Miracle-dz/UniFAR-FTUs huggingface dataset:
Insight into Viral Hijacking of CRL4 Ubiquitin Ligase through Structural Analysis of the pUL145-DDB1 Complex

Many different viruses modulate the protein machinery required for ubiquitination to enhance viral fitness. Specifically, several viruses hijack the cullin-RING ligase CRL4DDB1 to degrade host resistance factors. ABSTRACT Viruses evolve mechanisms to exploit cellular pathways that increase viral fitness, e.g., enhance viral replication or evade the host cell immune response. The ubiquitin-proteosome system, a fundamental pathway-regulating protein fate in eukaryotes, is hijacked by all seven classes of viruses. Members of the Cullin-RING family of ubiquitin (Ub) ligases are frequently co-opted by divergent viruses because they can target a broad array of substrates by forming multisubunit assemblies comprised of a variety of adapters and substrate receptors. For example, the linker subunit DDB1 in the cullin 4-RING (CRL4)-DDB1 Ub ligase (CRL4DDB1) interacts with an H-box motif found in several unrelated viral proteins, including the V protein of simian virus 5 (SV5-V), the HBx protein of hepatitis B virus (HBV), and the recently identified pUL145 protein of human cytomegalovirus (HCMV). In HCMV-infected cells, pUL145 repurposes CRL4DDB1 to target STAT2, a protein vital to the antiviral immune response. However, the details of how these divergent viral sequences hijack DDB1 is not well understood. Here, we use a combination of binding assays, X-ray crystallography, alanine scanning, cell-based assays, and computational analysis to reveal that viral H-box motifs appear to bind to DDB1 with a higher affinity than the H-box motifs from host proteins DCAF1 and DDB2. This analysis reveals that viruses maintain native hot-spot residues in the H-box motif of host DCAFs and also acquire favorable interactions at neighboring residues within the H-box. Overall, these studies reveal how viruses evolve strategies to produce high-affinity binding and quality interactions with DDB1 to repurpose its Ub ligase machinery. IMPORTANCE Many different viruses modulate the protein machinery required for ubiquitination to enhance viral fitness. Specifically, several viruses hijack the cullin-RING ligase CRL4DDB1 to degrade host resistance factors. Human cytomegalovirus (HCMV) encodes pUL145 that redirects CRL4DDB1 to evade the immune system through the targeted degradation of the antiviral immune response protein STAT2. However, it is unclear why several viruses bind specific surfaces on ubiquitin ligases to repurpose their activity. We demonstrate that viruses have optimized H-box motifs that bind DDB1 with higher affinity than the H-box of native binders. For viral H-boxes, native interactions are maintained, but additional interactions that are absent in host cell H-boxes are formed, indicating that rewiring CRL4DDB1 creates a selective advantage for the virus. The DDB1-pUL145 peptide structure reveals that water-mediated interactions are critical to the higher affinity. Together, our data present an interesting example of how viral evolution can exploit a weakness in the ubiquitination machinery.
Adapt and Adjust: Doing UK-Based Ethnographic Fieldwork During the Covid-19 Pandemic

ABSTRACT The Covid-19 pandemic has required many anthropologists to do fieldwork differently: research that would otherwise have been done face-to-face has been shifted online, sometimes very quickly. When doing research with people with chronic illnesses, it is important to acknowledge both the histories of online ethnography and the way that disability studies has engaged with the internet over time. This article uses the example of my PhD fieldwork, based in Northeast England, to explore how living in an increasingly digital world may impact how medical anthropologists could, and perhaps should, do ethnography.
Superior Hypogastric Plexus Block for Pain Management Post-Hysterectomy: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

Abstract We aimed to evaluate the efficacy of superior hypogastric plexus (SHP) block in pain relief among women undergoing hysterectomy. Cochrane Library, PubMed, ISI web of science, and Scopus were searched from inception to May 2021 for the available randomized clinical trials (RCTs). We included RCTs that compared SHP block (intervention group) to saline (control group) in hysterectomy. Our primary outcomes were pain scores at different time intervals using the Visual Analog Scale (VAS). Our secondary outcomes were postoperative opioid consumption within 24 hours and postoperative nausea and vomiting incidence. We extracted the available data from included studies and pooled them in a meta-analysis model using RevMan software. Four RCTs with a total number of 289 patients met our inclusion criteria. The VAS pain scores were significantly declined at post-anesthesia care unit (PACU), 2, 6, and 12 hours postoperatively among SHP block group (p < 0.05). However, no significant difference was reported in VAS pain score 1 day postoperatively between intervention and control groups. Moreover, SHP block significantly reduced the postoperative opioid consumption and incidence of nausea and vomiting (p = 0.03 & p = 0.003). In conclusion, superior hypogastric plexus block effectively reduces postoperative pain, opioid consumption, and incidence of nausea and vomiting post-hysterectomy.
Helminth-induced reprogramming of the stem cell compartment inhibits type 2 immunity

Karo-Atar et al. demonstrate direct regulation of the intestinal stem cell compartment by an enteric helminth, resulting in expansion of fetal-like stem cells and inhibition of secretory cells. They establish how a helminth parasite co-opts a tissue development program to counter type 2 immune-mediated expulsion.
Municipal amalgamations and the quality of public services: A study based on city-county mergers in China

Municipal amalgamation is one of the core policy tools for Chinese government intervention in urbanization. The city-county merger policy provides a valuable research object for examining whether government-led urban expansion improves the quality of public services. By using city panel data from 2003 to 2019, this paper examines the policy effects of city-county mergers on the quality of public services using the Propensity Score Matching-Difference-in-Differences (PSM-DID) model. The results indicate that, after controlling for other factors, city-county mergers have increased the quality of public services by 1.2%. A placebo test has validated the robustness of this positive effect. Through further tests, the paper finds that the policy has positively affected all three aspects of the quality of public services in China: education, health care, and transport infrastructure, with the greatest impact being on education. Using a case study of a city-county merger in the Fenghua District of Ningbo, this paper depicts the transmission mechanism and argues that the policy affects the quality of public services by providing institutional security (financial and administrative power) and promoting regional integration in the new city area.
Gestational exposure to silver nanoparticles enhances immune adaptation and protection against streptozotocin-induced diabetic nephropathy in mice offspring

Abstract Silver nanoparticles (AgNPs) possess unique antimicrobial properties. As a result, they are being increasingly used in a wide range of applications. Several studies have shown detrimental effects of AgNPs exposure, including inflammation, accumulation, and cellular damage to different organs. However, the effect of AgNPs exposure during gestation, a critical and susceptible period of human development, on pregnant females and its long-term effects on offspring’s health has not been studied. Therefore, we conducted a long-term study where we assessed the effect of gestational AgNPs exposure on pregnant mice and followed their offspring until the age of 12 months. Gestational exposure to AgNPs induced systemic inflammation in the pregnant mice at gestational day (GD) 18. Interestingly, developing fetuses exposed to AgNPs, showed anti-inflammatory conditions as indicated by reduced expression of inflammatory genes in fetal organs at GD 18 and reduced serum levels of TNF-α, IFN-γ, IL-17A, IL-6, and MCP-1 in AgNPs exposed pups at postnatal day (PD) 2. Surprisingly, post-weaning, AgNPs exposed offspring showed a heightened immune activation as shown by upregulation of inflammatory cytokines at PD 28, which persisted till late in life. Moreover, we observed metabolic alterations which persisted until adulthood in mice. To understand the impact of long-term immunometabolic changes on the progression of diabetes and kidney diseases under stressed conditions, we exposed offspring to streptozotocin which revealed a protective role of low-dose gestational AgNPs exposure against streptozotocin-induced diabetes and associated nephropathy.
A comprehensive model to understand and assess the motivational background of video game use: The Gaming Motivation Inventory (GMI)

Abstract Background and aims The popularity of video gaming has generated significant interest in research methods to examine motivations for gaming. Current measures of gaming motives are limited by lack of scope and/or their applicability to specific game genres only. We aimed to create a comprehensive motivation inventory applicable to any gaming genre and to evaluate its psychometric properties in a large sample of highly engaged video gamers. Methods Stage 1 of this project involved a systematic review that generated the items for the Gaming Motivation Inventory (GMI). Stages 2–4 involved an evaluation of the psychometric properties of the GMI. A sample of 14,740 video gamers (89.3% male; mean age 24.1 years) were recruited via an online survey promoted by a popular gaming magazine. Results In Stage 2, twenty-six gaming motives were identified, which clustered into six higher-order dimensions (Mastery, Immersion/Escapism, Competition, Stimulation, Social, Habit/Boredom). In Stage 3, construct validity of the six higher-order motives was assessed by associations with gaming-related, personality, and psychological variables. In Stage 4, the relationships between motives and depression symptoms and gaming disorder symptoms were explored. Although gaming motives had weak associations with gaming genres, they were moderately related to variables such as competitiveness, sociability, and positive and negative affect. Gaming disorder symptoms were directly predicted by depression symptoms and indirectly via Immersion/Escapism, Habit/Boredom, and Competition motives. Discussion and conclusions These findings support the notion that motives are one of the primary causes of gaming behavior and play an important role in predicting its problematic nature. The GMI is a psychometrically valid tool that will be useful for gaining insights into factors underlying gaming behaviors.
A Quasi Time Optimal Receding Horizon Control

This paper presents a quasi time optimal receding horizon control algorithm. The proposed algorithm generates near time optimal control when the state of the system is far from the target. When the state attains a certain neighbourhood of the aim, it begins the adaptation of the cost function. The purpose of this adaptation is to move from the time optimal control to the stabilizing control. Sufficient conditions for the stability of the closed loop system and the manner of the adaptation of the cost function have been given. Considerations are illustrated with examples. Keywords: Receding horizon control ;predictive control; nonlinear stability; optimal control.
Large time asymptotics for evolution problems: convergence to equilibrium, functional inequalities and hypocoercivity

2. The asymptotics of porous medium and fast diffusion equations will then be tackled, by the entropy/entropy production method [4], using functional inequalities of Gagliardo-Nirenberg type [5], gradient flow techniques based on mass transport [6, 12] and linearization of the entropy [3], which allow to give optimal asymptotic rates of convergence without restriction on the the exponent of the nonlinearity.
Spatiotemporal dynamics of human high gamma discriminate naturalistic behavioral states

In analyzing the neural correlates of naturalistic and unstructured behaviors, features of neural activity that are ignored in a trial-based experimental paradigm can be more fully studied and investigated. Here, we analyze neural activity from two patients using electrocorticography (ECoG) and stereo-electroencephalography (sEEG) recordings, and reveal that multiple neural signal characteristics exist that discriminate between unstructured and naturalistic behavioral states such as “engaging in dialogue” and “using electronics”. Using the high gamma amplitude as an estimate of neuronal firing rate, we demonstrate that behavioral states in a naturalistic setting are discriminable based on long-term mean shifts, variance shifts, and differences in the specific neural activity’s covariance structure. Both the rapid and slow changes in high gamma band activity separate unstructured behavioral states. We also use Gaussian process factor analysis (GPFA) to show the existence of salient spatiotemporal features with variable smoothness in time. Further, we demonstrate that both temporally smooth and stochastic spatiotemporal activity can be used to differentiate unstructured behavioral states. This is the first attempt to elucidate how different neural signal features contain information about behavioral states collected outside the conventional experimental paradigm.
Patient-Centered Pain Care Using Artificial Intelligence and Mobile Health Tools: A Randomized Comparative Effectiveness Trial.

Importance Cognitive behavioral therapy for chronic pain (CBT-CP) is a safe and effective alternative to opioid analgesics. Because CBT-CP requires multiple sessions and therapists are scarce, many patients have limited access or fail to complete treatment. Objectives To determine if a CBT-CP program that personalizes patient treatment using reinforcement learning, a field of artificial intelligence (AI), and interactive voice response (IVR) calls is noninferior to standard telephone CBT-CP and saves therapist time. Design, Setting, and Participants This was a randomized noninferiority, comparative effectiveness trial including 278 patients with chronic back pain from the Department of Veterans Affairs health system (recruitment and data collection from July 11, 2017-April 9, 2020). More patients were randomized to the AI-CBT-CP group than to the control (1.4:1) to maximize the system's ability to learn from patient interactions. Interventions All patients received 10 weeks of CBT-CP. For the AI-CBT-CP group, patient feedback via daily IVR calls was used by the AI engine to make weekly recommendations for either a 45-minute or 15-minute therapist-delivered telephone session or an individualized IVR-delivered therapist message. Patients in the comparison group were offered 10 therapist-delivered telephone CBT-CP sessions (45 minutes/session). Main Outcomes and Measures The primary outcome was the Roland Morris Disability Questionnaire (RMDQ; range 0-24), measured at 3 months (primary end point) and 6 months. Secondary outcomes included pain intensity and pain interference. Consensus guidelines were used to identify clinically meaningful improvements for responder analyses (eg, a 30% improvement in RMDQ scores and pain intensity). Data analyses were performed from April 2021 to May 2022. Results The study population included 278 patients (mean [SD] age, 63.9 [12.2] years; 248 [89.2%] men; 225 [81.8%] White individuals). The 3-month mean RMDQ score difference between AI-CBT-CP and standard CBT-CP was -0.72 points (95% CI, -2.06 to 0.62) and the 6-month difference was -1.24 (95% CI, -2.48 to 0); noninferiority criterion were met at both the 3- and 6-month end points (P < .001 for both). A greater proportion of patients receiving AI-CBT-CP had clinically meaningful improvements at 6 months as indicated by RMDQ (37% vs 19%; P = .01) and pain intensity scores (29% vs 17%; P = .03). There were no significant differences in secondary outcomes. Pain therapy using AI-CBT-CP required less than half of the therapist time as standard CBT-CP. Conclusions and Relevance The findings of this randomized comparative effectiveness trial indicated that AI-CBT-CP was noninferior to therapist-delivered telephone CBT-CP and required substantially less therapist time. Interventions like AI-CBT-CP could allow many more patients to be served effectively by CBT-CP programs using the same number of therapists. Trial Registration ClinicalTrials.gov Identifier: NCT02464449.
‘Poppers Maculopathy’ and the adverse ophthalmic outcomes from the recreational use of alkyl nitrate inhalants: a systematic review

ABSTRACT Objective The aim of this systematic review and meta-analysis was to provide an overview of reported cases of poppers maculopathy and a statistical analysis of the clinical presentations, anatomical changes and treatment and follow-up of the rare disease. Methods A systematic search of CINAHL, Embase and PubMed databases was conducted, including a search of the grey literature. Data were pooled to provide a summary of the clinical characteristics and outcomes of poppers maculopathy. Studies were critically appraised using the Joanna Briggs Institute or the Authority, Accuracy, Coverage, Objectivity, Date, Significance checklists. Results Of the 493 articles obtained, 32 were included, consisting of 113 participants with a mean age of 40.2. Most patients were male with bilateral maculopathy and presented with either vision loss or a visual disturbance. Cessation of popper use was the most common form of management prescribed. The mean VA at baseline was 0.22 (logMAR units). For those followed-up, the mean VA significantly improved from 0.24 to 0.11 (Z = −5.800, p = <0.001). Bilateral yellow foveal spots were viewed on fundoscopy in 53 patients, and a sub-foveal disturbance of the ellipsoid layer was reported on spectral domain optical coherence tomography in 89 patients. By 6 months, SD-OCT anatomical changes mostly improved or resolved. Conclusion Recreational users of poppers who develop maculopathy generally present with vision loss or a visual disturbance secondary to foveal disruption. Patients have a good visual prognosis, with cessation of poppers potentially having a role in improved outcomes. With the high prevalence of use among gay and bisexual men, awareness of related maculopathy and presenting symptoms by clinicians is important to mitigate side effects.
Contributions of von Willebrand factor to clinical severity of sickle cell disease: a systematic review and metanalysis

ABSTRACT Aim To evaluate the contributions of VWF to the clinical manifestation and severity of SCD Design A systematic review of peer-reviewed articles published in English. The review was carried out in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses checklist. Methods The data sources for the review included MEDLINE, PubMed, CINAHL, and Academic Search Complete. Articles that applied a quantitative approach to the investigation of the relationship of vWF with clinical manifestations and severity indices were included. The risk of bias assessment was carried out with a mixed-method appraisal tool. We computed I 2 to estimate the degree of heterogeneity. Result There was a significantly higher level of VWF in SCD than in the control (d = 2.7, Z = 4.865, P < 0.001, I 2 = 96.41%). Significant positive correlations were obtained for the relationship of VWF with vasoocclusive crisis (r= 0.277, Z= 5.077, P < 0.001, 1 2 =15.62), rate of hemolysis (r=0.441; Z= 4.440, I 2 = <1%), extracellular haemoglobin (r=-0.397, Z=-4.155, I 2 =<1%) and CRP (r = 0.331, Z = 4.566, P < 0.001, I 2 < 1%). The VWF is important in determining the clinical severity of sickle cell disease, which constitutes a putative therapeutic target. More work is required to understand the causal direction underlying the association between VWF levels and the clinical severity of sickle cell disease and the potential role that VWF plays in the clinical manifestations of sickle cell disease. Protocol registration The protocol was registered with PROSPERO (CRD42021262625).
Biomarkers of endothelial cell dysfunction persist beyond resuscitation in patients with hemorrhagic shock

In a prospective observational study of severe trauma/hemorrhagic shock patients, markers of endothelial dysfunction/activation remained high through 24-hours post resuscitation and achieving hemostasis. Admission Syndecan-1 level was the strongest predictor of clinical outcomes. BACKGROUND It has been shown that microRNA-19b (miR-19b) binds to and degrades syndecan-1 after hemorrhagic shock (HS) and contributes to endothelial dysfunction in vitro and in vivo. The objective of the current study was to assess longitudinal changes in miR-19b and syndecan-1 in HS patients. METHODS Blood samples from HS patients (blood pressure <90 mm Hg and ≥2 U blood) were collected upon admission, completion of hemostasis, and after 24 hours for miR-19b (quantitative reverse transcription PCR) and syndecan-1 (enzyme-linked immunosorbent assay) and compared with controls and minimally injured (Injury Severity Score, ≤9). Inflammatory cytokines were measured (Luminex [Thermo Fisher, Waltham, MA]). Correlations between syndecan-1, miR-19b, inflammatory markers, and patient outcomes were performed. Logistic regression models were developed for outcomes. RESULTS Thirty-four HS patients were studied: age, 46 (19–89) years; male, 82%; penetrating, 35%; Injury Severity Score, 24 ± 10; and blood products at 24 hours, 21 ± 19 U. MicroRNA-19b was increased upon arrival and further increased over time: 4.6 → 6.7 → 24.1-fold change compared with 0.1 and 1.2 for minimally injured patients and controls, respectively. Syndecan-1 was increased to 42.6 → 50 → 51.5 ng/mL over time compared with 14.7 and 23.5 for minimally injured and controls, respectively. Values for both biomarkers remained significantly increased through 24 hours and were associated with a persistent increase in inflammatory cytokines. Admission syndecan-1 significantly predicted mortality, coagulopathy, and massive transfusion. CONCLUSION We have shown for the first time that miR-19b and syndecan-1 were biomarkers for endothelial dysfunction independent of resuscitation. MicroRNA-19b did not demonstrate a strong correlation with syndecan-1 nor outcomes. Admission syndecan-1, however, remains a strong prognostic marker, but its elevation over time suggests a versatile role following HS that requires further investigation. LEVEL OF EVIDENCE Prognostic/Epidemiological; Level II.
A portrait drawing of the 17th century Korean scholar based on craniofacial reconstruction

As a technique mainly hiring in forensic investigation field to identify the descents, craniofacial reconstruction (CFR) is also used in archaeology to create the faces from ancient or medieval human remains, when there is little information about his/her appearance. Eung-Cheok Ko (1531–1605) was a writer and scholar in the mid Joseon period. In January of 2019, His mummified body was found at Gumi, Kyeonsangbuk-do, Korea. The remains were anthropologically examined, and archaeological CFR was also requested for this case. This report reveals the case’s facial reconstruction process and his portrait that is drawn based on the 3-dimensional CFR result.