liver of Sod1KO mice. We propose that these two cell fates interact through a positive feedback loop resulting in a cycle amplifying both cellular senescence and necroptosis leading to inflammaging and age-associated pathology in the Sod1KO mice.
Hecatomb: An End-to-End Research Platform for Viral Metagenomics
Authors: Roach Michael J. , Beecroft Sarah J. , Mihindukulasuriya Kathie A. , Wang Leran , Paredes Anne , Henry-Cocks Kara , Oliveira Lima Lais Farias , Dinsdale Elizabeth A. , Edwards Robert A. , Handley Scott A. 
Published: May 2022

AbstractBackgroundAnalysis of viral diversity using modern sequencing technologies offers extraordinary opportunities for discovery. However, these analyses present a number of bioinformatic challenges due to viral genetic diversity and virome complexity. Due to the lack of conserved marker sequences, metagenomic detection of viral sequences requires a non-targeted, random (shotgun) approach. Annotation and enumeration of viral sequences relies on rigorous quality control and effective search strategies against appropriate reference databases. Virome analysis also benefits from the analysis of both individual metagenomic sequences as well as assembled contigs. Combined, virome analysis results in large amounts of data requiring sophisticated visualization and statistical tools.ResultsHere we introduce Hecatomb, a bioinformatics platform enabling both read and contig based analysis. Hecatomb integrates query information from both amino acid and nucleotide reference sequence databases. Hecatomb integrates data collected throughout the workflow enabling analyst driven virome analysis and discovery. Hecatomb is available on GitHub at https://github.com/shandley/hecatomb.ConclusionsHecatomb provides a single, modular software solution to the complex tasks required of many virome analysis. We demonstrate the value of the approach by applying Hecatomb to both a host-associated (enteric) and an environmental (marine) virome data set. Hecatomb provided data to determine true- or false-positive viral sequences in both data sets and revealed complex virome structure at distinct marine reef sites.
MultiCens: Multilayer network centrality measures to uncover molecular mediators of tissue-tissue communication
Authors: Kumar Tarun , Sethuraman Ramanathan , Mitra Sanga , Ravindran Balaraman , Narayanan Manikandan 
Published: May 2022

AbstractWith the evolution of multicellularity, communication among cells in different organs/tissues became pivotal to life. Molecular basis of such communication has long been studied, but genome-wide screens for biomolecules/genes mediating tissue-tissue signaling are lacking. To systematically identify inter-tissue mediators, we present a novel computational approach MultiCens (Multilayer/Multi-tissue network Centrality measures). Unlike single-layer network methods, MultiCens can distinguish within- vs. across-layer connectivity to quantify the “influence” of any gene in a tissue on a query set of genes of interest in another tissue. MultiCens enjoys theoretical guarantees on convergence and decomposability, and excels on synthetic benchmarks. On human multi-tissue datasets, MultiCens predicts known and novel genes linked to hormones. MultiCens further reveals shifts in gene network architecture among four brain regions in Alzheimer’s disease. MultiCens-prioritized hypotheses from these two diverse applications, and potential future ones like “Multi-tissue-expanded Gene Ontology” analysis, can enable whole-body yet molecular-level investigations in humans.
Neuropathic symptoms with SARS-CoV-2 vaccination
Authors: Safavi Farinaz , Gustafson Lindsey , Walitt Brian , Lehky Tanya , Dehbashi Sara , Wiebold Amanda , Mina Yair , Shin Susan , Pan Baohan , Polydefkis Michael , Oaklander Anne Louise , Nath Avindra 
Published: May 2022

AbstractBackground and ObjectivesVarious peripheral neuropathies, particularly those with sensory and autonomic dysfunction may occur during or shortly after acute COVID-19 illnesses. These appear most likely to reflect immune dysregulation. If similar manifestations can occur with the vaccination remains unknown.ResultsIn an observational study, we studied 23 patients (92% female; median age 40years) reporting new neuropathic symptoms beginning within 1 month after SARS-CoV-2 vaccination. 100% reported sensory symptoms comprising severe face and/or limb paresthesias, and 61% had orthostasis, heat intolerance and palpitations. Autonomic testing in 12 identified seven with reduced distal sweat production and six with positional orthostatic tachycardia syndrome. Among 16 with lower-leg skin biopsies, 31% had diagnostic/subthreshold epidermal neurite densities (≤5%), 13% were borderline (5.01-10%) and 19% showed abnormal axonal swelling. Biopsies from randomly selected five patients that were evaluated for immune complexes showed deposition of complement C4d in endothelial cells. Electrodiagnostic test results were normal in 94% (16/17). Together, 52% (12/23) of patients had objective evidence of small-fiber peripheral neuropathy. 58% patients (7/12) treated with oral corticosteroids had complete or near-complete improvement after two weeks as compared to 9% (1/11) of patients who did not receive immunotherapy having full recovery at 12 weeks. At 5-9 months post-symptom onset, 3 non-recovering patients received intravenous immunoglobulin with symptom resolution within two weeks.ConclusionsThis observational study suggests that a variety of neuropathic symptoms may manifest after SARS-CoV-2 vaccinations and in some patients might be an immune-mediated process.
Reductions and pronounced regional differences in morphine distribution in the United States
Authors: Dowd Megan E. , Tang E. Jessica , Yan Kurlya T. , McCall Kenneth L. , Piper Brian J. 
Published: May 2022

AbstractBackgroundMorphine is one of the oldest, most commonly prescribed, and widely used opioids in the United States (US). Morphine’s potent analgesic properties have also been associated with the increase in misuse, addiction and opioid-related deaths in the US since the 1990s. Despite federal regulations, population-adjusted prescription opioid distribution varies markedly between states. The objective of this study was to describe the temporal pattern of morphine distribution nationally and between states.MethodsDrug weight and population data were obtained from Report 5 of the US Drug Enforcement Administration’s Automation of Reports and Consolidated Orders System (ARCOS) to characterize patterns in the distribution of morphine from 2012 to 2020.Morphine distribution amounts were separated by state and business type and corrected for population. States outside a 95% confidence interval relative to the national average were considered statistically significant.ResultsPharmacies and hospitals distributed 24,200 kilograms of morphine in 2012. Tennessee (180.2 mg/person) was 4.7-fold higher than Texas (39.4 mg/person).National distribution decreased 56.4% to 10,723 kilograms in 2020. Tennessee (56.4 mg/person) was 3.8-fold higher than the District of Columbia (15.0 mg/person). The decline in Illinois (−40.9%) was significantly less than the national average (−56.8%) while that of Oregon (−71.1%) and Arizona (−70.4%) were significantly higher. Hospital decrease (−72.7%) from 2012-2020 was larger than that of pharmacies (−56.12%).ConclusionsThe national 56% decline in the distribution of morphine in the last decade may be attributable to prioritization of the opioid crisis as a public concern, including subsequent growth of opioid misuse and treatment programs and decreased production quotas for opioids, including morphine. This decline also coincides with the national shortage of parenteral opioids resulting in greater prescriptions of alternative opioids such as nalbuphine and buprenorphine. Further research is necessary to understand the persistent four-fold regional difference between states.
Development of a Single Molecule Counting Assay to Differentiate Chromophobe Renal Cancer and Oncocytoma in Clinics
Authors: Satter Khaled Bin , Ramsey Zach , Tran Paul M.H. , Hopkins Diane , Bearden Gregory , Richardson Katherine P. , Terris Martha K. , Savage Natasha M. , Kavuri Sravan K. , Purohit Sharad 
Published: May 2022

AbstractMalignant chromophobe renal cancer (chRCC) and benign oncocytoma (RO) are two renal tumor types difficult to differentiate using histology and immunohistochemistry-based methods because of their similarity in appearance. We previously developed a transcriptomics-based classification pipeline with “Chromophobe-Oncocytoma Gene Signature” (COGS) on a single-molecule counting platform. Renal cancer patients (n=32, chRCC=17, RO=15) were recruited from Augusta University Medical Center (AUMC). Formalin-fixed paraffin-embedded (FFPE) blocks from their excised tumors were collected. We created a custom single-molecule counting code set for COGS to assay RNA from FFPE blocks. Utilizing hematoxylin-eosin stain, pathologists were able to correctly classify these tumor types (91.8%). Our unsupervised learning with UMAP (accuracy = 0.97) and hierarchical clustering (accuracy = 1.0) identified two clusters congruent with their histology. We next developed and compared four supervised models (random forest, support vector machine, generalized linear model with L2 regularization, and supervised UMAP). Supervised UMAP has shown to classify all the cases correctly (sensitivity = 1, specificity = 1, accuracy = 1) followed by random forest models (sensitivity = 0.84, specificity = 1, accuracy = 1). This pipeline can be used as a clinical tool by pathologists to differentiate chRCC from RO.Simple SummaryWe previously reported a gene signature, “Chromophobe-Oncocytoma Gene Signature” (COGS), to differentiate Chromophobe renal cell carcinoma from oncocytoma. Here, we report our results on a single-molecule counting assay with machine learning as a diagnostic pipeline to differentiate chromophobe and oncocytoma tumors utilizing the COGS signature to be used in clinics.
Linking brain maturation and puberty during early adolescence using longitudinal brain age prediction in the ABCD cohort
Authors: Holm Madelene C. , Leonardsen Esten H. , Beck Dani , Dahl Andreas , Kjelkenes Rikka , de Lange Ann-Marie G. , Westlye Lars T. 
Published: May 2022

AbstractThe temporal characteristics of brain maturation could potentially represent a mediating effect between pubertal development and life outcomes. Using a large longitudinal dataset of children aged 9-12 from the Adolescent Brain Cognitive Development (ABCD) study we tested the associations between pubertal status and brain maturation. Brain maturation was assessed using brain age prediction with a deep learning approach based on convolutional neural networks and minimally processed T1-weighted structural MRI data. Brain age prediction provided highly accurate and reliable estimates of individual age, with an overall mean absolute error of 0.7 and 1.4 years at the two timepoints respectively, and an intraclass correlation of 0.65. Linear mixed effects (LME) models accounting for age and sex showed that on average, advancing pubertal development by one pubertal stage was associated with a 2.4 months higher brain age across time points (β= 0.10, p<.001). Further, significant interactions with time demonstrated that higher rates of pubertal development were associated with larger positive changes in brain age over time (p<.001). These results demonstrate a link between sexual development and brain maturation in early adolescence, and provides a basis for further investigations of the complex sociobiological impacts of puberty on the adolescent brain and mind.
Work-Family conflict among hotel housekeepers in the Balearic Islands (Spain)
Authors: Chela-Alvarez Xenia , Garcia-Buades M. Esther , Ferrer-Perez Victoria A. , Bulilete Oana , Llobera Joan 
Published: May 2022

ABSTRACTThe massive incorporation of women to the labour market has increased academic and applied interest on work-life issues throughout the years. This article aims to describe the domestic burden and difficulties in work-life balance (WLB) and at understanding the intersection of work and family spheres among hotel housekeepers (HHs). A cross-sectional study was conducted through Primary Health Care in the Balearic Islands (Spain); 1,043 HHs were enrolled. 56.7% report difficulties in WLB. Risk factors for perceiving difficulties in WLB were: living with one or two co-habitants, low social support, having difficulties making ends meet, being the main responsible person for domestic tasks, having a dependant, presenting higher levels of stress at work and being younger. Protective factors from experiencing work-family conflict (WFC) were job and wage satisfaction. WFC is strongly influenced by individual, economic, labour and domestic factors: these relationships show that labour and domestic spheres are non-separate worlds.
Decoding individual differences in mental information from human brain response predicted by convolutional neural networks
Authors: Kawahata Kiichi , Wang Jiaxin , Blanc Antoine , Maeda Naoya , Nishimoto Shinji , Nishida Satoshi 
Published: May 2022

AbstractRecent advantages in brain decoding with functional magnetic resonance imaging (fMRI) have enabled us to estimate individual differences in mental information from brain responses to natural stimuli. However, the physical constraints and costs of fMRI measurements prevent brain decoding from achieving real-world applications. We address this issue by building a novel framework to decode individual differences in mental information under natural situations from brain responses predicted using convolutional neural networks (CNNs). Once the CNN-based prediction model is trained using measured response, mental information can be decoded from the predicted responses of individual brains with no need for additional fMRI measurements. The model was found to capture individual-difference patterns consistent with conventional decoding using measured responses in 81/87 items to be decoded. Our framework has great potential to decode personal mental information with low dependence on fMRI measurements, which could help substantially expand the applicability of brain decoding in daily life.
Ants act as olfactory bio-detectors of tumour in patient-derived xenograft mice
Authors: Piqueret Baptiste , Montaudon Élodie , Devienne Paul , Leroy Chloé , Marangoni Elisabetta , Sandoz Jean-Christophe , d’Ettorre Patrizia 
Published: May 2022

AbstractEarly detection of cancer is critical in medical sciences, as the sooner a cancer is diagnosed, the higher the chances of recovery. Tumour cells are characterized by specific volatile organic compounds (VOCs) that can be used as cancer biomarkers. Through olfactory associative learning, animals can be trained to detect these VOCs. Insects, such as ants, have a refined sense of smell and can be easily and rapidly trained with olfactory conditioning. Using urine from patient-derived xenograft mice as stimulus, we demonstrate that individual ants can learn to discriminate the odour of healthy mice from that of tumour bearing mice, and do so after only three conditioning trials. Chemical analyses confirmed that the presence of the tumour changed the urine odour, supporting the behavioural results. Our study demonstrates that ants reliably detect tumour cues in mice urine and have the potential to act as efficient and inexpensive cancer bio detectors.