bluuebunny/crossref_metadata_2025_split huggingface dataset:
New drugs for multiple sclerosis: new treatment algorithms
Authors: Cree Bruce A.C. , Hartung Hans-Peter , Barnett Michael 
Published: June 2022

Purpose of review
To discuss recent changes in the multiple sclerosis (MS) treatment algorithm and to present therapies currently in MS clinical trials.

Recent findings
High efficacy disease modifying therapies are optimally beneficial when used in the early, inflammatory phase of MS. Bruton's tyrosine kinase has emerged as an important therapeutic target for both relapsing and progressive forms of MS. Multiple therapies targeting remyelination failed to provide conclusive evidence of broad therapeutic benefit; however, more targeted approaches offer hope that myelin repair might be achieved resulting in specific clinical improvements. Strategies targeting chronic Epstein–Barr virus infection and dysbiosis of the gut microbiome are the first to link microbial risk factors for MS and therapeutic interventions.

Summary
A striking number of diverse treatments under investigation bodes well for development of better and more effective therapies in MS.
Return-to-work interventions for persons/employees with mental illnesses
Authors: Hamann Johannes , Lang Anne , Riedl Lina , Brieger Peter 
Published: June 2022

Purpose of review
Mental illnesses are among the most common diseases worldwide. Cases of inability to work caused by mental illness are frequent and the related economic burden is immense. A successful reintegration into their work environment of those patients who were on sick leave due to a mental illness is an important prognostic factor for the further course of the disease and helps reducing financial consequences. It was the aim of the present review to give an overview of the status quo of return-to-work interventions in the international literature.

Recent findings
Main themes of interventions addressing return to work of persons with mental illnesses are the provision of psychotherapeutic support with or without combining these approaches with work directed interventions. Personal contact of employees, mental healthcare staff and supervisors may be helpful with regard to facilitating return to work.

Summary
Current return to work interventions are mostly elaborate, extensive and expensive without convincing results regarding work related outcome parameters. A variety of reasons might be responsible for this finding, including heterogeneity of outcomes, a poor definition of return-to-work-interventions and the complexity of the issue (involving multiple stakeholders).
Telemedicine in the treatment of addictions
Authors: Caballeria Elsa , López-Pelayo Hugo , Matrai Silvia , Gual Antoni 
Published: June 2022

Purpose of review
The purpose of this update is to provide an overview of recent research publications (January 2020–January 2022) on real-time telemedicine solutions for the management of addictions (alcohol, tobacco, opioids, and other drugs).

Recent findings
Motivational interviewing by real-time telemedicine showed effectiveness in youth and adults for risky alcohol use and alcohol use disorders, even when a concurrent mental health disorder exists. Live telemedicine is well accepted for managing tobacco use disorders. The range of interventions for treating opioid use disorder by real-time telemedicine is large and has been increased due to the coronavirus disease 2019 (COVID-19) pandemic (prescription of opioid agonists, peer-to-peer support, counseling, and group therapy).

Summary
The COVID-19 pandemic has accelerated the implementation of real-time telemedicine and, in parallel, research has been conducted to test its effectiveness. Videoconferencing and telephone interventions are supported by solid evidence for risky alcohol use and alcohol use disorder, tobacco use disorder and opioid use disorder. The Integration of other types of telemedicine (asynchronous telemedicine and remote monitoring) and with the entire health system is lacking. Many areas and vulnerable populations (e.g., homeless, elderly, and cannabis use disorders) need more attention.
Development of Restricted and Repetitive Behaviors from 2-19 and Internalizing Symptom Outcomes in a Longitudinal Study of Autism
Authors: Masjedi Nina , Clarke Elaine B. , Lord Catherine 
Published: June 2022

AbstractUsing data from a well-characterized longitudinal cohort, this study examined trajectories of restricted and repetitive behaviors (RRBs), specifically repetitive sensorimotor (RSM), insistence on sameness (IS), and verbal RRBs, as measured by the Autism Diagnostic Interview, Revised (ADI-R) from ages 2 to 19. Additionally, this study investigated relationships between RSM and IS trajectories and parent- and self-report depression and anxiety symptoms in early adulthood. Group-based trajectory modeling and multilevel modeling were used to investigate change in RRB subtypes. RSM and IS behaviors generally decreased from 2 to 19, though some participants experienced increases in these RRB subtypes from ages 2 to 9. 65% of this sample had sufficient verbal ability prior to age 19 to calculate trajectories of verbal RRBs. Of this subset, 49% had few to no verbal RRBs throughout development; in contrast, the remaining 51% experienced increasing verbal RRBs from 2 to 9, followed by a plateau in verbal RRBs from 9-19. Higher ADOS Social Affect (SA) CSS scores in early childhood were linked with more RSM symptoms across development, but not related to the IS and Verbal trajectories. Non-verbal IQ from early childhood was not connected to change in any of the identified RRB trajectories. There were no associations between IS trajectories and internalizing symptom in early adulthood. However, preliminary data suggests that a Moderate-Decreasing pattern of RSM development may be linked to anxiety in early adulthood. These findings illustrate continuity and change in a core ASD symptom domain, RRBs, from early childhood to early adulthood.
Persistence of immunity against omicron BA.1 and BA.2 following homologous and heterologous COVID-19 booster vaccines in healthy adults after a two-doses AZD1222 vaccination
Authors: Assawakosri Suvichada , Kanokudom Sitthichai , Chansaenroj Jira , Suntronwong Nungruthai , Auphimai Chompoonut , Nilyanimit Pornjarim , Vichaiwattana Preeyaporn , Thongmee Thanunrat , Duangchinda Thaneeya , Chantima Warangkana , Pakchotanon Pattarakul , Srimuan Donchida , Thatsanatorn Thaksaporn , Klinfueng Sirapa , Sudhinaraset Natthinee , Wanlapakorn Nasamon , Mongkolsapaya Juthathip , Honsawek Sittisak , Poovorawan Yong 
Published: June 2022

AbstractObjectivesThe SARS-CoV-2 Omicron variant presents numerous mutations potentially able to evade neutralizing antibodies (NAbs) elicited by COVID-19 vaccines. Therefore, this study aimed to provide evidence on a heterologous booster strategy to overcome the waning immunity against Omicron variants.MethodsParticipants who completed Oxford/AstraZeneca (hereafter AZD1222) for 5-7 months were enrolled. The reactogenicity and persistence of immunogenicity in both humoral and cellular response after a homologous or heterologous booster with the AZD1222 and mRNA vaccines (BNT162B2, full or half-dose mRNA-1273) administered six months after primary vaccination were determined.ResultsTotal 229 individuals enrolled, a waning of immunity was observed 5-7 months after the AZD1222-primed. Total RBD immunoglobulin (Ig) levels, anti-RBD IgG and focus reduction neutralization test against Omicron BA.1 and BA.2 and T cell response peaked 14-28 days after booster vaccination. Both the full and half dose of mRNA-1273 induced the highest response, followed by BNT162b2 and AZD1222. At 90 days, the persistence of immunogenicity was observed among all mRNA-boosted individuals. Adverse events were acceptable and well tolerated for all vaccines.ConclusionsA heterologous mRNA booster provided a significantly superior boost of binding and NAbs levels against the Omicron variant compared to a homologous booster in individuals with AZD1222-primed vaccinations.
Neutralization of Omicron sublineages and Deltacron SARS-CoV-2 by 3 doses of BNT162b2 vaccine or BA.1 infection
Authors: Kurhade Chaitanya , Zou Jing , Xia Hongjie , Liu Mingru , Yang Qi , Cutler Mark , Cooper David , Muik Alexander , Sahin Ugur , Jansen Kathrin U. , Ren Ping , Xie Xuping , Swanson Kena A. , Shi Pei-Yong 
Published: June 2022

AbstractDistinct SARS-CoV-2 Omicron sublineages have evolved showing increased fitness and immune evasion than the original Omicron variant BA.1. Here we report the neutralization activity of sera from BNT162b2 vaccinated individuals or unimmunized Omicron BA.1-infected individuals against Omicron sublineages and “Deltacron” variant (XD). BNT162b2 post-dose 3 immune sera neutralized USA-WA1/2020, Omicron BA.1-, BA.2-, BA.2.12.1-, BA.3-, BA.4/5-, and XD-spike SARS-CoV-2s with geometric mean titers (GMTs) of 1335, 393, 298, 315, 216, 103, and 301, respectively; thus, BA.4/5 SARS-CoV-2 spike variant showed the highest propensity to evade vaccine neutralization compared to the original Omicron variants BA.1. BA.1-convalescent sera neutralized USA-WA1/2020, BA.1-, BA.2-, BA.2.12.1-, BA.3-, BA.4/5-, and Deltacron-spike SARS-CoV-2s with GMTs of 15, 430, 110, 109, 102, 25, and 284, respectively. The low neutralization titers of vaccinated sera or convalescent sera from BA. 1 infected individuals against the emerging and rapidly spreading Omicron BA.4/5 variants provide important results for consideration in the selection of an updated vaccine in the current Omicron wave.
Evolution of long-term vaccine induced and hybrid immunity in healthcare workers after different COVID-19 vaccination regimens: a longitudinal observational cohort study
Authors: Moore Shona C. , Kronsteiner Barbara , Longet Stephanie , Adele Sandra , Deeks Alexandra S. , Liu Chang , Dejnirattisai Wanwisa , Reyes Laura Silva , Meardon Naomi , Faustini Sian , Al-Taei Saly , Tipton Tom , Hering Luisa M , Angyal Adrienn , Brown Rebecca , Nicols Alexander R , Dobson Susan L , Supasa Piyada , Tuekprakhon Aekkachai , Cross Andrew , Tyerman Jessica K , Hornsby Hailey , Grouneva Irina , Plowright Megan , Zhang Peijun , Newman Thomas A.H. , Nell Jeremy M. , Abraham Priyanka , Ali Mohammad , Malone Tom , Neale Isabel , Phillips Eloise , Wilson Joseph D. , Murray Sam M. , Zewdie Martha , Shields Adrian , Horner Emily C. , Booth Lucy H. , Stafford Lizzie , Bibi Sagida , Wootton Daniel G. , Mentzer Alexander J. , Conlon Christopher P. , Jeffery Katie , Matthews Philippa C. , Pollard Andrew J. , Brown Anthony , Rowland-Jones Sarah L. , Mongkolsapaya Juthathip , Payne Rebecca P. , Dold Christina , Lambe Teresa , Thaventhiran James E.D. , Screaton Gavin , Barnes Eleanor , Hopkins Susan , Hall Victoria , Duncan Christopher JA , Richter Alex , Carroll Miles , de Silva Thushan I. , Klenerman Paul , Dunachie Susanna , Turtle Lance 
Published: June 2022

AbstractBoth infection and vaccination, alone or in combination, generate antibody and T cell responses against SARS-CoV-2. However, the maintenance of such responses – and hence protection from disease – requires careful characterisation. In a large prospective study of UK healthcare workers (Protective immunity from T cells in Healthcare workers (PITCH), within the larger SARS-CoV-2 immunity & reinfection evaluation (SIREN) study) we previously observed that prior infection impacted strongly on subsequent cellular and humoral immunity induced after long and short dosing intervals of BNT162b2 (Pfizer/BioNTech) vaccination. Here, we report longer follow up of 684 HCWs in this cohort over 6-9 months following two doses of BNT162b2 or AZD1222 (Oxford/AstraZeneca) vaccination and up to 6 months following a subsequent mRNA booster vaccination. We make three observations: Firstly, the dynamics of humoral and cellular responses differ; binding and neutralising antibodies declined whereas T and memory B cell responses were maintained after the second vaccine dose. Secondly, vaccine boosting restored IgG levels, broadened neutralising activity against variants of concern including omicron BA.1, BA.2 and BA.5, and boosted T cell responses above the 6 month level post dose 2. Thirdly, prior infection maintained its impact driving larger as well as broader T cell responses compared with never-infected people – a feature maintained until 6 months after the third dose. In conclusion, broadly cross-reactive T cell responses are well maintained over time – especially in those with combined vaccine and infection-induced immunity (“hybrid” immunity) – and may contribute to continued protection against severe disease.
Ecology, not host phylogeny, shapes the oral microbiome in closely related species of gorillas
Authors: Moraitou Markella , Forsythe Adrian , Fellows Yates James A. , Brealey Jaelle C. , Warinner Christina , Guschanski Katerina 
Published: June 2022

AbstractHost-associated microbiomes are essential for a multitude of biological processes. Placed at the contact zone between external and internal environments, the little-studied oral microbiome has important roles in host physiology and health. Here we investigate the contribution of host evolutionary relationships and ecology in shaping the oral microbiome in three closely related gorilla subspecies (mountain, Grauer’s, and western lowland gorillas) using shotgun metagenomics of 46 museum-preserved dental calculus samples. We find that the oral microbiomes of mountain gorillas are functionally and taxonomically distinct from the other two subspecies, despite close evolutionary relationships and geographic proximity with Grauer’s gorillas. Grauer’s gorillas show intermediate bacterial taxonomic and functional, and dietary profiles. Altitudinal differences in gorilla subspecies ranges appear to explain these patterns, proposing a close connection between dental calculus microbiome and the environment, which is further supported by the presence of gorilla subspecies-specific phyllosphere/rhizosphere taxa. Mountain gorillas show high abundance of nitrate-reducing oral taxa, which may contribute to high altitude adaptation by modulating blood pressure. Our results suggest that ecology, rather than evolutionary relationships and geographic proximity, primarily shape the oral microbiome in these closely related species.
Comparing supervised machine learning algorithms for the prediction of partial arterial pressure of oxygen during craniotomy
Authors: Becker-Pennrich Andrea S , Mandl Maximilian M , Rieder Clemens , Hoechter Dominik J , Dietz Konstantin , Geisler Benjamin P , Boulesteix Anne-Laure , Tomasi Roland , Hinske Ludwig C 
Published: June 2022

ABSTRACTObjectiveTo evaluate the feasibility of continuous paO2 prediction in an intraoperative setting among neurosurgical patients with modern machine learning methods.Materials and MethodsData were extracted from routine clinical care of lung-healthy, neurosurgical patients. We used recursive feature elimination to identify relevant features for the prediction of paO2. Five machine learning algorithms (gradient boosting regressor, k-nearest neighbors regressor, random forest regressor, support vector regression, multi-layer perceptron regressor) and a multivariate linear regression were then tuned and fitted to the selected features. A performance matrix consisting of Spearman’s ρ, mean absolute percentage error (MAPE) and root mean squared error (RMSE) was finally computed based on the test set and used to compare and rank each algorithm.ResultsWe analyzed 4,180 patients with 12,497 observations. A total of 20 features were selected from analysis of the training dataset comprising 836 patients with 9,992 observations. The best algorithm, random forest, was able to predict paO2 values with ρ=0.90, MAPE=10.4%, and RMSE=30.9mmHg, closely followed by gradient boosting and multi-layer perceptron. Support vector regression, k-nearest neighbors regressor and the linear regression did not achieve the performance metrics.DiscussionWe successfully applied and compared several machine learning algorithms to estimate continuous paO2 values in neurosurgical patients. The random forest regressor performed best over all three categories of the performance matrix.ConclusionPaO2 can be predicted by perioperative routine data in neurosurgical patients.
Formation of protein-mediated bilayer tubes is governed by a snapthrough transition
Authors: Mahapatra A. , Rangamani P. 
Published: June 2022

AbstractPlasma membrane tubes are ubiquitous in cellular membranes and in the membranes of intracellular organelles. They play crucial roles in trafficking, ion transport, and cellular motility. These tubes can be formed due to localized forces acting on the membrane or by the curvature induced by membrane-bound proteins. Here, we present a mathematical framework to model cylindrical tubular protrusions formed by proteins that induce anisotropic spontaneous curvature. Our analysis revealed that the tube radius depends on an effective tension that includes contributions from the bare membrane tension and the protein-induced curvature. We also found that the length of the tube undergoes an abrupt transition from a short, domeshaped membrane to a long cylinder and this transition is characteristic of a snapthrough instability. Finally, we show that the snapthrough instability depends on the different parameters including coat area, bending modulus, and extent of protein-induced curvature. Our findings have implications for tube formation due to BAR-domain proteins in processes such as endocytosis, t-tubule formation in myocytes, and cristae formation in mitochondria.
“Cheater” particles render the VEGAS platform unsuitable for mammalian directed evolution
Authors: Denes Christopher E. , Cole Alexander J. , Tran Minh Thuan Nguyen , Mohd Khalid Mohd Khairul Nizam , Hewitt Alex W. , Hesselson Daniel , Neely G. Gregory 
Published: June 2022

ABSTRACTDirected evolution uses cycles of gene diversification and selection to generate proteins with novel properties. While traditionally directed evolution is performed in prokaryotic systems, recently a mammalian directed evolution system (viral evolution of genetically actuating sequences, or “VEGAS”) has been described. Here we report that the VEGAS system has major limitations precluding its use for directed evolution. The primary technical issue with the VEGAS system is an immediate contamination with “cheater” particles that bypass directed evolution circuits. By sequencing we find these cheater particles contain Sindbis structural genes instead of the intended directed evolution target transgene. These cheaters outcompete the VEGAS transgenes within 2 rounds of transduction but cannot themselves activate synthetic circuits that drive expression of Sindbis structural genes, preventing directed evolution campaigns. Similar results have been obtained in independent labs. Taken together, the VEGAS system does not work as described and, without significant redesign to suppress cheaters, cannot be used for mammalian directed evolution campaigns.
A hybrid model combining evolutionary probability and machine learning leverages data-driven protein engineering
Authors: Illig Alexander-Maurice , Siedhoff Niklas E. , Schwaneberg Ulrich , Davari Mehdi D. 
Published: June 2022

AbstractProtein engineering through directed evolution and (semi-)rational approaches has been applied successfully to optimize protein properties for broad applications in molecular biology, biotechnology, and biomedicine. The potential of protein engineering is not yet fully realized due to the limited screening throughput hampering the efficient exploration of the vast protein sequence space. Data-driven strategies have emerged as a powerful tool to leverage protein engineering by providing a model of the sequence-fitness landscape that can exhaustively be explored in silico and capitalize on the high diversity potential offered by nature However, as both the quality and quantity of the inputted data determine the success of such approaches, the applicability of data-driven strategies is often limited due to sparse data. Here, we present a hybrid model that combines direct coupling analysis and machine learning techniques to enable data-driven protein engineering when only few labeled sequences are available. Our method achieves high performance in predicting a protein’s fitness based on its sequence regardless of the number of sequences-fitness pairs in the training dataset. Besides reducing the computational effort compared to state-of-the-art methods, it outperforms them for sparse data situations, i.e., 50 − 250 labeled sequences available for training. In essence, the developed method is auspicious for data-driven protein engineering, especially for protein engineers who have only access to a limited amount of data for sequence-fitness landscape modeling.
SARS-CoV-2 spike protein induces TLR-4-mediated long-term cognitive dysfunction recapitulating post-COVID syndrome
Authors: Fontes-Dantas Fabricia L. , Fernandes Gabriel G. , Gutman Elisa G. , De Lima Emanuelle V. , Antonio Leticia S. , Hammerle Mariana B. , Mota-Araujo Hannah P. , Colodeti Lilian C. , Araújo Suzana M. B. , da Silva Talita N. , Duarte Larissa A. , Salvio Andreza L. , Pires Karina L. , Leon Luciane A. A. , Vasconcelos Claudia Cristina F. , Romão Luciana , Savio Luiz Eduardo B. , Silva Jerson L. , da Costa Robson , Clarke Julia R. , Da Poian Andrea T. , Alves-Leon Soniza V. , Passos Giselle F. , Figueiredo Claudia P. 
Published: June 2022

AbstractCognitive dysfunction is often reported in post-COVID patients, but its underlying mechanisms remain unknown. While some evidence indicate that SARS-CoV-2 can reach and directly impact the brain, others suggest viral neuroinvasion as a rare event. Independently of brain viral infection, the ability of SARS-CoV-2 spike (S) protein to cross the BBB and reach memory-related brain regions has already been shown. Here, we demonstrate that brain infusion of S protein in mice induces late cognitive impairment and increases serum levels of neurofilament light chain (NFL), which recapitulates post-COVID features. Neuroinflammation, hippocampal microgliosis and synapse loss are induced by S protein. Increased engulfment of hippocampal presynaptic terminals late after S protein brain infusion were found to temporally correlate with cognitive deficit in mice. Blockage of TLR4 signaling prevented S-associated detrimental effects on synapse and memory loss. In a cohort of 86 patients recovered from mild COVID-19, genotype GG TLR4 -2604G>A (rs10759931) was associated with poor cognitive outcome. Collectively, these findings indicate that S protein directly impacts the brain and suggest that TLR4 is a potential target to prevent post-COVID cognitive dysfunction.One Sentence SummaryTLR4 mediates long-term cognitive impairment in mice and its genetic variant increases the risk of poor cognitive outcome in post-COVID patients.