Miracle-dz/UniFAR-FTUs huggingface dataset:
Cognitive Enhancers in Schizophrenia: A Systematic Review and Meta-Analysis of Alpha-7 Nicotinic Acetylcholine Receptor Agonists for Cognitive Deficits and Negative Symptoms

Background: Schizophrenia is a severe and enduring disease and is one of the leading causes of disability worldwide. Cognitive impairment is a core clinical symptom that plays a crucial role in functional outcomes and prognosis, thus making it a relevant treatment target. The aim of this study was to assess the efficacy of alpha-7 nicotinic acetylcholine receptor agonists (α7 nAChR) as adjunctive treatment to enhance cognition and ameliorate negative symptoms in patients with schizophrenia. Methods: A search strategy was developed for MEDLINE, Embase, and the Cochrane Central Register of Controlled Trials up to May 2019. We included randomized controlled trials (RCTs) that compared antipsychotic treatment plus α7 nAChR agonists with antipsychotic treatment plus placebo and determined their effects on the main cognitive domains proposed by the MATRICS initiative and on negative symptoms. Two authors independently reviewed study eligibility and data extraction and assessed the risk of bias of the studies included. According to the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) framework, we used a random-effects model and assessed the quality of the evidence. Results: Thirteen studies were included in the quantitative analysis. No differences were found in any of the cognitive domains assessed in four RCTs (n = 414). In contrast, nine RCTs (n = 978) presented a small effect in support of α7 nAChR agonists for negative symptoms [standardized mean difference −0.28, 95% CI (−0.56 to −0.00); P = 0.05], even though the confidence to support this evidence is low according to the GRADE system. Conclusions: Current evidence is too weak to consider α7 nAChR agonists as an effective add-on treatment to antipsychotics to enhance cognition and negative symptoms.
Vividness of Visual Imagery and Personality Impact Motor-Imagery Brain Computer Interfaces

Brain-computer interfaces (BCIs) are communication bridges between a human brain and external world, enabling humans to interact with their environment without muscle intervention. Their functionality, therefore, depends on both the BCI system and the cognitive capacities of the user. Motor-imagery BCIs (MI-BCI) rely on the users’ mental imagination of body movements. However, not all users have the ability to sufficiently modulate their brain activity for control of a MI-BCI; a problem known as BCI illiteracy or inefficiency. The underlying mechanism of this phenomenon and the cause of such difference among users is yet not fully understood. In this study, we investigated the impact of several cognitive and psychological measures on MI-BCI performance. Fifty-five novice BCI-users participated in a left- versus right-hand motor imagery task. In addition to their BCI classification error rate and demographics, psychological measures including personality factors, affinity for technology, and motivation during the experiment, as well as cognitive measures including visuospatial memory and spatial ability and Vividness of Visual Imagery were collected. Factors that were found to have a significant impact on MI-BCI performance were Vividness of Visual Imagery, and the personality factors of orderliness and autonomy. These findings shed light on individual traits that lead to difficulty in BCI operation and hence can help with early prediction of inefficiency among users to optimize training for them.
Base Composition and Host Adaptation of the SARS-CoV-2: Insight From the Codon Usage Perspective

The novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been spreading rapidly all over the world and has raised grave concern globally. The present research aims to conduct a robust base compositional analysis of SARS-CoV-2 to reveal adaptive intricacies to the human host. Multivariate statistical analysis revealed a complex interplay of various factors including compositional constraint, natural selection, length of viral coding sequences, hydropathicity, and aromaticity of the viral gene products that are operational to codon usage patterns, with compositional bias being the most crucial determinant. UpG and CpA dinucleotides were found to be highly preferred whereas, CpG dinucleotide was mostly avoided in SARS-CoV-2, a pattern consistent with the human host. Strict avoidance of the CpG dinucleotide might be attributed to a strategy for evading a human immune response. A lower degree of adaptation of SARS-CoV-2 to the human host, compared to Middle East respiratory syndrome (MERS) coronavirus and SARS-CoV, might be indicative of its milder clinical severity and progression contrasted to SARS and MERS. Similar patterns of enhanced adaptation between viral isolates from intermediate and human hosts, contrasted with those isolated from the natural bat reservoir, signifies an indispensable role of the intermediate host in transmission dynamics and spillover events of the virus to human populations. The information regarding avoided codon pairs in SARS-CoV-2, as conferred by the present analysis, promises to be useful for the design of vaccines employing codon pair deoptimization based synthetic attenuated virus engineering.
Huanglongbing and Foliar Spray Programs Affect the Chemical Profile of “Valencia” Orange Peel Oil

Florida orange trees have been affected by huanglongbing (HLB) for more than a decade. To alleviate disease-caused tree decline, maintain fruit productivity, and reduce disease transmission, enhanced foliar spray programs combining vector control and nutritional supplementation have been applied to healthy and diseased trees. The aim of this research was to discover if the various foliar sprays affect fruit peel oil chemical components. In this study, “Valencia” orange trees, with or without HLB (HLB±), were treated with the grower standard program (control, C) or one of four proprietary enhanced foliar spray programs (N1, N2, N3, and N4) over 16 months. Compared with HLB−, HLB+ samples had lower concentrations of typical peel oil components, including valencene, octanal, and decanal, and were abundant in oxidative/dehydrogenated terpenes, such as carvone and limonene oxide. However, limonene, the dominant component, was not affected by any treatment. Control and three out of four enhanced foliar spray programs, N2, N3, and N4, had very little influence on the chemical profiles of both HLB− and HLB+ samples, while N1 treatment greatly altered the chemical profile of HLB+ samples, resulting in peel oil similar to that of HLB− samples.
Ross Sea Benthic Ecosystems: Macro- and Mega-faunal Community Patterns From a Multi-environment Survey

The Ross Sea, Antarctica, is amongst the least human-impacted marine environments, and the site of the world’s largest Marine Protected Area. We present research on two components of the Ross Sea benthic fauna: mega-epifauna, and macro-infauna, sampled using video and multicore, respectively, on the continental shelf and in previously unsampled habitats on the northern continental slope and abyssal plain. We describe physical habitat characteristics and community composition, in terms of faunal diversity, abundance, and functional traits, and compare similarities within and between habitats. We also examine relationships between faunal distributions and ice cover and productivity, using summaries of satellite-derived data over the decade prior to our sampling. Clear differences in seafloor characteristics and communities were noted between environments. Seafloor substrates were more diverse on the Slope and Abyss, while taxa were generally more diverse on the Shelf. Mega-epifauna were predominantly suspension feeders across the Shelf and Slope, with deposit feeder-grazers found in higher or equal abundances in the Abyss. In contrast, suspension feeders were the least common macro-infaunal feeding type on the Shelf and Slope. Concordance between the mega-epifauna and macro-infauna data suggests that non-destructive video sampling of mega-epifauna can be used to indicate likely composition of macro-infauna, at larger spatial scales, at least. Primary productivity, seabed organic flux, and sea ice concentrations, and their variability over time, were important structuring factors for both community types. This illustrates the importance of better understanding bentho-pelagic coupling and incorporating this in biogeographic and process-distribution models, to enable meaningful predictions of how these ecosystems may be impacted by projected environmental changes. This study has enhanced our understanding of the distributions and functions of seabed habitats and fauna inside and outside the Ross Sea MPA boundaries, expanding the baseline dataset against which the success of the MPA, as well as variability and change in benthic communities can be evaluated longer term.
Comparison of Three Methods of Mint Propagation and Their Effect on the Yield of Fresh Material and Essential Oil

ABSTRACT Three methods of mint propagation were compared, using six different cultivars and clonal selections of Mentha piperita and Mentha arvensis var. piperascens. Propagation methods included autumn-planted rooted cuttings and autumn- and summer-planted rhizomes. All tested selections except one produced the highest yields of fresh herbage when propagated by rooted cuttings. Essential oil yields and menthol content varied among the tested selections based on method of propagation. However, it remains within the Bulgarian standards for respective cultivars.
Preventive Effects of Bacillus licheniformis on Heat Stroke in Rats by Sustaining Intestinal Barrier Function and Modulating Gut Microbiota

Heat stroke (HS) models in rats are associated with severe intestinal injury, which is often considered as the key event at the onset of HS. Probiotics can regulate the gut microbiota by inhibiting the colonization of harmful bacteria and promoting the proliferation of beneficial bacteria. Here, we investigated the preventive effects of a probiotic Bacillus licheniformis strain (BL, CMCC 63516) on HS rats as well as its effects on intestinal barrier function and gut microbiota. All rats were randomly divided into four groups: control (Con) + PBS (pre-administration with 1 ml PBS twice a day for 7 days, without HS induction), Con + BL group (pre-administration with 1 ml 1 × 108 CFU/ml BL twice a day for 7 days, without HS induction), HS + PBS (PBS, with HS induction), and HS + BL (BL, with HS induction). Before the study, the BL strain was identified by genomic DNA analysis. Experimental HS was induced by placing rats in a hot and humid chamber for 60 min until meeting the diagnostic criterion of HS onset. Body weight, core body temperature, survival rate, biochemical markers, inflammatory cytokines, and histopathology were investigated to evaluate the preventive effects of BL on HS. D-Lactate, I-FABP, endotoxin, and tight-junction proteins were investigated, and the fluorescein isothiocyanate-dextran (FD-4) test administered, to assess the degree of intestinal injury and integrity. Gut microbiota of rats in each group were analyzed by 16S rRNA sequencing. The results showed that pre-administration with BL significantly attenuated hyperthermia, reduced HS-induced death, alleviated multiple-organ injury, and decreased the levels of serum inflammatory cytokines. Furthermore, BL sustained the intestinal barrier integrity of HS rats by alleviating intestinal injury and improving tight junctions. We also found that BL significantly increased the ratios of two probiotic bacteria, Lactobacillus and Lactococcus. In addition, Romboutsia, a candidate biomarker for HS diagnosis, was unexpectedly detected. In summary, BL pre-administration for 7 days has preventative effects on HS that may be mediated by sustaining intestinal barrier function and modulating gut microbiota.
Delineating the Association Between Soluble CD26 and Autoantibodies Against G-Protein Coupled Receptors, Immunological and Cardiovascular Parameters Identifies Distinct Patterns in Post-Infectious vs. Non-Infection-Triggered Myalgic Encephalomyelitis/Chronic Fatigue Syndrome

Soluble cluster of differentiation 26 (sCD26) has a wide range of enzymatic functions affecting immunological, metabolic and vascular regulation. Diminished sCD26 concentrations have been reported in various autoimmune diseases and also in Myalgic Encephalomyelitis/Chronic fatigue syndrome (ME/CFS). Here we re-evaluate sCD26 as a diagnostic marker and perform a comprehensive correlation analysis of sCD26 concentrations with clinical and paraclinical parameters in ME/CFS patients. Though this study did find significantly lower concentrations of sCD26 only in the female cohort and could not confirm diagnostic suitability, results from correlation analyses provide striking pathomechanistic insights. In patients with infection-triggered onset, the associations of low sCD26 with elevated autoantibodies (AAB) against alpha1 adrenergic (AR) and M3 muscarinic acetylcholine receptors (mAChR) point to a pathomechanism of infection-triggered autoimmune-mediated vascular and immunological dysregulation. sCD26 concentrations in infection-triggered ME/CFS were found to be associated with activated T cells, liver enzymes, creatin kinase (CK) and lactate dehydrogenase (LDH) and inversely with Interleukin-1 beta (IL-1b). Most associations are in line with the known effects of sCD26/DPP-4 inhibition. Remarkably, in non-infection-triggered ME/CFS lower sCD26 in patients with higher heart rate after orthostatic challenge and postural orthostatic tachycardia syndrome (POTS) suggest an association with orthostatic regulation. These findings provide evidence that the key enzyme sCD26 is linked to immunological alterations in infection-triggered ME/CFS and delineate a different pathomechanism in the non-infectious ME/CFS subset.
Identification of Novel Prognostic Risk Signatures of Soft Tissue Sarcoma Based on Ferroptosis-Related Genes

Background The role of ferroptosis in tumorigenesis has been confirmed in previous studies. However, the comprehensive analysis of ferroptosis-related gene (FRG) to study the role of FRG in soft tissue sarcoma (STS) is lacking. Methods RNA sequencing profile of TCGA-SARC cohort and GTEx were used to select differentially expressed FRGs (DEFRGs). Univariate, LASSO, and multivariate Cox analyses were selected to determine overall survival (OS)- and disease-free survival (PFS)-related FRGs. Two prognostic signatures were established and validated in two independent sets from Gene Expression Omnibus (GEO). Finally, the expression of key FRGs were validated with RT-qPCR. Results In total, 198 FRGs (90.4%) were abnormally expressed in STS. Twelve DEFRGs were incorporated in the final signatures and showed favorable discrimination in both training and validation cohorts. Patients in the different risk groups not only showed different prognosis, but also showed different infiltration of immune cells. Two nomograms combining signature and clinical variables were established and the C-indexes were 0.852 and 0.752 for the OS and DFS nomograms, respectively. Finally, the expression of NOX5, HELLS, and RPL8 were validated with RT-qPCR. Conclusion This comprehensive analysis of the FRG landscape in STS revealed novel FRGs related to carcinogenesis and prognosis. These findings have implications for prognosis and therapeutic responses, which revealed potential prognostic biomarkers and promote precision medicine.
Development of a Prognostic AI-Monitor for Metastatic Urothelial Cancer Patients Receiving Immunotherapy

Background: Immune checkpoint inhibitor efficacy in advanced cancer patients remains difficult to predict. Imaging is the only technique available that can non-invasively provide whole body information of a patient's response to treatment. We hypothesize that quantitative whole-body prognostic information can be extracted by leveraging artificial intelligence (AI) for treatment monitoring, superior and complementary to the current response evaluation methods. Methods: To test this, a cohort of 74 stage-IV urothelial cancer patients (37 in the discovery set, 37 in the independent test, 1087 CTs), who received anti-PD1 or anti-PDL1 were retrospectively collected. We designed an AI system [named prognostic AI-monitor (PAM)] able to identify morphological changes in chest and abdominal CT scans acquired during follow-up, and link them to survival. Results: Our findings showed significant performance of PAM in the independent test set to predict 1-year overall survival from the date of image acquisition, with an average area under the curve (AUC) of 0.73 (p < 0.001) for abdominal imaging, and 0.67 AUC (p < 0.001) for chest imaging. Subanalysis revealed higher accuracy of abdominal imaging around and in the first 6 months of treatment, reaching an AUC of 0.82 (p < 0.001). Similar accuracy was found by chest imaging, 5–11 months after start of treatment. Univariate comparison with current monitoring methods (laboratory results and radiological assessments) revealed higher or similar prognostic performance. In multivariate analysis, PAM remained significant against all other methods (p < 0.001), suggesting its complementary value in current clinical settings. Conclusions: Our study demonstrates that a comprehensive AI-based method such as PAM, can provide prognostic information in advanced urothelial cancer patients receiving immunotherapy, leveraging morphological changes not only in tumor lesions, but also tumor spread, and side-effects. Further investigations should focus beyond anatomical imaging. Prospective studies are warranted to test and validate our findings.
Treatment for Major Depressive Disorder by Repetitive Transcranial Magnetic Stimulation in Different Parameters: A Randomized Double-Blinded Controlled Trial

Background: Repetitive transcranial magnetic stimulation (rTMS) has been proven to be safe and effective in treating major depressive disorder (MDD). However, the treatment parameters of rTMS are still divergent and need to be optimized further. The aim of this study was to compare the efficacy of rTMS in treating MDD with different parameters of stimulating frequency and location, and course of treatment. Methods: A total of 221 patients with MDD were recruited in the randomized, double-blind, controlled trial. All eligible patients were randomly assigned into four treatment groups: (1) 10 Hz in left dorsolateral pre-frontal cortex (DLPFC) (n = 55), (2) 5 Hz in left DLPFC (n = 53), (3) 10 Hz in bilateral DLPFC (n = 57), and (4) 5 Hz in bilateral DLPFC (n = 56). The patients received treatment for 6 weeks and an additional 6-week optional treatment. The efficacies were evaluated by Hamilton Depression Rating Scale-24 items (HDRS) and Clinical Global Impressions Scale (CGI). The trial is registered at the Chinese Clinical Trial Registry as ChiCTR-TRC-12002248. Results: The ANOVAs of HDRS scores up to 6 weeks and 12 weeks with repeated measure of time showed a significant effect of duration without statistical difference among four treatment groups and no significance when time was interacted with inter-group as well. The response rates up until the 5th week were significantly different with the previous week. Conclusions: It concludes that there were no statistical differences in the efficacy of rTMS between unilateral left and bilateral DLPFC, and between 5 and 10 Hz for treating MDD.
Long-term yield of pancreatic cancer surveillance in high-risk individuals

Objective We aimed to determine the long-term yield of pancreatic cancer surveillance in hereditary predisposed high-risk individuals. Design From 2006 to 2019, we prospectively enrolled asymptomatic individuals with an estimated 10% or greater lifetime risk of pancreatic ductal adenocarcinoma (PDAC) after obligatory evaluation by a clinical geneticist and genetic testing, and subjected them to annual surveillance with both endoscopic ultrasonography (EUS) and MRI/cholangiopancreatography (MRI/MRCP) at each visit. Results 366 individuals (201 mutation-negative familial pancreatic cancer (FPC) kindreds and 165 PDAC susceptibility gene mutation carriers; mean age 54 years, SD 9.9) were followed for 63 months on average (SD 43.2). Ten individuals developed PDAC, of which four presented with a symptomatic interval carcinoma and six underwent resection. The cumulative PDAC incidence was 9.3% in the mutation carriers and 0% in the FPC kindreds (p<0.001). Median PDAC survival was 18 months (range 1–32). Surgery was performed in 17 individuals (4.6%), whose pathology revealed 6 PDACs (3 T1N0M0), 7 low-grade precursor lesions, 2 neuroendocrine tumours <2 cm, 1 autoimmune pancreatitis and in 1 individual no abnormality. There was no surgery-related mortality. EUS detected more solid lesions than MRI/MRCP (100% vs 22%, p<0.001), but less cystic lesions (42% vs 83%, p<0.001). Conclusion The diagnostic yield of PDAC was substantial in established high-risk mutation carriers, but non-existent in the mutation-negative proven FPC kindreds. Nevertheless, timely identification of resectable lesions proved challenging despite the concurrent use of two imaging modalities, with EUS outperforming MRI/MRCP. Overall, surveillance by imaging yields suboptimal results with a clear need for more sensitive diagnostic markers, including biomarkers.
Improved clinical outcome in a randomized phase II study of anti-PD-1 camrelizumab plus decitabine in relapsed/refractory Hodgkin lymphoma

Background Programmed death-1 (PD-1) blockade monotherapy induced durable remission in a subset of patients with relapsed/refractory classical Hodgkin lymphoma (cHL). We asked whether the anti-PD-1 agent, camrelizumab, combined with the DNA demethylating agent, decitabine, improves progression-free survival (PFS) in patients with relapsed/refractory cHL over camrelizumab alone. Methods This extended follow-up of an ongoing randomized phase II trial analyzed PFS among patients enrolled from January 2017 through July 2018. Sixty-one patients with relapsed/refractory cHL who were clinically naïve to PD-1 blockade and had received ≥2 previous therapies were randomized 1:2 to receive either camrelizumab (200 mg) monotherapy or camrelizumab (200 mg, day 8) combined with decitabine (10 mg/day, days 1–5) every 3 weeks. Results With a median follow-up of 34.5 months, complete remission was 79% (95% CI 63% to 90%) in the decitabine-plus-camrelizumab group versus 32% (95% CI 13% to 57%) in the camrelizumab group (p=0.001). Median duration of response was not reached in the decitabine-plus-camrelizumab group, with an estimated 63% (95% CI 46% to 75%) of patients maintaining a response at 24 months. Median PFS with decitabine-plus-camrelizumab therapy was 35.0 months (95% CI not reached) and 15.5 months (95% CI 8.4 to 22.7 months) with camrelizumab monotherapy (HR, 0.46; 95% CI 0.21 to 1.01; p=0.02). Female gender, lower tumor burden, and fewer previous therapies were favorable prognostic factors for durable remission with camrelizumab monotherapy. The PFS benefits of decitabine-plus-camrelizumab versus camrelizumab were observed in most subgroups, especially in patients with relative larger tumor burdens and those treated with ≥3 prior therapies. After decitabine-plus-camrelizumab treatment, the percentage increase of circulating peripheral central memory T-cells correlated with both improved clinical response and PFS, suggesting a putative biomarker of decitabine-plus-camrelizumab therapy for cHL. Conclusions Decitabine-plus-camrelizumab results in longer PFS compared with camrelizumab alone in patients with relapsed/refractory cHL. Trial registration numbers NCT02961101 and NCT03250962.