bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effect of lysergic acid diethylamide (LSD) on reinforcement learning in humans
Authors: Kanen Jonathan W. , Luo Qiang , Kandroodi Mojtaba R. , Cardinal Rudolf N. , Robbins Trevor W. , Carhart-Harris Robin L. , den Ouden Hanneke E.M. 
Published: December 2020

AbstractThe non-selective serotonin 2A (5-HT2A) receptor agonist lysergic acid diethylamide (LSD) holds promise as a treatment for some psychiatric disorders. Psychedelic drugs such as LSD have been suggested to have therapeutic actions through their effects on learning. The behavioural effects of LSD in humans, however, remain largely unexplored. Here we examined how LSD affects probabilistic reversal learning in healthy humans. Healthy volunteers received intravenous LSD (75μg in 10 mL saline) or placebo (10mL saline) in a within-subjects design and completed a probabilistic reversal learning task. Participants had to learn through trial and error which of three stimuli was rewarded most of the time, and these contingencies switched in a reversal phase. Computational models of reinforcement learning were fitted to the behavioural data to assess how LSD affected the updating (“learning rates”) and deployment (“reinforcement sensitivity”) of value representations during choice, as well as “stimulus stickiness”, which assays choice repetition irrespective of reinforcement history. Conventional measures assessing sensitivity to immediate feedback (“win-stay” and “lose-shift” probabilities) were unaffected, whereas LSD increased the impact of the strength of initial learning on perseveration. Computational modelling revealed that the most pronounced effect of LSD was enhancement of the reward learning rate. The punishment learning rate was also elevated. Stimulus stickiness was decreased by LSD, reflecting heightened exploratory behaviour, while reinforcement sensitivity was unaffected. Increased reinforcement learning rates suggest LSD induced a state of heightened plasticity. These results indicate a potential mechanism through which revision of maladaptive associations could occur in the clinical application of LSD.Significance statementThe psychedelic (“mind-manifesting”) drug LSD holds promise for the treatment of some psychiatric disorders. Theories have postulated its therapeutic potential centres on enhancing learning and flexible thinking. Here we provide substantiating empirical evidence by examining the computations underlying behaviour as healthy volunteers learned through trial and error under LSD. Viewing choice as based on representations of an action’s value, LSD increased the speed at which value was updated following feedback, which was more pronounced following reward than punishment. Behaviour was also more exploratory under LSD, irrespective of the outcome of actions. These results indicate that LSD impacted a fundamental belief-updating process inherent in the brain which can be leveraged to revise maladaptive associations characteristic of a range of mental disorders.
Amphibian Collapses Exacerbated Malaria Outbreaks in Central America
Authors: Springborn Michael R. , Weill Joakim A. , Lips Karen R. , Ibáñez Roberto , Ghosh Aniruddha 
Published: December 2020

AbstractEcosystems play an important role in supporting human welfare, including regulating the transmission of infectious diseases. Many of these services are not fully-appreciated due to complex environmental dynamics and lack of baseline data. Multicontinental amphibian decline due to the fungal pathogen Batrachochytrium dendrobatidis (Bd) provides a stark example. Even though amphibians are known to affect natural food webs—including mosquitoes that transmit human diseases—the human health impacts connected to their massive decline have received little attention. Here we show a causal link between a wave of Bd-driven collapse of amphibians in Central America and increased human malaria incidence. At the canton-level in Costa Rica and district-level in Panama, expected malaria incidence increased for eight years subsequent to amphibian losses, peaking at an additional 1.0 cases per 1,000 population (CPK). The increase is substantial in comparison to annual incidence levels from outbreaks in these countries, which peaked at 1.1-1.5 CPK during our period of study from 1976-2016. This pattern holds across multiple alternative approaches to the estimation model. This previously unidentified impact of biodiversity loss illustrates the often hidden human welfare costs of conservation failures. These findings also show the importance of mitigating international trade-driven spread of similar emergent pathogens like Batrachochytrium salamandrivorans.Significance StatementDespite substantial multicontinental collapses in amphibian populations from spread of the fungal pathogen Batrachochytrium dendrobatidis (Bd), the implications for humans have not been systematically studied. Amphibians are known to affect food webs, including mosquitoes that serve as a vector for the spread of disease. However, little is known about how their loss erodes ecosystem services, including the regulation of the transmission of infectious diseases. Using Central America as a case study, this study shows that Bd-driven amphibian loss led to a substantial increase in malaria incidence. The results highlight the often underappreciated social costs of biodiversity loss, including the potential stakes of ecosystem disruption from failing to stop spread of future novel pathogens.
CDK5 Inhibitor Seliciclib Promotes Osteoblastic Differentiation of MSCs and Suppresses the Migration of MG-63 Osteosarcoma Cells
Authors: Fu Hong , Zhao Haoyu , Yang Yali , Duan Ke , Guo Tailin 
Published: December 2020

AbstractCDK5 belongs to the cycling dependent kinase family, which is multifunctional and plays an important role in neural differentiation. However, the role of CDK5 in osteoblastic differentiation remains unclear. The present study investigated functions and molecular mechanism of CDK5 in osteoblastic differentiation. It was found that, the addition of CDK5 inhibitor Seliciclib promoted the expression ofRunx2,ALP,OCNandOPNof MSCs and the mineralization of MC-3T3E1 cells. Seliciclib enhanced the development of F-actin, nuclear localization of β-catenin and YAP, as well as the expression of RMRP RNA. When F-actin was suppressed by Blebbistatin, the nuclear localization of YAP and β-catenin, and expression ofRMRP RNAas well asRunx2andALPwere decreased. These indicate Seliciclib promotes osteoblastic differentiation mainly by F-actin. Moreover, Seliciclib also suppressed the migration of MG-63, suggesting a potential application for Seliciclib in bone defect repair and inhibition of the migratiion of osteosarcoma cells.
Risk Model for Intraoperative Complication during Cataract Surgery Based on Data from 900,000 Eyes – Previous Intravitreal Injection is a Risk Factor
Authors: af Segerstad Poya Hård 
Published: December 2020

ABSTRACTBackground/AimsThe aim of this study was to develop a risk model for intraoperative complication during cataract surgery and to include previous intravitreal therapy in the model.MethodsThis retrospective register-based study covered patients reported to the Swedish National Cataract Register (SNCR) between Jan. 1, 2010 and Jun. 30, 2018. Odds ratios (OR) were used to quantify association strength of each variable with intraoperative complication. Data from the SNCR were cross referenced with the Swedish Macula Register (SMR) to include data on previous intravitreal therapy. Variables statistically significant in the univariate analyses (P<0.05) were included in a multivariate logistic regression model.ResultsThe inclusion criteria were met by 907,499 eyes. The overall rate of intraoperative complication was 0.86%. After cross referencing, 3,451 eyes were identified in the SMR as having undergone intravitreal therapy prior to cataract surgery. Variables significantly associated with intraoperative complication (P<0.05) were best corrected visual acuity ≥1.0 LogMAR (adjusted OR): 1.75), age ≥90 years (OR: 1.25), male sex (OR: 1.09), pseudoexfoliation (OR: 1.33), glaucoma (OR: 1.11), diabetic retinopathy (OR: 1.35), previous intravitreal therapy (OR: 1.45), surgeon’s experience <600 surgeries (OR: 2.77), use of rhexis hooks (OR: 6.14), blue staining (OR: 1.87), and mechanical pupil dilation (OR: 1.52).ConclusionThe risk model can be used in the preoperative setting to predict the probability of intraoperative complication, to facilitate planning of surgery, and improving patient communication. Patients who have undergone intravitreal therapy prior to cataract surgery have an increased risk of intraoperative complication during cataract surgery.
The physiological demands of Singing for Lung Health compared to treadmill walking
Authors: Philip Keir EJ , Lewis Adam , Buttery Sara C , McCabe Colm , Manivannan Bishman , Fancourt Daisy , Orton Christopher , Polkey Michael I , Hopkinson Nicholas S 
Published: December 2020

AbstractParticipating in singing is considered to have a range of social and psychological benefits. However, the physiological demands of singing, whether it can be considered exercise, and its intensity as a physical activity are not well understood. We therefore compared cardiorespiratory parameters while completing components of Singing for Lung Health (SLH) sessions, with treadmill walking at differing speeds (2, 4, and 6km/hr). Eight healthy adults were included, none of whom reported regular participation in formal singing activities. Singing induced physiological responses that were consistent with moderate intensity activity (METS: median 4.12, IQR 2.72 - 4.78), with oxygen consumption, heart rate, and volume per breath above those seen walking at 4km/hr. Minute ventilation was higher during singing (median 22.42L/min, IQR 16.83 - 30.54) than at rest (11L/min, 9 - 13), lower than 6km/hr walking (30.35L/min, 26.94 - 41.11), but not statistically different from 2km/hr (18.77L/min, 16.89 - 21.35) or 4km/hr (23.27L/min, 20.09 - 26.37) walking. Our findings suggest the metabolic demands of singing may contribute to the health and wellbeing benefits attributed to participation. However, if physical training benefits result remains uncertain. Further research including different singing styles, singers, and physical performance impacts when used as a training modality is encouraged.
Prevalence of anxiety and depressive symptoms among physicians during the COVID-19 pandemic in Bangladesh: a cross-sectional study
Authors: Hasan M.Tasdik , Hossain Sahadat , Safa Farhana , Anjum Afifa , Khan Abid Hasan , Koly Kamrun Nahar , Alam Syeda Fatema , Rafi Md. Abdur , Podder Vivek , Trisa Tonima Islam , Nodi Rhedeya Nury , Azad Dewan Tasnia , Ashraf Fatema , Akther S.M Quamrul , Ahmed Helal Uddin , Rosenbaum Simon , Thornicroft Graham 
Published: December 2020

ABSTRACTObjectivesIn addition to risking their physical well-being, frontline physicians are enduring significant emotional burden both at work and home during the COVID-19 pandemic. This study aims to investigate the levels of anxiety and depressive symptoms and to identify associated factors among Bangladeshi physicians during the COVID-19 outbreak.Methods and designA cross-sectional study using an online survey was conducted between April 21 and May 10, 2020. Outcomes assessed included demographic questions, COVID-19 related questions, and the Hospital Anxiety and Depression Scale (HADS).ResultsThe survey was completed by 412 Bangladeshi physicians. The findings revealed that, in terms of standardized HADS cut-off points, the prevalence of anxiety and depressive symptoms among physicians was 67.72% and 48.5% respectively. Risk factors for higher rates of anxiety or depressive symptoms were: being female, physicians who had experienced COVID-19 like symptoms during the pandemic, those who had not received incentives, those who used self-funded PPE, not received adequate training, lacking perceived self-efficacy to manage COVID -19 positive patients, greater perceived stress of being infected, fear of getting assaulted/humiliated, being more connected with social media, having lower income levels to support the family, feeling more agitated, less than 2 hours of leisure activity per day and short sleep duration. All these factors were found to be positively associated with anxiety and depression in unadjusted and adjusted statistical models.ConclusionsThis study identifies a real concern about the prevalence of anxiety and depressive symptoms among Bangladeshi physicians and identifies several associated factors during the COVID-19 pandemic. Given the vulnerability of the physicians in this extraordinary period whilst they are putting their own lives at risk to help people infected by COVID-19, health authorities should address the psychological needs of medical staff and formulate effective strategies to support vital frontline health workers.STHRENGHTS & LIMITATIONS OF THE STUDYThis study reports a novel and concerning findings on the prevalence of anxiety and depression symptoms with identification of several important associated factors among Bangladeshi physicians during the COVID-19 pandemic.The cross-sectional nature of the study design could not establish causal relationship between the dependent and independent variables.This study was carried out by conducting a web-based survey, which might generate sampling bias by excluding the physicians who do not have access to internet or inactive in social medias, and thus limit the generalizability of the findings.
SARS-CoV-2 infections in kindergartens and associated households at the start of the second wave in Berlin, Germany – a cross sectional study
Authors: Thielecke Marlene , Theuring Stefanie , van Loon Welmoed , Hommes Franziska , Mall Marcus A. , Rosen Alexander , Böhringer Falko , von Kalle Christof , Kirchberger Valerie , Kurth Tobias , Seybold Joachim , Mockenhaupt Frank P. 
Published: December 2020

AbstractObjectivesThe comparatively large proportion of asymptomatic SARS-CoV-2 infections in the youngest children opens up the possibility that kindergartens represent reservoirs of infection. However, actual surveys in kindergartens beyond individual outbreaks are rare. At the beginning of the second pandemic wave in Berlin, Germany, i.e., end of September 2020, we screened SARS-CoV-2 infections among kindergarten children, staff and connected household members.MethodsTwelve kindergartens were randomly selected in the Berlin metropolitan area, and a total of 720 participants were recruited (155 pre-school children, 78 staff, 487 household members). Participants were briefly examined and interviewed, and SARS-CoV-2 infections and anti-SARS-Cov-2 IgG antibodies were assessed.ResultsSigns and symptoms, largely resembling common cold, were present in 24.2% of children and 28.9% of staff. However, no SARS-CoV-2 infection was detected among 701 PCR-tested individuals, and only one childcare worker showed IgG seroreactivity (0.15%; 1/672).ConclusionsAgainst a backdrop of increased pandemic activity in the community, this cross-sectional study does not suggest that kindergartens are silent transmission reservoirs. Nevertheless, at increasing pandemic activity, reinforced precautionary measures and repeated routine testing appears advisable.
Efficacy of pulmonary rehabilitation in severe and critical-ill COVID-19 patients: a controlled study
Authors: Büsching Gilbert , Zhang Zhongxing , Schmid Jean Paul , Sigrist Thomas , Khatami Ramin 
Published: December 2020

AbstractSevere and critical ill COVID-19 patients frequently need acute care hospitalization including mechanical ventilation at ICU due to acute respiratory distress. A high proportion of these patients will develop ICU-acquired weakness and a need for rehabilitation. However data on rehabilitation outcomes in these patients are scarce and the efficacy of rehabilitation remains essentially unclear. We therefore compared the rehabilitation outcomes between COVID-19 patients with pneumonia and other patients with common pneumonia to assess their rehabilitation efficacies.We retrospectively compared the performances of six-min walk test (6MWT), chronic respiratory questionnaire (CRQ), and functional independence measure (FIM) at the discharge from pulmonary rehabilitation between 51 Covid-19 patients and 51 patients with common pneumonia using linear regression controlled for baseline values at entrance, age, sex and cumulative Illness rating scale. Fisher exact test was applied to test whether the odd ratios (ORs) of non-improvement/improvement in 6MWT (>30-m) and CRQ (>10-point) at discharge were different between the two groups.Covid-19 patients had similar performances at discharge in 6MWT (P-value=0.14), CRQ (P-value=0.55), and 4.2-point higher (P-value=0.004) in FIM compared to the control group. No differences in the outcomes were found between severe and critical COVID-19 patients. The OR of non-improvement/improvement in 6MWT was 0.30 (P-value=0.13) between COVID-19 and control groups; but the odd of non-improvement in CRQ tended to be 3.02 times higher (P-value =0.075) in COVID-19 group.In-house rehabilitation is effective and suitable for COVID-19 patients irrespective from disease severity. The discrepancy of high physical improvement and relatively low gains of disease related quality of life compared to control patients with common pneumonia is however remarkable. Further studies need to evaluate whether this discrepancy is an indicator of chronic disease development.
Spatial multi-omic map of human myocardial infarction
Authors: Kuppe Christoph , Ramirez Flores Ricardo O. , Li Zhijian , Hannani Monica , Tanevski Jovan , Halder Maurice , Cheng Mingbo , Ziegler Susanne , Zhang Xiaoting , Preisker Fabian , Kaesler Nadine , Xu Yaoxian , Hoogenboezem Remco M. , Bindels Eric M.J. , Schneider Rebekka K. , Milting Hendrik , Costa Ivan G. , Saez-Rodriguez Julio , Kramann Rafael 
Published: December 2020

AbstractMyocardial infarction is a leading cause of mortality. While advances in the acute treatment have been made, the late-stage mortality is still high, driven by an incomplete understanding of cardiac remodeling processes1,2. Here we used single-cell gene expression, chromatin accessibility and spatial transcriptomic profiling of different physiological zones and timepoints of human myocardial infarction and human control myocardium to generate an integrative high-resolution map of cardiac remodeling. This approach allowed us to increase spatial resolution of cell-type composition and provide spatially resolved insights into the cardiac transcriptome and epigenome with identification of distinct cellular zones of injury, repair and remodeling. We here identified and validated mechanisms of fibroblast to myofibroblast differentiation that drive cardiac fibrosis. Our study provides an integrative molecular map of human myocardial infarction and represents a reference to advance mechanistic and therapeutic studies of cardiac disease.
Constitutive activation of canonical Wnt signaling disrupts choroid plexus epithelial fate
Authors: Parichha Arpan , Suresh Varun , Chatterjee Mallika , Kshirsagar Aditya , Ben-Reuven Lihi , Olender Tsviya , Mark Taketo M. , Radosevic Velena , Bobic-Rasonja Mihaela , Trnski Sara , Holtzman Michael J. , Jovanov Milošević Nataša , Reiner Orly , Tole Shubha 
Published: December 2020

AbstractThe choroid plexus (ChP) secretes cerebrospinal fluid and is critical for the development and function of the brain. In the telencephalon, the ChP epithelium (ChPe) arises from theWnt-expressing cortical hem. Embryonic mouse and human ChPe both express nuclear β-CATENIN, a canonical Wnt signaling pathway effector, indicating that this pathway is active during ChPe development. Point mutations in humanβ-CATENINresult in the constitutive activation of canonical Wnt signaling. In a mouse model that recapitulates this perturbation, we report a loss of ChPe identity and an apparent transformation of the ChPe to a neuronal identity. Aspects of this phenomenon are recapitulated in human embryonic stem cell (hESC)-derived organoids. The ChPe is also disrupted whenβ-Cateninis conditionally inactivated in the mouse. Together, our results indicate that canonical Wnt signaling is required in a precise and regulated manner for normal ChPe development in the mammalian brain.
A nanodomain anchored-scaffolding complex is required for PI4Kα function and localization in plants
Authors: Noack Lise C , Bayle Vincent , Armengot Laia , Frédérique Rozier F , Mamode-Cassim Adiilah , Stevens Floris D , Caillaud Marie-Cécile , Munnik Teun , Mongrand Sébastein , Pleskot Roman , Jaillais Yvon 
Published: December 2020

ABSTRACTPhosphoinositides are low-abundant lipids that participate in the acquisition of membrane identity through their spatiotemporal enrichment in specific compartments. PI4P accumulates at the plant plasma membrane driving its high electrostatic potential, and thereby facilitating interactions with polybasic regions of proteins. PI4Kα1 has been suggested to produce PI4P at the plasma membrane, but how it is recruited to this compartment is unknown. Here, we pin-point the mechanism that tethers PI4Kα1 to the plasma membrane via a nanodomain-anchored scaffolding complex. We identified that PI4Kα1 is part of a complex composed of proteins from the NO-POLLEN-GERMINATION, EFR3-OF-PLANTS, and HYCCIN-CONTAINING families. Comprehensive knock-out and knock-down strategies revealed that subunits of the PI4Kα1 complex are essential for pollen, embryonic and post-embryonic development. We further found that the PI4Kα1 complex is immobilized in plasma membrane nanodomains. Using synthetic mis-targeting strategies, we demonstrate that a combination of lipid anchoring and scaffolding localizes PI4Kα1 to the plasma membrane, which is essential for its function. Together, this work opens new perspectives on the mechanisms and function of plasma membrane nanopatterning by lipid kinases.
Information transfer and recovery for the sense of touch
Authors: Huang Chao , Englitz Bernhard , Reznik Andrey , Zeldenrust Fleur , Celikel Tansu 
Published: December 2020

AbstractTransformation of postsynaptic potentials (PSPs) into action potentials (APs) is the rate-limiting step of communication in neural networks. The efficiency of this intracellular information transfer also powerfully shapes stimulus representations in sensory cortices. Using whole-cell recordings and information-theoretic measures, we show herein that somatic PSPs accurately represent stimulus location on a trial-by-trial basis in single neurons even 4 synapses away from the sensory periphery in the whisker system. This information is largely lost during AP generation but can be rapidly (<20 ms) recovered using complementary information in local populations in a cell-type-specific manner. These results show that as sensory information is transferred from one neural locus to another, the circuits reconstruct the stimulus with high fidelity so that sensory representations of single neurons faithfully represent the stimulus in the periphery, but only in their PSPs, resulting in lossless information processing for the sense of touch in the primary somatosensory cortex.