julilili42/papers huggingface dataset:
Preexisting and Post–COVID-19 Immune Responses to SARS-CoV-2 in Patients with Cancer
2021-05-19

Abstract Patients with cancer, in particular patients with hematologic malignancies, are at increased risk for critical illness upon COVID-19. We here assessed antibody as well as CD4+ and CD8+ T-cell responses in unexposed and SARS-CoV-2–infected patients with cancer to characterize SARS-CoV-2 immunity and to identify immunologic parameters contributing to COVID-19 outcome. Unexposed patients with hematologic malignancies presented with reduced prevalence of preexisting SARS-CoV-2 cross-reactive CD4+ T-cell responses and signs of T-cell exhaustion compared with patients with solid tumors and healthy volunteers. Whereas SARS-CoV-2 antibody responses did not differ between patients with COVID-19 and cancer and healthy volunteers, intensity, expandability, and diversity of SARS-CoV-2 T-cell responses were profoundly reduced in patients with cancer, and the latter associated with a severe course of COVID-19. This identifies impaired SARS-CoV-2 T-cell immunity as a potential determinant for dismal outcome of COVID-19 in patients with cancer. Significance: This first comprehensive analysis of SARS-CoV-2 immune responses in patients with cancer reports on the potential implications of impaired SARS-CoV-2 T-cell responses for understanding pathophysiology and predicting severity of COVID-19, which in turn might allow for the development of therapeutic measures and vaccines for this vulnerable patient population. See related commentary by Salomé and Horowitz, p. 1877. This article is highlighted in the In This Issue feature, p. 1861
Benzylammonium‐Mediated Formamidinium Lead Iodide Perovskite Phase Stabilization for Photovoltaics
2021-05-19

Abstract There is an ongoing surge of interest in the use of formamidinium (FA) lead iodide perovskites in photovoltaics due to their exceptional optoelectronic properties. However, thermodynamic instability of the desired cubic perovskite (α‐FAPbI 3 ) phase at ambient conditions leads to the formation of a yellow non‐perovskite (δ‐FAPbI 3 ) phase that compromises its utility. A stable α‐FAPbI 3 perovskite phase is achieved by employing benzylammonium iodide (BzI) and the microscopic structure is elucidated by using solid‐state NMR spectroscopy and X‐ray scattering measurements. Perovskite solar cells based on the FAPbI 3 (BzI) 0.25 composition achieve power conversion efficiencies exceeding 20%, which is accompanied by enhanced shelf‐life and operational stability, maintaining 80% of the performance after one year at ambient conditions.
Sparse Reduced-Rank Regression for Exploratory Visualisation of Paired Multivariate Data
2021-05-19

Abstract In genomics, transcriptomics, and related biological fields (collectively known as omics), combinations of experimental techniques can yield multiple sets of features for the same set of biological replicates. One example is Patch-seq, a method combining single-cell RNA sequencing with electrophysiological recordings from the same cells. Here we present a framework based on sparse reduced-rank regression (RRR) for obtaining an interpretable visualisation of the relationship between the transcriptomic and the electrophysiological data. We use elastic net regularisation that yields sparse solutions and allows for an efficient computational implementation. Using several Patch-seq datasets, we show that sparse RRR outperforms both sparse full-rank regression and non-sparse RRR, as well as previous sparse RRR approaches, in terms of predictive performance. We introduce a bibiplot visualisation in order to display the dominant factors determining the relationship between transcriptomic and electrophysiological properties of neurons. We believe that sparse RRR can provide a valuable tool for the exploration and visualisation of paired multivariate datasets.
Soccer goalkeeper expertise identification based on eye movements
2021-05-19

By focusing on high experimental control and realistic presentation, the latest research in expertise assessment of soccer players demonstrates the importance of perceptual skills, especially in decision making. Our work captured omnidirectional in-field scenes displayed through virtual reality glasses to 12 expert players (picked by DFB), 10 regional league intermediate players, and13 novice soccer goalkeepers in order to assess the perceptual skills of athletes in an optimized manner. All scenes were shown from the perspective of the same natural goalkeeper and ended after the return pass to that goalkeeper. Based on the gaze behavior of each player, we classified their expertise with common machine learning techniques. Our results show that eye movements contain highly informative features and thus enable a classification of goalkeepers between three stages of expertise, namely elite youth player, regional league player, and novice, at a high accuracy of 78.2%. This research underscores the importance of eye tracking and machine learning in perceptual expertise research and paves the way for perceptual-cognitive diagnosis as well as future training systems.
Twelve-Year Single Center Experience Shows Safe Implementation of Developed Peritoneal Surface Malignancy Treatment Protocols for Gastrointestinal and Gynecological Primary Tumors
2021-05-19

(1) Background: Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy provide survival benefits to selected patients. We aimed to report our experience and the evolution of our peritoneal surface malignancy program. (2) Methods: From June 2005 to June 2017, 399 patients who underwent cytoreductive surgery plus hyperthermic intraperitoneal chemotherapy at the Tübingen University Hospital were analyzed from a prospectively collected database. (3) Results: Peritoneal metastasis from colorectal cancer was the leading indication (group 1: 28%; group 2: 32%). The median PCI was 15.5 (range, 1–39) in group 1 and 11 (range, 1–39) in group 2 (p = 0.002). Regarding the completeness of cytoreduction (CC), a score of 0 was achieved in 63% vs. 69% for group 1 and 2, respectively (p = 0.010). Median overall survival rates for patients in group 1 and 2 for colon cancer, ovarian cancer, gastric cancer and appendix cancer were 34 and 25 months; 45 months and not reached; 30 and 16 months; 39 months and not reached, respectively. The occurrence of grade-III and -IV complications slightly differed between groups (14.5% vs. 15.6%). No 30-day mortality occurred. (4) Conclusions: Specialized centers are able to provide low-morbidity cytoreductive surgery and hyperthermic intraperitoneal chemotherapy without mortality. Strict patient selection during the time period significantly improved CC scores.
OO-REMP: Approaching Chemical Accuracy with Second-Order Perturbation Theory
2021-05-19

We present a perturbation theory (PT) providing second-order energies that reproduce main group chemistry benchmark sets for reaction energies, barrier heights, and atomization energies with mean absolute deviations below 1 kcal mol<sup>-1</sup>. The PT is defined as a constrained mixture of the unperturbed Hamiltonians of the Retaining the Excitation degree (RE) and the Møller-Plesset (MP) PTs. The orbitals of the reference wave function, a single unrestricted Slater determinant, are iteratively optimized to minimize the total energy. For all benchmark sets, good and near optimal performance of OO-REMP was observed for an unperturbed Hamiltonian consisting of 25% MP and 75% RE contributions.
The microbiome of Lotus nodules varies with plant health in a species-specific manner
2021-05-19

ABSTRACT Nitrogen fixation is carried out inside nodules of legumes by symbiotic rhizobia. Rhizobia dominate the nodule microbiome, however other non-rhizobial bacteria also colonise root nodules. It is not clear whether these less abundant nodule colonisers impact nodule function. In order to investigate the relationship between the nodule microbiome and nodule function as influenced by the soil microbiome, we used a metabarcoding approach to characterise the communities inside Lotus burttii, Lotus japonicus and Lotus corniculatus nodules from plants that were either starved or healthy resulting from inoculations with different soil suspensions in a closed pot experiment. We found that the nodule microbiome of all tested Lotus species differed according to inoculum, but only that of L. burttii varied with plant health. Using a machine learning algorithm, we also found that among the many non-rhizobial bacteria inside the nodule, amplicon sequence variants that were related to Pseudomonas were the most indicative signatures of a healthy plant nodule microbiome. These results support the hypothesis that legume nodule endophytes may play a role in the overall success of root-nodule symbiosis, albeit in a plant host specific manner.
Evidence-Based Examination Techniques for the Knee
2021-05-19

Abstract Objective Digitalisation now almost covers all areas of medical student teaching. Teaching videos are a good way to help students learn practical skills. The existing evidence is a recognised aid for the classification of the respective technology. Method This video presents the usual examination techniques of the knee joint on a patient with an unstable knee. The respective techniques, if available, were backed up with the appropriate evidence. Conclusion The examination techniques presented allow students to view the examination techniques in a standardised manner on a patient. The evidence for the examination techniques can help with the classification of the respective technique.
A baseline transcriptional signature associates with clinical malaria risk in RTS,S/AS01-vaccinated African children
2021-05-19

Abstract In a phase 3 trial in African infants/children, the RTS,S/AS01 (GSK) vaccine showed moderate efficacy against clinical malaria. We aimed to identify RTS,S/AS01-induced signatures associated with clinical malaria by analyzing antigen-stimulated peripheral blood mononuclear cells sampled from a subset of trial participants at baseline and month 3 (one month post-third dose). RTS,S/AS01 vaccination was associated with downregulation of B-cell and monocyte-related blood transcriptional modules (BTMs) and upregulation of T-cell related BTMs, as well as higher month 3 (vs baseline) circumsporozoite protein (CSP)-specific CD4 + T-cell responses. There were few RTS,S/AS01-associated BTMs whose month 3 levels correlated with malaria risk. In contrast, baseline levels of BTMs associated with dendritic cells and with monocytes (among others) correlated with malaria risk. A cross-study analysis supported generalizability of the baseline dendritic cell- and monocyte-related BTM correlations with malaria risk to healthy, malaria-naïve adults, suggesting inflammatory monocytes may inhibit protective RTS,S/AS01-induced responses.
Antibody-mediated procoagulant platelets in SARS-CoV-2-vaccination associated immune thrombotic thrombocytopenia
2021-05-20

The COVID-19 pandemic has resulted in significant morbidity and mortality worldwide. To prevent severe infection, mass COVID-19 vaccination campaigns with several vaccine types are currently underway. We report pathological and immunological findings in 8 patients who developed vaccine-induced immune thrombotic thrombocytopenia (VITT) after administration of SARS-CoV-2 vaccine ChAdOx1 nCoV-19. We analyzed patient material using enzyme immune assays, flow cytometry and heparin-induced platelet aggregation assay and performed autopsies on two fatal cases. Eight patients (5 female, 3 male) with a median age of 41.5 years (range, 24 to 53) were referred to us with suspected thrombotic complications 6 to 20 days after ChAdOx1 nCoV-19 vaccination. All patients had thrombocytopenia at admission. Patients had a median platelet count of 46.5 x109/L (range, 8 to 92). Three had a fatal outcome and 5 were successfully treated. Autopsies showed arterial and venous thromboses in various organs and the occlusion of glomerular capillaries by hyaline thrombi. Sera from VITT patients contain high titer antibodies against platelet factor 4 (PF4) (OD 2.59±0.64). PF4 antibodies in VITT patients induced significant increase in procoagulant markers (P-selectin and phosphatidylserine externalization) compared to healthy volunteers and healthy vaccinated volunteers. The generation of procoagulant platelets was PF4 and heparin dependent. We demonstrate the contribution of antibody-mediated platelet activation in the pathogenesis of VITT.
Pembrolizumab (pembro) plus axitinib (axi) versus sunitinib as first-line therapy for advanced clear cell renal cell carcinoma (ccRCC): Results from 42-month follow-up of KEYNOTE-426.
2021-05-20

4500 Background: In the first interim analysis of the randomized, multicenter, open-label, phase 3 KEYNOTE-426 study (NCT02853331), treatment with pembro + axi significantly improved OS, PFS, and ORR vs sunitinib monotherapy in treatment-naive advanced ccRCC. Extended follow-up (median, 30.6 mo) continued to demonstrate the superior efficacy of pembro + axi vs sunitinib monotherapy in this patient population. Here, we present the results of the prespecified final analysis with 42.8-mo median follow-up. Methods: Treatment-naive patients (pts) with advanced ccRCC, KPS ≥70%, and measurable disease (RECIST v1.1) were randomly assigned 1:1 to receive pembro 200 mg IV Q3W for up to 35 doses + axi 5 mg orally BID or sunitinib 50 mg orally QD on a 4-wk on/2-wk off schedule until progression, intolerable toxicity, or withdrawal. Randomization was stratified by IMDC risk (favorable vs intermediate vs poor) and geographic region (North America vs Western Europe vs Rest of World). Dual primary endpoints were OS and PFS. Secondary endpoints were ORR, DOR, and safety. The protocol-specified final analysis was based on a target of 404 OS events. No formal hypothesis testing was performed because all efficacy endpoints were met previously at the first interim analysis; nominal P values are reported. Results: Overall, 861 pts were randomly assigned to receive pembro + axi (n=432) or sunitinib (n=429). Median duration of follow-up, defined as time from randomization to the database cutoff date, was 42.8 mo (range, 35.6-50.6). At data cutoff, 418 pts had died: 193 (44.7%) of 432 pts in the pembro + axi arm vs 225 (52.4%) of 429 pts in the sunitinib arm. Compared with sunitinib, pembro + axi improved OS (median: 45.7 vs 40.1 mo; HR, 0.73 [95% CI, 0.60-0.88]; P&lt;0.001) and PFS (median: 15.7 vs 11.1 mo; HR, 0.68 [95% CI, 0.58-0.80]; P&lt;0.0001). The 42-mo OS rate was 57.5% with pembro + axi vs 48.5% with sunitinib; the 42-mo PFS rate was 25.1% with pembro + axi vs 10.6% with sunitinib. For pembro + axi vs sunitinib, ORR was 60.4% vs 39.6% ( P&lt;0.0001); CR rate was 10.0% vs 3.5%; median DOR was 23.6 mo (range 1.4+ to 43.4+) vs 15.3 mo (range, 2.3-42.8+). Subsequent anticancer therapy was administered to 47.2% of pts in pembro + axi arm vs 65.5% of pts in sunitinib arm. Although a similar proportion of pts in each arm received VEGF/VEGFR inhibitors, only 10.2% of pts in the pembro + axi arm received subsequent treatment with a PD-1/L1 inhibitor compared to 48.7% of pts in the sunitinib arm. No new safety signals were observed. Conclusions: With a median follow-up of 42.8 mo, this is the longest follow-up of an anti-PD–1/L1 immunotherapy combined with a VEGF/VEGFR inhibitor for first-line RCC. These results show that pembro + axi continues to demonstrate superior efficacy over sunitinib with respect to OS, PFS, and ORR, with no new safety signals. Clinical trial information: NCT02853331.
Meta-omics Reveal Gallionellaceae and Rhodanobacter Species as Interdependent Key Players for Fe(II) Oxidation and Nitrate Reduction in the Autotrophic Enrichment Culture KS
2021-05-20

Nitrate-reducing iron(II)-oxidizing bacteria are widespread in the environment, contribute to nitrate removal, and influence the fate of the greenhouse gases nitrous oxide and carbon dioxide. The autotrophic growth of nitrate-reducing iron(II)-oxidizing bacteria is rarely investigated and not fully understood.
Trends in Prevalence and Severity of Pre/Perinatal Cerebral Palsy Among Children Born Preterm From 2004 to 2010: A SCPE Collaboration Study
2021-05-20

Aim: To report on prevalence of cerebral palsy (CP), severity rates, and types of brain lesions in children born preterm 2004 to 2010 by gestational age groups. Methods: Data from 12 population-based registries of the Surveillance of Cerebral Palsy in Europe network were used. Children with CP were eligible if they were born preterm (&amp;lt;37 weeks of gestational age) between 2004 and 2010, and were at least 4 years at time of registration. Severity was assessed using the impairment index. The findings of postnatal brain imaging were classified according to the predominant pathogenic pattern. Prevalences were estimated per 1,000 live births with exact 95% confidence intervals within each stratum of gestational age: ≤27, 28–31, 32–36 weeks. Time trends of both overall prevalence and prevalence of severe CP were investigated using multilevel negative binomial regression models. Results: The sample comprised 2,273 children. 25.8% were born from multiple pregnancies. About 2-thirds had a bilateral spastic CP. 43.5% of children born ≤27 weeks had a high impairment index compared to 37.0 and 38.5% in the two other groups. Overall prevalence significantly decreased (incidence rate ratio per year: 0.96 [0.92–1.00[) in children born 32–36 weeks. We showed a decrease until 2009 for children born 28–31 weeks but an increase in 2010 again, and a steady prevalence (incidence rate ratio per year = 0.97 [0.92–1.02] for those born ≤27 weeks. The prevalence of the most severely affected children with CP revealed a similar but not significant trend to the overall prevalence in the corresponding GA groups. Predominant white matter injuries were more frequent in children born &amp;lt;32 weeks: 81.5% (≤27 weeks) and 86.4% (28–31 weeks), compared to 63.6% for children born 32–36 weeks. Conclusion: Prevalence of CP in preterm born children continues to decrease in Europe excepting the extremely immature children, with the most severely affected children showing a similar trend.
KEYNOTE-B15/EV-304: Randomized phase 3 study of perioperative enfortumab vedotin plus pembrolizumab versus chemotherapy in cisplatin-eligible patients with muscle-invasive bladder cancer (MIBC).
2021-05-20

TPS4587 Background: Standard of care for MIBC is neoadjuvant cisplatin-based chemotherapy followed by radical cystectomy and pelvic lymph node dissection (RC+PLND); however, in time, patients experience disease recurrence or progression. Enfortumab vedotin (EV) is a Nectin-4–directed antibody–drug conjugate comprising a fully human, monoclonal antibody and the microtubule-disrupting agent monomethyl auristatin E. The KEYNOTE-869/EV-103 phase 1/2 study (NCT03288545) showed that the PD-1 inhibitor pembrolizumab + EV had encouraging antitumor activity and acceptable safety as first-line treatment for cisplatin-ineligible patients with metastatic urothelial cancer (Rosenberg JE et al. J Clin Oncol. 2020;38[15 suppl]:5044). Based on these data, investigating EV + pembrolizumab in an earlier setting such as MIBC and in a perioperative fashion is appropriate. KEYNOTE-B15/EV-304 (NCT04700124) is a randomized, open-label, phase 3 study to evaluate the efficacy and safety of perioperative EV + pembrolizumab versus neoadjuvant chemotherapy using gemcitabine/cisplatin in cisplatin-eligible patients with MIBC. Methods: Patients must have histologically confirmed urothelial cancer/MIBC (clinical stage T2-T4aN0M0 or T1-T4aN1M0) with predominant (≥50%) urothelial histology, have nonmetastatic disease (≥N2 disease and/or M1 excluded) confirmed by blinded independent central review (BICR), have ECOG PS 0 or 1, and not have previously received systemic therapy for MIBC. Approximately 784 patients will be randomly assigned 1:1 to receive either 4 cycles of neoadjuvant EV + pembrolizumab followed by 5 cycles of adjuvant EV + 13 cycles of adjuvant pembrolizumab after RC+PLND or 4 cycles of neoadjuvant cisplatin-based chemotherapy followed by observation after RC+PLND. Neoadjuvant and adjuvant pembrolizumab 200 mg + EV 1.25 mg/kg will be administered intravenously every 3 weeks (Q3W), and neoadjuvant chemotherapy will consist of gemcitabine 1000 mg/m 2 + cisplatin 70 mg/m 2 Q3W. Randomization will be stratified by centrally determined (pathology or imaging) initial T and N stage (T2N0 or T3/T4aN0 or T1-T4aN1), PD-L1 combined positive score (CPS ≥10 or CPS &lt; 10), and geographic region (United States or Europe or most of world). Imaging (CT or MRI) will be performed ≤6 weeks before cystectomy and 6 weeks after cystectomy. After postcystectomy imaging, additional imaging will be performed Q12W up to the end of year 2 (week 96) and at discontinuation. In year 3 and beyond, imaging will be performed Q24W. Primary end points are pathological complete response and event-free survival by BICR. Secondary end points are overall survival, disease-free survival, pathological downstaging, and safety and tolerability. Clinical trial information: NCT04700124.
Clinical Characteristics of POC1B-Associated Retinopathy and Assignment of Pathogenicity to Novel Deep Intronic and Non-Canonical Splice Site Variants
2021-05-20

Mutations in POC1B are a rare cause of inherited retinal degeneration. In this study, we present a thorough phenotypic and genotypic characterization of three individuals harboring putatively pathogenic variants in the POC1B gene. All patients displayed a similar, slowly progressive retinopathy (cone dystrophy or cone-rod dystrophy) with normal funduscopy but disrupted outer retinal layers on optical coherence tomography and variable age of onset. Other symptoms were decreased visual acuity and photophobia. Whole genome sequencing revealed a novel homozygous frameshift variant in one patient. Another patient was shown to harbor a novel deep intronic variant in compound heterozygous state with a previously reported canonical splice site variant. The third patient showed a novel nonsense variant and a novel non-canonical splice site variant. We aimed to validate the effect of the deep intronic variant and the non-canonical splice site variant by means of in vitro splice assays. In addition, direct RNA analysis was performed in one patient. Splicing analysis revealed that the non-canonical splice site variant c.561-3T&gt;C leads to exon skipping while the novel deep intronic variant c.1033-327T&gt;A causes pseudoexon activation. Our data expand the genetic landscape of POC1B mutations and confirm the benefit of genome sequencing in combination with downstream functional validation using minigene assays for the analysis of putative splice variants. In addition, we provide clinical multimodal phenotyping of the affected individuals.