Miracle-dz/UniFAR-FTUs huggingface dataset:
Omicron-Specific Cytotoxic T-Cell Responses After a Third Dose of mRNA COVID-19 Vaccine Among Patients With Multiple Sclerosis Treated With Ocrelizumab.

Importance The SARS-CoV-2 variant B.1. 1.529 (Omicron) escapes neutralizing antibodies elicited after COVID-19 vaccination, while T-cell responses might be better conserved. It is crucial to assess how a third vaccination modifies these responses, particularly for immunocompromised patients with readily impaired antibody responses. Objective To determine T-cell responses to the Omicron spike protein in anti-CD20-treated patients with multiple sclerosis (MS) before and after a third messenger RNA COVID-19 vaccination. Design, Setting, and Participants In this prospective cohort study conducted from March 2021 to November 2021 at the University Hospital Geneva, adults with MS receiving anti-CD20 treatment (ocrelizumab) were identified by their treating neurologists and enrolled in the study. A total of 20 patients received their third dose of messenger RNA COVID-19 vaccine and were included in this analysis. Interventions Blood sampling before and 1 month after the third vaccine dose. Main Outcomes and Measures Quantification of CD4 and CD8 (cytotoxic) T cells specific for the SARS-CoV-2 spike proteins of the vaccine strain as well as the Delta and Omicron variants, comparing frequencies before and after the third vaccine dose. Results Of 20 included patients, 11 (55%) were male, and the median (IQR) age was 45.8 (37.8-53.3) years. Spike-specific CD4 and CD8 T-cell memory against all variants were maintained in 9 to 12 patients 6 months after their second vaccination, albeit at lower median frequencies against the Delta and Omicron variants compared with the vaccine strain (CD8 T cells: Delta, 83.0%; 95% CI, 73.6-114.5; Omicron, 78.9%; 95% CI, 59.4-100.0; CD4 T cells: Delta, 72.2%; 95% CI, 67.4-90.5; Omicron, 62.5%; 95% CI, 51.0-89.0). A third dose enhanced the number of responders to all variants (11 to 15 patients) and significantly increased CD8 T-cell responses, but the frequencies of Omicron-specific CD8 T cells remained 71.1% (95% CI, 41.6-96.2) of the responses specific to the vaccine strain. Conclusions and Relevance In this cohort study of patients with MS treated with ocrelizumab, there were robust T-cell responses recognizing spike proteins from the Delta and Omicron variants, suggesting that COVID-19 vaccination in patients taking B-cell-depleting drugs may protect them against serious complications from COVID-19 infection. T-cell response rates increased after the third dose, demonstrating the importance of a booster dose for this population.
Mechanism of Signal Sequence Handover From NAC To SRP on Ribosomes During ER-protein Targeting

The nascent polypeptide–associated complex (NAC) interacts with newly synthesized proteins at the ribosomal tunnel exit and competes with the signal recognition particle (SRP) to prevent mistargeting of cytosolic and mitochondrial polypeptides to the endoplasmic reticulum (ER). How NAC antagonizes SRP and how this is overcome by ER targeting signals are unknown. Here, we found that NAC uses two domains with opposing effects to control SRP access. The core globular domain prevented SRP from binding to signal-less ribosomes, whereas a flexibly attached domain transiently captured SRP to permit scanning of nascent chains. The emergence of an ER-targeting signal destabilized NAC’s globular domain and facilitated SRP access to the nascent chain. These findings elucidate how NAC hands over the signal sequence to SRP and imparts specificity of protein localization. Description NAC acts as a gatekeeper on the ribosome In eukaryotes, signal recognition particle (SRP) targets membrane and secretory proteins to the endoplasmic reticulum (ER) while they are being synthesized on the ribosome. To prevent erroneous targeting of proteins to the ER, access of SRP is regulated by the nascent polypeptide–associated complex (NAC). Jomaa et al. investigated how NAC can prevent SRP from binding ribosomes that are synthesizing cytosolic and mitochondrial proteins while at the same time recruiting SRP to ribosomes translating an ER protein client. Their findings reveal the role of NAC as a key sorting factor for nascent chains that helps to ensure the specificity of membrane and secretory protein localization in eukaryotes. —SMH The nascent polypeptide–associated complex regulates signal recognition particle function and controls endoplasmic reticulum targeting.
Detecting Blastocyst Components by Artificial Intelligence for Human Embryological Analysis to Improve Success Rate of In Vitro Fertilization

Morphological attributes of human blastocyst components and their characteristics are highly correlated with the success rate of in vitro fertilization (IVF). Blastocyst component analysis aims to choose the most viable embryos to improve the success rate of IVF. The embryologist evaluates blastocyst viability by manual microscopic assessment of its components, such as zona pellucida (ZP), trophectoderm (TE), blastocoel (BL), and inner cell mass (ICM). With the success of deep learning in the medical diagnosis domain, semantic segmentation has the potential to detect crucial components of human blastocysts for computerized analysis. In this study, a sprint semantic segmentation network (SSS-Net) is proposed to accurately detect blastocyst components for embryological analysis. The proposed method is based on a fully convolutional semantic segmentation scheme that provides the pixel-wise classification of important blastocyst components that help to automatically check the morphologies of these elements. The proposed SSS-Net uses the sprint convolutional block (SCB), which uses asymmetric kernel convolutions in combination with depth-wise separable convolutions to reduce the overall cost of the network. SSS-Net is a shallow architecture with dense feature aggregation, which helps in better segmentation. The proposed SSS-Net consumes a smaller number of trainable parameters (4.04 million) compared to state-of-the-art methods. The SSS-Net was evaluated using a publicly available human blastocyst image dataset for component segmentation. The experimental results confirm that our proposal provides promising segmentation performance with a Jaccard Index of 82.88%, 77.40%, 88.39%, 84.94%, and 96.03% for ZP, TE, BL, ICM, and background, with residual connectivity, respectively. It is also provides a Jaccard Index of 84.51%, 78.15%, 88.68%, 84.50%, and 95.82% for ZP, TE, BL, ICM, and background, with dense connectivity, respectively. The proposed SSS-Net is providing a mean Jaccard Index (Mean JI) of 85.93% and 86.34% with residual and dense connectivity, respectively; this shows effective segmentation of blastocyst components for embryological analysis.
Evolution of immunotherapy in the treatment of non-muscle-invasive bladder cancer

ABSTRACT Introduction Immunotherapy with intravesical bacillus Calmette–Guérin (BCG) has been the gold standard treatment for intermediate- and high-risk non-muscle-invasive bladder cancer (NMIBC) for nearly half a century. Yet, many patients with high-risk disease will experience recurrence, including those who progress and eventually become unresponsive to BCG. For decades, apart from radical cystectomy, few therapeutic options existed for this at-risk population. However, the advent of novel immunotherapeutic agents has transformed treatment in a range of tumor types, including urothelial carcinoma. These immunotherapies have yielded promising results in the treatment of metastatic urothelial carcinoma and, as such, are also being investigated for use in NIMIBC. Areas covered This article provides an overview of the evolution of immunotherapy for NMIBC, beginning from the original immunotherapy-BCG – to current agents including checkpoint inhibitors, IL-15 agonists, viral gene therapies and therapeutic cancer vaccines. Expert opinion Emerging insights over the last decade have led to the development of novel immunotherapiesfor the treatment of NMIBC whilst providing new opportunities to enhance the anti-tumour activity of BCG. In particular, the KEYNOTE-057 trial represents a pivotal moment for immunotherapy in NMIBC, leading to approval of pembrolizumab by the US Food & Drug Administration for patients with BCG-unresponsive disease. However, patient selection and the development of biomarkers to guide the identification of patients who will benefit most from a particular immunotherapy remains critical. As research efforts come to fruition, these novel immunotherapies may become integrated into the standard treatment paradigm for intermediate- and high-risk NMBIC.
Higher epicardial fat in older adults living with HIV with viral suppression and relationship with liver steatosis, coronary calcium and cardiometabolic risks

Objectives: HIV infection is associated with ectopic fat deposition, which leads to chronic inflammation and cardiometabolic dysregulation. We assessed the epicardial adipose tissue (EAT) volume and its associated factors among people with HIV (PWH). Design: A cross-sectional study. Methods: We conducted a cross-sectional study among PWH aged at least 50 years and age-matched and sex-matched HIV-negative older individuals in Bangkok, Thailand. Participants underwent a noncontrast, cardiac computed tomography (CT) scan to assess coronary artery calcium (CAC) score and EAT between March 2016 and June 2017. Multivariate linear regression analyses were used to investigate HIV-related factors, cardiac and metabolic markers associated with EAT volume. Results: Median age was 55 years [interquartile range (IQR) 52–60] and 63% were men. Median duration of antiretroviral therapy (ART) was 16 years with 97% had HIV-1 RNA less than 50 copies/ml and median CD4+ cell count of 617 cells/μl. Median EAT volume was significantly higher in PWH [99 (IQR 75–122) cm3] than HIV-negative individuals [93 (IQR 69–117) cm3], P = 0.022. In adjusted model, factors associated with EAT volume included male sex (P = 0.045), older age (P < 0.001), abnormal waist circumference (P < 0.001) and HOMA-IR (P = 0.01). In addition, higher CAC score was independently associated with EAT volume. Higher mean EAT volume was seen in PWH with severe liver steatosis than those without steatosis (P = 0.018). In adjusted PWH-only model, duration of HIV was significantly associated with higher EAT volume (P = 0.028). Conclusion: In an aging cohort, PWH had higher EAT volume than HIV-negative controls. EAT was also independently associated with central fat accumulation, insulin resistance, liver steatosis and CAC score.
Immunotoxic effects of metal-based nanoparticles in fish and bivalves

Abstract There is a global research interest in metal nanoparticles (MNPs) due to their diverse applications, rapidly increasing use, and increased presence in the aquatic environment. Currently, most MNPs in the environment are at levels unlikely to cause overt toxicity. Sub-lethal effects that MNPs may induce, notable immunotoxicity, could however have significant health implications. Thus, deciphering the immunological interactions of MNPs with aquatic organisms constitutes a much-needed area of research. In this article, we critically assess the evidence for immunotoxic effects of MNPs in bivalves and fish, as key wildlife sentinels with widely differing ecological niches that are used as models in ecotoxicology. The first part of this review details the properties, fate, and fundamental physicochemical behavior of MNPs in the aquatic ecosystem. We then consider the toxicokinetics of MNP uptake, accumulation, and deposition in fish and bivalves. The main body of the review then focuses on immune reactions in response to MNPs exposure in bivalves and fish illustrating their immunotoxic potential. Finally, we identify major knowledge gaps in our current understanding of the implications of MNPs exposure for immunological functions and the associated health consequences for bivalves and fish, as well as the general lessons learned on the immunotoxic properties of the emerging class of nanoparticulate contaminants in fish and bivalves.
PET/CT versus triple endoscopy in initial workup of HPV+ oropharyngeal squamous cell carcinoma

Synchronous primary tumors (SPTs) are detected via triple endoscopy or positron emission tomography/computed tomography (PET/CT). Patients with human papillomavirus‐associated oropharyngeal squamous cell carcinoma (HPV+ OPSCC) lack risk factors for SPTs.
Risk factors for surgical site infection following spinal surgery

Abstract Study design: A meta-analysis. Background: We performed a meta-analysis to explore risk factors of surgical site infection (SSI) following spinal surgery. Methods: An extensive search of literature was performed in English database of PubMed, Embase, and Cochrane Library and Chinese database of CNKI and WANFANG (up to October 2020). We collected factors including demographic data and surgical factor. Data analysis was conducted with RevMan 5.3 and STATA 12.0. Results: Totally, 26 studies were included in the final analysis. In our study, the rate of SSI after spinal surgery was 2.9% (1222 of 41,624). Our data also showed that fusion approach (anterior vs posterior; anterior vs combined), osteotomy, transfusion, a history of diabetes and surgery, hypertension, surgical location (cervical vs thoracic; lumbar vs thoracic), osteoporosis and the number of fusion levels were associated with SSI after spinal surgery. However, age, sex, a history of smoking, body mass index, fusion approach (posterior vs combined), surgical location (cervical vs lumbar), duration of surgery, blood loss, using steroid, dural tear and albumin were not associated with development of SSI. Conclusions: In our study, many factors were associated with increased risk of SSI after spinal surgery. We hope this article can provide a reference for spinal surgeons to prevent SSI after spinal surgery.
Adipose tissue regulatory T cells: differentiation and function

Abstract Rising obesity levels, worldwide, are resulting in substantial increases in cardiovascular disease, diabetes, kidney disease, musculoskeletal disorders, and certain cancers, and obesity-associated illnesses are estimated to cause ∼4 million deaths worldwide per year. A common theme in this disease epidemic is the chronic systemic inflammation that accompanies obesity. CD4+ Foxp3+ regulatory T cells residing in visceral adipose tissues (VAT Tregs) are a unique immune cell population that play essential functions in restricting obesity-associated systemic inflammation through regulation of adipose tissue homeostasis. The distinct transcriptional program that defines VAT Tregs has been described, but directly linking VAT Treg differentiation and function to improving insulin sensitivity has proven more complex. Here we review new findings which have clarified how VAT Tregs differentiate, and how distinct VAT Treg subsets regulate VAT homeostasis, energy expenditure, and insulin sensitivity. Graphical Abstract
Early complementary acupuncture improves the clinical prognosis of traumatic brain edema

Abstract Background: Traumatic brain edema occurs commonly brain injury, and most manifests as pericontusional edema of brain contusions. On the basis of evidence-based medicine, apart from recommending craniotomy and mannitol, there are few particularly effective measures to prevent and treat traumatic brain edema. It is uncertain whether an early complementary acupuncture treatment would improve long-term outcomes of patients with traumatic brain edema. The aim of this study is to assess the efficacy and the safety of early complementary acupuncture for patients with traumatic brain edema. Methods: This study is an actively accruing, single-center, single-blinded, 2-arm, randomized controlled trial. Patients with traumatic brain injury, a Glasgow Coma Scale score of 6∼12, and brain edema on computed tomography scan will be divided into 2 groups on the basis of stratified block randomization. All patients will receive conventional treatment, and the study group will undergo additional acupuncture therapy (start within 72 hours after the injury) once a day for 28 days. The primary outcome is the dichotomized Glasgow Outcome Score at 6 months and 12 months after injury, and the secondary outcomes are the Glasgow Coma Scale, the volume of traumatic brain edema, the serum levels of C-reactive protein and interleukin-6, and the Modified Barthel Index. Discussion: This study will provide data regarding the efficacy of early complementary acupuncture for traumatic brain edema. If the study yields positive results, its findings may offer insights into a valuable complementary option of acupuncture for traumatic brain edema that could provide pilot evidence for large, randomized, controlled trials. Trial registration: This trial has been published in the Chinese Clinical Trial Register, http://www.chictr. org.cn/edit.aspx? pid=141208&htm=4 (Identifier: ChiCTR2100053794, registered on December 3, 2021).
The health returns of attending university for the marginally eligible student

Abstract A key policy question is whether continued expansion of university education is beneficial for the marginally eligible student. In this paper we exploit an arbitrary university eligibility rule combined with regression discontinuity design to estimate the causal effect of university attendance on healthcare utilization amongst young adults in Sweden. We find that the eligibility rule leads to a clear jump in university attendance of between 10% and 14% points for both males and females. 2SLS estimates find that a 10% point increase in university attendance causes a roughly one percentage point increase in hospital admissions due to mental ill health for males, almost exclusively related to alcohol and narcotics. Our findings for females, however, imply the opposite, suggesting that university attendance decreases hospital admissions related to mental health. The results for males sit in contrast to results from previous studies, and suggest that the effect of university education on health for the male student at the margin of eligibility is different to that of the average student.
Safety profile of MenB-FHBp vaccine among adolescents: data from surveillance of Adverse Events Following Immunization in Puglia (Italy), 2018–2020

ABSTRACT MenB-FHBp was licensed in Europe in 2017 from the age of 10. In the “postmarketing life” of a new vaccine, surveillance of Adverse Events Following Immunization (AEFI) is crucial, to better understand the pattern of safety and the effectiveness. This paper describes the MenB-FHBp AEFIs notified in Puglia in 2018–2021, to take a picture of the safety profile of this vaccine in the real life, four years after its introduction in Italy. This is a retrospective observational study. Data were collected from the list of AEFIs notified after MenB-FHBp vaccine administration in Puglia in 2018–2020, and the number of doses of this vaccine administered in the same period. AEFIs were classified according to WHOʻs algorithm, and causality assessment was carried out for serious AEFIs. From January 2018 to December 2020, in Puglia, 43,061 doses of MenB-FHBp were administered and 42 MenB-FHBp AEFIs (reporting rate: 97.5 per 100,000 doses administered) were reported. Among these, 12 were classified as severe (28.6%; reporting rate 27.9 per 100,000 doses). Overall, the male/female ratio in AEFIs was 1:1. The median age of people who suffered from AEFIs was 12 years (range 11–13). For the 11 serious AEFIs for which the classification was “consistent causal association,” the diagnosis was hyperpyrexia (reporting rate 13.9 per 100,000 doses), fainting (rate 4.6 per 100,000 doses), urticaria (rate 2,3 per 100,000 doses), convulsions (rate 2,3 per 100,000 doses), and vomit (rate 2,3 per 100,000 doses). No deaths or impairment were notified in studied AEFIs. The picture of MenB-FHBp vaccine supports that the risk of AEFIs is in line with previous published data and in general acceptable.
On the homology of crocodylian post‐dentary bones and their macroevolution throughout Pseudosuchia

The lower jaw of early tetrapods is composed of several intramembranous ossifications. However, a tendency toward the independent reduction of the number of bones has been observed in the mandible of mammals, lepidosaurs, turtles, crocodiles, and birds. Regarding archosaurs, the coronoid and prearticular bones are interpreted to be lost during the evolution of stem‐birds and stem‐crocodiles, respectively, but the homology of the post‐dentary bones retained in living pseudosuchians remains unclear. Here, we combine paleontological and embryological evidence to explore in detail the homology of the crocodylian post‐dentary bones. We study the mandible embryogenesis on a sample of 71 embryos of Caiman and compare this pattern with the mandibular transformations observed across pseudosuchian evolution. In the pre‐hatching ontogeny of caimans, at least five intramembranous ossification centers are formed along the margins of the internal mandibular fenestra (perifenestral centers) and, subsequently, merge to form the coronoid (three intramembranous centers), angular (one intramembranous center), and articular (one intramembranous and one chondral center). In the fossil record, an independent prearticular is lost around the base of Mesoeucrocodylia (optimized as reappearing in Thalattosuchia if they are placed within Neosuchia), and the coronoid is apomorphically lost in notosuchians. The integration of embryological and paleontological data indicates that most perifenestral centers are involved in the origin of the prearticular of non‐mesoeucrocodylian pseudosuchians. These centers are rearranged during the evolution to contribute to different post‐dentary bones in mesoeucrocodylians bolstering the idea that the coronoid and the articular of Crocodylia are not completely homologous to those of other diapsids.
Using a statistical learning approach to identify sociodemographic and clinical predictors of response to clozapine

Background: A proportion of people with treatment-resistant schizophrenia fail to show improvement on clozapine treatment. Knowledge of the sociodemographic and clinical factors predicting clozapine response may be useful in developing personalised approaches to treatment. Methods: This retrospective cohort study used data from the electronic health records of the South London and Maudsley (SLaM) hospital between 2007 and 2011. Using the Least Absolute Shrinkage and Selection Operator (LASSO) regression statistical learning approach, we examined 35 sociodemographic and clinical factors’ predictive ability of response to clozapine at 3 months of treatment. Response was assessed by the level of change in the severity of the symptoms using the Clinical Global Impression (CGI) scale. Results: We identified 242 service-users with a treatment-resistant psychotic disorder who had their first trial of clozapine and continued the treatment for at least 3 months. The LASSO regression identified three predictors of response to clozapine: higher severity of illness at baseline, female gender and having a comorbid mood disorder. These factors are estimated to explain 18% of the variance in clozapine response. The model’s optimism-corrected calibration slope was 1.37, suggesting that the model will underfit when applied to new data. Conclusions: These findings suggest that women, people with a comorbid mood disorder and those who are most ill at baseline respond better to clozapine. However, the accuracy of the internally validated and recalibrated model was low. Therefore, future research should indicate whether a prediction model developed by including routinely collected data, in combination with biological information, presents adequate predictive ability to be applied in clinical settings.