bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effective connectivity of emotion and cognition under psilocybin
Authors: Stoliker Devon , Novelli Leonardo , Vollenweider Franz X. , Egan Gary F. , Preller Katrin H. , Razi Adeel 
Published: September 2022

AbstractClassic psychedelics alter sense of self and patterns of self-related thought. These changes are hypothesised to underlie their therapeutic efficacy across internalising pathologies such as addiction and depression. Using resting-state functional MRI images from a randomised, double blinded, placebo-controlled clinical trial of 24 healthy adults under 0.215mg/kg psilocybin, we investigated how psilocybin modulates the effective connectivity between resting state networks and the amygdala that are involved in the appraisal and regulation of emotion and association with clinical symptoms. The networks included the default mode network (DMN), salience network (SN) and central executive network (CEN). Psilocybin decreased top-down effective connectivity from the resting state networks to the amygdala and decreased effective connectivity within the DMN and SN, while the within CEN effective connectivity increased. Effective connectivity changes were also associated with altered emotion and meaning under psilocybin. Our findings identify changes to cognitive-emotional connectivity associated with the subjective effects of psilocybin and the attenuation of the amygdala signal as a potential biomarker of psilocybin’s therapeutic efficacy.
The Relationship Between Symptoms and Job Loss among Japanese Workers During the COVID-19 Pandemic: A Prospective Cohort Study
Authors: Okahara Shintaro , Fujino Yoshihisa , Nagata Tomohisa , Kuwamura Mami , Mafune Kosuke , Muramatsu Keiji , Tateishi Seiichiro , Ogami Akira , Mori Koji ,   the CORoNaWork project
Published: September 2022

AbstractObjectivesThe aim of this study was to clarify which workers’ symptoms led to unemployment during the COVID-19 pandemic.MethodsThis was a prospective cohort study using questionnaires about COVID-19 administered to Japanese workers. A baseline survey conducted in December 2020 was used to determine workers’ health history. Unemployment since the baseline survey was ascertained with a follow-up survey in December 2021. The odds ratios (ORs) of unemployment were estimated using a multilevel logistic model with adjusted covariates nested in prefecture of residence.ResultsMales (n= 8,682) accounted for 58.2% of the total sample (n= 14,910), and the mean age was 48.2 years. Multivariate analysis showed that workers with “pain-related problems,” “limited physical movement and mobility,” “fatigue, loss of strength or appetite, fever, dizziness, and moodiness,” “mental health problems,” or “sleep” had a greater probability of resigning for health reasons, resigning for all reasons other than retirement, and being unemployed. Those with “skin, hair, and cosmetic concerns” or “eye-related matters” had a greater probability of becoming unemployed.ConclusionsWe identified an association between workers’ symptoms and resignation or unemployment, with different symptoms having different ORs. Furthermore, there were differences in the associations among the effects of symptoms, work dysfunction, resignation/unemployment, and attitudes of others. Preventive interventions to help workers resolve or improve their symptoms could prevent their becoming unemployed or resigning.
Low Molecular Weight Hyaluronan Inhibits Lung Epithelial Ion Channels by Activating the Calcium-Sensing Receptor
Authors: Lazrak Ahmed , Song Weifeng , Yu Zhihong , Zhang Shaoyan , Nellore Anoma , Hoopes Charles W. , Woodworth Bradford A. , Matalon Sadis 
Published: September 2022

AbstractHerein, we tested the hypothesis low molecular weight hyaluronan (LMW-HA) inhibits lung epithelial ion transport in-vivo, ex-vivo, and in-vitro by activating the calcium-sensing receptor (CaSR). Intranasal instillation of LMW-HA (150μg/ml) to C57BL/6 mice inhibited their alveolar fluid clearance (AFC) by 75%, increased the epithelial lining fluid (ELF) thickness threefold, and lung wet/dry (W/D) ratio by 20% 24hrs later. Incubation of lung slices from mouse and human lungs with 150μg/ml LMW-HA decreased the open probability (Po) of ENaC in ATII cell by more than 50% in 4hrs, inhibited amiloride sensitive short circuit current (SCC) 4hrs post exposure, and Cl−current through CFTR by more than 70%, and Na,K-ATPase current by 66% at 24hrs. In all cases the inhibitory effect of LMW-HA on lung epithelial ion transport in vivo, ex vivo, and in vitro preparations were reversed by the administration of 1μM of NPS2143, a CaSR inhibitor, or 150μg/ml HMW-HA. In HEK-293 cells co-transfected with CaSR and the calcium sensitive Cl−channel TMEM16-A, LMW-HA activated an inward Cl−current. These data are the first demonstration of the inhibitory effects of LMW-HA on lung epithelial ion and water transport, and are due to the activation of CaSR and its downstream signaling cascades.
Biologically relevant integration of transcriptomics profiles from cancer cell lines, patient-derived xenografts and clinical tumors using deep learning
Authors: Dimitrieva Slavica , Janssens Rens , Li Gang , Szalata Artur , Gopal Raja , Parmar Chintan , Kauffmann Audrey , Durand Eric Y. 
Published: September 2022

AbstractCell lines and patient-derived xenografts are essential to cancer research, however, the results derived from such models often lack clinical translatability, as these models do not fully recapitulate the complex cancer biology. It is critically important to better understand the systematic differences between cell lines, xenografts and clinical tumors, and to be able to identify pre-clinical models that sufficiently resemble the biological characteristics of clinical tumors across different cancers. On another side, direct comparison of transcriptional profiles from pre-clinical models and clinical tumors is infeasible due to the mixture of technical artifacts and inherent biological signals.To address these challenges, we developed MOBER, Multi-Origin Batch Effect Remover method, to simultaneously extract biologically meaningful embeddings and remove batch effects from transcriptomic datasets of different origin. MOBER consists of two neural networks: conditional variational autoencoder and source discriminator neural network that is trained in adversarial fashion. We applied MOBER on transcriptional profiles from 932 cancer cell lines, 434 patient-derived tumor xenografts and 11’159 clinical tumors and identified pre-clinical models with greatest transcriptional fidelity to clinical tumors, and models that are transcriptionally unrepresentative of their respective clinical tumors. MOBER can conserve the biological signals from the original datasets, while generating embeddings that do not encode confounder information. In addition, it allows for transformation of transcriptional profiles of pre-clinical models to resemble the ones of clinical tumors, and therefore can be used to improve the clinical translation of insights gained from pre-clinical models. As a batch effect removal method, MOBER can be applied widely to transcriptomics datasets of different origin, allowing for integration of multiple datasets simultaneously.
Open spaced ridged hydrogel scaffolds containing TiSAMP surface chemistry promotes regeneration and recovery following spinal cord injury
Authors: Siddiqui Ahad M. , Thiele Fredric , Stewart Rachel , Rangnick Simone , Weiss Georgina , Chen Bingkun K. , Silvernail Jodi , Strickland Tammy , Nesbitt Jarred , Lim Kelly , Schwarzbauer Jean E. , Schwartz Jeffrey , Yaszemski Michael J. , Windebank Anthony J. , Madigan Nicolas N. 
Published: September 2022

AbstractThe spinal cord has poor ability to regenerate after injury, which may be due to cell loss, cyst formation, inflammation, and scarring. A promising approach to treat spinal cord injury (SCI) is the use of biomaterials. We have developed a novel hydrogel scaffold fabricated from oligo(poly(ethylene glycol) fumarate) (OPF) as a 0.08 mm thick sheet containing polymer ridges and a cell-attractive surface chemistry on the other side. When the cells are cultured on OPF with the chemical patterning, the cells attach, align, and deposit ECM along the direction of the pattern. Animals implanted with the rolled scaffold sheets had greater hindlimb recovery compared to the multichannel scaffold control, likely due to the greater number of axons growing across. Inflammation, scarring, and ECM deposits were equal across conditions. Overall, the results suggest that the scaffold sheets promote axon outgrowth that can be guided across the scaffold, thereby promoting hindlimb recovery.
Whole-body sorcin invalidation does not cause hypothalamic ER stress nor worsens obesity in C57BL/6 male mice fed a westernized diet
Authors: Parks Steven Z. , Rutter Guy A. , Leclerc Isabelle 
Published: September 2022

ABSTRACTBackgroundSoluble Resistance Related Calcium Binding Protein (sorcin) is a calcium (Ca2+) binding protein which has been shown to play a role in maintaining intracellular endoplasmic reticulum (ER) Ca2+ stores and lowering ER stress. Recently, our lab has demonstrated that sorcin expression was downregulated in the islets of Langerhans of mice fed a high-fat diet or in human islets incubated with the saturated fatty acid palmitate. We also showed that overexpression of sorcin under control of the rat insulin promoter (RIP7) in C57BL/6J mice, or whole body sorcin deletion in 129S1/SvImJ mice, improves or impairs insulin secretion and pancreatic β-cell function respectively. The mechanisms behind this beneficial role of sorcin in the pancreatic β-cell might depend on protection against lipotoxic endoplasmic reticulum (ER) stress through improved ER Ca2+ dynamics and activation of the Activating Transcription Factor 6 (ATF6) branch of the unfolded protein response (UPR). Whether sorcin is also implicated in hypothalamic ER stress during the progression of obesity is unknown. This could potentially contribute to the diminished satiety typically observed in overweight individuals.AimTo investigate a potential role of sorcin in hypothalamic ER stress, leptin resistance, hyperphagia and obesity.MethodsWhole-body sorcin null mice, backcrossed onto the C57BL/6J genetic background, were used. Body weight, food intake and EchoMRI body composition were measured in vivo whereas qRT-PCR analysis of sorcin and ER stress markers expression were performed on the arcuate nucleus of the hypothalamus. Leptin signalling through STAT3 phosphorylation was measured by Western blots on sorcin-null HEK293 cells, engineered by CRISPR/Cas9, and transfected with leptin receptor (LepRb).ResultsSorcin expression was not influenced in the arcuate nucleus (ARC) of the hypothalamus by diet-induced obesity. Whole-body sorcin ablation did not cause ARC ER stress nor changes in body weight, body composition or food intake in C57BL/6 male mice exposed to a high-fat, high-sugar diet. STAT3 phosphorylation (Y705) in response to leptin was not impaired in sorcin-null HEK293 cells.ConclusionIn our model, whole body sorcin ablation did not increase hypothalamic ER stress nor influenced food intake or body weight.
Amount of Pannexin 1 in smooth muscle cells regulates sympathetic nerve induced vasoconstriction
Authors: Dunaway Luke S. , Billaud Marie , Macal Edgar , Good Miranda E. , Medina Christopher B. , Lorenz Ulrike , Ravichandran Kodi , Koval Michael , Isakson Brant E 
Published: September 2022

AbstractPannexin 1 (Panx1) forms high conductance channels that secrete ATP upon stimulation. The role of Panx1 in mediating constriction in response to direct sympathetic nerve stimulation is not known. Additionally, it is unknown how the expression level of Panx1 in SMCs influences a-adrenergic responses. We hypothesized that the amount of Panx1 in SMCs dictates the levels of sympathetic constriction and blood pressure. To test this hypothesis, we used genetically modified mouse models enabling expression of Panx1 in vascular cells to be varied. Genetic deletion of SMC Panx1 prevented constriction by electric field stimulation of sympathetic nerves. Conversely, over-expression of Panx1 in SMCs using a ROSA26 transgenic model increased sympathetic nerve-mediated constriction. Cx43 hemichannel inhibitors did not alter constriction. Next, we evaluated the effects of altered SMC Panx1 expression on blood pressure. To do this, we created mice combining a global Panx1 deletion, with ROSA26-Panx1 under the control of an inducible SMC specific Cre (Myh11). This resulted in mice that could express only human Panx1, only in SMCs. After tamoxifen, these mice had increased blood pressure that was acutely decreased by the Panx1 inhibitor spironolactone. Control mice genetically devoid of Panx1 did not respond to spironolactone. These data suggest Panx1 in SMCs could regulate the extent of sympathetic nerve constriction and blood pressure. The results also show the feasibility humanized Panx1-mouse models to test pharmacological candidates.
Expression Ratios of the Anti-Apoptotic BCL2 Family Members Dictate the Selective Addiction of KSHV-Transformed Primary Effusion Lymphoma Cell Lines to MCL1
Authors: Dunham Daniel , Viswanathan Prasanth , Gill Jackson , Manzano Mark 
Published: September 2022

ABSTRACTKaposi’s sarcoma-associated herpesvirus (KSHV) causes several malignancies in people living with HIV, including primary effusion lymphoma (PEL). PEL cell lines exhibit oncogene addictions to both viral and cellular genes. Using CRISPR screens, we previously identified cellular oncogene addictions in PEL cell lines, including MCL1. MCL1 is a member of the BCL2 family, which functions to prevent intrinsic apoptosis and has been implicated in several cancers. Despite the overlapping functions of the BCL2 family members, PEL cells are only dependent on MCL1 suggesting that MCL1 may have non-redundant functions. To investigate why PEL cells exhibit selective addiction to MCL1, we inactivated the intrinsic apoptosis pathway by engineering BAX/BAK1 double knockout cells. In this context, PEL cells become resistant to MCL1 knockdown or MCL1 inactivation by the MCL1 inhibitor S63845, indicating that the main function of MCL1 in PEL cells is to prevent BAX/BAK1-mediated apoptosis. The selective requirement to MCL1 is due to MCL1 being expressed in excess over the BCL2 family. Ectopic expression of several BCL2 family proteins, as well as the KSHV BCL2 homolog, significantly decreased basal caspase 3/7 activity and buffered against staurosporine-induced apoptosis. Finally, over-expressed BCL2 family members can functionally substitute for MCL1, when it is inhibited by S63845. Together our data indicate that the expression levels of the BCL2 family likely explain why PEL tumor cells are highly addicted to MCL1. Importantly, our results suggest that caution should be taken when considering MCL1i as a monotherapy regimen for PEL, because resistance can easily develop.IMPORTANCEPrimary effusion lymphoma (PEL) is caused by Kaposi’s sarcoma-associated herpesvirus. We previously showed that PEL cell lines require the anti-apoptotic protein MCL1 for survival, but not the other BCL2 family proteins. This selective dependence to MCL1 is unexpected as the BCL2 family functions similarly in preventing intrinsic apoptosis. Recently, new roles for MCL1 not shared with the BCL2 family have emerged. Here, we show that non-canonical functions of MCL1 are unlikely essential. Instead, MCL1 mainly functions to prevent apoptosis. The specific requirement to MCL1 is due to MCL1 being expressed in excess over the BCL2 family.Consistent with this model, shifting these expression ratios changes the requirement away from MCL1 and towards the dominant BCL2 family gene. Together, our results indicate that although MCL1 is an attractive chemotherapeutic target to treat PEL, careful consideration must be taken as resistance to MCL1-specific inhibitors easily develops through BCL2 family overexpression.
HPV E6 upregulates MARCHF8 ubiquitin ligase and inhibits apoptosis by degrading the death receptors in head and neck cancer
Authors: Khalil Mohamed I. , Yang Canchai , Vu Lexi , Chadha Smriti , Welbon Craig , James Claire D. , Morgan Iain M. , Spanos William C. , Pyeon Dohun 
Published: September 2022

ABSTRACTThe membrane-associated RING-CH-type finger ubiquitin ligase MARCHF8 is a human homolog of the viral ubiquitin ligases Kaposi’s sarcoma herpesvirus K3 and K5 that promote host immune evasion. Previous studies have shown that MARCHF8 ubiquitinates several immune receptors, such as the major histocompatibility complex II and CD86. While human papillomavirus (HPV) does not encode any ubiquitin ligase, the viral oncoproteins E6 and E7 are known to regulate host ubiquitin ligases. Here, we report that MARCHF8 expression is upregulated in HPV-positive head and neck cancer patients but not in HPV-negative head and neck cancer patients compared to normal individuals. MARCHF8 expression is highly upregulated by HPV oncoprotein E6-induced MYC/MAX transcriptional activation. The knockdown of MARCHF8 expression in human HPV-positive HNC cells restores cell surface expression of the tumor necrosis factor receptor superfamily (TNFRSF) death receptors, FAS, TRAIL-R1, and TRAIL-R2, and enhances apoptosis. MARCHF8 protein directly interacts with and ubiquitinates the TNFRSF death receptors. Further, MARCHF8 knockout in mouse oral cancer cells expressing HPV16 E6 and E7 augments cancer cell apoptosis and suppresses tumor growth in vivo. Our findings suggest that HPV inhibits host cell apoptosis by upregulating MARCHF8 and degrading TNFRSF death receptors in HPV-positive HNC cells.IMPORTANCESince host cell survival is essential for viruses to replicate persistently, many viruses have evolved to prevent host cell apoptosis. The human papillomavirus (HPV) oncoproteins are known to dysregulate proapoptotic proteins. However, our understanding of detailed mechanisms for HPV to inhibit apoptosis is limited. Here, we report that HPV E6 induces transcription of the membrane-associated ubiquitin ligase MARCHF8, which is upregulated in HPV-positive head and neck cancer. MARCHF8 ubiquitinates the tumor necrosis factor receptor superfamily (TNFRSF) death receptors, FAS, TRAIL-R1, and TRAIL-R2 for degradation. We further revealed that downregulation of the death receptors by MARCHF8 prevents cancer cell apoptosis and that knockout of MARCHF8 expression significantly inhibits in vivo tumor growth and enhances tumor-free survival of mice transplanted with mouse oral cancer cells expressing HPV16 E6 and E7.These results suggest that virus-induced degradation of death receptors leads to cancer cell survival in HPV-positive head and neck cancer.
Disparities in research capacity for tobacco control: an inventory of peer-reviewed publications using the Global Tobacco Surveillance System data
Authors: de Quevedo Isabel Garcia , Marellapudi Amulya , Rainey Edward , Twentyman Evelyn 
Published: September 2022

AbstractPeer-reviewed publications using tobacco surveillance data represent a critical step toward evidence-based tobacco control, but research and publication capacity in countries with fewer resources may be limited. This paper describes patterns in use of the Global Adult Tobacco Survey (GATS) and/or Global Youth Tobacco Survey (GYTS) data for publications, investigates the origin of the data versus the origin of lead authorship, and describes geographic patterns of publications by country, region, and country income. A bibliometric inventory using six search engines was conducted for relevant studies using data from either of these surveys between January 1999 and January 2021. Descriptive statistics, including frequencies and percentages,were used to analyze publication characteristics. Our search strategy retrieved 1,834 initial records; 493 publications were ultimately included: 249 (50.5%) used adult surveillance data (GATS) and 248 (50.3%) used youth surveillance data (GYTS). Most publications were in English (97.2%, n=479). Data published 50 or more times represented 12 low- and middle-income countries (LMIC): India, Bangladesh, Vietnam, Mexico, Egypt, Thailand, Poland, Philippines, China, Russian Federation, Turkey and Ukraine. While many of the papers analyzed data from low- and middle-income countries, the number of publications by origin of lead author was the highest for the United States (n=135) and India (n=84). Over 80% of the world’s 1.3 billion tobacco users live in low- and middle-income countries (LMIC) and we found underrepresentation of these countries as lead authors. These findings can be used to identify opportunities to enhance capacity for analysis, research and dissemination of global tobacco control data in LMIC.
Genetic and environmental etiology of the broad avoidant restrictive food intake disorder phenotype in 6- to-12-year-old Swedish twins
Authors: Dinkler Lisa , Lichtenstein Paul , Lundström Sebastian , Larsson Henrik , Micali Nadia , Taylor Mark J. , Bulik Cynthia M. 
Published: September 2022

IMPORTANCEAvoidant restrictive food intake disorder (ARFID) is characterized by an extremely limited range and/or amount of food eaten, resulting in the persistent failure to meet nutritional and/or energy needs. Its etiology is poorly understood and knowledge of genetic and environmental contributions to ARFID is needed to guide future research.OBJECTIVETo determine the extent to which genetic and environmental factors contribute to the liability to the broad ARFID phenotype.DESIGN, SETTING, AND PARTICIPANTSA nationwide Swedish twin cohort including 16,951 twin pairs born 1992-2010 whose parents participated in the Child and Adolescent Twin Study in Sweden (CATSS) at twin age 9 or 12 years (49.4% female). CATSS was linked to the National Patient Register (NPR) and the Prescribed Drug Register (PDR).MAIN OUTCOME/MEASURESFrom CATSS, NPR, and PDR, we extracted all parent-reports, diagnoses, procedures, and prescribed drugs between age 6 and 12 that were relevant to the DSM-5 ARFID criteria and developed a composite measure for the ARFID phenotype (i.e., avoidant/restrictive eating with clinically significant impact such as low weight or nutritional deficiency, and with fear of weight gain as an exclusion). In sensitivity analyses, we controlled for autism and medical conditions that could account for the eating disturbance. We fitted univariate liability threshold models to estimate the relative contribution of genetic and environmental variation to the liability to the ARFID phenotype.RESULTSWe identified 667 children (2.0%, 38.2% female) with the ARFID phenotype between age 6 and 12. Variation in the liability to ARFID was largely explained by additive genetic factors (0.79, 95% confidence interval [CI] 0.71-0.86), with significant contributions from non-shared environmental factors (0.21, 95% CI 0.14-0.29). Heritability was very similar when excluding children with autism (0.77, 95% CI 0.67-0.84) or medical illnesses that could account for the eating disturbance (0.80, 95% CI 0.71-0.86).CONCLUSIONS AND RELEVANCEPrevalence and sex distribution of the broad ARFID phenotype were similar to previous studies, supporting the use of existing epidemiological data to identify ARFID. This first study of the genetic and environmental etiology of ARFID suggests that ARFID is highly heritable, encouraging future twin and molecular genetic studies.