Miracle-dz/UniFAR-FTUs huggingface dataset:
Identifying the Epileptogenic Zone With the Relative Strength of High-Frequency Oscillation: A Stereoelectroencephalography Study

Background High-frequency oscillation (HFO) represents a promising biomarker of epileptogenicity. However, the significant interindividual differences among patients limit its application in clinical practice. Here, we applied and evaluated an individualized, frequency-based approach of HFO analysis in stereoelectroencephalography (SEEG) data for localizing the epileptogenic zones (EZs). Methods Clinical and SEEG data of 19 patients with drug-resistant focal epilepsy were retrospectively analyzed. The individualized spectral power of all signals recorded by electrode array, i.e., the relative strength of HFO, was computed with a wavelet method for each patient. Subsequently, the clinical value of the relative strength of HFO for identifying the EZ was evaluated. Results Focal increase in the relative strength of HFO in SEEG recordings were identified in all 19 patients. HFOs identified inside the clinically identified seizure onset zone had more spectral power than those identified outside (p < 0.001), and HFOs in 250–500 Hz band (fast ripples) seemed to be more specific identifying the EZ than in those in 80–250 Hz band (ripples) (p < 0.01). The resection of brain regions generating HFOs resulted in a favorable seizure outcome in 17 patients (17/19; 89.5%), while in the cases of other patients with poor outcomes, the brain regions generating HFOs were not removed completely. Conclusion The relative strength of HFO, especially fast ripples, is a promising effective biomarker for identifying the EZ and can lead to a favorable seizure outcome if used to guide epilepsy surgery.
The Immature Gut Barrier and Its Importance in Establishing Immunity in Newborn Mammals

The gut is an efficient barrier which protects against the passage of pathogenic microorganisms and potential harmful macromolecules into the body, in addition to its primary function of nutrient digestion and absorption. Contrary to the restricted macromolecular passage in adulthood, enhanced transfer takes place across the intestines during early life, due to the high endocytic capacity of the immature intestinal epithelial cells during the fetal and/or neonatal periods. The timing and extent of this enhanced endocytic capacity is dependent on animal species, with a prominent non-selective intestinal macromolecular transfer in newborn ungulates, e.g., pigs, during the first few days of life, and a selective transfer of mainly immunoglobulin G (IgG), mediated by the FcRn receptor, in suckling rodents, e.g., rats and mice. In primates, maternal IgG is transferred during fetal life via the placenta, and intestinal macromolecular transfer is largely restricted in human neonates. The period of intestinal macromolecular transmission provides passive immune protection through the transfer of IgG antibodies from an immune competent mother; and may even have extra-immune beneficial effects on organ maturation in the offspring. Moreover, intestinal transfer during the fetal/neonatal periods results in increased exposure to microbial and food antigens which are then presented to the underlying immune system, which is both naïve and immature. This likely stimulates the maturation of the immune system and shifts the response toward tolerance induction instead of activation or inflammation, as usually seen in adulthood. Ingestion of mother's milk and the dietary transition to complex food at weaning, as well as the transient changes in the gut microbiota during the neonatal period, are also involved in the resulting immune response. Any disturbances in timing and/or balance of these parallel processes, i.e., intestinal epithelial maturation, luminal microbial colonization and mucosal immune maturation due to, e.g., preterm birth, infection, antibiotic use or nutrient changes during the neonatal period, might affect the establishment of the immune system in the infant. This review will focus on how differing developmental processes in the intestinal epithelium affect the macromolecular passage in different species and the possible impact of such passage on the establishment of immunity during the critical perinatal period in young mammals.
Ancestral Haplotype Mapping for GWAS and Detection of Signatures of Selection in Admixed Dairy Cattle of Kenya

Understanding the genetic structure of adaptation and productivity in challenging environments is necessary for designing breeding programs that suit such conditions. Crossbred dairy cattle in East Africa resulting from over 60 years of crossing exotic dairy breeds with indigenous cattle plus inter se matings form a highly variable admixed population. This population has been subject to natural selection in response to environmental stresses, such as harsh climate, low-quality feeds, poor management, and strong disease challenge. Here, we combine two complementary sets of analyses, genome-wide association (GWA) and signatures of selection (SoS), to identify genomic regions that contribute to variation in milk yield and/or contribute to adaptation in admixed dairy cattle of Kenya. Our GWA separates SNP effects due to ancestral origin of alleles from effects due to within-population linkage disequilibrium. The results indicate that many genomic regions contributed to the high milk production potential of modern dairy breeds with no region having an exceptional effect. For SoS, we used two haplotype-based tests to compare haplotype length variation within admixed and between admixed and East African Shorthorn Zebu cattle populations. The integrated haplotype score (iHS) analysis identified 16 candidate regions for positive selection in the admixed cattle while the between population Rsb test detected 24 divergently selected regions in the admixed cattle compared to East African Shorthorn Zebu. We compare the results from GWA and SoS in an attempt to validate the most significant SoS results. Only four candidate regions for SoS intersect with GWA regions using a low stringency test. The identified SoS candidate regions harbored genes in several enriched annotation clusters and overlapped with previously found QTLs and associations for different traits in cattle. If validated, the GWA and SoS results indicate potential for SNP-based genomic selection for genetic improvement of smallholder crossbred cattle.
Volatiles from damaged plants as major cues in long‐range host‐searching by the specialist parasitoid Cotesia rubecula

The role of volatile stimuli in the long‐range host‐searching behaviour of the specialist parasitoid Cotesia rubecula Marshall (Hymenoptera: Braconidae) was studied. Components from the plant‐host‐complex Brussels sprouts (Brassica oleracea L. var. gemmifera (DC.) Schulz. cv. ‘Titurel’)‐Pieris rapae L. (Lepidoptera: Pieridae) were compared for their attractiveness in dual choice tests in a windtunnel. Stimuli from cabbage plants that were mechanically damaged or damaged by P. rapae caterpillars were more attractive to this parasitoid species than stimuli emitted by the host larvae or their faeces. Parasitoids preferred leaves from the plant‐host‐complex over artificially damaged leaves. Undamaged cabbage plants were the least attractive to the foraging females. These results indicate that in‐flight searching behaviour of C. rubecula is guided by plant‐derived information and that for this specialist species more reliable and specific host‐derived cues play a minor role at longer distances.
CD2 Immunobiology

The glycoprotein CD2 is a costimulatory receptor expressed mainly on T and NK cells that binds to LFA3, a cell surface protein expressed on e.g., antigen-presenting cells. CD2 has an important role in the formation and organization of the immunological synapse that is formed between T cells and antigen-presenting cells upon cell-cell conjugation and associated intracellular signaling. CD2 expression is upregulated on memory T cells as well as activated T cells and plays an important role in activation of memory T cells despite the coexistence of several other costimulatory pathways. Anti-CD2 monoclonal antibodies have been shown to induce immune modulatory effects in vitro and clinical studies have proven the safety and efficacy of CD2-targeting biologics. Investigators have highlighted that the lack of attention to the CD2/LFA3 costimulatory pathway is a missed opportunity. Overall, CD2 is an attractive target for monoclonal antibodies intended for treatment of pathologies characterized by undesired T cell activation and offers an avenue to more selectively target memory T cells while favoring immune regulation.
Conditional Knockout of PKC-δ in Osteoclasts Favors Bone Mass Accrual in Males Due to Decreased Osteoclast Function

Protein kinase C delta (PKC-δ) functions as an important regulator in bone metabolism. However, the precise involvement of PKC-δ in the regulation of osteoclasts remains elusive. We generated an osteoclast specific PKC-δ knockout mouse strain to investigate the function of PKC-δ in osteoclast biology. Bone phenotype was investigated using microcomputed tomography. Osteoclast and osteoblast parameters were assessed using bone histomorphometry, and analysis of osteoclast formation and function with osteoclastogensis and hydroxyapatite resorption assays. The molecular mechanisms by which PKC-δ regulated osteoclast function were dissected by Western Blotting, TUNEL assay, transfection and transcriptome sequencing. We found that ablation of PKC-δ in osteoclasts resulted in an increase in trabecular and cortical bone volume in male mice, however, the bone mass phenotype was not observed in female mice. This was accompanied by decreased osteoclast number and surface, and Cathepsin-K protein levels in vivo, as well as decreased osteoclast formation and resorption in vitro in a male-specific manner. PKC-δ regulated androgen receptor transcription by binding to its promoter, moreover, PKC-δ conditional knockout did not increase osteoclast apoptosis but increased MAPK signaling and enhanced androgen receptor transcription and expression, finally leding to significant alterations in gene expression and signaling changes related to extracellular matrix proteins specifically in male mice. In conclusion, PKC-δ plays an important role in osteoclast formation and function in a male-specific manner. Our work reveals a previously unknown target for treatment of gender-related bone diseases.
Fc Gamma Receptors and Complement Component 3 Facilitate Anti-fVIII Antibody Formation

Anti-factor VIII (fVIII) alloantibodies, which can develop in patients with hemophilia A, limit the therapeutic options and increase morbidity and mortality of these patients. However, the factors that influence anti-fVIII antibody development remain incompletely understood. Recent studies suggest that Fc gamma receptors (FcγRs) may facilitate recognition and uptake of fVIII by recently developed or pre-existing naturally occurring anti-fVIII antibodies, providing a mechanism whereby the immune system may recognize fVIII following infusion. However, the role of FcγRs in anti-fVIII antibody formation remains unknown. In order to define the influence of FcγRs on the development of anti-fVIII antibodies, fVIII was injected into WT or FcγR knockout recipients, followed by evaluation of anti-fVIII antibodies. Anti-fVIII antibodies were readily observed following fVIII injection into FcγR knockouts, with similar anti-fVIII antibody levels occurring in FcγR knockouts as detected in WT mice injected in parallel. As antibodies can also fix complement, providing a potential mechanism whereby anti-fVIII antibodies may influence anti-fVIII antibody formation independent of FcγRs, fVIII was also injected into complement component 3 (C3) knockout recipients in parallel. Similar to FcγR knockouts, C3 knockout recipients developed a robust response to fVIII, which was likewise similar to that observed in WT recipients. As FcγRs or C3 may compensate for each other in recipients only deficient in FcγRs or C3 alone, we generated mice deficient in both FcγRs and C3 to test for potential antibody effector redundancy in anti-fVIII antibody formation. Infusion of fVIII into FcγRs and C3 (FcγR × C3) double knockouts likewise induced anti-fVIII antibodies. However, unlike individual knockouts, anti-fVIII antibodies in FcγRs × C3 knockouts were initially lower than WT recipients, although anti-fVIII antibodies increased to WT levels following additional fVIII exposure. In contrast, infusion of RBCs expressing distinct alloantigens into FcγRs, C3 or FcγR × C3 knockout recipients either failed to change anti-RBC levels when compared to WT recipients or actually increased antibody responses, depending on the target antigen. Taken together, these results suggest FcγRs and C3 can differentially impact antibody formation following exposure to distinct alloantigens and that FcγRs and C3 work in concert to facilitate early anti-fVIII antibody formation.
Behind Enemy Lines: Immunomodulatory Armamentarium of the Schistosome Parasite

The deeply rooted, intricate relationship between the Schistosoma parasite and the human host has enabled the parasite to successfully survive within the host and surreptitiously evade the host's immune attacks. The parasite has developed a variety of strategies in its immunomodulatory armamentarium to promote infection without getting harmed or killed in the battlefield of immune responses. These include the production of immunomodulatory molecules, alteration of membranes, and the promotion of granuloma formation. Schistosomiasis thus serves as a paradigm for understanding the Th2 immune responses seen in various helminthiases. This review therefore aims to summarize the immunomodulatory mechanisms of the schistosome parasites to survive inside the host. Understanding these immunomodulatory strategies not only provides information on parasite-host interactions, but also forms the basis in the development of novel drugs and vaccines against the schistosome infection, as well as various types of autoimmune and inflammatory conditions.
Unimodal Bandits with Continuous Arms

We consider stochastic bandit problems with a continuous set of arms and where the expected reward is a continuous and unimodal function of the arm. For these problems, we propose the Stochastic Polychotomy (SP) algorithms, and derive finite-time upper bounds on its regret and optimization error. We show that, for a class of reward functions, the SP algorithm achieves a regret and an optimization error with optimal scalings, i.e., $O(\sqrtT )$ and $O(1/\sqrtT )$ (up to a logarithmic factor), respectively. SP constitutes the first order-optimal algorithm for non-smooth expected reward functions, as well as for smooth functions with unknown smoothness. The algorithm is based on sequential statistical tests used to successively trim an interval that contains the best arm with high probability. These tests exhibit a minimal sample complexity which confers to SP its adaptivity and optimality. Numerical experiments actually reveal that the algorithm even outperforms state-of-the-art algorithms that exploit the knowledge of the smoothness of the reward function. The performance of SP is further illustrated on the problem of setting optimal reserve prices in repeated second-price auctions; there, the algorithm is evaluated on real-world data.
Independent Low-Rank Matrix Analysis-Based Automatic Artifact Reduction Technique Applied to Three BCI Paradigms

Electroencephalogram (EEG)-based brain-computer interfaces (BCIs) can potentially enable people to non-invasively and directly communicate with others using brain activities. Artifacts generated from body activities (e.g., eyeblinks and teeth clenches) often contaminate EEGs and make EEG-based classification/identification hard. Although independent component analysis (ICA) is the gold-standard technique for attenuating the effects of such contamination, the estimated independent components are still mixed with artifactual and neuronal information because ICA relies only on the independence assumption. The same problem occurs when using independent vector analysis (IVA), an extended ICA method. To solve this problem, we designed an independent low-rank matrix analysis (ILRMA)-based automatic artifact reduction technique that clearly models sources from observations under the independence assumption and a low-rank nature in the frequency domain. For automatic artifact reduction, we combined the signal separation technique with an independent component classifier for EEGs named ICLabel. To assess the comparative efficiency of the proposed method, the discriminabilities of artifact-reduced EEGs using ICA, IVA, and ILRMA were determined using an open-access EEG dataset named OpenBMI, which contains EEG data obtained through three BCI paradigms [motor-imagery (MI), event-related potential (ERP), and steady-state visual evoked potential (SSVEP)]. BCI performances were obtained using these three paradigms after applying artifact reduction techniques, and the results suggested that our proposed method has the potential to achieve higher discriminability than ICA and IVA for BCIs. In addition, artifact reduction using the ILRMA approach clearly improved (by over 70%) the averaged BCI performances using artifact-reduced data sufficiently for most needs of the BCI community. The extension of ICA families to supervised separation that leaves the discriminative ability would further improve the usability of BCIs for real-life environments in which artifacts frequently contaminate EEGs.
Mechanotransduction across the cell surface and through the cytoskeleton

Mechanical stresses were applied directly to cell surface receptors with a magnetic twisting device. The extracellular matrix receptor, integrin beta 1, induced focal adhesion formation and supported a force-dependent stiffening response, whereas nonadhesion receptors did not. The cytoskeletal stiffness (ratio of stress to strain) increased in direct proportion to the applied stress and required intact microtubules and intermediate filaments as well as microfilaments. Tensegrity models that incorporate mechanically interdependent struts and strings that reorient globally in response to a localized stress mimicked this response. These results suggest that integrins act as mechanoreceptors and transmit mechanical signals to the cytoskeleton. Mechanotransduction, in turn, may be mediated simultaneously at multiple locations inside the cell through force-induced rearrangements within a tensionally integrated cytoskeleton.
Genome Data Uncover Conservation Status, Historical Relatedness and Candidate Genes Under Selection in Chinese Indigenous Pigs in the Taihu Lake Region

Chinese indigenous pig breeds in the Taihu Lake (TL) region of Eastern China are well documented by their exceptional prolificacy. There are seven breeds in this region including Meishan (MS), Erhualian (EHL), Jiaxing Black (JXB), Fengjing (FJ), Shawutou (SWT), Mi (MI), and Hongdenglong (HDL). At present, these breeds are facing a great threat of population decline, inbreeding depression and lineage admixture since Western commercial pigs have dominated in Chinese pig industry. To provide better conservation strategies and identify candidate genes under selection for these breeds, we explored genome-wide single nucleotide polymorphism (SNP) markers to uncover genetic variability and relatedness, population structure, historical admixture and genomic signature of selection of 440 pigs representing the most comprehensive lineages of these breeds in TL region in a context of 1228 pigs from 45 Eurasian breeds. We showed that these breeds were more closely related to each other as compared to other Eurasian breeds, defining one of the main ancestral lineages of Chinese indigenous pigs. These breeds can be divided into two subgroups, one including JXB and FJ, and the other comprising of EHL, MI, HDL, MS, and SWT. In addition, HDL was highly inbred whereas EHL and MS had more abundant genetic diversity owing to their multiple conservation populations. Moreover, we identified a list of candidate genes under selection for body size and prolificacy. Our results would benefit the conservation of these valuable breeds and improve our understanding of the genetic mechanisms of body size and fecundity in pigs.
Combined Targeted and Non-targeted PCR Based Methods Reveal High Levels of Compliance in Probiotic Products Sold as Dietary Supplements in United States and Canada

Probiotics are defined as “live microorganisms that, when administered in adequate amounts, confer a health benefit on the host. ” The diverse health benefits have contributed to rapid increase in probiotic consumption and in the value of probiotic market, valued at USD 46 billion in 2019. For probiotics to be effective, the correct species/strains should be delivered viable in an adequate dose. The most commonly used methods for species/strain identification are DNA based methods including targeted and non-targeted methods (e.g., high-throughput sequencing, HTS). Using different DNA based methods, previous studies reported several cases of non-compliance in probiotic products. The objectives of this study are to evaluate levels of compliance in probiotic products (presence of all declared species/strains, absence of any contaminants or undeclared species, and meeting the declared minimum viable cell count) and to compare the performance of targeted and non-targeted methods in probiotic authentication. To the best of our knowledge, this is the largest study of its kind, testing 182 probiotic products, containing a total of 520 strains, collected from United States and Canada. Using species-specific assays, 11 species could not be detected in ten products. Missing species were Lactobacillus casei in seven products, Bifidobacterium longum and Bifidobacterium bifidum in one product, B. longum in one product while B. longum subsp. longum was mislabeled as B. longum subsp. infantis in another. Additionally, undeclared Bifidobacterium animalis subsp. lactis was detected in one product. Viable count was determined for 72 samples and was found to be lower than declared in five samples, including one product showing no viable cells. Overall, non-compliance was observed in 15 out of 182 products (8%). Additionally, undeclared species at relative abundance of ∼1–2% were found in 14 products using HTS, however, their presence could not be confirmed using species-specific assays. The results show that targeted PCR based methods enable species and strain level identification. The results also highlight the need to continue to develop strain-specific assays appropriate for use with multi-strain products. True strain-specific assays will enable strain authentication in both single-strain products and multi-strain products to ensure probiotic products meet the label claims and ensure probiotic efficacy.