Miracle-dz/UniFAR-FTUs huggingface dataset:
Dynamic subcellular compartmentalization ensures fidelity of piRNA biogenesis in silkworms

PIWI‐interacting RNAs (piRNAs) guide PIWI proteins to silence transposable elements and safeguard fertility in germ cells. Many protein factors required for piRNA biogenesis localize to perinuclear ribonucleoprotein (RNP) condensates named nuage, where target silencing and piRNA amplification are thought to occur. In mice, some of the piRNA factors are found in discrete cytoplasmic foci called processing bodies (P‐bodies). However, the dynamics and biological significance of such compartmentalization of the piRNA pathway remain unclear. Here, by analyzing the subcellular localization of functional mutants of piRNA factors, we show that piRNA factors are actively compartmentalized into nuage and P‐bodies in silkworm cells. Proper demixing of nuage and P‐bodies requires target cleavage by the PIWI protein Siwi and ATP hydrolysis by the DEAD‐box helicase BmVasa, disruption of which leads to promiscuous overproduction of piRNAs deriving from non‐transposable elements. Our study highlights a role of dynamic subcellular compartmentalization in ensuring the fidelity of piRNA biogenesis.
Autistic traits as a potential confounding factor in the relationship between schizotypy and conspiracy beliefs

ABSTRACT Background Conspiracy Theories (CT) are complex belief systems that view the world as being manipulated by multiple actors collaborating in the pursuit of malevolent goals. Although culture, education and sociological factors have been implicated in their development, psychological factors are recognized as important. Certain individual differences, including schizotypy and cognitive processing style, have been shown to make some individuals susceptible to CTs. However, the finding that schizotypy often co-occurs with autism spectrum disorder raises a question as to the relative and potentially confounding role of autistic traits in increasing vulnerability to CT beliefs. Method A total of 508 adults were recruited from an international online panel. The study included measures of conspiracy beliefs, schizotypy and autistic traits as well as measures of information searching and cognitive style. Results The results confirmed that both autistic and schizotypy traits were positively associated with CT beliefs, but that schizotypy traits were the strongest predictor. Exploratory analyses of cognitive style measures indicated potential avenues for further investigation in relation in differences in cognitive processes that might underlie the development of CTs for in people with autistic traits as opposed to schizotypal traits. Limitations The study was based on a self-report methodology and did not utilise a clinical sample. Conclusion Both schizotypal and autistic traits are reliable predictors of conspiracy beliefs, but schizotypy appears to be the stronger predictor and that autistic traits are not a strong confounding factor in this relationship. However, autistic traits may pose an additional risk factor for CT beliefs.
The Effect of Cochlear Implantation on Tinnitus and Quality of Life: A Systematic Review and Meta-analysis

Supplemental Digital Content is available in the text Objective: To ascertain the effect of cochlear implantation (CI) on tinnitus and quality of life. Databases Sources: PubMed, Scopus, Web of Science, and Cochrane Library were searched through August 21, 2020. Search strategies used a combination of subject headings (e.g., MeSH in PubMed) and keywords for the following two concepts: cochlear implantation and tinnitus. Study Selection: English articles reporting on pre-intervention tinnitus-related patient-reported outcome measures (e.g., Tinnitus Handicap Inventory [THI], Tinnitus Questionnaire [TQ], Visual Analogue Scale [VAS] for loudness) and quality of life measures (e.g., Nijmegen Cochlear Implantation Questionnaire [NCIQ] and Hospital Anxiety and Depression Scale [HADS]) for CI recipients were included. Data Extraction: Demographics, baseline, and follow-up data. Data Synthesis: Total of 27 articles reporting on 1,285 patients (mean age 54.5 years, range 14–81) were included. Meta-analysis of all tinnitus-related measures demonstrated improvement following implantation, with a mean difference of −23.2 [95% CI: −28.8 to –17.7], –12.6 [95% CI: −17.5 to –7.8], and –4.5 [95% CI: −5.5 to –3.4] (p < 0.05 for all) for THI, TQ, and VAS, respectively. NCIQ increased by 12.2 points [95% CI: 8.2–16.2] (p < 0.05), indicating improved quality of life among CI recipients. Psychological comorbidities were also ameliorated, as evidenced by reductions in HADS depression (−1.7 [95% CI: −2.4 to −0.9]) and anxiety (−1.3 [95% CI: −2.1 to −0.5]) (p < 0.05 for both) scores. Conclusion: Following CI, patients reported significant improvement in tinnitus via several validated questionnaires. Additional benefits include improved quality of life and reduction in psychological comorbidities.
Facile fabrication of core/shell structured SiO2/polypyrrole nanoparticles with surface modification and their electrorheology

We synthesized conductive polypyrrole (PPy) coated silica core–shell structured nanoparticles, and investigated their electrorheological (ER) characteristics under electric fields applied when dispersed in silicone oil. Silica nanoparticle surfaces were initially modified using 3-(trimethoxysilyl)propyl methacrylate as a modifying agent to enhance the chemical affinity for more stable core–shell particle formation with PPy shells. Scanning electron microscopy and transmission electron microscopy images provided evidence of the structure and morphology of the fabricated particles. ER behavior of the obtained particles dispersed in an insulating silicone oil were observed via a controlled shear rate test using a rotational rheometer, while fibrillation of the ER fluid was observed using optical microscopy. The resulting responses show that the fluid composed of silica/PPy nanoparticles exhibits typical ER fluid behavior under an applied electric field. A CCJ model was used to explain the flow curves for overall shear rate range along with dielectric spectral measurements.
The Role of Gut Microbiota in Modulating Tumor Growth and Anticancer Agent Efficacy

An increasing number of studies have revealed an interaction between gut microbiota and tumors. The enrichment of specific bacteria strains in the intestines has been found to modulate tumor growth and influence the mechanisms of tumor treatment. Various bacteria are involved in modulating the effects of chemotherapeutic drugs currently used to treat patients with cancer, and they affect not only gastrointestinal tract tumors but also distant organ tumors. In addition, changes in the gut microbiota are known to be involved in the antitumor immune response as well as the modulation of the intestinal immune system. As a result, the gut microbiota plays an important role in modulating the efficacy of immune checkpoint inhibitors. Therefore, gut microbiota could be considered as an adjuvant treatment option with other cancer treatment or as another marker for predicting treatment response. In this review, we examine how gut microbiota affects cancer treatments.
TMEM16C is involved in thermoregulation and protects rodent pups from febrile seizures

Significance As the most common convulsive disorder in infancy and childhood, affecting 2 to 5% of American children in their first 5 y of life, febrile seizures (FSs) are associated with genetic risk factors, including the Tmem16c (Ano3) gene. Whereas central neuronal hyperexcitability has been implicated in FSs, whether FSs may result from compromised body temperature regulation is unknown. To approach this question, we developed rodent models of FSs associated with deficient thermoregulation, including conditional knockout mice with TMEM16C eliminated from a hypothalamic neuronal population important for maintaining body temperature but not from most of the cortical and hippocampal neurons and sensory neurons. Our findings raise the possibility that impaired homeostatic thermoregulation could contribute to the risk of FSs. Febrile seizures (FSs) are the most common convulsion in infancy and childhood. Considering the limitations of current treatments, it is important to examine the mechanistic cause of FSs. Prompted by a genome-wide association study identifying TMEM16C (also known as ANO3) as a risk factor of FSs, we showed previously that loss of TMEM16C function causes hippocampal neuronal hyperexcitability [Feenstra et al., Nat. Genet. 46, 1274–1282 (2014)]. Our previous study further revealed a reduction in the number of warm-sensitive neurons that increase their action potential firing rate with rising temperature of the brain region harboring these hypothalamic neurons. Whereas central neuronal hyperexcitability has been implicated in FSs, it is unclear whether the maximal temperature reached during fever or the rate of body temperature rise affects FSs. Here we report that mutant rodent pups with TMEM16C eliminated from all or a subset of their central neurons serve as FS models with deficient thermoregulation. Tmem16c knockout (KO) rat pups at postnatal day 10 (P10) are more susceptible to hyperthermia-induced seizures. Moreover, they display a more rapid rise of body temperature upon heat exposure. In addition, conditional knockout (cKO) mouse pups (P11) with TMEM16C deletion from the brain display greater susceptibility of hyperthermia-induced seizures as well as deficiency in thermoregulation. We also found similar phenotypes in P11 cKO mouse pups with TMEM16C deletion from Ptgds-expressing cells, including temperature-sensitive neurons in the preoptic area (POA) of the anterior hypothalamus, the brain region that controls body temperature. These findings suggest that homeostatic thermoregulation plays an important role in FSs.
Using heterogeneity in disease to understand the relationship between health and personality

ABSTRACT The aim of this study was to compare the relationship between two health outcomes (pain and self-reported health) and personality while accounting for heterogeneity in arthritic disease. Traditionally health research has treated patients’ disease experiences as homogeneous but stratified medicine suggests that doing so might over-generalise findings and miss important effects. We present a longitudinal analysis over 14 years, on a subsample of 443 arthritic respondents from the English Longitudinal Study of Ageing (ELSA). Using linear regressions, we modelled how the Big Five domains of personality (wave 5) moderated the relationship between past (at wave 1) and present health (at wave 7). Then, to model heterogeneity in arthritis experience we included assignment to 4 different sub-groups based on their experience of pain progression. The results showed that modelling heterogeneity led to the identification of specific stratified effects for personality (neuroticism, agreeableness, and extraversion) not observed when these data are treated as homogenous. Higher agreeableness was associated with worse pain for those in a sub-group reporting the greatest pain, and higher extraversion was protective against pain among those whose pain improved. The results highlight the importance of modelling heterogeneity of disease.
A state-of-the-art review of the current role of cardioprotective techniques in cardiac transplantation.

OBJECTIVES METHODS The use of 'extended criteria' donor hearts and reconditioned hearts from donation after circulatory death has corresponded with an increase in primary graft dysfunction, with ischaemia-reperfusion injury being a major contributing factor in its pathogenesis. Limiting ischaemia-reperfusion injury through optimising donor heart preservation may significantly improve outcomes. We sought to review the literature to evaluate the evidence for this. RESULTS A review of the published literature was performed to assess the potential impact of organ preservation optimisation on cardiac transplantation outcomes. CONCLUSIONS Ischaemia-reperfusion injury is a major factor in myocardial injury during transplantation with multiple potential therapeutic targets. Innate survival pathways have been identified, which can be mimicked with pharmacological conditioning. Although incompletely understood, discoveries in this domain have yielded extremely encouraging results with one of the most exciting prospects being the synergistic effect of selected agents. Ex situ heart perfusion is an additional promising adjunct.
Transcranial color‐coded duplex sonography reliably identifies intracranial vasculopathy in adult patients with sickle cell disease

In order to prevent stroke, screening for disease‐related intracranial vasculopathy using Doppler ultrasound is recommended in sickle‐cell disease (SCD) children. How to screen such vasculopathy in adults remains largely unknown. The objective of this study was to assess whether transcranial color‐coded duplex sonography (TCCD) is sensitive and specific enough to identify SCD adult patients with vasculopathy, compared with magnetic resonance angiography (MRA). Sickle cell disease adults followed in referral centers at high risk of vasculopathy were included in this study. Transcranial color‐coded duplex sonography examination and 3‐D time‐of‐flight MRA were performed on the same day. On MRA, vasculopathy was defined by the presence of at least one ≥50% arterial stenosis. On TCCD, vasculopathy was defined by a time‐averaged mean of the maximum velocity (TAMx) stenotic/prestenotic ratio ≥ 3, an occlusion, or a Moyamoya pattern. Vasculopathy was also considered as present when TAMx ratio could not be calculated because of the presence of severe cervical lesions. Among 80 included patients, quality of MRA was insufficient in three patients. Among the 38 patients with vasculopathy on MRA, 37 had a vasculopathy according to TCCD criteria: TAMx ratio ≥ 3 or intracranial occlusion in 33 patients and cervical lesion in four patients. A Moyamoya pattern was identified with TCCD in all 17 patients with Moyamoya on MRA. Sensitivity and specificity of TCCD to identify patients with ≥50% vasculopathy on MRA were (n = 37/38) 97% and (n = 28/34) 82%, respectively. Positive and negative predictive values were (n = 37/43) 86% and (n = 28/29) 97%, respectively. Note, TCCD may be used to identify SCD adult patients with vasculopathy.
Promoting the Mental Health of University Students in China: Protocol for Contextual Assessment to Inform Intervention Design and Adaptation

Background Chinese students are extremely vulnerable to developing mental illness. The stigma associated with mental illness presents a barrier to seeking help for their mental health. Objective The Linking Hearts—Linking Youth and ‘Xin’ (hearts) project is an implementation science project that seeks to reduce mental illness stigma and promote the mental health of university students in Jinan, China. The Linking Hearts project consists of 3 components. In this paper, we outline the protocol for the first component, that is, the contextual assessment and analysis of the mental health needs of university students as the first step to inform the adaptation of an evidence-based intervention to be implemented in Jinan, China. Methods Six local universities will participate in the Linking Hearts project. A total of 100 students from each university (n=600) will engage in the contextual assessment through self-report surveys on depression, anxiety, stress, mental health knowledge, and mental health stigma. Quantitative data will be analyzed using several descriptive and inferential analyses via SPSS. A small number of participants (144 students and 144 service providers) will also be engaged in focus groups to assess the socio-environmental contexts of university students’ health and availability of mental health resources. Qualitative data will be transcribed verbatim and NVivo will be used for data management. Social network analysis will also be performed using EgoNet. Results Linking Hearts was funded in January 2018 for 5 years. The protocol of Linking Hearts and its 3 components was approved by the research ethics boards of all participating institutions in China in November 2018. Canadian institutions that gave approval were Ryerson University (REB2018-455) in January 2019, University of Alberta (Pro00089364), York University (e2019-162) in May 2019, and University of Toronto (RIS37724) in August 2019. Data collection took place upon ethics approval and was completed in January 2020. A total of 600 students were surveyed. An additional 147 students and 138 service providers took part in focus groups. Data analysis is ongoing. Results will be published in 2021. Conclusions Findings from this contextual assessment and analysis will generate new knowledge on university students’ mental health status, mental health knowledge, and resources available for them. These findings will be used to adapt and refine the Acceptance and Commitment to Empowerment-Linking Youth N’ Xin intervention model. The results of this contextual assessment will be used to inform the adaptation and refinement of the mental health intervention to promote the mental health of Chinese university students in Jinan. International Registered Report Identifier (IRRID) RR1-10.2196/25009
Interannual variability in net ecosystem carbon production in a rain-fed maize ecosystem and its climatic and biotic controls during 2005–2018

Interannual variability (IAV) in net ecosystem carbon production (NEP) plays an important role in the processes of the carbon cycle, but the long-term trends in NEP and the climatic and biotic control of IAV in NEP still remain unclear in agroecosystems. We investigated interannual variability in NEP, expressed as annual values and anomalies, and its climatic and biotic controls using an eddy-covariance dataset for 2005–2018 for rain-fed spring maize in northeastern China. Average annual NEP was 270±31 g C m−2yr −1, with no significant changes over time. The effects on interannual variability in NEP of gross ecosystem productivity (GEP) that was mainly controlled by soil water content (SWC) and leaf area index (LAI), were more than those of respiration (RE) that was controlled by temperature and LAI. Further, maximum daily NEP (NEPmax) that was dominated by summer vapor pressure deficit explained the largest fraction of annual anomalies in NEP, followed by carbon dioxide uptake period (CUP) that was defined by the beginning date (BDOY) and the end date (EDOY) of CUP. The variability in BDOY was mainly determined by spring precipitation and the effective accumulated temperature, and the variability in EDOY was determined by autumn precipitation, SWC and LAI. NEP may decrease with declining precipitation in the future due to decreasing GEP, NEPmax, or CUP, and irrigation and residues cover may be useful in efforts to maintain current NEP levels. Our results indicate that interannual variability in NEP in agroecosystems may be more sensitive to changes in water conditions (such as precipitation, SWC and VPD) induced by climate changes, while temperature may be an important indirect factor when VPD is dominated.
Presynaptic coupling by electrical synapses coordinates a rhythmic behavior by synchronizing the activities of a neuron pair

Significance Central pattern generators produce rhythmic behaviors that occur on a variety of timescales. Here, using a simple behavioral circuit that repeats every 50 s in Caenorhabditis elegans, we show that electrical synapses composed of the gap junction protein INX-1/innexin are necessary for the precise and accurate timing of the behavioral outputs that are controlled by a biological clock. Electrical synapses do so by both promoting synchronized activation of a pair of coupled neurons in response to the signals from the clock and by inhibiting their inappropriate activation when clock signaling is low. Our findings represent one of the first examples of how the execution of a rhythmic behavior is shaped by electrical synapses through coordinating the activities of coupled neurons. Electrical synapses are specialized structures that mediate the flow of electrical currents between neurons and have well known roles in synchronizing the activities of neuronal populations, both by mediating the current transfer from more active to less active neurons and by shunting currents from active neurons to their less active neighbors. However, how these positive and negative functions of electrical synapses are coordinated to shape rhythmic synaptic outputs and behavior is not well understood. Here, using a combination of genetics, behavioral analysis, and live calcium imaging in Caenorhabditis elegans, we show that electrical synapses formed by the gap junction protein INX-1/innexin couple the presynaptic terminals of a pair of motor neurons (AVL and DVB) to synchronize their activation in response to a pacemaker signal. Live calcium imaging reveals that inx-1/innexin mutations lead to asynchronous activation of AVL and DVB, due, in part, to loss of AVL-mediated activation of DVB by the pacemaker. In addition, loss of inx-1 leads to the ectopic activation of DVB at inappropriate times during the cycle through the activation of the L-type voltage-gated calcium channel EGL-19. We propose that electrical synapses between AVL and DVB presynaptic terminals function to ensure the precise and robust execution of a specific step in a rhythmic behavior by both synchronizing the activities of presynaptic terminals in response to pacemaker signaling and by inhibiting their activation in between cycles when pacemaker signaling is low.
Prognostic biomarkers for cholangiocarcinoma (CCA): state of the art

ABSTRACT Introduction:Although advances in understanding the molecular basis of cholangiocarcinoma (CCA) have been made, surgery is the only curative therapy option and the overall prognosis of patients suffering from the disease remains poor. Therefore, estimation of prognosis based on known and novel biomarkers is essential for therapy guidance of CCA in both, curative and palliative settings. Areas covered:An extensive literature search on biomarkers for CCA with special emphasis on prognosis was performed. Based on this, prognostic biomarkers from serum, tumor tissue and other compartments that are currently in use or under evaluation for CCA were summarized in this review. Furthermore, an overview of new biomarkers was provided including those determined from extracellular vesicles (EVs), metabolites and nucleic acids. Finally, prognostic markers associated with potential new therapy options for the treatment of CCA were summed up. Expert opinion:So far, an optimal prognostic biomarker for CCA has not been described. However, based on the increasing knowledge about the molecular basis of CCA but also due to novel, innovative technologies, a plethora of novel prognostic biomarkers is currently under evaluation and will be available for CCA in future.
Controllable growth of bulk cubic-phase CH3NH3PbI3 single crystal with exciting room-temperature stability

To obtain bulk cubic CH3NH3PbI3, chlorobenzene was employed to regulate the CH3NH3PbI3 γ-butyrolactone solution with high saturated solubility at room temperature and a high yield of crystal at 60 °C. As a result, bulk cubic CH3NH3PbI3 single crystal was successfully synthesized for the first time in mixed-solvent method at 60 °C, which is a little higher than the tetragonal–cubic phase inversion temperature.