bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effectiveness of Nirmatrelvir-Ritonavir for the treatment of patients with mild to moderate COVID-19 and at high risk of hospitalization: Systematic review and meta-analyses of observational studies
Authors: Miranda Souza Kathiaja , Carrasco Gabriela , Rojas-Cortés Robin , Michel Barbosa Mariana , Henrique Ferreira Bambirra Eduardo , Luis Castro José , Alvares-Teodoro Juliana 
Published: March 2023

AbstractObjectiveTo assess the effectiveness of nirmatrelvir-ritonavir in the treatment of outpatients with mild to moderate COVID-19 who are at higher risk of developing severe illness, through a systematic review with meta-analyses of observational studies.MethodsA systematic search was performed, in accordance with the Cochrane search methods, to identify observational studies that met the inclusion criteria. The outcomes of mortality and hospitalization were analyzed. Search was conducted on PubMed, EMBASE, and The Cochrane Library. Two reviewers independently screened references, selected the studies, extracted the data, assessed the risk of bias using ROBINS-I tool and evaluated the quality of evidence using the GRADE tool. This study followed the PRISMA reporting guideline.ResultsA total of 16 observational studies and 1,482,923 patients were finally included. The results of the meta-analysis showed that in comparison to standard treatment without antivirals, nirmatrelvir-ritonavir reduced the risk of death by 62% (OR= 0.38; 95% CI: 0.30-0.46; moderate certainty of evidence). In addition, a 53% reduction in the risk of hospital admission was observed (OR = 0.47; 95% CI: 0.36–0.60, with very low certainty of evidence). For the composite outcome of hospitalization and/or mortality, there was a 56% risk reduction (OR=0.44; 95% CI: 0.31-0.64, moderate certainty of evidence).ConclusionThe results suggest that nirmatrelvir-ritonavir could be effective in reducing mortality and hospitalization. The results were valid in vaccinated or unvaccinated high-risk individuals with COVID-19. Data from ongoing and future trials may further advance our understanding of the effectiveness and safety of nirmatrelvir-ritonavir and help improve treatment guidelines for COVID-19.
Rare variants inPPFIA3cause delayed development, intellectual disability, autism, and epilepsy
Authors: Paul Maimuna S. , Michener Sydney L. , Pan Hongling , Pfliger Jessica M. , Rosenfeld Jill A. , Lerma Vanesa C. , Tran Alyssa , Longley Megan A. , Lewis Richard A. , Weisz-Hubshman Monika , Bekheirnia Mir Reza , Bekheirnia Nasim , Massingham Lauren , Zech Michael , Wagner Matias , Engels Hartmut , Cremer Kirsten , Mangold Elisabeth , Peters Sophia , Trautmann Jessica , Mester Jessica L. , Guillen Sacoto Maria J. , Person Richard , McDonnell Pamela P. , Cohen Stacey R. , Lusk Laina , Cohen Ana S.A. , Pichon Jean-Baptiste Le , Pastinen Tomi , Zhou Dihong , Engleman Kendra , Racine Caroline , Faivre Laurence , Moutton Sébastien , Pichon Anne-Sophie Denommé- , Schuhmann Sarah , Vasileiou Georgia , Russ-Hall Sophie , Scheffer Ingrid E. , Carvill Gemma L. , Mefford Heather , Network Undiagnosed Diseases , Bacino Carlos A. , Lee Brendan H. , Chao Hsiao-Tuan 
Published: March 2023

AbstractPPFIA3encodes the Protein-Tyrosine Phosphatase, Receptor-Type, F Polypeptide-Interacting Protein Alpha-3 (PPFIA3), which is a member of the LAR protein-tyrosine phosphatase-interacting protein (liprin) family involved in synaptic vesicle transport and presynaptic active zone assembly. The protein structure and function are well conserved in both invertebrates and vertebrates, but human diseases related to PPFIA3 dysfunction are not yet known. Here, we report 14 individuals with rare mono-allelicPPFIA3variants presenting with features including developmental delay, intellectual disability, hypotonia, autism, and epilepsy. To determine the pathogenicity ofPPFIA3variantsin vivo, we generated transgenic fruit flies expressing either human PPFIA3 wildtype (WT) or variant protein using GAL4-UAS targeted gene expression systems. Ubiquitous expression with Actin-GAL4 showed that thePPFIA3variants had variable penetrance of pupal lethality, eclosion defects, and anatomical leg defects. Neuronal expression with elav-GAL4 showed that thePPFIA3variants had seizure-like behaviors, motor defects, and bouton loss at the 3rdinstar larval neuromuscular junction (NMJ). Altogether, in the fly overexpression assays, we found that thePPFIA3variants in the N-terminal coiled coil domain exhibited stronger phenotypes compared to those in the C-terminal region. In the loss-of-function fly assay, we show that the homozygous loss of flyLiprin-α leads to embryonic lethality. This lethality is partially rescued by the expression of humanPPFIA3WT, suggesting human PPFIA3 protein function is partially conserved in the fly. However, thePPFIA3variants failed to rescue lethality. Altogether, the human and fruit fly data reveal that the rarePPFIA3variants are dominant negative loss-of-function alleles that perturb multiple developmental processes and synapse formation.
mTOR inhibition improves the formation of functional T cell memory following COVID-19 vaccination of kidney transplant recipients
Authors: Perkins Griffith B. , Tunbridge Matthew J. , Chai Cheng Sheng , Hope Christopher M. , Yeow Arthur Eng Lip , Salehi Tania , Singer Julian , Shi Bree , Masavuli Makutiro G. , Mekonnen Zelalem Addis , Garcia-Valtanen Pablo , Kireta Svjetlana , Johnston Julie K. , Drogemuller Christopher J. , Sim Beatrice Z. , Spencer Shane M. , Sallustio Benedetta C. , Comerford Iain , Bouras George , Weiskopf Daniela , Sette Alessandro , Aggarwal Anupriya , Milogiannakis Vanessa , Akerman Anouschka , Turville Stuart , Hurtado Plinio R. , Ying Tracey , Hissaria Pravin , Barry Simon C. , Chadban Steven J. , Grubor-Bauk Branka , Coates P. Toby 
Published: March 2023

AbstractInadequate immune response to vaccination is a long-standing problem faced by immunosuppressed kidney transplant recipients (KTRs), requiring novel strategies to improve vaccine efficacy. In this study, the potential of mechanistic target of rapamycin inhibitors (mTORi) to improve T cell responses to COVID-19 vaccination was investigated. Following primary vaccination with adenoviral (ChAdOx1) or mRNA (BNT162b2) COVID-19 vaccines, KTRs receiving rapamycin demonstrated T cell responses greater than those of healthy individuals, characterized by increased frequencies of vaccine-specific central memory, effector memory and TEMRAT cells, in both the CD4+and CD8+compartments. Relative to standard-of-care triple therapy, mTORi-based therapy was associated with a 12-fold greater functional T cell response to primary vaccination of KTRs. The use of rapamycin to augment T cell responses to COVID-19 booster (third dose) vaccination was next investigated in a randomized, controlled trial. Immunosuppression modification with rapamycin was feasible and well-tolerated, but did not improve vaccine-specific T cell responses in this cohort. To understand the parameters for effective use of rapamycin as a vaccine adjuvant, mice were treated with rapamycin before primary or booster vaccination with ancestral and/or Omicron COVID-19 vaccines. Supporting the findings from KTRs, significant enhancement of functional and stem-like memory T cell responses was observed when rapamycin was administered from the time of primary, rather than booster, vaccination. Collectively, a positive effect of mTOR inhibitors on vaccine-induced T cell immunity against COVID-19 in humans was demonstrated.One Sentence SummaryRapamycin use at the time of primary COVID-19 vaccination augments the formation of functional, vaccine-specific T cell memory in immunosuppressed kidney transplant recipients.
Timing and magnitude of the next wave of COVID-19 in China: lessons from 189 countries and territories
Authors: Niu Beidi , Ji Shuyi , Zhao Shi , Lei Hao 
Published: March 2023

AbstractBecause of the fading immunity to COVID-19 and continuous evolution of the SARS-CoV-2 Omicron variants, the next epidemic wave of COVID-19 is inevitable. The Omicron variant has been the cause of several waves of the COVID-19 epidemics in the majority of countries. Thus, lessons from other countries may provide guidance regarding the timing and magnitude of the next COVID-19 wave of the pandemic in China. In this study, the COVID-19 surveillance data from 189 countries that experienced two or more waves of the SARS-CoV-2 Omicron variant were analysed. The median peak timing between the first and second/third waves of the SARS-CoV-2 Omicron variant was 164/243 days. The peaks of the second and third waves were much lower than that of the first wave. The median relative peaks of the second and third compared with the first waves were 14.5% and 11.2%, respectively. The time window between the peak timings of the first and second waves showed no significant rank correlation with the five socioeconomic factors included in this study. However, the relative peak of the second wave increased significantly with gross domestic product per capita (P<0.001), urbanisation rate (P=0.003), population density (P=0.007), and proportion of older adults >65 years (P<0.001), although decreased significantly with the proportion of 0-14 teenagers (P<0.001). In summary, the historical situations and progression of COVID-19 outbreaks in other countries may inform the risk assessment of incoming outbreaks in mainland China; however, the timing and magnitude of the next COVID-19 wave may also be influenced by several unknown factors, including rapid viral evaluation of SARS-CoV-2
Impact of marginal donor to marginal recipient kidney transplant on delayed graft function and outcome
Authors: Bocchi Federica , Beldi Guido , Kuhn Christian , Storni Federico , Müller Nathalie , Sidler Daniel 
Published: March 2023

ABSTRACTThe demographics of donor and recipient candidates for kidney transplantation (KT) have substantially changed. Recipients tend to be older and polymorbid and KT to marginal recipients is associated with delayed graft function (DGF), prolonged hospitalization, inferior long-term allograft function, and poorer patient survival. In parallel, donors are also older, suffer from several comorbidities, and donations coming from circulatory death (DCD) predominate, which in turn leads to early and late complications. However, it is unclear how donor and recipient risk factors interact. In this retrospective cohort study, we assess the overall and combined impact of a KT from marginal donors to marginal recipients. We focused on: 1) DGF; 2) hospital stay and number of dialysis days after KT and 3) allograft function at 6 months. Among the 369 KT included, the overall DGF rate was 25% (n = 92) and median time from reperfusion to DGF resolution was 7.8 days (IQR: 3.0-13.8 days). Overall, patients received four dialysis sessions (IQR: 2-8). The combination of pre-KT anuria (< 200 ml/24h, 32%) and DCD procurement (14%) was significantly associated with DGF, length of hospital stay, and severe perioperative complications, predominantly in recipients 50 years and older.
Early-Onset Complete Atrioventricular Block – Prevalence, Etiology and Utilization of Cardiac Implantable Electronic Devices
Authors: Margolis Gilad , Chee Jennifer , Kazatsker Mark , Roguin Ariel , Madias Christopher , Homoud Munther , Kobo Ofer , Hamuda Nashed , Dimri Inon , Heist E.Kevin , Ruskin Jeremy N. , Leshem Eran , Rozen Guy 
Published: March 2023

ABSTRACTBackgroundInformation regarding the prevalence and etiologies of complete atrioventricular block (CAVB) in younger patients is scarce. We aimed to investigate the potential causes for non-iatrogenic CAVB, the prevalence of CAVB without an identified etiology, the utilization of guidelines-recommended advanced imaging modalities in adults presenting with an early-onset CAVB of unidentified etiology, as well as to identify the predictors for cardiac implantable electronic device (CIED) insertion.MethodsUsing the National Inpatient Sample (NIS) database, we identified patients aged 18-60 hospitalized with non-iatrogenic CAVB in the US between 2015 (last quarter)-2019. Baseline demographics, clinical characteristics, potential etiologies for CAVB, advanced imaging utilization as well as outcomes including the need for temporary cardiac pacing (TCP) and CIED implantation were analyzed. Multivariable logistic regression models were used to identify predictors of CIED implantation.ResultsAn estimated total of 14,495 patients aged 18-60 with non-iatrogenic CAVB were identified. The mean age was 51 years, 60% were males and 3,050 (21%) had documentation of a prior conduction disorder. Eleven percent of the patients had a diagnosis of syncope and 6% suffered from a cardiac arrest. Two third of the patients (9,735, 67%) had no identified etiology for CAVB, of whom 8,205 (84%) were implanted with a permanent pacemaker (PPM), 180 patients (2%) with an implantable cardioverter-defibrillator (ICD), and 295 patients (3%) with a cardiac resynchronization therapy device. Only 40 patients (0.3%) underwent advanced imaging during their hospitalization. In multivariate analyses, older age [adjusted OR 1.046 (1.04-1.05), p<0.001] and the need for TCP [adjusted OR 1.543 (1.29-1.84), p<0.001], emerged as predictors for PPM implantation. Cardiac arrest [adjusted OR 2.786 (1.69-4.58), p<0.001] and younger age [adjusted OR 0.98 (0.96-0.99), p=0.02], were associated with ICD implantation. 185 patients (1.3%) died during their hospitalization.ConclusionThe majority of patients, hospitalized in the US for non-iatrogenic early-onset CAVB, had no identified etiology for their conduction disease. Despite the current US and European guidelines recommendation, advanced imaging prior to CIED implantation was under-utilized in this patient population.
The Effects of Medication Strategies on Cardiovascular Outcomes in Patients with Marfan Syndrome: A Consistency Model Analysis
Authors: Huang Sih-Huan , Lin Chin-Yi , Wu Mei-Hwan , Kang Yi-No , Hui-Chiu Hsin 
Published: March 2023

ABSTRACTBACKGROUNDDrug options for the treatment of Marfan syndrome (MFS) still warrant further investigation. Beta-blockers (BB) have long been considered the standard treatment, though several medications other than BB and angiotensin receptor blockers (ARB) have entered clinical practice and trials. However, no synthesis gathers evidence on medications other than BB or ARB. Therefore, this study aimed to investigate the effects and safety of medication strategies in managing MFS by synthesizing relevant randomized controlled trials (RCT).METHODSThree databases were searched for potential evidence using relevant keywords in both free-text and medical subject headings. Outcomes of interests were aortic root growth, aortic root Z score, aortic surgery, moderate-to-severe adverse events, cardiovascular and all-cause mortality. Quantitative data were pooled using frequentist-approach network meta-analysis in random-effects model.RESULTSSixteen reports derived from 13 RCTs contributed to a seven-node consistency model including no treatment, BB, ARB, ARB+BB, calcium channel blockers (CCB), angiotensin converting enzyme inhibitor (ACEI), and combination of BB and renin inhibitor (RI). As compared with no treatment, RI+BB showed significant protection of aortic root growth (standardized mean difference [SMD]= -1.90, 95% confidence interval [CI]: -2.91, -0.89), followed by ARB+BB (SMD= -1.75, 95%CI: -2.40, -1.10). Nevertheless, no significant findings were seen in other clinical outcomes.CONCLUSIONRI or ARB added on BB appear to be the optimal medication strategies to slow the progression of aortic root growth in MFS patients. However, we found no statistically significant difference in the risk of aortic surgeries, adverse effects, cardiovascular and all-cause mortality among medications. More RCTs with longer follow-up periods or bigger populations are needed to draw stronger evidence for clinical practices.
Factors associated with acceptance of COVID-19 vaccination among women in Guinea: Analysis of the first vaccination phase in March 2021
Authors: Touré Almamy Amara , Barry Ibrahima , Magassouba Aboubacar Sidiki , Bah Kadiatou , Cisse Diao , Sylla Younoussa , Camara Alsény Yarie , Loua Gaspard , Diallo Abdourahamane 
Published: March 2023

AbstractVaccination remains the primary strategy for ending the COVID-19 pandemic. However, vaccination rates are still low in low-income countries. The primary goal of this study was to describe the status of COVID-19 vaccine acceptance and hesitancy among women in Guinea and to identify associated predictors.Weconducted a cross-sectional study in five Guinean cities (Conakry, Mamou, Kindia, Kankan and N’zérékoré) across the four natural regions between Mar 22 and Aug 25 2021. Participants aged 18 were randomly recruited from the healthcare workers (HCWs) and the general population (GP). We used multivariate logistic regression to identify facilitators and barriers to acceptance of COVID-19 vaccination and a classification and regression tree (CART) to extract the profile of predictors.We included2,208 women among the HCWs and 1,121 in the GP. Most HCWs (63%) were already vaccinated, compared to only 28% of GP. The main factors associated with acceptance of a COVID-19 vaccine in the HCWs were an absence of pregnancy ORA = 4.46 [CI95%: 3.08, 6.52] and positive subjective norms ORA = 2.34 [CI95%: 1.92, 2.84].Regarding the GP, the main factors were the ability to receive the vaccine ORA = 5.20 [CI95%: 3.45, 8.01] and being adult ORA = 2.25 [CI95%: 1.34, 3.79] associated with acceptance of vaccination. Vaccination rates were higher in the HCWs. Favourable subjective norms and ability to receive the vaccine were facilitators of acceptance of COVID-19 vaccination, while youth and pregnancy were barriers to the approval of the COVID-19 vaccine.
Tools and methods for high-throughput single-cell imaging with the mother machine
Authors: Thiermann Ryan , Sandler Michael , Ahir Gursharan , Sauls John T. , Schroeder Jeremy W. , Brown Steven D. , Treut Guillaume Le , Si Fangwei , Li Dongyang , Wang Jue D. , Jun Suckjoon 
Published: March 2023

AbstractDespite much progress, image processing remains a significant bottleneck for high-throughput analysis of microscopy data. One popular platform for single-cell time-lapse imaging is the mother machine, which enables long-term tracking of microbial cells under precisely controlled growth conditions. While several mother machine image analysis pipelines have been developed in the past several years, adoption by a non-expert audience remains a challenge. To fill this gap, we implemented our own software, MM3, as a plugin for the multidimensional image viewer napari. napari-MM3 is a complete and modular image analysis pipeline for mother machine data, which takes advantage of the high-level interactivity of napari. Here, we give an overview of napari-MM3 and test it against several well-designed and widely-used image analysis pipelines, including BACMMAN and DeLTA. Researchers often analyze mother machine data with custom scripts using varied image analysis methods, but a quantitative comparison of the output of different pipelines has been lacking. To this end, we show that key single-cell physiological parameter correlations and distributions are robust to the choice of analysis method. However, we also find that small changes in thresholding parameters can systematically alter parameters extracted from single-cell imaging experiments. Moreover, we explicitly show that in deep learning based segmentation, “what you put is what you get” (WYPIWYG) – i.e., pixel-level variation in training data for cell segmentation can propagate to the model output and bias spatial and temporal measurements. Finally, while the primary purpose of this work is to introduce the image analysis software that we have developed over the last decade in our lab, we also provide information for those who want to implement mother-machine-based high-throughput imaging and analysis methods in their research.
Expanding the family of genetically encoded voltage indicators: Insights from heliorhodopsins
Authors: Ganapathy Srividya , Meng Xin , Mossel Delizzia , Jagt Mels , Brinks Daan 
Published: March 2023

AbstractGenetically encoded voltage indicators (GEVIs), particularly those based on microbial rhodopsins, are gaining traction in neuroscience as fluorescent sensors for imaging voltage dynamics with high-spatiotemporal precision. Here we establish a novel GEVI candidate based on the recently discovered subfamily of the microbial rhodopsin clade, termed heliorhodopsins. We discovered that upon excitation at 530-560nm, wild type heliorhodopsin exhibits near infra-red fluorescence which is sensitive to membrane voltage. We characterized the fluorescence brightness, photostability, voltage sensitivity and kinetics of wild type heliorhodopsin in HEK293T cells and further examined the impact of mutating key residues near the retinal chromophore. The S237A mutation significantly improved the fluorescence response of heliorhodopsin by 76% providing a highly promising starting point for further protein evolution.
Energetics and kinetics of membrane permeation of photoresists for bioprinting
Authors: Diedrich Lucas , Brosz Matthias , Abele Tobias , Steinke Salome , Gräter Frauke , Göpfrich Kerstin , Aponte-Santamaría Camilo 
Published: March 2023

AbstractThree-dimensional (3D) bioprinting is a promising technology which typically uses bioinks to pattern cells and their scaffolds. The selection of cytocompatible inks is critical for the printing success. In laserbased 3D bioprinting, photoresist molecules are used as bioinks. We propose that cytotoxicity can be a consequence of the interaction of photoresists with lipid membranes and their permeation into the cell. Here, molecular dynamics simulations and in vitro assays address this issue, retrieving partition coefficients, free energies, and permeabilities for eight commonly-used photoresists in model lipid bilayers. Crossing the hydrophobic center of the membrane constitutes the rate limiting step during permeation. In addition, three photoresists feature a preferential localization site at the acyl chain headgroup interface. Photoresist permeabilities range over eight orders of magnitude, with some molecules being membrane-permeable on bioprinting timescales. Moreover, permeation correlates well with the oil-water partition coefficients and is severely hampered by the lipid ordering imposed by the lipid saturation. Overall, the mechanism of interaction of photoresists with model lipid bilayers is provided here, helping to classify them according to their residence in the membrane and permeation through it. This is useful information to guide the selection of cytocompatible photoresists for 3D bioprinting.