Miracle-dz/UniFAR-FTUs huggingface dataset:
Malaria-driven expansion of adaptive-like functional CD56-negative NK cells correlates with clinical immunity to malaria

Natural killer (NK) cells likely play an important role in immunity to malaria, but the effect of repeated malaria on NK cell responses remains unclear. Here, we comprehensively profiled the NK cell response in a cohort of 264 Ugandan children. Repeated malaria exposure was associated with expansion of an atypical, CD56neg population of NK cells that differed transcriptionally, epigenetically, and phenotypically from CD56dim NK cells, including decreased expression of PLZF and the Fc receptor γ-chain, increased histone methylation, and increased protein expression of LAG-3, KIR, and LILRB1. CD56neg NK cells were highly functional and displayed greater antibody-dependent cellular cytotoxicity than CD56dim NK cells. Higher frequencies of CD56neg NK cells were associated with protection against symptomatic malaria and high parasite densities. After marked reductions in malaria transmission, frequencies of these cells rapidly declined, suggesting that continuous exposure to Plasmodium falciparum is required to maintain this modified, adaptive-like NK cell subset. Description Repeated malaria in children is followed by expansion of functional CD56neg NK cells associated with protection from symptomatic malaria. Protection amidst continuous exposure Natural killer (NK) cells have been linked to protective immune responses to Plasmodium falciparum, a parasite that causes malaria. Ty et al. identified an atypical CD56neg NK cell subset that expands during repeated parasite exposure and correlated with protection against symptomatic malaria. They profiled NK cells in a cohort of 264 Ugandan children using transcriptional, epigenetic, and phenotypic analysis. CD56neg NK cells were distinct from CD56dim NK cells, with decreased expression of PLZF and Fc receptor γchain and greater KIR, LAG-3, and LILRB1 protein expression. CD56neg NK cells displayed antibody dependent cellular cytotoxicity, and higher CD56neg NK cell frequencies correlated with protection against symptomatic malaria. In the absence of malaria transmission, CD56neg NK cells rapidly decreased. These findings a suggest that continuous exposure to P. falciparum is needed to maintain this NK cell subset. —CF
The Ramanujan identities under modular substitutions

they appear in a form which suggests certain group-theoretical considerations, similar to those employed by Hecke in his theory of modular forms. In this way we transform the identities into new ones which are noteworthy because of the occurrence of the Legendre symbol and which, by a simple further argument, lead also to a proof of (1.1) and (1.2). An analogous identity for the modulus 13, given by Zuckerman, can be treated in the same way. G. N. Watson and H. S. Zuckerman have also derived identities for the moduli 52 and 72. These will lead us to certain modular equations, which in turn will shed some light on those identities.
A new isolate of Mesorhabditis monhystera (Bütschli, 1873) Dougherty, 1955 (Rhabditida: Rhabditidae): re-evaluated with molecular data and scanning electron microscopic observations

Abstract A new isolate of Mesorhabditis monhystera (Bütschli, 1873) Dougherty, 1955 is described and illustrated with morphological and molecular data. The phylogenetic analysis based on the D2/D3 segment of 28S rDNA using the Bayesian inference method, revealed monophyly of the genus Mesorhabditis as the subordinate taxa clustered in one clade. The clade further divided into two subclades representing the Monhystera-group and Spiculigera-group with 100% posterior probability values. However, GenBank sequences of several species constituting the Monhystera-group, showed high similarity and very little genetic divergence (98–99%) of up to 4–5 bases. In order to ascertain the status of those isolates, detailed morphological comparison is provided along with a pictorial key. A sequence-based phylogeography of haplogroups of Mesorhabditis using the median-joining network method, was also inferred. The results suggested the need for morphological validation of a species before its sequences are deposited in GenBank.
Prognostic Value of WNT1, NOTCH1, PDGFRβ, and CXCR4 in Oral Squamous Cell Carcinoma

Background/Aim: The biological behaviour of oral squamous cell carcinoma (OSCC) might be an effect of aberrant activation of several signalling pathways, like WNT and NOTCH pathways. The purpose of this study was to investigate the prognostic significance of WNT1 and NOTCH1 in patients with OSCC in relation to pro-angiogenic factors (PDGFRβ, CXCR4). Materials and Methods: Immunohistochemistry was performed in 60 OSCC tissue samples to compare WNT1, NOTCH1, PDGFRβ, and CXCR4 expression and correlate it with clinicopathological parameters. Results: Immunoreactivity of WNT1, NOTCH1, PDGFRβ, and CXCR4 was found in 51.7%, 25.0%, 63.3%, and 70.0% of the patients, respectively. WNT1 expression was positively correlated with NOTCH1 (r=0.269, p=0.037) and CXCR4 (r=0.268, p=0.038). Positive correlation was observed also between NOTCH1 and CXCR4 (r=0.493, p<0.001). WNT1 and PDGFRβ expression was significantly associated with shorter overall survival (p=0.042, p=0.033, respectively). Multivariate Cox regression model revealed that WNT1 and CXCR4 were independent prognostic factors (p=0.009, p=0.021, respectively). Conclusion: WNT1 and NOTCH1 expression is associated with CXCR4 expression in OSCC, suggesting that WNT and NOTCH pathways are important in oral tumour angiogenesis. Moreover, WNT1 and CXCR4 could serve as independent prognostic factors for patients with OSCC.
Lenvatinib Versus Sorafenib in Advanced Hepatic Cell Carcinoma: A Double Center Retrospective Analysis

Background/Aim: We conducted a retrospective analysis in our center (Umberto I Polyclinic) in collaboration with Campus Biomedico Polyclinic to assess the results of the REFLECT study, which was the first study that demonstrated the non-inferiority of Lenvatinib to Sorafenib. Patients and Methods: We identified 21 patients affected by advanced hepatocellular carcinoma during the last 3 years who were treated in our centers. They were subdivided according to the treatment administered (Lenvatinib or Sorafenib). Progression-free survival (PFS) and overall survival (OS) were calculated, and subgroups were compared using the log-rank test. Specific predictive and prognostic factors were identified. The safety profile of the two drugs and the collateral effects were evaluated. Results: The OS in patients in the Lenvatinib arm was 19 (months and 12.5 months in the Sorafenib arm. PFS in patients in the Lenvatinib arm was 6 months and 2.5 months in the Sorafenib arm. OS and PFS in patients treated with Lenvatinib were higher in any subcategory analyzed whereas no positive predictors of response to Sorafenib were found. Based on data from literature, the albumin bilirubin index (ALBI) grade was found to be a key prognostic factor. Patients treated with Sorafenib had more adverse events than those treated with Lenvatinib (100% versus 81.8%, respectively). Patients treated with Sorafenib had more frequently hand-foot syndromes, diarrhea, and nausea whereas patients treated with Lenvatinib commonly had hypertension, proteinuria, and weight loss. Conclusion: Lenvatinib was found to be better than Sorafenib in terms of both survival and toxicity, in advanced hepatic cell carcinoma patients.
Anti-VEGF and Anti-EGFR Antibody Therapy on T-Cell Infiltration and TCR Variation in Metastatic Colorectal Cancer

Background/Aim: Chemotherapy combined with anti-EGFR or anti-VEGF monoclonal antibodies (mAb) is widely used to treat patients with metastatic colorectal cancer (mCRC). Here, we investigated the effects of these antibodies on T-cell infiltration and T-cell receptor (TCR) repertoire variation in CRC liver metastases. Materials and Methods: Ten patients with mCRC received chemotherapy in combination with anti-EGFR (n=6) or anti-VEGF (n=4) mAb. T-cell infiltration was examined for CD3 and CD8 by carrying out immunohistochemistry on biopsy or surgical specimens from liver metastases before and after treatment. TCR repertoire analysis was carried out on specimens with post-treatment CD3+ T-cell infiltration. Results: T-cell infiltrations were approximately 83% (5/6) and 50% (2/4), following treatment with anti-EGFR or anti-VEGF mAb, respectively. TCR repertoire analysis revealed higher clonality and lower diversity of TCR alpha and beta (TRA and TRB) in the anti-VEGF mAb group than that in the anti-EGFR group mAb. Furthermore, the percentage of the common TCR clones between infiltrating T cells and T cells in peripheral blood was significantly lower in the anti-VEGF mAb group compared to that in the anti-EGFR mAb group. Conclusion: The population of T cells infiltrating liver metastases in the anti-VEGF mAb group differed from that in the anti-EGFR mAb group.
Independent Validation of a Risk Stratification Model Predicting Survival in Elderly Patients Irradiated for Bone Metastases

Background/Aim: Many patients with bone metastases receive palliative radiotherapy. However, treatment personalization tools are needed, due to heterogeneous survival. The aim of this study was to analyze the validity of the prognostic survival model, originally developed by Rades et al., because international variations in clinical practice and survival outcomes may impact on the performance of predictive tools. Patients and Methods: Data from a single institution were retrospectively analyzed. The study included 305 patients managed with palliative radiotherapy for bone metastases. The Rades et al. score was assigned and the resulting 3 prognostic strata were compared. Results: The median overall survival for the 3 strata was 48, 248, and 1065 days, respectively (p<0.001). However, the original break-down (17 points versus 18-25 points versus >25 points) was not in accordance with the overlapping survival curves in some of the subgroups, leading us to propose slight adjustments. The modified model also performed satisfactorily in older patients (age ≥80 years; median survival 26, 192 and 489 days, respectively, p<0.001). Conclusion: The original Rades et al. survival score was a valid prognostic model in our Norwegian validation database. However, inclusion of patients with 18 points into the poor prognosis group is suggested as a modification to enhance the score’s performance.
Evaluation of the Impact of Smoking and Alcohol Consumption on Toxicity and Outcomes of Chemoradiation for Head and Neck Cancer

Background/Aim: Smoking and alcohol abuse may impair outcomes of chemoradiation for squamous cell head and neck cancer (SCCHN). Potential associations with toxicity, loco-regional control (LRC), and overall survival (OS) were investigated. Patients and Methods: Ninety-six patients were retrospectively analyzed for impacts of pre-radiotherapy (pre-RT) smoking history, smoking during radiotherapy, and pre-RT alcohol abuse on toxicity, LRC, and OS. Results: A trend was found for associations between pre-RT smoking history and grade ≥2 dermatitis. Smoking during radiotherapy was significantly associated with grade ≥3 mucositis and showed trends regarding grade ≥2 mucositis and dermatitis. On univariate analyses, smoking during radiotherapy was negatively associated with LRC and OS, pre-RT alcohol abuse with OS, and >40 pack years with LRC and OS. In multivariate analyses, smoking during radiotherapy remained significant for decreased OS, and pack years showed a trend. Conclusion: Smoking during radiotherapy was an independent predictor of OS and associated with increased toxicity. Thus, it is important to stop smoking prior to the start of radiotherapy.
A Model for Turbulent Compressible Vortices

In this thesis the effects of turbulence are introduced by combining the past turbulent tangential velocity model with the preceding work on the laminar compressible vortices. The radial and axial velocity components are derived from the tangential and mass conservation equations. The temperature is then found numerically from the energy equation. Upon code verification several characteristics of the problem have been examined in detail. The mysterious temperature separation is known since 1933 from the work of first Ranque and then Hilsch. Although several possibilities for its origin have been suggested no comprehensive theory for its causality has yet reported. The present novel approach is used to show conclusively that the cause of the thermal effect is the product of competition between the heating up of the gas because of friction and cooling due to material element expansion as it moves towards the region of decreasing pressure. As originally inferred empirically, it is now shown theoretically that stream wise vortices within supersonic flow fields and high Rossby number atmospheric vortices such as tornadoes and waterspouts, display the classical heating/cooling effect. The new information is used to elaborate on several, yet inexplicable instrument recordings related to these natural phenomena. Finally the new results are used to justify some odd physiological encounters made by several witnesses, trapped inside overpassing tornado’s funnels, and lived to tell their unusual experiences. The new basic methodology and findings can now be used to improve the design of vortex tubes. Keywords: Vortex model, compressible vortices, turbulent vortices, temperature separation.
Study on the Thermal Kinetics of Baijiao Anthracite Oxidation Induced by Water and Associated Pyrite

ABSTRACT Water and pyrite (FeS2) in coal have great synergistic effect on coal self-ignite. In order to explore the characteristics of spontaneous combustion of high humidity and high sulfur coal, this paper selected different concentrations of water and pyrite to carry out thermogravimetric experiment and oxidation reaction kinetics analysis. The changes of coal samples oxidation under low temperature in mass and characteristic temperatures were studied through thermogravimetric (TG) analysis. The results indicate that the promoting effect of water on coal spontaneous combustion turns to restrain when it reaches 15%, and water and pyrite have substantial synergistic effect on coal oxygen absorption and mass gain stage (T 3–T 5 in TG temperatures), besides there is a range of water/pyrite contents (10–15 mass% water and 2–4 mass% pyrite) that have the largest effect on coal oxidation reactions. Through the analysis of oxidation reaction kinetics, it was found that the change rule of the apparent activation energy (E a) in coal oxygen absorption and mass gain stage is similar to that of the thermogravimetric change, and it was the lowest at 2–4 mass% pyrite and 10–15 mass% water content. The reaction process of coal oxidation by water and pyrite conforms to the equation n = 4 Avrami-Erofeev, therefore water and pyrite just can promote coal oxidation externally. This research provides support for further understanding and control the influence of water and associated pyrite on coal self-ignite.
Novel gut microbiota and microbiota-metabolites signatures in gliomas and its predictive/prognosis functions

Gliomas are the most common malignant tumors in the central nervous system. Host genetic and environmental factors have been implicated as the causes and regulators of gliomas. Evidence shows that alterations of the gut microbiome play an important role in multiple diseases including central nervous system disorders. However, the influence of gut microbiome to the epigenesis of gliomas remains largely unknown. Here we profiled the gut microbiome and metabolome in fecal samples from healthy volunteers and the patients with gliomas through the 16S rRNA gene sequencing and LC-MS analyses. The fecal samples from primary glioma patients (n=51), recurrent glioma patients (n=11), patients who underwent TMZ radio-chemotherapy (n=16) and healthy volunteers (n=37) were collected. 56 discriminatory OTUs and 144 metabolites were observed in gliomas compared to those in healthy volunteers, and some species were correlated with clinical parameters, such as tumor grade, IDH-1 and MGMT status. Moreover, the gliomas group showed increased activity in pathways associated with ectoine biosynthesis, fatty acid elongation (saturated), and protocatechuate degradation. At the same time, we revealed 4 fatty-acid metabolites(palmitic acid, oleic acid, DL−beta−Hydroxypalmitic acid, 4−(Methylamino)−4−(3−pyridyl)butyric acid) as possibly interacting with glioma growth. Random forest modeling indicated that a model involving 8 genera and 10 metabolite biomarkers achieved a high accuracy in gliomas prediction (AUC=94.4%). We investigated interassociations between the microbial genera in glioblastoma multiforme (GBM) and progression-free survival (PFS) and overall survival (OS) by Spearman’s correlation analysis. Patients with high proportions of fecal Faecalibacterium had significantly better median PFS or OS than those with low proportions (mPFS 495 vs. 281 days, p=0.005; mOS 604 vs. 395 days, p=0.044). Moreover, animal experiments have verified the causal relationship between the structural changes of gut microbiome and glioma growth. Our current study comprehensively characterizes the perturbed interface of gut microbiome and metabolites in glioma patients, which may be used as diagnostic and prognostic biomarkers of gliomas.
Loss of FAM111B protease mutated in hereditary fibrosing poikiloderma syndrome negatively regulates telomere length

Hereditary fibrosing poikiloderma (HFP) is a rare human dominant negative disorder caused by mutations in the FAM111B gene that encodes a nuclear trypsin-like serine protease. HFP patients present with symptoms including skin abnormalities, tendon contractures, myopathy and lung fibrosis. We characterised the cellular roles of human FAM111B using U2OS and MCF7 cell lines and report here that the protease interacts with components of the nuclear pore complex. Loss of FAM111B expression resulted in abnormal nuclear shape and reduced telomeric DNA content suggesting that FAM111B protease is required for normal telomere length; we show that this function is independent of telomerase or recombination driven telomere extension. Even though FAM111B-deficient cells were proficient in DNA repair, they showed hallmarks of genomic instability such as increased levels of micronuclei and ultra-fine DNA bridges. Interestingly, FAM111B variants, including mutations that cause HFP, showed more frequent localisation to the nuclear lamina suggesting that accumulation of mutant FAM111B at the nuclear periphery may drive the disease pathology.
Insights into the mechanism of oligodendrocyte protection and remyelination enhancement by the integrated stress response

CNS inflammation triggers activation of the integrated stress response (ISR). We previously reported that prolonging the ISR protects remyelinating oligodendrocytes and promotes remyelination in the presence of inflammation (Chen et al., eLife, 2021). However, the exact mechanisms through which this occurs remain unknown. Here, we investigated whether the ISR modulator Sephin1 in combination with the oligodendrocyte differentiation enhancing reagent bazedoxifene (BZA) is able to accelerate remyelination under inflammation, and the underlying mechanisms mediating this pathway. We find that the combined treatment of Sephin1 and BZA is sufficient to accelerate early-stage remyelination in mice with ectopic IFN-γ expression in the CNS. IFN-γ, which is a critical inflammatory cytokine in multiple sclerosis (MS), inhibits oligodendrocyte precursor cell (OPC) differentiation in culture and triggers a mild ISR. Mechanistically, we further show that BZA promotes OPC differentiation in the presence of IFN-γ, while Sephin1 enhances the IFN-γ-induced ISR by reducing protein synthesis and increasing RNA stress granule formation in differentiating oligodendrocytes. Finally, the ISR suppressor 2BAct is able to partially lessen the beneficial effect of Sephin1 on disease progression, in an MS mouse model of experimental autoimmune encephalitis (EAE). Overall, our findings uncover distinct mechanisms of action of BZA and Sephin1 on oligodendrocyte lineage cells under inflammatory stress, suggesting that a combination therapy may effectively promote restoring neuronal function in MS patients.
Pot1 promotes telomere DNA replication via the Stn1-Ten1 complex in fission yeast

Telomeres are nucleoprotein complexes that protect the chromosome-ends from eliciting DNA repair while ensuring their complete duplication. Pot1 is a subunit of telomere capping complex that binds to the G-rich overhang and inhibits the activation of DNA damage checkpoints. In this study, we explore new functions of fission yeast Pot1 by using a pot1-1 temperature sensitive mutant. We show that pot1 inactivation impairs telomere DNA replication resulting in the accumulation of ssDNA leading to the complete loss of telomeric DNA. Recruitment of Stn1 to telomeres, an auxiliary factor of DNA lagging strand synthesis, is reduced in pot1-1 mutants and overexpression of Stn1 rescues loss of telomeres and cell viability at restrictive temperature. We propose that Pot1 plays a crucial function in telomere DNA replication by recruiting Stn1-Ten1 and Polα-primase complex to telomeres, thus promoting lagging-strand DNA synthesis at stalled replication forks.
Valid Bayesian Estimation of the Cointegrating Error Correction Model

Two methods of identifying cointegrating vectors are commonly used: linear restrictions and the nonlinear method of Johansen's maximum likelihood procedure. That the linear method can produce invalid estimates while the Johansen approach always produces valid estimates has been recognized in several recent articles. Because all Bayesian studies to date have used linear restrictions, this article presents a Bayesian method for obtaining estimates of cointegrating vectors that will always be valid. In addition, it also presents an approach for evaluating the validity of linear restrictions.
On CRDTs in Byzantine Environments

: Conflict-free Replicated Data Types (CRDTs) allow updates to be applied to different replicas independently and concurrently, without the need for a remote conflict resolution. Thus, they provide a building block for scalability and performance of fault-tolerant distributed systems. Currently, CRDTs are typically used in a crash fault setting for global scale, partition-tolerant, highly available databases or collaborative applications. In this paper, we explore the use of CRDTs in Byzantine environments. This exploration is inspired by the popular Matrix messaging system: as recently shown, the underlying Matrix Event Graph replicated data type represents a CRDT that can very well deal with Byzantine behavior. This “Byzantine Tolerance” is due to mechanisms inherent in CRDTs and in the hash-based directed acyclic graph (HashDAG) data structure used in Matrix. These mechanisms restrict Byzantine behavior. We, therefore, discuss Byzantine behavior in a context of CRDTs, and how the notion of Byzantine tolerance relates to equivocation. We show that a subclass of CRDTs is equivocation-tolerant, i.e., without equivocation detection, prevention or remediation, this subclass still fulfills the CRDT properties, which leads to Byzantine tolerance. We conjecture that an operation-based Byzantine-tolerant CRDT design supporting non-commutative operations needs to be based on a HashDAG data structure. We close the paper with thoughts on chances and limits of this data type.