Miracle-dz/UniFAR-FTUs huggingface dataset:
Identification of key genes and crucial pathways for major depressive disorder using peripheral blood samples and chronic unpredictable mild stress rat models

Background Accurate diagnosis of major depressive disorder (MDD) remains difficult, and one of the key challenges in diagnosing MDD is the lack of reliable diagnostic biomarkers. The objective of this study was to explore gene networks and identify potential biomarkers for MDD. Methods In the present study, we performed a comprehensive analysis of the mRNA expression profiles using blood samples of four patients with MDD and four controls by RNA sequencing. Differentially expressed genes (DEGs) were screened, and functional and pathway enrichment analyses were performed using the Database for Annotation, Visualization, and Integrated Discovery. All DEGs were inputted to the STRING database to build a PPI network, and the top 10 hub genes were screened using the cytoHubba plugin of the Cytoscape software. The relative expression of 10 key genes was identified by quantitative real-time polymerase chain reaction (qRT-PCR) of blood samples from 50 MDD patients and 50 controls. Plasma levels of SQSTM1 and TNFα were measured using an enzyme-linked immunosorbent assay in blood samples of 44 MDD patients and 44 controls. A sucrose preference test was used to evaluate depression-like behavior in chronic unpredictable mild stress (CUMS) model rats. Immunofluorescence assay and western blotting were performed to study the expression of proteins in the brain samples of CUMS model rats Results We identified 247 DEGs that were closely associated with MDD. Gene ontology analyses suggested that the DEGs were mainly enriched in negative regulation of transcription by RNA polymerase II promoter, cytoplasm, and protein binding. Moreover, Kyoto Encyclopedia of Genes and Genomes pathway analysis suggested that the DEGs were significantly enriched in the MAPK signaling pathway. Ten hub genes were screened through the PPI network, and qRT-PCR assay revealed that one and six genes were downregulated and upregulated, respectively; however, SMARCA2, PPP3CB, and RAB5C were not detected. Pathway enrichment analysis for the 10 genes showed that the mTOR signaling pathway was also enriched. A strong positive correlation was observed between SQSTM1 and TNFα protein levels in patients with MDD. LC3 II and SQSTM1 protein levels were increased in the CUMS rat model; however, p-mTOR protein levels were decreased. The sucrose preference values decreased in the CUMS rat model. Conclusions We identified 247 DEGs and constructed an MDD-specific network; thereafter, 10 hub genes were selected for further analysis. Our results provide novel insights into the pathogenesis of MDD. Moreover, SQSTM1, which is related to autophagy and inflammatory reactions, may play a key role in MDD. SQSTM1 may be used as a promising therapeutic target in MDD; additionally, more molecular mechanisms have been suggested that should be focused on in future in vivo and in vitro studies.
Therapeutic Effect of Matrine on Collagen-Induced Arthritis Rats and Its Regulatory Effect on RANKL and OPG Expression

Objective To investigate the effect of matrine on rats with collagen-induced arthritis (CIA) and its regulatory effect on receptor activator of nuclear factor-κB ligand (RANKL) and osteoprotegerin (OPG) expression. Methods Wistar rats (n = 6) and CIA rats (n = 30) were randomly divided into six groups: healthy, CIA control, low/medium/high matrine (25, 50, or 100 mg/kg, once per day for six weeks), and methotrexate (MTX) (2 mg/kg, once per week for six weeks). The degree of joint damage was evaluated by X-ray and HE staining. Bone marrow suppression was assessed by routine blood analysis. In addition, the levels of serum RANKL and OPG in the rats were measured by ELISA. Results The level of joint swelling and degree of joint damage assessed by ankle swelling measurements, AI score, X-ray, and HE staining were alleviated in the CIA rats treated with MTX or different doses of matrine. Furthermore, no obvious inhibitory effect was observed on the bone marrow of the CIA rats, regardless of the dose of matrine or treatment with 2 mg/kg MTX (P > 0.05). The levels of OPG in serum and the ratio of OPG/RANKL were higher, and RANKL expression was lower in the low/medium/high matrine group compared with that of the CIA control group. The serum levels of OPG and OPG/RANKL ratio increased with the matrine dose, while the opposite was observed for RANKL expression. Conclusion Matrine treatment was associated with a lower degree of bone destruction, increased OPG expression and OPG/RANKL ratio, and decreased RANKL expression in CIA rats. Thus, matrine may represent a novel drug candidate for the treatment of RA.
“If I’ve got latent TB, I would like to get rid of it”: Derivation of the CARD (Constraints, Actions, Risks, and Desires) Framework informed by South African healthcare worker perspectives on latent tuberculosis treatment

Background Healthcare workers (HWs) have at least twice the risk of tuberculosis (TB) compared to the general population. There is growing emphasis on latent TB infection (LTBI) in high-risk populations. Yet we know little about HWs’ perspectives of LTBI testing and treatment to inform implementation in high-incidence settings. We developed a qualitative networked approach to analyze HWs’ perspectives on LTBI testing and treatment. Methods We conducted 22 in-depth interviews with nurse and physician stakeholders, who had been recruited as part of a larger study evaluating TB transmission risk in HWs at Tygerberg Hospital, Cape Town, South Africa. We performed open coding to identify emergent themes and selective coding to identify relevant text citations. We used thematic analysis to inductively derive the CARD (Constraints, Actions, Risks, Desires) framework. Results All HWs desired to avoid developing TB but few felt this was actionable. Despite LTBI knowledge gaps, safety and cost concerns, most HWs reported hypothetical willingness to take LTBI treatment. The CARD framework showed that desire and action related to LTBI testing and treatment was clearly framed by the interactions between constraints, administrative action, and risk. The surprise HWs described on receiving a negative LTBI (Quantiferon-Plus) result suggests LTBI testing may recalibrate HWs’ perceptions regarding the futility of actions to reduce their TB risk. Conclusions LTBI testing and treatment are acceptable to HWs and could counteract the perceived inevitability of occupational TB infection that currently may limit risk reduction action. This should be coupled with administrative leadership and infrastructural support. The CARD analytic framework is a helpful tool for implementation scientists to understand current practices within complex health systems. Application of CARD could facilitate the development of contextually-relevant interventions to address important public health problems such as occupational TB.
Bioinformatic Analysis for Potential Biomarkers and Therapeutic Targets of T2DM-related MI

Background Type 2 diabetes mellitus (T2DM), a major risk factor of coronary heart disease, is associated with an approximately twofold increase in the risk of myocardial infarction (MI). We studied co-expressed genes to demonstrate relationships between DM and MI and revealed the potential biomarkers and therapeutic targets of T2DM-related MI. Methods DM and MI-related differentially expressed genes (DEGs) were identified by bioinformatic analysis, Gene Expression Omnibus (GEO) datasets GSE42148 and GSE61144 of MI patients, and the normal control and GSE26168 and GSE15932 of DM patients and normal controls, respectively. Further target prediction and network analysis method were used to detect protein-protein interaction (PPI) networks, gene ontology (GO) terms, and pathway enrichment of DEGs. Co-expressed DEGs of T2DM-related MI were analyzed as well. Results We identified 210 upregulated and 127 downregulated DEGs in T2DM, as well as 264 upregulated and 242 downregulated DEGs in MI. Eighteen upregulated and four downregulated DEGs were identified as co-DEGs of T2DM and MI. Functional analysis revealed that T2DM-related DEGs were mostly enriched in the viral process and ubiquitin-mediated proteolysis, while MI-related DEGs were mostly enriched in protein phosphorylation and TNF signaling pathway. MPO, MMP9, CAMP, LTF, AZU1, DEFA4, STAT3, and PECAM1 were recognized as the hub genes of the co-DEGs with acceptable diagnostic values in T2DM and MI datasets. Adenosine receptor agonist IB-MECA was predicted to be a potential drug for T2DM-related MI with the highest CMap connectivity score. Conclusion Our study identified that the co-DEGs of MPO, MMP9, CAMP, LTF, AZU1, DEFA4, STAT3, and PECAM1 are significantly associated with novel biomarkers involved in T2DM-related MI. However, more experimental research and clinical trials are demanded to verify our results.
Soft robotic manipulator for intraoperative MRI-guided transoral laser microsurgery

A compact and dexterous magnetic resonance (MR)–safe soft robot enables MR imaging–guided transoral laser microsurgery. Magnetic resonance (MR) imaging (MRI) provides compelling features for the guidance of interventional procedures, including high-contrast soft tissue imaging, detailed visualization of physiological changes, and thermometry. Laser-based tumor ablation stands to benefit greatly from MRI guidance because 3D resection margins alongside thermal distributions can be evaluated in real time to protect critical structures while ensuring adequate resection margins. However, few studies have investigated the use of projection-based lasers like those for transoral laser microsurgery, potentially because dexterous laser steering is required at the ablation site, raising substantial challenges in the confined MRI bore and its strong magnetic field. Here, we propose an MR-safe soft robotic system for MRI-guided transoral laser microsurgery. Owing to its miniature size (Ø12 × 100 mm), inherent compliance, and five degrees of freedom, the soft robot ensures zero electromagnetic interference with MRI and enables safe and dexterous operation within the confined oral and pharyngeal cavities. The laser manipulator is rapidly fabricated with hybrid soft and hard structures and is powered by microvolume (<0.004 milliter) fluid flow to enable laser steering with enhanced stiffness and lowered hysteresis. A learning-based controller accommodates the inherent nonlinear robot actuation, which was validated with laser path–following tests. Submillimeter laser steering accuracy was demonstrated with a mean error < 0.20 mm. MRI compatibility testing demonstrated zero observable image artifacts during robot operation. Ex vivo tissue ablation and a cadaveric head-and-neck trial were carried out under MRI, where we employed MR thermometry to monitor the tissue ablation margin and thermal diffusion intraoperatively.
Teleoncology for Veterans: High Patient Satisfaction Coupled With Positive Financial and Environmental Impacts

PURPOSE: There was rapid adoption of teleoncology care in the Veterans Health Administration during the COVID-19 pandemic. One third of 9 million Veterans Health Administration enrolled Veterans live in rural areas. Although digital solutions can expand capacity, enhance care access, and reduce financial burden, they may also exacerbate rural-urban health disparities. Careful evaluation of patients' perceptions and policy tradeoffs are necessary to optimize teleoncology postpandemic. METHODS: Patients with ≥ 1 teleoncology visit with medical, surgical, or radiation oncology between March 2020 and June 2020 were identified retrospectively. Validated, Likert-type survey assessing patient satisfaction was developed. Follow-up survey was conducted on patients with ≥ 1 teleoncology visit from August 2020 to January 2021. Travel distance, time, cost, and carbon dioxide emissions were calculated based on zip codes. RESULTS: A hundred surveys were completed (response rate, 62%). Patients overall were satisfied with teleoncology (83% Agree or Strongly Agree) but felt less satisfied than in-person visits (47% Agree or Strongly Agree). Audiovisual component improved patient perception of involvement in care, ability to self-manage health or medical needs, and comparability to in-person visits. Follow-up survey demonstrated similar satisfaction. Total travel-related savings are as follows: 86,470 miles, 84,374 minutes, $49,720 US dollars, and 35.5 metric tons of carbon dioxide. CONCLUSION: Veterans are broadly satisfied with teleoncology. Audiovisual capabilities are critical to satisfaction. This is challenging for rural populations with lack of technology access. Patients experienced financial and time savings, and society benefitted from reduced carbon emissions. Continued optimization is needed to enhance patient experience and address secondary effects. Teleoncology provides high patient satisfaction plus positive financial and environmental impacts
Indomethacin has no effect on trigeminally provoked parasympathetic output

Background Unlike other non-steroidal anti-inflammatory drugs, indomethacin has been shown to be highly effective in two forms of trigeminal autonomic cephalalgias, hemicrania continua and paroxysmal hemicrania and in some forms of idiopathic stabbing headaches. This specificity is unique in the headache field. Previous findings suggest the involvement of the trigeminal autonomic reflex to play an important role in the pathophysiology of these diseases. Methods 22 healthy participants were enrolled in a double-blind, three-day within-subject design. The participants received indomethacin, ibuprofen or placebo in a randomized order. After an incubation period of 65 min the baseline lacrimation and the lacrimation during intranasal stimulation evoked by kinetic oscillation stimulation were assessed using Schirmer II lacrimation tests. The lacrimation difference in mm was calculated and compared in a repeated measures ANOVA. Results No significant differences were found between the three conditions. Conclusion In our study, neither indomethacin nor ibuprofen had an inhibitory effect on the trigeminal autonomic reflex. We suggest that blocking this reflex may not be the treatment mechanism of indomethacin.
Real‐world outcomes of anti‐VEGF therapy in treatment‐naïve neovascular age‐related macular degeneration diagnosed on OCT angiography: the REVEAL study

To compare the 12 months visual and anatomical outcomes of treatment‐naïve neovascular age‐related macular degeneration (nAMD) patients diagnosed by optical coherence tomography angiography (OCT‐A) compared with fluorescein angiography (FA)/indocyanine green angiography (ICGA), after anti‐VEGF treatment in a real‐world setting.
Improving the Use of Deictic Verbs in Children with Autism Spectrum Disorder

ABSTRACT Background: Children with autism spectrum disorder (ASD) show difficulty in comprehension and production of the deictic verbs “come/go. ” Objective: To examine whether introducing conditions related to daily conversations into training would improve the use of deictic verbs. Methods: Six Japanese children with ASD participated. We set up multiple scenes where the questioner presented the sentence using “come/go” with/without deictic gestures, and children with ASD replied with “come/go. ” The conditions such as spatial relations between the two parties (face-to-face or side-by-side) and presentations of the gestures (moving one’s arm toward or away from the body or moving one’s upper body forward/backward) were introduced. Results: The appropriate use of deictic verbs during training and in daily life situations among children with ASD increased. Conclusions: Training children with ASD to look in the direction indicated by the questioner and to synchronize their bodies with the questioner’s movements promotes their acquisition of deictic verbs.
Astaxanthin Induces the Expression of CatSper1 Gene and Protects Sperms in Toxicity Induced by Cadmium in Mice

Abstract Cadmium (Cd) as a heavy metal damages testis and decreases fertility, however, antioxidants can improve sperm parameters and decrease male infertility. In this study we investigated the effect of astaxanthin (AST) on sperm parameters, expression levels of CatSper1 and CatSper2 genes in presence of Cd in mice. Thirty adults’ mice were divided into 4 groups, sham group received olive oil and saline (olive oil is the solvent of AST and saline is the solvent of Cd), Cd group received 1 mg/kg Cdcl2, a group received 10 mg/kg AST and 1 mg/kg Cdcl2 and a group received 10 mg/kg AST. The treatments were done intraperitoneally for 14 days. After 14 days sperm parameters were analyzed. Malondialdehyde level, catalase enzyme activity, the alteration of CatSper1 and CatSper2 genes expression were measured in testis. Results showed that Sperm count, viability, CatSper1 gene expression and catalase activity significantly decreased by Cd compared to sham group. Cd significantly increased sperm DNA fragmentation (SDF), abnormal sperm morphology and malondialdehyd level compared to sham group. AST significantly increased sperm count, viability and CatSper1 gene expression and decreased SDF and abnormal sperm in comparison with Cd group. AST protected testis and decreased oxidative stress induced by Cd. Our findings indicated that AST could protect sperm DNA, enhanced CatSper1 gene expression and sperm quality in presence of Cd. No significant differences were found in CatSper2 expression among treatments. Therefore, AST as a strong antioxidant can help to protect the potential of fertility against Cd toxicity.
A phase I trial of inotuzumab ozogamicin in combination with temsirolimus in patients with relapsed or refractory CD22-positive B-cell non-Hodgkin lymphomas

Abstract This phase I trial evaluated the safety, tolerability, and preliminary activity of inotuzumab ozogamicin in combination with temsirolimus in patients with relapsed/refractory CD22 positive B-cell non-Hodgkin lymphomas. Nineteen patients received at least one dose of both study drugs. Dose-limiting toxicities consisted of thrombocytopenia, hypertriglyceridemia, oral mucositis, clinical deterioration, and the inability to receive at least three doses of temsirolimus during cycle 1. The most common grade ≥3 treatment-related adverse events were thrombocytopenia (n = 8), neutropenia (n = 5), and two patients each hyperphosphatemia, lymphopenia, and hypertriglyceridemia. The recommended phase II dose was inotuzumab ozogamicin 0.8 mg/m2 on day 1 in combination with temsirolimus 10 mg on days 8, 15, and 22 every 28 days. Among 18 patients evaluable, seven (39%) with follicular lymphoma had a partial remission. This drug combination is not possible within a therapeutically useful range of doses due to toxicities. Antitumor activity was observed in heavily pretreated patients (ClinicalTrials.gov, Identifier NCT01535989).
Father-child dyads exhibit unique inter-subject synchronisation during co-viewing of animation video stimuli

Inter-subject synchronisation reflects the entrainment of two individuals to each other’s brain signals during passive joint tasks. Within the parent-child dyad, the temporal coordination of signals indicates an attunement to each other’s emotional states. Despite the ubiquity with which parents and their children watch screen media together, no study has investigated intersubject synchronisation in father-child dyads during such a co-viewing activity. The present study examined whether father-child dyads would exhibit unique inter-subject synchronisation during co-viewing of narrative visual scenes that is unique to the dyad and hence would not be observed in control dyads (i.e. randomly paired signals). Hyperscanning fNIRS was used to record the prefrontal cortex (PFC) signals of 29 fathers and their preschool-aged children (11 girls, 18 boys) as each pair engaged in a typical activity of watching children’s shows together. Three 1-min video clips from “Brave”, “Peppa Pig” and “The Incredibles” were presented to each dyad and children’s ratings of video positivity and familiarity were obtained afterwards. PFC activity was analysed according to four clusters: medial left, medial right, frontal left and frontal right clusters. Results from synchrony analyses demonstrated that true father-child dyads showed significantly greater inter-subject synchronisation than control dyads, especially in the medial left cluster during the emotionally arousing conflict scene. Dyads with older fathers displayed less synchrony and older fathers, compared to younger ones, were also found to exhibit greater activity in the frontal right cluster. These findings point to a unique inter-subject synchronisation that exists in father-child relationships during shared co-viewing of narrative scenes which could be potentially modulated by parental age.
Reduced knee extensor torque production at low to moderate velocities in postmenopausal women with knee osteoarthritis

This study aimed to determine deficits in knee extensor muscle function through the torque‐time and torque‐velocity relationships and whether these deficits are associated with reduced functional performance in postmenopausal women with knee osteoarthritis (KOA). A clinical sample of postmenopausal women with established KOA (n = 18, ≥55 years) was compared to an age‐matched healthy control sample (CON) (n = 26). The deficits in different parameters of the knee extensor torque‐time (maximal isometric torque and rate of torque development) and torque‐velocity relationship (maximum muscle power, maximal velocity and torque at 0–500°·s−1) were assessed through a protocol consisting of isometric, isotonic and isokinetic tests. Functional performance was evaluated with sit‐to‐stand and stair‐climbing tasks using a sensor‐based technology (ie, time‐ and power‐based outcomes). Postmenopausal women with KOA showed reduced maximal isometric torque (Hedge's g effect size (g) = 1.05, p = 0.001) and rate of torque development (g = 0.77‒1.17, all p ≤ 0.02), combined with impaired torque production at slow to moderate velocities (g = 0.92‒1.70, p ≤ 0.004), but not at high or maximal velocities (g = 0.16, p > 0.05). KOA were slower (g = 0.81‒0.92, p ≤ 0.011) and less powerful (g = 1.11‒1.29, p ≤ 0.001) during functional tasks. Additionally, knee extensor deficits were moderately associated with power deficits in stair climbing (r = 0.492‒0.659). To conclude, knee extensor muscle weakness was presented in postmenopausal women with KOA, not only as limited maximal and rapid torque development during isometric contractions, but also dynamically at low to moderate velocities. These deficits were related to impaired functional performance. The assessment of knee extensor muscle weakness through the torque‐time and torque‐velocity relationships might enable individual targets for tailored exercise interventions in KOA.
Molecular mimicry between SARS‐CoV‐2 and the female reproductive system

Oogenesis, the process of egg production by the ovary, involves a complex differentiation program leading to the production of functional oocytes. This process comprises a sequential pathway of steps that are finely regulated. The question related to SARS‐CoV‐2 infection and fertility has been evoked for several reasons, including the mechanism of molecular mimicry, which may contribute to female infertility by leading to the generation of deleterious autoantibodies, possibly contributing to the onset of an autoimmune disease in infected patients.