Miracle-dz/UniFAR-FTUs huggingface dataset:
Finding and Keeping the Beat: Neural Mechanisms Differ as Beat Perception Unfolds

Perception of a regular beat is essential to our ability to synchronize movements to music in an anticipatory fashion. Beat perception requires multiple, distinct neural functions, corresponding to the perceptual stages that occur over time, including 1) detection that regularity is present (beat finding), 2) prediction of future regular events to enable anticipation (beat continuation), and 3) dynamic adjustment of predictions as the rhythmic stimulus changes (beat adjustment). The striatum has been shown to be crucial for beat perception generally, although it is unclear how, or whether, distinct regions of the striatum contribute to these different stages of beat perception. Here, we used fMRI to investigate the activity of striatal subregions during the different stages of beat perception. Participants listened to pairs of rhythms (polyrhythms) whose temporal structure induced distinct perceptual stages—finding, continuation, and adjustment of the beat. Dorsal putamen was preferentially active during beat finding, whereas the ventral putamen was preferentially active during beat adjustment. We also observed that anterior insula activity was sensitive to metrical structure (greater when polyrhythms were metrically incongruent than when they were congruent). These data implicate the dorsal putamen in the detection of regularity, possibly by detection of coincidences between cortical oscillations, and the ventral putamen in the adjustment of regularity perception, possibly by integration of prediction errors in ongoing beat predictions. Additionally, activity in the supramarginal and superior temporal gyri correlated with beat tapping performance, and activity in the superior temporal gyrus correlated with beat perception (performance on the Beat Alignment Test).
Effects of chronic dietary hexavalent chromium on bioaccumulation and immune responses in the sea cucumber Apostichopus japonicus

Sea cucumbers Apostichopus japonicus (3.54 ± 0.01 g of wet weight) were exposed to five concentrations of dietary hexavalent chromium [0 (control), 100, 200, 400, and 800 mg Cr6+/kg dry weight] amended with K2Cr2O7 for 30 days. The bioaccumulation and immune responses [antioxidant enzymes: superoxide dismutase (SOD) and catalase (CAT); hydrolytic enzymes: acid phosphatase (ACP) and alkaline phosphatase (AKP)] of sea cucumbers were subsequently evaluated. This study found that the order of Cr accumulation in the experimental tissues was respiratory tree > intestine > body wall. Significantly lower SOD activities occurred in the 400 mg/kg group compared to that in the control group. Higher dietary Cr6+ exposure (400 and 800 mg Cr6+ /kg dry weight) did not negatively alter the CAT activities, but significantly inhibited CAT activities in 100 mg/kg group, compared to control group. ACP activities in groups 200, 400 and 800 mg/kg were significantly lower than those in control group, while no significant differences occurred in AKP activities among groups. The present study provides important information into the bioaccumulation and immune responses of the sea cucumber A. japonicus in response to chronic dietary Cr6+ exposure.
Anatomical and functional connectivity support the existence of a salience network node within the caudal ventrolateral prefrontal cortex

Three large-scale brain networks are considered essential to cognitive flexibility: the ventral and dorsal attention (VAN and DAN) and salience (SN) networks. The ventrolateral prefrontal cortex (vlPFC) is a known component of the VAN and DAN, but its role in the SN is controversial. In this study, we used a translational and multimodal approach to demonstrate the existence of a SN node within the vlPFC. First, we used tract-tracing methods in non-human primates (NHP) to quantify the anatomic connectivity strength between the different vlPFC areas and the frontal and insular cortices. The strongest connections with the dorsal anterior cingulate cortex (dACC) and anterior insula (AI) locations comprising the two main cortical SN nodes were derived from the caudal area 47/12. This location also has strong axonal projections to subcortical structures of the salience network, including the dorsomedial thalamus, hypothalamus, sublenticular extended amygdala, and periaqueductal gray. Second, we used a seed-based functional connectivity analysis in NHP resting-state functional MRI (rsfMRI) data to validate the caudal area 47/12 as an SN node. Third, we used the same approach in human rsfMRI data to identify a homologous structure in caudal area 47/12, also showing strong connections with the SN cortical nodes, thus confirming the caudal area 47/12 as the SN node in the vlPFC. Taken together, the vlPFC contains nodes for all three cognitive networks, the VAN, DAN, and SN. Thus, the vlPFC is in a position to switch between these three cognitive networks, suggesting a key role as an attentional hub. Its tight additional connections to the orbitofrontal, dorsolateral, and ventral premotor cortices, places the vlPFC at the center for switching behaviors based on environmental stimuli, computing value and cognitive control.
Modeling hepatitis C micro-elimination among people who inject drugs with direct-acting antivirals in metropolitan Chicago

Hepatitis C virus (HCV) infection is a leading cause of chronic liver disease and mortality worldwide. Direct-acting antiviral (DAA) therapy leads to high cure rates. However, persons who inject drugs (PWID) are at risk for reinfection after cure and may require multiple DAA treatments to reach the World Health Organization’s (WHO) goal of HCV elimination by 2030. Using an agent-based model (ABM) that accounts for the complex interplay of demographic factors, risk behaviors, social networks, and geographic location for HCV transmission among PWID, we examined the combination(s) of DAA enrollment (2.5%, 5%, 7.5%, 10%), adherence (60%, 70%, 80%, 90%) and frequency of DAA treatment courses needed to achieve the WHO’s goal of reducing incident chronic infections by 90% by 2030 among a large population of PWID from Chicago, IL and surrounding suburbs. We also estimated the economic DAA costs associated with each scenario. Our results indicate that a DAA treatment rate of >7.5% per year with 90% adherence results in 75% of enrolled PWID requiring only a single DAA course; however19% would require 2 courses, 5%, 3 courses and <2%, 4 courses), with an overall DAA cost of $325 million to achieve the WHO goal in metropolitan Chicago. We estimate a 28% increase in the overall DAA cost under low adherence (70%) compared to high adherence (90%). Our modeling results have important public health implications for HCV elimination among U.S. PWID. Using a range of feasible treatment enrollment and adherence rates, we report robust findings supporting the need to address re-exposure and reinfection among PWID to reduce HCV incidence.
Multiplex Genome-Editing Technologies for Revolutionizing Plant Biology and Crop Improvement

Multiplex genome-editing (MGE) technologies are recently developed versatile bioengineering tools for modifying two or more specific DNA loci in a genome with high precision. These genome-editing tools have greatly increased the feasibility of introducing desired changes at multiple nucleotide levels into a target genome. In particular, clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein (Cas) [CRISPR/Cas] system-based MGE tools allow the simultaneous generation of direct mutations precisely at multiple loci in a gene or multiple genes. MGE is enhancing the field of plant molecular biology and providing capabilities for revolutionizing modern crop-breeding methods as it was virtually impossible to edit genomes so precisely at the single base-pair level with prior genome-editing tools, such as zinc-finger nucleases (ZFNs) and transcription activator-like effector nucleases (TALENs). Recently, researchers have not only started using MGE tools to advance genome-editing applications in certain plant science fields but also have attempted to decipher and answer basic questions related to plant biology. In this review, we discuss the current progress that has been made toward the development and utilization of MGE tools with an emphasis on the improvements in plant biology after the discovery of CRISPR/Cas9. Furthermore, the most recent advancements involving CRISPR/Cas applications for editing multiple loci or genes are described. Finally, insights into the strengths and importance of MGE technology in advancing crop-improvement programs are presented.
Association of Anthropometric Indices With the Development of Diabetes Among Hypertensive Patients in China: A Cohort Study

Background Patients with comorbidity of hypertension and diabetes are associated with higher morbidity and mortality of cardiovascular disease than those with hypertension or diabetes alone. The present study aimed to identify anthropometric risk factors for diabetes among hypertensive patients who were included in a retrospective cohort study. Methods Hypertensive adults without diabetes were recruited in China. Demographic, clinical, biochemical, and anthropometric indices were collected at baseline and during the follow-up. Anthropometric measures included BMI, waist circumference, waist-to-height ratio (WHtR), and waist-to-hip ratio, and several novel indices. To estimate the effect of baseline and dynamic changes of each anthropometric index on risk of new-onset diabetes (defined as self-reported physician-diagnosed diabetes and/or use of hypoglycemic medication, or new-onset FPG≥7.0 mmol/L during follow-up), Cox regression models were used. Results A total of 3852 hypertensive patients were studied, of whom 1167 developed diabetes during follow-up. Multivariate Cox regression analyses showed that there was a graded increased risk of incident diabetes with successively increasing anthropometric indices mentioned above (all P<0.05). Regardless of the baseline general obesity status, elevated WHtR was both related to higher risk of diabetes; the HRs (95%CI) of baseline BMI<24 kg/m2 & WHtR≥0.5 group and BMI≥24 kg/m2 & WHtR≥0.5 group were 1.34 (1.05, 1.72), 1.85 (1.48, 2.31), respectively. Moreover, the dynamic changes of WHtR could sensitively reflect diabetes risk. Diabetes risk significantly increased when patients with baseline WHtR<0.5 progressed to WHtR≥0.5 during the follow-up (HR=1.63; 95%CI, 1.11, 2.40). There was also a decreasing trend towards the risk of incident diabetes when baseline abnormal WHtR reversed to normal at follow-up (HR=1.93; 95%CI, 1.36, 2.72) compared with those whose WHtR remained abnormal at follow-up (HR=2.04; 95%CI, 1.54, 2.71). Conclusions Central obesity is an independent and modifiable risk factor for the development of diabetes among hypertensive patients. Measuring indices of central obesity in addition to BMI in clinics could provide incremental benefits in the discrimination of diabetes among Chinese hypertensive patients. Dynamic changes of WHtR could sensitively reflect changes in the risk of diabetes. Therefore, long-term monitoring of hypertensive patients using non-invasive anthropometric measures and timely lifestyle intervention could effectively reduce the development of diabetes.
Different Non-cage Housing Systems Alter Duodenal and Cecal Microbiota Composition in Shendan Chickens

Housing systems are among the most important non-genetic factors affecting hen production performance and intestinal microbes. With increased interest in animal welfare, cage-free laying hen housing systems have become common, providing behavioral freedom and health benefits. The present study aimed to compare the effects of plastic net housing system (NRS) and floor litter housing system (LRS) on the composition and function of the duodenal and cecal microbiota in Shendan chicken, one of the most popular laying hen strains in China. The associations between the differential microbiota abundance and production traits and intestinal morphological parameters were determined. Compared with the LRS, the NRS improved the laying rate (p < 0.05) and increased the villus height (VH) of the duodenum (p < 0.05) and the VH-to-crypt depth ratio (VCR) of the cecum (p < 0.05). Alpha diversity analysis showed that LRS chickens had a significantly higher diversity and richness than NRS chickens. Beta diversity analysis demonstrated differences in the microbiota composition based on housing systems. Within the cecum, Proteobacteria and Kiritimatiellaeota were significantly more abundant in the LRS than in the NRS (p < 0.05), while Bacteroidetes were significantly less abundant in the LRS (p < 0.05). Phascolarctobacterium and Ruminococcaceae_UCG-005 were significantly less abundant in the LRS (p < 0.05) compare to the NRS. Within the duodenum, Lactobacillus was significantly less abundant in the LRS (p < 0.05) than in the NRS, while Pseudomonas was significantly more abundant in the LRS (p < 0.05). Cecal Phascolarctobacterium and Ruminococcaceae_UCG-005 were significantly positively correlated with eggshell strength (R = 0.608, p < 0.01) and egg weight (R = 0.526, p < 0.05), respectively. Duodenal Lactobacillus was significantly positively correlated with VH and VCR (R = 0.548 and 0.565, p < 0.05), while Pseudomonas was significantly negatively correlated with the Haugh unit (R = −0.550, p < 0.05). In conclusion, there are differences in the cecal and duodenal microbiota compositions of Shendan laying hens reared in different non-cage housing systems, and the NRS was superior to the LRS in improving the laying performance and intestinal morphology and microecological environment.
A Virtual Approach to Promote Inter-Professional Learning (IPL) Between Biomedical Science and Medicine in Higher Education for the Benefit of Patient Care

In the clinical setting, collaboration between multidisciplinary teams is core to providing effective patient care. The delivery of traditional interprofessional education is associated with a number of logistical challenges, which were heightened by the Covid-19 pandemic. This workshop was developed to bring together Biomedical Science and Medical students using an online platform. The workshop consisted of (1) defining interprofessional education, (2) introducing the role of the Pathology laboratory, (3) Professional registration with regulatory bodies and (4) an insight into Covid-19 laboratory diagnosis. The session was supported by mixed group breakout rooms and interactive polling. Thirty four percent of students completed a post-workshop online survey which included open and closed questions. Thematic analysis revealed a better understanding the role of the pathology laboratory in diagnosing disease, an increased awareness of the similarities and differences in the roles of a Biomedical Scientist and a Medic and the importance of a multi-disciplinary team in achieving effective patient care. Quantitative analysis of survey data revealed that the majority of students reported positive experiences of interprofessional education online. Approximately 90% of students agreed that the workshop enabled them to increase their understanding of their own roles within healthcare, in addition to increasing their understanding of the roles of other healthcare professionals. 74.3% of participants reported that working with students from a different programme provided an alternative perspective. Seventy nine percent of students agreed that the online format enabled interactivity and discussion of the tasks. Of the 204 students, 85% engaged with the four polls during the workshop. This online workshop enabled discussion between degree programmes, enabled interactivity and allowed the learning outcomes to be met. Universities should embrace online platforms to provide a novel, engaging and effective interprofessional educational experience.
From Biology to Clinical Practice: Iron Chelation Therapy With Deferasirox

Iron chelation therapy (ICT) has become a mainstay in heavily transfused hematological patients, with the aim to reduce iron overload (IOL) and prevent organ damage. This therapeutic approach is already widely used in thalassemic patients and in low-risk Myelodysplastic Syndrome (MDS) patients. More recently, ICT has been proposed for high-risk MDS, especially when an allogeneic bone marrow transplantation has been planned. Furthermore, other hematological and hereditary disorders, characterized by considerable transfusion support to manage anemia, could benefit from this therapy. Meanwhile, data accumulated on how iron toxicity could exacerbate anemia and other clinical comorbidities due to oxidative stress radical oxygen species (ROS) mediated by free iron species. Taking all into consideration, together with the availability of approved oral iron chelators, we envision a larger use of ICT in the near future. The aim of this review is to better identify those non-thalassemic patients who can benefit from ICT and give practical tips for management of this therapeutic strategy.
Psychological Difficulties Mediate and Self-Efficacy Moderates the Relationship Between Family Cumulative Risk and Hope Among Chinese Children From Low-Income Families

This longitudinal study investigated the role of psychological difficulties and self-efficacy in the relationship between family cumulative risk and hope among children from low-income families. The participants were 392 Chinese children from low-income families; the study extended for 2 years, and participants completed data that were collected with the following questionnaires: the Family Cumulative Risk Index, Children's Hope Scale, Strengths and Difficulties Questionnaire-Difficulties subscale, and General Self-efficacy Scale. The results demonstrated that psychological difficulties played a mediating role in the relationship between family cumulative risk and hope; specifically, family cumulative risk predicted hope of children via psychological difficulties. Self-efficacy moderated the relationship between psychological difficulties and hope. This moderation supported “a drop in the ocean effect”; the protective effect of high self-efficacy worked only when psychological difficulties were at low levels. When psychological difficulties were at high levels, the buffering effect of self-efficacy on family cumulative risk was gradually weakened and eventually lost.
Identification of Components of the Hippo Pathway in Hydra and Potential Role of YAP in Cell Division and Differentiation

The Hippo signaling pathway has been shown to be involved in regulating cellular identity, cell/tissue size maintenance and mechanotransduction. The Hippo pathway consists of a kinase cascade which determines the nucleo-cytoplasmic localization of YAP in the cell. YAP is the effector protein in the Hippo pathway, which acts as a transcriptional cofactor for TEAD. Phosphorylation of YAP upon activation of the Hippo pathway prevents it from entering the nucleus and abrogates its function in the transcription of the target genes. In Cnidaria, the information on the regulatory roles of the Hippo pathway is virtually lacking. Here, we report the existence of a complete set of Hippo pathway core components in Hydra for the first time. By studying their phylogeny and domain organization, we report evolutionary conservation of the components of the Hippo pathway. Protein modelling suggested the conservation of YAP-TEAD interaction in Hydra. Further, we characterized the expression pattern of the homologs of yap, hippo, mob and sav in Hydra using whole-mount RNA in situ hybridization and report their possible role in stem cell maintenance. Immunofluorescence assay revealed that Hvul_YAP expressing cells occur in clusters in the body column and are excluded in the terminally differentiated regions. Actively proliferating cells marked by Ki67 exhibit YAP colocalization in their nuclei. Strikingly, a subset of these colocalized cells is actively recruited to the newly developing bud. Disruption of the YAP-TEAD interaction increased the budding rate indicating a critical role of YAP in regulating cell proliferation in Hydra. Collectively, we posit that the Hippo pathway is an essential signaling system in Hydra; its components are ubiquitously expressed in the Hydra body column and play a crucial role in Hydra tissue homeostasis.
Fas Ligand as a Circulating Apoptosis Marker in Carcinoma Breast

Background : Circulating apoptosis markers such as soluble Fas receptors and Fas ligand, are a new set of blood parameter that might affect tumor growth and aggressiveness as well as being able to monitor the effect of antitumor therapy. We evaluate serially by ELISA the levels of FasL in the serum of breast cancer patients at presentation, post surgery, and post chemotherapy and also correlate levels of apoptosis markers with tumor response. Methods : This prospective study undertaken on 24 patients of carcinoma breast of any stage in Department of General Surgery, IMS BHU in collaboration with the Department of Pathology, IMS, BHU between July 2012 to July 2014. Informed and written consent was obtained from all patients. Response Evaluation Criteria In Solid Tumors (RECIST) was used to determine objective tumor response for target lesions. Circulating levels of Fas Ligand in the serum of breast cancer patient was studied by ELISA technique. Results: The mean age of the patients was 44.75 years (ranging from 25 to 75 years). In cases, the median Fas level at the time of presentation was 73.0 (35.76-90.0), at post surgery 58.0 (40.0-85.0) and at post-chemotherapy was 64.85 (26.75-89.5). As compared to control group, Fas level is significantly increased in patient of carcinoma breast at different time interval (p=0.004, 0.001, 0.010). In our study FasL levels were comparable in ER, PR and HER-2 positive and negative cases. There was no difference in serum levels of FasL among triple negative and non triple negative cases. Patients with lymph node positive status had a higher FasL level compared to those who had no lymph node status. The difference was greatest among patients who had 1–3 lymph nodes compared to N0 patients (p<0.01). Conclusion: Our study indicates a considerable prognostic potential for FasL in breast cancer patients. Lack of these molecules is related to a significantly worse prognosis. This is the result of resistance of FasL deficient breast tumors to the mechanism of apoptosis.
Multiallelic Rare Variants in BBS Genes Support an Oligogenic Ciliopathy in a Non-obese Juvenile-Onset Syndromic Diabetic Patient: A Case Report

Juvenile-onset diabetes may occur in the context of a rare syndromic presentation, suggesting a monogenic etiology rather than a common multifactorial diabetes. In the present study, we report the case of a young diabetic Tunisian patient presenting learning problems, speech deficits, short stature, brachydactyly, and a normal weight. Whole exome sequencing analysis revealed five heterozygous genetic variants in BBS1, BBS4, BBS8, MKS1, and CEP290. These genes are involved in the regulation of cilium biogenesis and function. We analyzed variant combinations pathogenicity using the recently developed ORVAL tool, and we hypothesized that cumulative synergetic effects of these variants could explain the syndromic phenotype observed in our patient. Therefore, our investigation suggested a genetic diagnosis of Bardet–Biedl syndrome with an oligogenic inheritance pattern rather than a monogenic diabetes. Although there is no curative therapy for this ciliopathy at the moment, a genetic diagnosis may offer other supportive care options, including the prevention of other possible clinical manifestations of this syndrome, mainly renal abnormalities, obesity, liver fibrosis, and hypertension, as well as the genetic counseling for family members.