bluuebunny/crossref_metadata_2025_split huggingface dataset:
Annotating off-label drug usage from unconventional sources
Authors: Avram Sorin , Halip Liliana , Curpan Ramona , Borota Ana , Bora Alina , Oprea Tudor I 
Published: September 2022

ABSTRACTPhysicians have the freedom to prescribe medicines outside the list of approved indications, to treat mild to life-threatening clinical conditions and diseases, particularly when conventional treatments fail or are lacking. Off-label drug usage is more frequently observed in specific populations not often represented in clinical trials, e.g., pediatric, geriatric, or pregnant patients. Despite conflicting reports on patient safety, exploring alternative treatment options in medical practice promotes innovation and extends the applicability of current medicines. This process can be significantly improved by properly documenting and discussing off-label usage. This paper aims to document off-label uses discussed in less conventional sources, such as the r/medicine Reddit subforum. We identified 66 “Reddit off-label uses” (ROLUs) not captured in our reference database, DrugCentral (https://drugcentral.org/), for a set of 40 drugs. These drugs are associated with 209 on-label drug indications (INDs) and 58 “non-Reddit” off-label uses (NROLUs). Most of these drugs are relatively ‘old’ (approved before 2000) and act on the nervous system, many with psychiatric applications. However, ROLUs are distinct from INDs and NROLUs. An automated scientific literature query showed that 90% of the ROLUs are linked to 4 scientific publications or more, with 80% linked to at least 10. A further search in the clinical trials database revealed 46 ROLUs mentioned; 39 are in phase 3 trials. These results indicate that most off-label uses discussed on the Reddit forum are supported by scientific evidence. We conclude that medical social media channels can provide a valuable source of alternative drug applications and should be scientifically explored and evaluated in the future.
Effects of a mindfulness-based intervention and a health self-management programme on psychological well-being in older adults with subjective cognitive decline: Secondary analyses from the SCD-Well randomised clinical trial
Authors: Schlosser Marco , Demnitz-King Harriet , Barnhofer Thorsten , Collette Fabienne , Gonneaud Julie , Chételat Gaël , Jessen Frank , Kliegel Matthias , Klimecki Olga M. , Lutz Antoine , Marchant Natalie L. ,   The Medit-Ageing Research Group
Published: September 2022

AbstractObjectivesOlder adults with subjective cognitive decline (SCD) recruited from memory clinics have an increased risk of developing dementia and regularly experience reduced psychological well-being related to memory concerns and fear of dementia. Research on improving well-being in SCD is limited and lacks non-pharmacological approaches. We investigated whether mindfulness-based and health education interventions can enhance well-being in SCD.MethodsThe SCD-Well trial (ClinicalTrials.gov: NCT03005652) randomised 147 older adults with SCD to an 8-week caring mindfulness-based approach for seniors (CMBAS) or an active comparator (health self-management programme [HSMP]). Well-being was assessed at baseline, post-intervention, and 6-month post-randomisation using the Psychological Well-being Scale (PWBS), the World Health Organisation’s Quality of Life (QoL) Assessment psychological subscale, and composites capturing meditation-based well-being dimensions of awareness, connection, and insight. Mixed effects models were used to assess between- and within-group differences in change.ResultsCMBAS was superior to HSMP on changes in connection at post-intervention. Within both groups, PWBS total scores, psychological QoL, and composite scores did not increase. Exploratory analyses indicated increases in PWBS autonomy at post-intervention in both groups.ConclusionTwo non-pharmacological interventions were associated with only limited effects on psychological well-being in SCD. Longer intervention studies with waitlist/retest control groups are needed to assess if our findings reflect intervention brevity and/or minimal base rate changes in well-being.
Deep Brain Stimulation Normalizes Amygdala Responsivity in Treatment-Resistant Depression
Authors: Runia N. , Bergfeld I.O. , de Kwaasteniet B.P. , Luigjes J. , van Laarhoven J. , Notten P. , Beute G. , van den Munckhof P. , Schuurman P.R. , Denys D.A.J.P. , van Wingen G.A. 
Published: September 2022

AbstractDeep brain stimulation (DBS) of the ventral anterior limb of the internal capsule (vALIC) is a promising intervention for treatment-resistant depression (TRD). However, the working mechanisms of vALIC DBS in TRD remain largely unexplored. As major depressive disorder has been associated with aberrant amygdala functioning, we investigated whether vALIC DBS affects amygdala responsivity and functional connectivity. To investigate the long-term effects of DBS, eleven patients with TRD performed an implicit emotional face viewing paradigm during functional magnetic resonance imaging (fMRI) before DBS surgery and after DBS parameter optimization. Sixteen matched healthy controls performed the fMRI paradigm at two time points to control for test-retest effects. To investigate the short-term effects of DBS de-activation after parameter optimization, thirteen patients additionally performed the fMRI paradigm after double-blind periods of active and sham stimulation. Results showed that TRD patients had decreased right amygdala responsivity compared to healthy controls at baseline. Long-term vALIC DBS normalized right amygdala responsivity, which was associated with faster reaction times. Furthermore, active compared to sham DBS increased amygdala connectivity with sensorimotor and cingulate cortices. These results suggest that vALIC DBS may relieve emotional blunting and depression by restoring amygdala responsivity and behavioral vigilance.
Dynamics of SARS-CoV-2 seroassay sensitivity: a systematic review and modeling study
Authors: Owusu-Boaitey Nana , Russell Timothy W. , Meyerowitz-Katz Gideon , Levin Andrew T. , Herrera-Esposito Daniel 
Published: September 2022

AbstractBackgroundSerological surveys have been the gold standard to estimate the numbers of SARS-CoV-2 infections, epidemic dynamics, and disease severity. Serological assays have decaying sensitivity with time that can bias their results, but there is a lack of guidelines to account for this phenomenon for SARS-CoV-2.AimOur goal is to assess the sensitivity decay of seroassays for detecting SARS-CoV-2 infections, the dependence of this decay on assay characteristics, and to provide a simple method to correct for this phenomenon.MethodsWe performed a systematic review and meta-analysis of SARS-CoV-2 serology studies. We included studies testing previously diagnosed individuals, without any SARS-CoV-2 vaccines, and excluded studies of cohorts highly unrepresentative of the general population (e.g. hospitalised patients).ResultsOf the 488 screened studies, 76 studies reporting on 50 different seroassays were included in the analysis. Sensitivity decay depends strongly on the antigen and the analytic technique used by the assay, with average sensitivities ranging between 26% and 98% at 6 months after infection, depending on assay characteristics. We find that a third of the included assays depart considerably from manufacturer specifications after 6 months.ConclusionsSeroassay sensitivity decay depends on assay characteristics, and for some types of assays it can make manufacturer specifications highly unreliable. We provide a tool to correct for this phenomenon, and to assess the risk of decay for a given assay. Our analysis can guide the design and interpretation of serosurveys for SARS-CoV-2 and other pathogens, and quantify systematic biases in the existing serology literature.
Postpartum estrogen withdrawal induces deficits in affective behaviors and increases ΔFosB in D1 and D2 neurons in the nucleus accumbens core in mice
Authors: Foster William B. , Beach Katherine F. , Carson Paige F. , Harris Kagan C. , Alonso Brandon L. , Costa Leo T. , Simamora Roy C. , Corbin Jaclyn E. , Hoag Keegan F. , Mercado Sophia I. , Bernhard Anya G. , Leung Cary H. , Nestler Eric J. , Been Laura E. 
Published: September 2022

AbstractIn placental mammals, estradiol levels are chronically elevated during pregnancy, but quickly drop to prepartum levels following birth. This may produce an “estrogen withdrawal” state that has been linked to changes in affective states in humans and rodents during the postpartum period. The neural mechanisms underlying these affective changes, however, are understudied. We used a hormone-simulated pseudopregnancy (HSP), a model of postpartum estrogen withdrawal, in adult female C57BL/6 mice to test the impact of postpartum estrogen withdrawal on several behavioral measures of anxiety and motivation. We found that estrogen withdrawal following HSP increased anxiety-like behavior in the elevated plus maze, but not in the open field or marble burying tests. Although hormone treatment during HSP consistently increased sucrose consumption, sucrose preference was generally not impacted by hormone treatment or subsequent estrogen withdrawal. In the social motivation test, estrogen withdrawal decreased the amount of time spent in proximity to a social stimulus animal. These behavioral changes were accompanied by changes in the expression of ΔFosB, a transcription factor correlated with stable long-term plasticity, in the nucleus accumbens (NAc). Specifically, estrogen-withdrawn females had higher ΔFosB expression in the nucleus accumbens core. Using transgenic reporter mice, we found that this increase in ΔFosB occurred in both D1- and D2-expressing cells in the NAc core. Together, these results suggest that postpartum estrogen withdrawal impacts anxiety and motivation and increases ΔFosB in the NAc core.
Synergising single-cell resolution and 4sU labelling boosts inference of transcriptional bursting
Authors: Edwards David M , Davies Philip , Hebenstreit Daniel 
Published: September 2022

AbstractDespite the recent rise of RNA-seq datasets combining single-cell (sc) resolution with 4-thiouridine (4sU) labelling, analytical methods exploiting their power to dissect transcriptional bursting are lacking. Here, we present a mathematical model and Bayesian inference implementation to facilitate genome-wide joint parameter estimation and confidence quantification. We demonstrate that, unlike conventional scRNA-seq, 4sU scRNA-seq resolves temporal parameters and furthermore boosts inference of dimensionless parameters via a synergy between single-cell resolution and 4sU labelling. We applied our method to published 4sU scRNA-seq data and linked with ChIP-seq data, uncovering previously obscured associations between different parameters and histone modifications.
Adaptive encoding speed in working memory
Authors: de Jong Joost , van Rijn Hedderik , Akyurek Elkan 
Published: September 2022

AbstractHumans can adapt when complex patterns unfold at a faster or slower pace, for instance when remembering a grocery list that is dictated at an increasingly fast pace. Integrating information over such timescales crucially depends on working memory, but although recent findings have shown that working memory capacity can be flexibly adapted, such adaptations have not yet been demonstrated for encoding speed. In a series of experiments, we found that young adults encoded at a faster rate when they were adapted to overall and recent rate of incoming information. Interestingly, our participants were unable to use explicit cues to speed up encoding, even though these cues were objectively more informative than statistical information. Our findings suggest that adaptive tuning of encoding speed in working memory is a fundamental but largely implicit mechanism underlying our ability to keep up with the pace of our surroundings.Significance StatementHumans can store information very quickly. For instance, when we hear someone speak twice as fast as normal, we can still follow quite well. How is this possible? We hypothesized that when humans expect limited time to store a piece of information (e.g. when listening to a sped-up podcast) they would ideally store that information more quickly before it’s gone. Indeed, we found that young adults encoded more information per second when they implicitly expect that they have little time to do so. However, they were unable to use explicit cues about how much time they have. It seems that young adults can, at least implicitly, tune the pace at which they store information.
A genome-wide CRISPR functional survey of the human phagocytosis molecular machinery
Authors: Essletzbichler Patrick , Sedlyarov Vitaly , Frommelt Fabian , Soulat Didier , Heinz Leonhard X , Stefanovic Adrijana , Neumayer Benedikt , Superti-Furga Giulio 
Published: September 2022

AbstractPhagocytosis, the process of engulfing large particles by cells, is a multilayered biological activity driving tissue clearance and host defense. Dysregulation of phagocytosis is connected to autoimmunity, accumulation of toxic disease proteins, and increased risks for infections. Despite its importance and multiple roles, we lack a full understanding of the cellular machinery involved in executing and regulating the process, including the coordination with other cellular events. To create a functional map in human cells, we performed a reporter- and FACS-based genome-wide CRISPR/Cas9 knock-out screen that identified 716 genes. Mapping the gene hits to a comprehensive protein-protein interaction network annotated for functional cellular processes, allowed to highlight those protein complexes identified multiple times, to identify missing components of the cellular phagocytosis network, and to suggest functional partition among complexes. We validate complexes known to be involved, such as the Arp2/3 complex, the vacuolar-ATPase-Rag machinery, and the Wave-2 complex, as well as processes previously not or only poorly associated with phagocytosis. Among the novel, phagocytosis-relevant cellular functions validated are the oligosaccharyltransferase complex (MAGT1/SLC58A1, DDOST, STT3B, and RPN2) as well as the hypusine pathway (eIF5A, DHPS, and DOHH). Overall, our network of phagocytosis regulators and effectors maps elements of cargo uptake, cargo shuffling and cargo biotransformation through the cell, providing a valuable resource for the identification of potential novel drivers for diseases of the endo-lysosomal system. We further propose that our approach of mining and integrating publicly available protein-protein interaction data with datasets derived from reporter-based genome-wide screens offers a broadly applicable way to functionally map biological processes onto the molecular machinery of the cell.Summary blurbThe validation and interpretation of a FACS reporter-based genome-wide CRISPR/Cas9 knock-out screen through protein-protein interaction data yields a comprehensive view of the molecular network regulating and executing phagocytosis in human cells.
Genomic and ecologic characteristics of the airway microbial-mucosal complex
Authors: Cuthbertson Leah , Löber Ulrike , Ish-Horowicz Jonathan S. , McBrien Claire N. , Churchward Colin , Parker Jeremy C. , Olanipekun Michael T. , Burke Conor , O’Carroll Orla , Faul John , Davies Gwyneth A. , Lewis Keir E. , Hopkin Julian M. , Creaser-Thomas Joy , Goshal Robin , Chung Kian Fan , Piatek Stefan , Willis-Owen Saffron A.G. , Bartolomaeus Theda U. P. , Birkner Till , Dwyer Sarah , Kumar Nitin , Turek Elena M. , Musk A. William , Hui Jenni , Hunter Michael , James Alan , Dumas Marc-Emmanuel , Filippi Sarah , Cox Michael J. , Lawley Trevor D. , Forslund Sofia K. , Moffatt Miriam F. , Cookson William O.C. 
Published: September 2022

Summary paragraphLung diseases due to infection and dysbiosis affect hundreds of millions of people world-wide1-4. Microbial communities at the airway mucosal barrier are conserved and highly ordered5, reflecting symbiosis and co-evolution with human host factors6. Freed of selection to digest nutrients for the host, the airway microbiome underpins cognate management of mucosal immunity and pathogen resistance. We show here the results of the first systematic culture and whole-genome sequencing of the principal airway bacterial species, identifying abundant novel organisms within the genera Streptococcus, Pauljensenia, Neisseria and Gemella. Bacterial genomes were enriched for genes encoding antimicrobial synthesis, adhesion and biofilm formation, immune modulation, iron utilisation, nitrous oxide (NO) metabolism and sphingolipid signalling. RNA-targeting CRISPR elements in some taxa suggest the potential to prevent or treat specific viral infections. Homologues of human RO60 present in Neisseria spp. provide a possible respiratory primer for autoimmunity in systemic lupus erythematosus (SLE) and Sjögren syndrome. We interpret the structure and biogeography of airway microbial communities from clinical surveys in the context of whole-genome content, identifying features of airway dysbiosis that may presage breakdown of homeostasis during acute attacks of asthma and chronic obstructive pulmonary disease (COPD). We match the gene content of isolates to human transcripts and metabolites expressed late in airway epithelial differentiation, identifying pathways that can sustain host interactions with the microbiota. Our results provide a systematic basis for decrypting interactions between commensals, pathogens, and mucosal immunity in lung diseases of global significance.
Extraction and characterization of cellulose from invasive weeds from central Nepal: A potential prospect of environmental management
Authors: Dhakal Samyog , Tiwari Achyut , Adhikari Archana , Shrestha Shyam Kumar , Adhikari Bikash 
Published: September 2022

AbstractThe cellulose is made up of long chains of polysaccharide of glucose molecules. Microfibrils are formed when numerous hydrogen-bonded cellulose chains unite, they are extremely stiff and contribute to physical stability, due to this general ability of forming these microfibrils to form long chains, cellulose is an ideal molecule for the manufacturing of packaging materials and bioplastics. On the other hand, Invasive plant species are one of the major constituents for environmental degradation and its application seems outmost. The main purpose of this study is to extract and identify the composition of cellulose fiber and characterize the fiber of invasive plant species that could be used as a replacement for plastics and textiles in some cases. In this study, Cellulose was isolated from 6 invasive species collected in Nepal’s Ramechhap district using various techniques, the composition of the fiber was identified using AOAC method 973.18, ASTM method D1106-96 and ASTM method E1755-01 and characterized using FTIR spectroscopy with weight analyses. Acid hydrolysis, chlorination, alkaline extraction, and bleaching were among the chemical methods adopted. In all of the samples, there were two primary absorbance peaks. The first occurred at low wavelengths in the 700−1,800 cm−1 range, while the second occurred at higher wavelengths in the 2,700–3,500 cm−1 range.The percentage of lignin within the final sample was determined in the range of 4.4-3.1% and the percentage yield of cellulose was determined within the range of 78-62%.The study shows that the cellulose can be extracted from the taken invasive plant species and can be used for further applications.
CTCF is a DNA-tension-dependent barrier to cohesin-mediated DNA loop extrusion
Authors: Davidson Iain F. , Barth Roman , Zaczek Maciej , van der Torre Jaco , Tang Wen , Nagasaka Kota , Janissen Richard , Kerssemakers Jacob , Wutz Gordana , Dekker Cees , Peters Jan-Michael 
Published: September 2022

AbstractIn eukaryotes, genomic DNA is extruded into loops by cohesin1. By restraining this process, the DNA-binding protein CTCF generates topologically associating domains (TADs)2-4 that play key roles in gene regulation and recombination during development and disease1,5-8. How CTCF establishes TAD boundaries and to what extent these are permeable to cohesin is unknown9. To address these questions, we visualize interactions of single CTCF and cohesin molecules on DNA in vitro. We show that CTCF is sufficient to block diffusing cohesin, possibly reflecting how cohesive cohesin accumulates at TAD boundaries, as well as to block loop-extruding cohesin, reflecting how CTCF establishes TAD boundaries. CTCF functions asymmetrically, as predicted, but unexpectedly is dependent on DNA tension. Moreover, CTCF regulates cohesin’s loop extrusion activity by changing its direction and by inducing loop shrinkage. Our data indicate that CTCF is not, as previously assumed, simply a barrier to cohesin-mediated loop extrusion but is an active regulator of this process, where the permeability of TAD boundaries can be modulated by DNA tension. These results reveal mechanistic principles of how CTCF controls loop extrusion and genome architecture.
Researchers and their experimental models: A pilot survey
Authors: Del Pace Lorenzo , Viviani Laura , Straccia Marco 
Published: September 2022

ABSTRACTA significant debate is ongoing on the effectiveness of animal experimentation due to the increasing reports of failure in the translation of results from preclinical animal experiments to human patients. Scientific, ethical, social and economic considerations linked to the use of animals raise concerns in a variety of societal contributors (regulators, policy makers, non-governmental organisations, industry, etc.).The aim of this study was to record researchers’ voice about their vision on this science evolution, to reconstruct as truthful as possible an image of the reality of health and life science research, by using a key instrument in the hands of the researcher: the experimental models.Hence, we surveyed European-based health and life sciences researchers, to reconstruct and decipher the varying orientations and opinions of this community over these large transformations. In the interest of advancing the public debate and more accurately guide the policy of research, it is important that policy makers, society, scientists and all stakeholders (1) mature as comprehensive as possible an understanding of the researchers perspectives on the selection and establishment of the experimental models, and (2) publicly share research community opinions, regarding the external factors influencing their professional work. Our results highlighted a general homogeneity of answers from the 117 respondents. However some discrepancies on specific key issues and topics were registered in the subgroups. These recorded divergent views might prove useful to research policy makers and regulators to calibrate their agenda and shape the future of the European health and life science research.