Miracle-dz/UniFAR-FTUs huggingface dataset:
Antigen-specific B-cell depletion for precision therapy of mucosal pemphigus vulgaris.

Desmoglein 3 chimeric autoantibody receptor T-cells (DSG3-CAART) expressing the pemphigus vulgaris (PV) autoantigen DSG3, fused to CD137-CD3ζ signaling domains, represent a precision cellular immunotherapy approach for antigen-specific B-cell depletion. Here, we present definitive preclinical studies enabling a first-in-human trial of DSG3-CAART for mucosal PV. DSG3-CAART specifically lysed human anti-DSG3 B-cells from PV patients and demonstrated activity consistent with a threshold dose in vivo, resulting in decreased target cell burden, decreased serum and tissue-bound autoantibodies, and increased DSG3-CAART engraftment. In a PV active immune model with physiologic anti-DSG3 IgG levels, DSG3-CAART inhibited antibody responses against pathogenic DSG3 epitopes and autoantibody binding to epithelial tissues, leading to clinical and histologic resolution of blisters. DSG3 autoantibodies stimulate DSG3-CAART IFNγ secretion and homotypic clustering, consistent with an activated phenotype. Toxicology screens using primary human cells and high-throughput membrane proteome arrays did not identify off-target cytotoxic interactions. These preclinical data guided the trial design for DSG3-CAART and may help inform CAART preclinical development for other antibody-mediated diseases.
Notes on some Papilionidae (Lepidoptera) from Indonesia

Study of literature and of specimens, mainly in the collection of the Zoelogical Museum of Amsterdam (ZMA), lead to the fo11owing conclusions and alterations. The correct from N. E. Sumatra is Pachliopta because Il is suppressed as invalid review ofthe species reasons Java and two specirnens of weiskei female of G"aphium encelades finally Papieio polytes aipheios Jordan appears synonymous Rothschild, whose range extends Minahasa to the lslands. Papitfo aicinclor OberthUr also occurs and maybe
A Driving Performance Forecasting System Based on Brain Dynamic State Analysis Using 4-D Convolutional Neural Networks

Vehicle accidents are the primary cause of fatalities worldwide. Most often, experiencing fatigue on the road leads to operator errors and behavioral lapses. Thus, there is a need to predict the cognitive state of drivers, particularly their fatigue level. Electroencephalography (EEG) has been demonstrated to be effective for monitoring changes in the human brain state and behavior. Thirty-seven subjects participated in this driving experiment and performed a perform lane-keeping task in a visual-reality environment. Three domains, namely, frequency, temporal, and 2-D spatial information, of the EEG channel location were comprehensively considered. A 4-D convolutional neural-network (4-D CNN) algorithm was then proposed to associate all information from the EEG signals and the changes in the human state and behavioral performance. A 4-D CNN achieves superior forecasting performance over 2-D CNN, 3-D CNN, and shallow networks. The results showed a 3.82% improvement in the root mean-square error, a 3.45% improvement in the error rate, and a 11.98% improvement in the correlation coefficient with 4-D CNN compared with 3-D CNN. The 4-D CNN algorithm extracts the significant theta and alpha activations in the frontal and posterior cingulate cortices under distinct fatigue levels. This work contributes to enhancing our understanding of deep learning methods in the analysis of EEG signals. We even envision that deep learning might serve as a bridge between translation neuroscience and further real-world applications.
Adverse event profile differences between rituximab and ocrelizumab: Findings from the FDA Adverse Event Reporting Database

Background: Rituximab and ocrelizumab are anti-CD20 monoclonal antibodies that have shown a marked reduction in multiple sclerosis (MS) inflammatory activity. However, their real-world safety profile has not been adequately compared. Objective: To investigate the adverse event (AE) profile of rituximab and ocrelizumab reported to the Food and Drug Administration Adverse Event Reporting System (FAERS) database. Methods: The FAERS database was filtered by indication (MS) and drug (rituximab or ocrelizumab). Disproportionality analyses including but not limited to reporting odds ratio (ROR) were conducted to identify drug–AE associations. A signal was detected if the lower limit of the 95% confidence interval of ROR (ROR025) exceeded 1. Results: There were 623 and 7948 reports for rituximab and ocrelizumab, respectively. The most frequent AEs with rituximab and ocrelizumab were infusion-related reaction (4.82%) and urinary tract infection (10.52%), respectively. The strongest drug–AE association for rituximab and ocrelizumab were ear pruritus (ROR025: 47.53) and oral herpes (ROR025: 38.99), respectively. Ocrelizumab was associated with an almost two times higher frequency of infections than rituximab (21.93% vs 11.05%, respectively). Conclusion: This study revealed differences in reporting AEs between rituximab and ocrelizumab. Infections were reported more frequently with ocrelizumab. Although speculative, a potentially different or more extensive B-cell depletion by ocrelizumab might explain these findings. Additional pharmacovigilance studies need to be performed to better characterize differences in the AE profile in B-cell-depleting therapies.
Transjugular intrahepatic portosystemic shunt in patients with cirrhosis: Indications and posttransjugular intrahepatic portosystemic shunt complications in 2020

Abstract Transjugular intrahepatic portosystemic shunt is a percutaneous radiologic‐guided procedure that aims to reduce portal hypertension by creating a shunt between the portal venous system and the hepatic venous system. The most common cause of portal hypertension is liver cirrhosis in Western countries. Two main indications of transjugular intrahepatic portosystemic shunt are validated by randomised controlled studies in patients with cirrhosis and variceal bleeding (salvage transjugular intrahepatic portosystemic shunt, early transjugular intrahepatic portosystemic shunt or rebleeding despite an optimal secondary prophylaxis) or refractory ascites. Careful selection of the patients is crucial in order to prevent posttransjugular intrahepatic portosystemic shunt complications, including liver failure, posttransjugular intrahepatic portosystemic shunt encephalopathy occurrence and cardiac decompensation, for a better long‐term outcome. In this review, we will discuss transjugular intrahepatic portosystemic shunt indications in 2020 in patients with cirrhosis and portal hypertension, with a special focus on variceal bleeding and refractory ascites. Then, we will describe transjugular intrahepatic portosystemic shunt‐related complications, the contraindications and the current knowledge on patient's selection.
The influence of programmed cell death ligand 2 (PD-L2) expression on survival outcome and tumor microenvironment in diffuse large B cell lymphoma

Abstract The frequency and significance of programmed cell death ligand (PD-L) 2 expression in diffuse large B cell lymphoma (DLBCL) remain undefined. We described the expression pattern of PD-L/PD-1 in 88 DLBCL patients using immunohistochemistry. The association between PD-L expression and clinical characteristics/outcomes were analyzed. PD-L1 and PD-L2 were expressed in 14.8% and 68.2% of DLBCL patients with median positivity on tumor cells of 100% and 90%, respectively. PD-1 on tumor-infiltrating lymphocytes (TILs) was expressed in 12.5% of patients. Interestingly, 45.5% of patients had PD-L2 expressing TILs which were significantly associated with bulky disease (p = .046) and elevated lactate dehydrogenase (p = .048). PD-L1 and/or PD-L2 expression on lymphoma cells was associated with inferior progression-free survival (Hazard ratio [HR] 2.20; 95% Confidence Interval [CI] 1.004–4.84, p = .049) and overall survival (HR 2.27; 95%CI 1.03–4.98, p = .042), using multivariate analysis. In summary, PD-L2 expression on DLBCL is common and, together with PD-L1, were related to poor outcomes.
Combined Treatment with JFKD and Gefitinib Overcomes Drug Resistance in Non-Small Cell Lung Cancer.

BACKGROUND Gefitinib is an important drug used to treat non-small cell lung cancer (NSCLC) with EGFR activating mutations, but drug resistance restricts its clinical application. In this present study, combined Jin Fu Kang Decoction (JFKD) and gefitinib showed specific cytotoxicity to gefitinib-resistant cancer cells (PC-9/gef). OBJECTIVE The aim of this study was to decipher the molecular mechanism of the JFKD on drug resistance when used together with Gefitinib and to find the contributing bio-active substance(s) in JFKD based on the putative mechanism. METHODS To investigate the combined effect of gefitinib and JFKD, in vitro experiments were conducted on the established gefitinib-resistant PC-9 subclone, while in vivo experiments were conducted on the Balbc nude mice with PC-9/gef xenografts. Western blot was used to evaluate the protein expression, and ultra-performance liquid chromatography (UPLC) coupled with quadrupole time-of-flight mass spectrometry (MS) was used to detect the bio-active compounds of JFKD. RESULTS The expression of the PTEN-relevant protein p-EGFR, p-Akt in vitro was inhibited more when combined JKFD and gefitinibwere used, whereas the activities of PDCD4 and PTEN were increased; remarkably, in vivo experiments showed enhanced tumor growth inhibition when treated with this combination . Due to this combination, the effect on the gefitinib-resistant cell line, one of the JFKD-induced anti-cancer mechanisms, was found. To link the putative mechanism and the anti-cancer compounds in JFKD, 14 saponins and flavonoids were detected. CONCLUSION The present results suggested that a promising TCM-participated therapy can be established by the putative mechanism of the combined treatment in resistant NSCLC and screening the contributing bio-active substance(s) in JFKD is meaningful on new TCM formula discovery.
Muscle‐Specific Relation of Acetylcarnitine and Intramyocellular Lipids to Chronic Hyperglycemia: A Pilot 3‐T 1H MRS Study

Acetylcarnitine plays an important role in fat metabolism and can be detected in proton magnetic resonance spectra in skeletal muscle. An inverse relationship of acetylcarnitine to intramyocellular lipids and metabolic markers of chronic hyperglycemia has been suggested. This study aimed to compare the acetylcarnitine concentrations and intramyocellular lipids measured noninvasively by proton magnetic resonance spectroscopy (1H MRS) in the tibialis anterior and the soleus of three different groups of volunteers with a broad range of glycemic control.
ERK1/2 Signaling Induces Upregulation of ANGPT2 and CXCR4 to Mediate Liver Metastasis in Colon Cancer

These findings identify amplified ERK1/2 signaling in KRAS-mutated colorectal cancer cells as a driver of tumor–stroma interactions that favor formation of metastases in the liver. Carcinoma development in colorectal cancer is driven by genetic alterations in numerous signaling pathways. Alterations in the RAS-ERK1/2 pathway are associated with the shortest overall survival for patients after diagnosis of colorectal cancer metastatic disease, yet how RAS–ERK signaling regulates colorectal cancer metastasis remains unknown. In this study, we used an unbiased screening approach based on selection of highly liver metastatic colorectal cancer cells in vivo to determine genes associated with metastasis. From this, an ERK1/2-controlled metastatic gene set (EMGS) was defined. EMGS was associated with increased recurrence and reduced survival in patients with colorectal cancer tumors. Higher levels of EMGS expression were detected in the colorectal cancer subsets consensus molecular subtype (CMS)1 and CMS4. ANGPT2 and CXCR4, two genes within the EMGS, were subjected to gain-of-function and loss-of-function studies in several colorectal cancer cell lines and then tested in clinical samples. The RAS–ERK1/2 axis controlled expression of the cytokine ANGPT2 and the cytokine receptor CXCR4 in colorectal cancer cells, which facilitated development of liver but not lung metastases, suggesting that ANGPT2 and CXCR4 are important for metastatic outgrowth in the liver. CXCR4 controlled the expression of cytokines IL10 and CXCL1, providing evidence for a causal role of IL10 in supporting liver colonization. In summary, these studies demonstrate that amplification of ERK1/2 signaling in KRAS-mutated colorectal cancer cells affects the cytokine milieu of the tumors, possibly affecting tumor–stroma interactions and favoring liver metastasis formation. Significance: These findings identify amplified ERK1/2 signaling in KRAS-mutated colorectal cancer cells as a driver of tumor–stroma interactions that favor formation of metastases in the liver.
Aberrantly activated Wnt/β‐catenin pathway co‐receptors LRP5 and LRP6 regulate osteoblast differentiation in the developing coronal sutures of an Apert syndrome (Fgfr2S252W/+) mouse model

Apert syndrome is an autosomal, dominant inherited disorder characterized by craniosynostosis and syndactyly caused by gain‐of‐function mutations in the fibroblast growth factor receptor 2 (FGFR2) gene. Wnt/β‐catenin signaling plays critical roles in regulating the skeletal development. Here, we analyzed the role of this pathway in the developing coronal sutures (CS) of a murine Apert syndrome model (Fgfr2S252W/+).
Costs Associated with Nontuberculous Mycobacteria Infection, Ontario, Canada, 2001–2012

To determine incidence-based healthcare costs attributable to nontuberculous mycobacterial (NTM) pulmonary disease (PD) and NTM pulmonary isolation (PI), from the healthcare payer perspective, we conducted a population-based matched cohort study in Ontario, Canada. We established cohorts of patients with incident NTM-PD and NTM-PI during 2001–2012 by using individually linked laboratory data and health administrative data, matched to unexposed persons from the general population. To estimate attributable costs for acute and long-term illness, we used a phase-of-care approach. Costs were stratified by age, sex, and healthcare resource, and reported in 2018 Canadian dollars (CAD) and US dollars (USD), standardized to 10 days. Costs were highest during the before-death phase (NTM-PD CAD $1,352 [USD $1,044]; NTM-PI CAD $731 [USD $565]). The cumulative mean attributable 1-year costs were CAD $14,953 (USD $11,541) for NTM-PD and CAD $8,729 (USD $6,737) for NTM-PI. Costs for patients with NTM-PD and NTM-PI were higher than those for unexposed persons.
Effects of a pineapple (Ananas comosus L.) cannery by-product on growth performance and carcass characteristics in finishing Hanwoo steers

Objective The aim of this study was to determine the effect of pineapple cannery by-product (PCB) level on the growth performance and carcass characteristics of finishing Hanwoo steers. Methods The feeding stage was divided into early and late finishing stages. A total of 60 castrated Hanwoo steers (13.9±0.8 months old, 418.8±36.5 kg initial body weight [BW]) were blocked by initial BW and then randomly allotted into 12 pens (five head/pen). The pens were randomly assigned to control (CONT), low PCB (LPCB), or high PCB (HPCB) treatments. These diets contained 0%, 1.5%, or 3.0% of PCB (on a dry matter [DM] basis; as-fed basis was 0%, 10.6%, or 21.2%), respectively. Results For the early finishing stage, body weight gain (BWG) and average daily gain (ADG) of the CONT and LPCB feeding groups were greater (p<0.05) than those of the HPCB feeding group. In addition, there were linear and quadratic effects on BWG and ADG with increasing dietary PCB level (p<0.05). The gain to feed (G:F) ratio tends to quadratically decrease with an increasing PCB level in the early finishing stage (p = 0.076). Growth performances of late finishing stage were not affected by PCB level. The marbling score of the LPCB feeding group was similar to that of the CONT feeding group. However, there was a linear decrease (p< 0.05) in marbling score and quality grade among treatments as PCB was increased in the diet. In the longissimus muscle free amino acid profile, histidine composition increased linearly (p<0.05) with an increasing level of PCB. Conclusion The level of PCB 1.5% DM in diet can be used for finishing steers without any adverse effects on growth and carcass performances. However, there were some negative effects on growth and carcass performance in the HPCB feeding group.
Complement C3 and allergic asthma: a cohort study of the general population

Complement C3 plays a role in asthma development and severity. We tested the hypothesis that high plasma complement C3 concentration is associated with high risks of asthma hospitalisation and exacerbation. We prospectively assessed the risk of asthma hospitalisation in 101 029 individuals from the Copenhagen General Population Study with baseline measurements of plasma complement C3, and genotyped for rs1065489, rs429608 and rs448260 determining levels of complement C3. Risk of asthma exacerbation was further assessed in 2248 individuals with allergic asthma. The multivariable adjusted hazard ratio of asthma hospitalisation was 1.23 (95% CI 1.04–1.45) for individuals in the highest tertile (>1.19 g·L−1) of plasma complement C3 compared with those in the lowest tertile (<1.03 g·L−1). The C3 rs448260 genotype was associated with risk of asthma hospitalisation with an observed hazard ratio of 1.17 (95% CI 1.06–1.28) for the CC genotype compared with the AA genotype. High plasma complement C3 was associated with high levels of blood eosinophils and IgE (p for trends ≤6×10−9), but only the SKIV2L rs429608 genotype was positively associated with blood eosinophil count (p=3×10−4) and IgE level (p=3×10−4). In allergic asthma, the multivariable adjusted incidence rate ratio for risk of exacerbation was 1.69 (95% CI 1.06–2.72) for individuals in the highest plasma complement C3 tertile (>1.24 g·L−1) versus the lowest (<1.06 g·L−1). In conclusion, a high concentration of plasma complement C3 was associated with a high risk of asthma hospitalisation in the general population and with a high risk of asthma exacerbation in individuals with allergic asthma. Our findings support a causal role of the complement system in asthma severity. High concentrations of plasma complement C3 are associated with asthma hospitalisation and exacerbation risk among individuals from the general population; genetic analyses indicate a causal role for complement C3 in asthma pathogenesis and severity https://bit.ly/30PIIwg
MicroRNAs for Diagnosis and Treatment of Colorectal Cancer.

Colorectal cancer (CRC) is the third most common cancer worldwide, with high morbidity and mortality rates. The diagnosis and treatment of CRC have the most significant value for disease-free survival. Early diagnosis and early surgical resection are generally considered to be the most effective ways to reduce CRC mortality. In the past few years, many researchers have focused on the role of microRNAs in different tumors, making the functions of microRNAs gradually clear. The present study reviews the role of microRNAs in the diagnosis and treatment of colorectal cancer. Compared with the usual diagnosis methods and biomarker, circulating microRNAs can be promising new effective biomarkers for CRCdiagnosis and treatment.
An Electrophysiological Abstractness Effect for Metaphorical Meaning Making

Abstract Neuroimaging studies show that metaphors activate sensorimotor areas. These findings were interpreted as metaphors contributing to conceptual thought by mapping concrete, somatosensory information onto abstract ideas. But is sensorimotor information a necessary constituent of figurative meaning? The present study employed event-related potentials (ERPs) in a divided visual field paradigm with healthy adults to explore the role of sensorimotor feature processing in the comprehension of novel metaphors via the electrophysiological concreteness effect. Participants read French, novel adjective-noun expressions that were either metaphorical (“fat sentence”) or literal (“fat hip”). While literal expressions evoked a typical concreteness effect, an enhanced frontal negativity during right hemisphere (RH) as opposed to left hemisphere (LH) presentation, metaphors showed no such sign of sensorimotor feature processing. Relative to literals, they evoked a sustained frontal negativity during LH presentation and similar amplitudes during RH presentation, but both of these effects were the greater the more abstract the metaphors were. It is the first time such an electrophysiological abstractness effect is reported, just the opposite of a concreteness effect. It is particularly noteworthy that ERPs evoked by metaphors were not contingent on figurativeness, novelty, meaningfulness, imageability, emotional valence, or arousal, only on abstractness. When compared with similarly novel literal expressions, metaphors did not evoke a typical N400 and did not activate the RH either. The findings shed new light on the neurocognitive machinery of figurative meaning construction, pervasive in everyday communication. Contrary to embodied cognition, the conceptual system might be organized around abstract representations and not sensorimotor information, even for lush, metaphorical language.
Lunge filter feeding biomechanics constrain rorqual foraging ecology across scale

ABSTRACT Fundamental scaling relationships influence the physiology of vital rates, which in turn shape the ecology and evolution of organisms. For diving mammals, benefits conferred by large body size include reduced transport costs and enhanced breath-holding capacity, thereby increasing overall foraging efficiency. Rorqual whales feed by engulfing a large mass of prey-laden water at high speed and filtering it through baleen plates. However, as engulfment capacity increases with body length (engulfment volume∝body length3.57), the surface area of the baleen filter does not increase proportionally (baleen area∝body length1.82), and thus the filtration time of larger rorquals predictably increases as the baleen surface area must filter a disproportionally large amount of water. We predicted that filtration time should scale with body length to the power of 1.75 (filter time∝body length1.75). We tested this hypothesis on four rorqual species using multi-sensor tags with corresponding unoccupied aircraft systems-based body length estimates. We found that filter time scales with body length to the power of 1.79 (95% CI: 1.61–1.97). This result highlights a scale-dependent trade-off between engulfment capacity and baleen area that creates a biomechanical constraint to foraging through increased filtration time. Consequently, larger whales must target high-density prey patches commensurate to the gulp size to meet their increased energetic demands. If these optimal patches are absent, larger rorquals may experience reduced foraging efficiency compared with smaller whales if they do not match their engulfment capacity to the size of targeted prey aggregations. Summary: Morphology predicts behavior and physiological performance, which for rorquals results in both biomechanical and ecological constraints.