bluuebunny/crossref_metadata_2025_split huggingface dataset:
Knowledge, attitude, and practice related to the COVID-19 pandemic among undergraduate medical students in Indonesia: a nationwide cross-sectional study
Authors: Adli Imam , Widyahening Indah S. , Lazarus Gilbert , Phowira Jason , Azzahra Lyanna , Ariffandi Bagas , Putera Azis Muhammad , Nugraha David , Gamalliel Nico , Findyartini Ardi 
Published: July 2021

ABSTRACTIntroductionThe potential role of medical students in raising awareness during public health emergencies has been acknowledged. To further explore their potentials as public educators and role models for the communities during the coronavirus disease 2019 (COVID-19) pandemic, a study is conducted to assess the knowledge, attitude, and practice of these students toward COVID-19.MethodsAn online cross-sectional survey was conducted among undergraduate medical students in Indonesia. Socio-demographical characteristics, social interaction history, information-seeking behavior, as well as knowledge, attitude, and practice toward COVID-19 were collected through a self-reported questionnaire. A p-value of <0.05 indicated statistical significance.ResultsOut of 4870 respondents, 64.9% and 51.5% had positive attitude and practice toward COVID-19 while only 29.8% had adequate knowledge. Knowledge was slightly positively correlated with attitude and practice (ρ=0.074 and ρ=0.054, respectively; both p<0.001), while attitude was weakly correlated with practice (ρ=0.234, p<0.001). Several factors including age, sex, place of residence, institution type, academic level, family income, history of chronic illness, prior volunteering experience, and perceptual awareness on COVID-19 were significantly associated with either knowledge, attitude, and/or practice toward COVID-19. Furthermore, health institution’s and the government’s press releases, as well as health expert opinions were deemed as the most reliable sources of COVID-19-related information – yet trivially none of these sources were associated with knowledge, attitude, and practice in the study population.ConclusionMany undergraduate medical students in Indonesia had positive attitude and practice against COVID-19, yet only a few had adequate knowledge. This warrants further interventions to keep them updated with COVID-19 evidence to maximize their potentials in raising public awareness on COVID-19.
Giving birth in a Pandemic: Women’s Birth Experiences in England during COVID-19
Authors: Aydin Ezra , Glasgow Kevin A. , Weiss Staci M. , Khan Zahra , Austin Topun , Johnson Mark H. , Barlow Jane , Lloyd-Fox Sarah 
Published: July 2021

AbstractBackgroundExpectant parents worldwide have experienced changes in the way they give birth as a result of COVID-19, including restrictions relating to access to birthing units and the presence of birthing partners during the birth, and changes to birth plans. This paper reports the experiences of women in England.MethodsData were obtained from both closed- and open-ended responses collected as part of the national COVID in Context of Pregnancy, Infancy and Parenting (CoCoPIP) Study online survey (n = 477 families) between 15th July 2020 – 29th March 2021. Frequency data are presented alongside the results of a sentiment analysis; the open-ended data was analysed thematically.ResultsTwo-thirds of expectant women reported giving birth via spontaneous vaginal delivery (SVD) (66.1%) and a third via caesarean section (CS) (32.6%) or ‘other’ (1.3%). Just under half (49.7%) of the CS were reported to have been elective/planned, with 47.7% being emergencies. A third (37.4%) of participants reported having no changes to their delivery, with a further 25% reporting COVID-related changes, and 37.4% reporting non-COVID related changes (e.g., medical intervention). Experiences of COVID-related changes included limited birthing options and reduced feelings of control; difficulties accessing pain-relief and assistance, and feelings of distress and anxiety. Under half of the respondents reported not knowing whether there could be someone present at the birth (44.8%), with 2.3% of respondents reporting no birthing partner being present due to COVID-related restrictions. Parental experiences of communication and advice provided by the hospital prior to delivery were mixed, with significant stress and anxiety being reported in relation to both the fluctuating guidance and lack of certainty regarding the presence of birthing partners at the birth. The sentiment analysis revealed that participant experiences of giving birth during the pandemic were predominately negative (46.9%) particularly in relation to the first national lockdown, with a smaller proportion of positive (33.2%) and neutral responses (19.9%).ConclusionParents reported an overall increase in birthing interventions (e.g., emergency CS), increased uncertainties related to the birth, and poor communication, leading to increased feelings of anxiety and high levels of negative emotions. The implications of these findings are discussed.
Special Issue: Demographic and Mental Health Assessments in the Adolescent Brain and Cognitive Development Study: Updates and Longitudinal Trajectories
Authors: Barch Deanna M. , Albaugh Matthew D. , Baskin-Sommers Arielle , Bryant Brittany E. , Clark Duncan B. , Dick Anthony Steven , Feczko Eric , Foxe John J. , Gee Dylan G. , Giedd Jay , Glantz Meyer D. , Hudziak James J. , Karcher Nicole R. , LeBlanc Kimberly , Maddox Melanie , McGlade Erin C. , Mulford Carrie , Nagel Bonnie J. , Neigh Gretchen , Palmer Clare E , Potter Alexandra S. , Sher Kenneth J. , Tapert Susan F. , Thompson Wesley K. , Xie Laili 
Published: July 2021

AbstractThe Adolescent Brain Cognitive Development (ABCD) Study of 11,880 youth incorporates a comprehensive range of measures assessing predictors and outcomes related to mental health across childhood and adolescence in participating youth, as well as information about family mental health history. We have previously described the logic and content of the mental health assessment battery at Baseline and Year 1. Here, we describe changes to that battery and issues and clarifications that have emerged, as well as additions to the mental health battery at the 2-, 3-, 4-, and 5-year follow-ups. We capitalize on the recent release of longitudinal data for caregiver and youth report of mental health data to evaluate trajectories of dimensions of psychopathology as a function of demographic factors. For both caregiver and self-reported mental health symptoms, males showed age-related decreases in internalizing and externalizing symptoms, while females showed an increase in internalizing symptoms with age. Multiple indicators of socioeconomic status (caregiver education, family income, financial adversity, neighborhood poverty) accounted for unique variance in both caregiver and youth-reported externalizing and internalizing symptoms. These data highlight the importance of examining developmental trajectories of mental health as a function of key factors such as sex and socioeconomic environment.
In vivo modelling of patient genetic heterogeneity identifies concurrent Wnt and PI3K activity as a potent driver of invasive cholangiocarcinoma growth
Authors: Younger Nicholas T. , Wilson Mollie L. , Jarman Edward J. , Meynert Alison M. , Grimes Graeme R , Gournopanos Konstantinos , Waddell Scott H. , Tennant Peter A. , Wilson David H. , Guest Rachel V. , Wigmore Stephen J. , Acosta Juan Carlos , Kendall Timothy J. , Taylor Martin S. , Sproul Duncan , Mill Pleasantine , Boulter Luke 
Published: July 2021

AbstractIntrahepatic cholangiocarcinoma (ICC) is an aggressive and lethal malignancy of the bile ducts within the liver characterised by high levels of genetic heterogeneity. In the context of such genetic variability, determining which oncogenic mutations drive ICC growth has been difficult and developing modes of patient stratification and targeted therapies remains challenging. As a result, survival rates following a diagnosis with ICC have remained static since the late 1970s, whilst incidence of ICC has increased. Here, we performed the first functional in vivo study into the role that genetic heterogeneity plays in drivinga ICC via modelling of interactions between rare mutations with more common driver genes. By leveraging human ICC sequencing data to stratify and then model genetic heterogeneity in the mouse, we uncovered numerous novel tumour suppressors which, when lost, cooperate with the RAS oncoprotein to drive ICC growth. In this study, we specifically focus on a set of driver mutations that interact with KRAS to initiate aggressive, sarcomatoid-type ICC. We show that tumour growth of this cancer relies on both Wnt and PI3K signalling to drive proliferation and suppress apoptosis. Finally, we demonstrate that pharmacological co-inhibition of Wnt and PI3K in vivo substantially impedes the growth of ICC, regardless of mutational profile. As such, Wnt and PI3K activity should be considered as a signature by which patients can be stratified for treatment and inhibitors of these pathways should be levied as a treatment for patients diagnosed with ICC.
Construction of a new chromosome-scale, long-read reference genome assembly for the Syrian hamster, Mesocricetus auratus
Authors: Harris R. Alan , Raveendran Muthuswamy , Lyfoung Dustin T. , Sedlazeck Fritz J , Mahmoud Medhat , Prall Trent M. , Karl Julie A. , Doddapaneni Harshavardhan , Meng Qingchang , Han Yi , Muzny Donna , Wiseman Roger W. , O’Connor David H. , Rogers Jeffrey 
Published: July 2021

AbstractBackgroundThe Syrian hamster (Mesocricetus auratus) has been suggested as a useful mammalian model for a variety of diseases and infections, including infection with respiratory viruses such as SARS-CoV-2. The MesAur1.0 genome assembly was generated in 2013 using whole-genome shotgun sequencing with short-read sequence data. Current more advanced sequencing technologies and assembly methods now permit the generation of near-complete genome assemblies with higher quality and greater continuity.FindingsHere, we report an improved assembly of the M. auratus genome (BCM_Maur_2.0) using Oxford Nanopore Technologies long-read sequencing to produce a chromosome-scale assembly. The total length of the new assembly is 2.46 Gbp, similar to the 2.50 Gbp length of a previous assembly of this genome, MesAur1.0. BCM_Maur_2.0 exhibits significantly improved continuity with a scaffold N50 that is 6.7 times greater than MesAur1.0. Furthermore, 21,616 protein coding genes and 10,459 noncoding genes are annotated in BCM_Maur_2.0 compared to 20,495 protein coding genes and 4,168 noncoding genes in MesAur1.0. This new assembly also improves the unresolved regions as measured by nucleotide ambiguities, where approximately 17.11% of bases in MesAur1.0 were unresolved compared to BCM_Maur_2.0 in which the number of unresolved bases is reduced to 3.00%.ConclusionsAccess to a more complete reference genome with improved accuracy and continuity will facilitate more detailed, comprehensive, and meaningful research results for a wide variety of future studies using Syrian hamsters as models.
CALR frameshift mutations in MPN patient-derived iPS cells accelerate maturation of megakaryocytes
Authors: Olschok Kathrin , Han Lijuan , de Toledo Marcelo A. S. , Böhnke Janik , Graßhoff Martin , Costa Ivan G. , Theocharides Alexandre , Maurer Angela , Schüler Herdit M. , Buhl Eva Miriam , Pannen Kristina , Baumeister Julian , Kalmer Milena , Gupta Siddharth , Boor Peter , Gezer Deniz , Brümmendorf Tim H. , Zenke Martin , Chatain Nicolas , Koschmieder Steffen 
Published: July 2021

AbstractCalreticulin (CALR) mutations are driver mutations in myeloproliferative neoplasms (MPNs), leading to activation of the thrombopoietin receptor, and causing abnormal megakaryopoiesis. Here, we generated patient-derived CALRins5- or CALRdel52-positive induced pluripotent stem (iPS) cells to establish a MPN disease model for molecular and mechanistic studies. We demonstrated myeloperoxidase deficiency in CD15+ granulocytic cells derived from homozygous CALR-mutant iPS cells, rescued by repairing the mutation using CRISPR/Cas9. iPS cell-derived megakaryocytes showed characteristics of primary megakaryocytes such as formation of demarcation membrane system and cytoplasmic pro-platelets protrusions. Importantly, CALR mutations led to enhanced megakaryopoiesis and accelerated megakaryocytic development in a thrombopoietin-independent manner. Mechanistically, our study identified differentially regulated pathways in mutated vs. unmutated megakaryocytes, such as hypoxia signaling, which represents a potential target for therapeutic intervention. Altogether, we demonstrate key aspects of mutated CALR-driven pathogenesis, dependent on its zygosity and found known and novel therapeutic targets, making our model a valuable tool for clinical drug screening in MPNs.
Polybasic patches in both C2 domains of Synaptotagmin-1 are required for evoked neurotransmitter release
Authors: Wu Zhenyong , Ma Lu , Courtney Nicholas A. , Zhu Jie , Zhang Yongli , Chapman Edwin R. , Karatekin Erdem 
Published: July 2021

ABSTRACTSynaptotagmin-1 (Syt1) is a vesicular calcium sensor required for synchronous neurotransmitter release. It is composed of a single-pass transmembrane domain linked to two tandem C2 domains (C2A and C2B) that bind calcium, acidic lipids, and SNARE proteins that drive fusion of the synaptic vesicle with the plasma membrane. Despite its essential role, how Syt1 couples calcium entry to synchronous release is not well understood. Calcium binding to C2B, but not to C2A, is critical for synchronous release and C2B additionally binds the SNARE complex. The C2A domain is also required for Syt1 function, but it is not clear why. Here we asked what critical feature of C2A may be responsible for its functional role, and compared this to the analogous feature in C2B. We focused on highly conserved poly-lysine patches located on the sides of C2A (K189-192) and C2B (K324-327). We tested effects of charge-neutralization mutations in either region (Syt1K189-192A and Syt1K326-327A) side-by-side to determine their relative contributions to Syt1 function in cultured cortical mouse neurons and in single-molecule experiments. Combining electrophysiological recordings and optical tweezers measurements to probe dynamic single C2 domain-membrane interactions, we show that both C2A and C2B polybasic patches contribute to membrane binding, and both are required for evoked release. The readily releasable vesicle pool or spontaneous release were not affected, so both patches are specifically required for synchronization of release. We suggest these patches contribute to cooperative binding to membranes, increasing the overall affinity of Syt1 for negatively charged membranes and facilitating evoked release.Significance StatementSynaptotagmin-1 is a vesicular calcium sensor required for synchronous neurotransmitter release. Its tandem cytosolic C2 domains (C2A and C2B) bind calcium, acidic lipids, and SNARE proteins that drive fusion of the synaptic vesicle with the plasma membrane. How calcium-binding to Synaptotagmin-1 leads to release and the relative contributions of the two C2 domains is not clear: unlike C2B, calcium-binding to C2A is not critical for evoked release, yet both domains are needed for Syt1 function. Combining electrophysiological recordings from cultured neurons and optical tweezers measurements that probe single C2 domain-membrane interactions, we show that conserved polybasic regions in both domains contribute to membrane binding cooperatively, and both are required for evoked release, likely by increasing the overall affinity of Synaptotagmin-1 for negatively charged membranes.
Exploring the Inner Workings of Neuron Circuits That Exhibit Persistent Activity To Explain How Working Memory and Executive Function Are Implemented in The Brain
Authors: Gomez Paul , Gomez Jeremy , Gomez Andres 
Published: July 2021

ABSTRACTIn this research we explore in detail how a phenomenon called “sustained persistent activity” is achieved by circuits of interconnected neurons. Persistent activity is a phenomenon that has been extensively studied (Papoutsi et al. 2013; Kaminski et. al. 2017; McCormick et al. 2003; Rahman, and Berger, 2011). Persistent activity consists of neuron circuits whose spiking activity remains even after the initial stimuli are removed. Persistent activity has been found in the prefrontal cortex (PFC) and has been correlated to working memory and decision making (Clayton E. Curtis and Daeyeol Lee, 2010).We go beyond the explanation of how persistent activity happens and show how arrangements of those basic circuits encode and store data and are used to perform more elaborated tasks and computations.The purpose of the model we propose here is to describe the minimum number of neurons and their interconnections required to explain persistent activity and how this phenomenon is actually a fast storage mechanism required for implementing working memory, task processing and decision making.
Feeding effects on liver mitochondrial bioenergetics of Boa constrictor (Serpentes: Boidae)
Authors: da Mota Araujo Helena Rachel , Sartori Marina Rincon , Navarro Claudia D. C. , de Carvalho José Eduardo , da Cruz André Luis 
Published: July 2021

ABSTRACTSnakes are interesting examples of overcoming energy metabolism challenges as many species can endure long periods without feeding, and their eventual meals are of reasonably large sizes, thus exhibiting dual extreme adaptations. Consequently, metabolic rate increases considerably to attend to the energetic demand of digestion, absorption and, protein synthesis. These animals should be adapted to transition from these two opposite states of energy fairly quickly, and therefore we investigated mitochondrial function plasticity in these states. Herein we compared liver mitochondrial bioenergetics of the boid snake Boa constrictor during fasting and after meal intake. We fasted the snakes for 60 days, then we fed a subgroup with 30% of their body size and evaluated their maximum postprandial response. We measured liver respiration rates from permeabilized tissue and isolated mitochondria, and from isolated mitochondria, we also measured Ca2+ retention capacity, the release of H2O2, and NAD(P) redox state. Mitochondrial respiration rates were maximized after feeding, reaching until 60% increase from fasting levels when energized with complex I-linked substrates. Interestingly, fasting and fed snakes exhibited similar respiratory control ratios and citrate synthase activity. Furthermore, we found no differences in Ca2+ retention capacity, indicating no increase in susceptibility to mitochondrial permeability transition pore (PTP), or redox state of NAD(P), although fed animals exhibited increases in the release of H2O2. Thus, we conclude that liver mitochondria from B. constrictor snakes increase the maintenance costs during the postprandial period and quickly improve the mitochondrial bioenergetics capacity without compromising the redox balance.
Individualized prediction of future cognition using baseline developmental changes in cortical anatomy
Authors: Khundrakpam Budhachandra , Booij Linda , Jeon Seun , Tohka Jussi , Evans Alan C. 
Published: July 2021

AbstractPredictive modeling studies have started to reveal brain measures underlying cognition; however, most studies are based on cross-sectional data (static ‘final’ brain measures acquired at one time point). Since brain development comprises of continuously ongoing events leading to cognitive development, predictive modeling studies need to consider‘dynamic’as opposed tostatic ‘final’brain measures. Using longitudinal neuroimaging and cognitive data (global executive composite score, an index of executive function) from 82 individuals (aged 5-14 years, scanned 3 times), we built highly accurate prediction models (r=0.61,p=1.6e-09) of future cognition (assessed at visit 3) based on baseline developmental changes in cortical anatomy (from visit 1 to 2). More importantly, dynamic brain measures (change in cortical anatomy from visit 1 to 2) and not static brain measures (cortical anatomy at visit 1 and 2) were critical for predicting future cognition, suggesting the need for considering dynamic brain measures in predicting cognitive outcomes.
Exocyst Inactivation in Urothelial Cells Disrupts Autophagy and Activates non-canonical NF-κB
Authors: Ortega Michael A. , Villiger Ross K. , Harrison-Chau Malia , Lieu Suzanna , Tamashiro Kadee-Kalia , Lee Amanda J. , Fujimoto Brent A. , Patwardhan Geetika Y. , Kepler Joshua , Fogelgren Ben 
Published: July 2021

AbstractUreter obstruction is a highly prevalent event during embryonic development and is a major cause of pediatric kidney disease. We have reported that ureteric bud-specific ablation of the exocyst Exoc5 subunit in late-murine gestation results in failure of urothelial stratification, cell death, and complete ureter obstruction. However, the mechanistic connection between disrupted exocyst activity, urothelial cell death, and subsequent ureter obstruction was unclear. Here, we report that inhibited urothelial stratification does not drive cell death during ureter development. Instead, we demonstrate that the exocyst plays a critical role in autophagy in urothelial cells, and that disruption of autophagy activates a urothelial NF-κB stress response. Impaired autophagy first provokes canonical NF-κB activity which is progressively followed by increasing non-canonical NF-κB activity and cell death if the stress remains unresolved. Furthermore, we demonstrate that ureter obstructions can be completely rescued in Exoc5 conditional knockout mice by administering a single dose of pan-caspase inhibitor z-VAD-FMK at E16.5 prior to urothelial cell death. Taken together, ablation of Exoc5 disrupts autophagic stress response and activates progressive NF-κB signaling which promotes obstructive uropathy.
Single-molecule imaging with cell-derived nanovesicles reveals early binding dynamics at a cyclic nucleotide-gated ion channel
Authors: Patel Vishal R. , Salinas Arturo M. , Qi Darong , Gupta Shipra , Sidote David J. , Goldschen-Ohm Marcel P. 
Published: July 2021

AbstractLigand binding to membrane proteins is critical for many biological signaling processes. However, individual binding events are rarely directly observed, and their asynchronous dynamics are occluded in ensemble-averaged measures. For membrane proteins, single-molecule approaches that resolve these dynamics are challenged by dysfunction in nonnative lipid environments, lack of access to intracellular sites, and costly sample preparation. Here, we introduce an approach combining cell-derived nanovesicles, microfluidics, and single-molecule fluorescence colocalization microscopy to track individual binding events at a cyclic nucleotide-gated TAX-4 ion channel critical for sensory transduction. Our observations reveal dynamics of both nucleotide binding and a subsequent conformational change likely preceding pore opening. We further show that binding of the second ligand in the tetrameric channel is less cooperative than previously estimated from ensemble-averaged binding measures. This approach is broadly applicable to studies of binding dynamics for proteins with extracellular or intracellular domains in native cell membrane.