Miracle-dz/UniFAR-FTUs huggingface dataset:
SARS-CoV-2 ORF8 Protein Induces Endoplasmic Reticulum Stress-like Responses and Facilitates Virus Replication by Triggering Calnexin: an Unbiased Study

Although SARS-CoV-2 is basically regarded as a homolog of SARS-CoV, with their genomic structure and the majority of their genes being highly homologous, the ORF8 genes of SARS-CoV and SARS-CoV-2 are distinct. The SARS-CoV-2 ORF8 protein also shows little homology with other viral or host proteins and is thus regarded as a novel special virulence gene of SARS-CoV-2. ABSTRACT Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the viral pathogen responsible for the worldwide coronavirus disease 2019 (COVID-19) pandemic. The novel SARS-CoV-2 ORF8 protein is not highly homologous with known proteins, including accessory proteins of other coronaviruses. ORF8 contains a 15-amino-acid signal peptide in the N terminus that localizes the mature protein to the endoplasmic reticulum. Oligomannose-type glycosylation has been identified at the N78 site. Here, the unbiased molecular functions of ORF8 are also demonstrated. Via an immunoglobulin-like fold in a glycan-independent manner, both exogenous and endogenous ORF8 interacts with human calnexin and HSPA5. The key ORF8-binding sites of Calnexin and HSPA5 are indicated on the globular domain and the core substrate-binding domain, respectively. ORF8 induces species-dependent endoplasmic reticulum stress-like responses in human cells exclusively via the IRE1 branch, including intensive HSPA5 and PDIA4 upregulation, with increases in other stress-responding effectors, including CHOP, EDEM and DERL3. ORF8 overexpression facilitates SARS-CoV-2 replication. Both stress-like responses and viral replication induced by ORF8 have been shown to result from triggering the Calnexin switch. Thus, ORF8 serves as a key unique virulence gene of SARS-CoV-2, potentially contributing to COVID-19-specific and/or human-specific pathogenesis. IMPORTANCE Although SARS-CoV-2 is basically regarded as a homolog of SARS-CoV, with their genomic structure and the majority of their genes being highly homologous, the ORF8 genes of SARS-CoV and SARS-CoV-2 are distinct. The SARS-CoV-2 ORF8 protein also shows little homology with other viral or host proteins and is thus regarded as a novel special virulence gene of SARS-CoV-2. The molecular function of ORF8 has not been clearly known until now. Our results reveal the unbiased molecular characteristics of the SARS-CoV-2 ORF8 protein and demonstrate that it induces rapidly generated but highly controllable endoplasmic reticulum stress-like responses and facilitates virus replication by triggering Calnexin in human but not mouse cells, providing an explanation for the superficially known in vivo virulence discrepancy of ORF8 between SARS-CoV-2-infected patients and mouse.
Mechanisms of cancer cell death induction by triptolide

Drug resistance is a hot topic issue in cancer research and therapy. Although cancer therapy including radiotherapy and anti‐cancer drugs can kill malignant cells within the tumor, cancer cells can develop a wide range of mechanisms to resist the toxic effects of anti‐cancer agents. Cancer cells may provide some mechanisms to resist oxidative stress and escape from apoptosis and attack by the immune system. Furthermore, cancer cells may resist senescence, pyroptosis, ferroptosis, necroptosis, and autophagic cell death by modulating several critical genes. The development of these mechanisms leads to resistance to anti‐cancer drugs and also radiotherapy. Resistance to therapy can increase mortality and reduce survival following cancer therapy. Thus, overcoming mechanisms of resistance to cell death in malignant cells can facilitate tumor elimination and increase the efficiency of anti‐cancer therapy. Natural‐derived molecules are intriguing agents that may be suggested to be used as an adjuvant in combination with other anticancer drugs or radiotherapy to sensitize cancer cells to therapy with at least side effects. This paper aims to review the potential of triptolide for inducing various types of cell death in cancer cells. We review the induction or resistance to different cell death mechanisms such as apoptosis, autophagic cell death, senescence, pyroptosis, ferroptosis, and necrosis following the administration of triptolide. We also review the safety and future perspectives for triptolide and its derivatives in experimental and human studies. The anticancer potential of triptolide and its derivatives may make them effective adjuvants for enhancing tumor suppression in combination with anticancer therapy.
Influence of Acute Melatonin Administration on Human Physical Performance: A Systematic Review

Context: Melatonin is an ancient molecule with a wide range of functions in mammals, such as antioxidant, anti-inflammatory, and hypothermic effects among others. However, the influence of acute melatonin administration on human physical performance is debatable. Objective: To summarize available data from controlled trials about the effects of acute melatonin administration on human physical performance, especially with respect to strength, power, speed, and short- and long-term continuous exercise. Data Sources: A systematic search of the PubMed, Web of Science, Scopus, Embase, and Cochrane databases up to December 10, 2021, was conducted using specified keywords and Boolean operators (“melatonin” AND “exercise OR circuit-based exercise OR plyometric exercise OR exercise tolerance OR exercise test”). Study Selection: Only controlled studies in the English language and with humans were accepted. Study Design: Systematic review. Level of Evidence: Level 1. Data Extraction: Participants’ characteristics (sex, age, body mass, height and fat percentage), melatonin dose and administration time, and outcomes from the performance trial were extracted. Results: A total of 10 studies were identified after the screening process. Overall, melatonin did not change speed or short-term continuous exercise performances. However, in relation to strength and power, the results are debatable since 5 articles showed no difference, while another 2 pointed to a decrease in performance. In terms of performance improvement, only 1 study reported an increase in balance and another in long-term continuous exercise performance in nonathletes, with no advantage found for athletes. Conclusion: Melatonin did not cause any significant change in strength, speed, power, and short-term continuous exercise performances. In fact, it led to reduced strength and power performances in specific tests. On the other hand, melatonin seems to have improved balance and long-term continuous exercise performance, at least in nonathletes. More investigations are required to corroborate these findings.
Telerehabilitation Initiated Early in Post-Stroke Recovery: A Feasibility Study

Background Enhanced neural plasticity early after stroke suggests the potential to improve outcomes with intensive rehabilitation therapy. Most patients do not get such therapy, however, due to limited access, changing rehabilitation therapy settings, low therapy doses, and poor compliance. Objective To examine the feasibility, safety, and potential efficacy of an established telerehabilitation (TR) program after stroke initiated during admission to an inpatient rehabilitation facility (IRF) and completed in the patient’s home. Methods Participants with hemiparetic stroke admitted to an IRF received daily TR targeting arm motor function in addition to usual care. Treatment consisted of 36, 70-minute sessions (half supervised by a licensed therapist via videoconference), over a 6-week period, that included functional games, exercise videos, education, and daily assessments. Results Sixteen participants of 19 allocated completed the intervention (age 61.3 ± 9.4 years; 6 female; baseline Upper Extremity Fugl–Meyer [UEFM] score 35.9 ± 6.4 points, mean ± SD; NIHSS score 4 (3.75, 5.25), median, IQR; intervention commenced 28.3 ± 13.0 days post-stroke). Compliance was 100%, retention 84%, and patient satisfaction 93%; 2 patients developed COVID-19 and continued TR. Post-intervention UEFM improvement was 18.1 ± 10.9 points (P < .0001); Box and Blocks, 22.4 ± 9.8 blocks (P = .0001). Digital motor assessments, acquired daily in the home, were concordant with these gains. The dose of rehabilitation therapy received as usual care during this 6-week interval was 33.9 ± 20.3 hours; adding TR more than doubled this to 73.6 ± 21.8 hours (P < .0001). Patients enrolled in Philadelphia could be treated remotely by therapists in Los Angeles. Conclusions These results support feasibility, safety, and potential efficacy of providing intense TR therapy early after stroke. Clinical Trial Registration: clinicaltrials.gov; NCT04657770
Italian immunization calendar implementation: Time to optimize number of vaccination appointments?

ABSTRACT In the Italian vaccination schedule, at least six vaccination appointments are scheduled in the first year of life. This implies more discomfort for both the patient and the parents. This was particularly evident during the COVID-19 pandemic, during which several appointments were missed. A UK experience with three injectable vaccines and an oral one co-administered at the same appointment (4-in-1) at 2 and 4 months of age showed interesting results. The vaccination coverage was high, consistent with previous practice, and no relevant increase in adverse events was reported. Translating the UK experience into the Italian context would not be immediate, due to several organizational and social issues. Nevertheless, this option warrants some further considerations, which are discussed in this manuscript.
Mapping and distortions of auroral structures in the quiet magnetosphere

The objective of this report is to identify those features of commonly observed dayside auroras that can be explained easily by either of two processes: mapping distortions or distortions caused by nearby Birkeland currents. Mapping distortions in a quiet closed magnetosphere model yield very elongated arclike ionospheric images in the dayside auroral zone for a wide range of circular or elliptical tubelike equatorial sources. The length of a dayside auroral arc provides a good measure of the equatorial source dimension normal to the magnetopause. The orientation of the dayside arc provides a crude estimate of the solar magnetospheric x location of the equatorial source. Dayside arcs and Birkeland currents are found to map to both the dayside and the nightside magnetopause current layer and low latitude boundary layer. Nightside auroral arcs and Birkeland currents map to the magnetotail plasma sheet and plasma sheet boundary layer. Localized Birkeland currents produce characteristic distortions that are dependent on the current density gradient. Single and multiple linear and hooked auroral forms are easy to understand in terms of mapping distortions in a quiet magnetosphere. The shapes of bright twisted or folded auroral forms are more easily explained as distortions produced by localized Birkeland currents.more » Measurement of the size of a spiral auroral structure provides an estimate of the current magnitude. Relationships between the motion of ionospheric objects and the motion of equatorial sources are summarized by two color plates. Such motion sometimes differs markedly from what one might intuitively expect. For example, some tailward moving sources near the magnetopause can map to sunward moving ionospheric images. « less
Comparison of patients with different cervical spine bone ages before and after arch expansion treatment based on cone-beam computed tomography.

OBJECTIVE The changes of maxillary basal arch width, molar angle, palatal suture width and nasal cavity width were analyzed in patients with different cervical bone ages before and after maxillary rapid arch expansion treatment, providing more reference for orthodontic design and treatment in the future. PATIENTS AND METHODS A total of 45 patients with maxillary lateral, insufficient development that underwent arch expansion treatment in Jiaxing Second Hospital between February 2021 and February 2022 were selected for the study. Patients were retrospectively grouped based on the cervical vertebra bone age, and divided into the pre-growth (15 cases), mid-growth (15 cases) and post-growth groups (15 cases). All patients had oral cone-beam computed tomography (CBCT) and lateral cranial radiographs taken before and after the treatment. Maxillary basal arch width, palatal suture width, nasal cavity width and molar angle were measured and analyzed using paired samples t-test, ANOVA and least significant difference test (LSD-T). RESULTS The maxillary basal arch width, palatal suture width, nasal cavity width and molar angle in the three groups were significantly changed after arch expansion treatment (p<0.05). There was no statistically significant difference in all measurement indexes between patients in the pre-growth and the mid-growth groups (p>0.05), but there was statistically significant difference between patients in the pre-growth and the late-growth groups (p<0.05). There were statistically significant differences in all measurement indexes between the middle-growth and the late-growth group (p<0.05). CONCLUSIONS Rapid expansion of arch can be used to enlarge the width of palatal suture, maxillary basal arch, and nasal cavity in adolescent patients of different bone ages. With the increase of cervical bone age, the bony effect of expansion of arch gradually decreases, while the dental effect increases. Appropriate overcorrection should be made during arch expansion in late growth and excessive tooth tilt should be avoided to conceal bony width irregularities.
Human resource time commitments and associated costs of Community Caregiver outreach team operations in South Africa

Introduction In South Africa, Community Caregivers (CCGs) visit households to provide basic healthcare services including those for tuberculosis and HIV. However, CCG workloads, costs, and time burden are largely unknown. Our objective was to assess the workloads and operational costs for CCG teams operating in different settings in South Africa. Methods Between March and October 2018, we collected standardized self-reported activity time forms from 11 CCG pairs working at two public health clinics in Ekurhuleni district, South Africa. CCG workloads were assessed based on activity unit times, per-household visit time, and mean daily number of successful household visits. Using activity-based times and CCG operating cost data, we assessed CCG annual and per-household visit costs (USD 2019) from the health system perspective. Results CCGs in clinic 1 (peri-urban, 7 CCG pairs) and 2 (urban, informal settlement; 4 CCG pairs) served an area of 3.1 km2 and 0.6 km2 with 8,035 and 5,200 registered households, respectively. CCG pairs spent a median 236 minutes per day conducting field activities at clinic 1 versus 235 minutes at clinic 2. CCG pairs at clinic 1 spent 49.5% of this time at households (versus traveling), compared to 35.0% at clinic 2. On average, CCG pairs successfully visited 9.5 vs 6.7 households per day for clinics 1 and 2, respectively. At clinic 1, 2.7% of household visits were unsuccessful, versus 28.5% at clinic 2. Total annual operating costs were higher in clinic 1 ($71,780 vs $49,097) but cost per successful visit was lower ($3.58) than clinic 2 ($5.85). Conclusions CCG home visits were more frequent, successful, and less costly in clinic 1, which served a larger and more formalized settlement. The variability in workload and cost observed across pairs and clinics suggests that circumstantial factors and CCG needs must be carefully assessed for optimized CCG outreach operations.
Cancer patients’ experiences of moments of relational depth during psychological therapy: a qualitative study

Abstract Objective Research into psychological interventions for cancer patients has focused on the effectiveness of different treatment methods. Investigating common factors across treatments, such as qualities within the therapeutic relationship, has been neglected. This study explores cancer patients’ experiences of moments of profound contact and engagement with their therapist, including any perceived impact. Methods Semi-structured interviews were conducted with ten cancer patients. Eight participants reported having experienced moments of relational depth. Their transcripts were analyzed using thematic analysis. Findings Five themes were identified: “Being physically and psychically vulnerable,” “Being rescued from the waves,” “Experiencing the calm after the storm,” “More than a feeling,” and “The therapist as ‘a stranger and not a stranger’. ” Conclusion Both novice and experienced practitioners should be aware of the potential power of moments of relational depth for cancer patients: to normalize patients’ increased vulnerability and emotionality, and to manage breaks and endings with relational sensitivity.
Comparison of the Diagnostic Accuracies of Monocyte Distribution Width, Procalcitonin, and C-Reactive Protein for Sepsis: A Systematic Review and Meta-Analysis

OBJECTIVES: We performed a systemic review and meta‐analysis to evaluate the diagnostic accuracy of monocyte distribution width (MDW) and to compare with procalcitonin and C‐reactive protein (CRP), in adult patients with sepsis. DATA SOURCES: A systematic literature search was performed in PubMed, Embase, and the Cochrane Library to identify all relevant diagnostic accuracy studies published before October 1, 2022. STUDY SELECTION: Original articles reporting the diagnostic accuracy of MDW for sepsis detection with the Sepsis-2 or Sepsis-3 criteria were included. DATA EXTRACTION: Study data were abstracted by two independent reviewers using a standardized data extraction form. DATA SYNTHESIS: Eighteen studies were included in the meta‐analysis. The pooled sensitivity and specificity of MDW were 84% (95% CI [79–88%]) and 68% (95% CI [60–75%]). The estimated diagnostic odds ratio and the area under the summary receiver operating characteristic curve (SROC) were 11.11 (95% CI [7.36–16.77]) and 0.85 (95% CI [0.81–0.89]). Significant heterogeneity was observed among the included studies. Eight studies compared the diagnostic accuracies of MDW and procalcitonin, and five studies compared the diagnostic accuracies of MDW and CRP. For MDW versus procalcitonin, the area under the SROC was similar (0.88, CI = 0.84–0.93 vs 0.82, CI = 0.76–0.88). For MDW versus CRP, the area under the SROC was similar (0.88, CI = 0.83–0.93 vs 0.86, CI = 0.78–0.95). CONCLUSIONS: The results of the meta-analysis indicate that MDW is a reliable diagnostic biomarker for sepsis as procalcitonin and CRP. Further studies investigating the combination of MDW and other biomarkers are advisable to increase the accuracy in sepsis detection.
Alcohol, tobacco and drug use among adults experiencing homelessness in Accra, Ghana: A cross-sectional study of risk levels and associated factors

Background Substance use contributes to poor health and increases the risk of mortality in the homeless population. This study assessed the prevalence and risk levels of substance use and associated factors among adults experiencing homelessness in Accra, Ghana. Methods 305 adults currently experiencing sheltered and unsheltered homelessness in Accra aged ≥ 18 years were recruited. The World Health Organization’s (WHO) Alcohol, Smoking, and Substance Involvement Screening Test (ASSIST) was used to assess substance use risk levels. Association of high-risk substance use with sociodemographic, migration, homelessness, and health characteristics were assessed using logistic regression. Results Nearly three-quarters (71%, n = 216) of the sample had ever used a substance, almost all of whom engaged in ASSIST-defined moderate-risk (55%) or high-risk (40%) use. Survivors of physical or emotional violence (AOR = 3.54; 95% confidence interval [CI] 1.89–6.65, p<.001) and sexual violence (AOR = 3.94; 95%CI 1.85–8.39, p<.001) had significantly higher odds of engaging in high-risk substance use, particularly alcohol, cocaine, and cannabis. The likelihood of engaging in high-risk substance use was higher for men than women (AOR = 4.09; 95%CI 2.06–8.12, p<.001) but lower for those in the middle-income group compared to low-income (AOR = 3.94; 95%CI 1.85–8.39, p<.001). Conclusions Risky substance use was common among adults experiencing homelessness in Accra, and strongly associated with violent victimisation, gender, and income levels. The findings highlight the urgent need for effective and targeted preventive and health-risk reduction strategies to address risky substance use in the homeless population in Accra and similar cities within Ghana and sub-Sahara Africa with a high burden of homelessness.
Modelling of ultrashort laser ablation of gold films in vacuum

Based on the concept of phase explosion, an enthalpy form of the two-step heating equations is proposed to model the superheating and material ablation of metals caused by ultrashort-pulse lasers. Numerical calculation of the electron and lattice temperatures is performed for gold films heated by a sub-picosecond UV laser in vacuum. When the lattice temperature at a material point equals 0.9Ttc (Ttc denoting the thermodynamic equilibrium critical temperature), phase explosion is assumed and that material point is removed. The calculated ablation depth matches well with experimental data.
Viricidal Efficacy of a 405‐nm Environmental Decontamination System for Inactivation of Bacteriophage Phi6: Surrogate for SARS‐CoV‐2

The highly transmittable nature of SARS‐CoV‐2 has increased the necessity for novel strategies to safely decontaminate public areas. This study investigates the efficacy of a low irradiance 405‐nm light environmental decontamination system for the inactivation of bacteriophage phi6 as a surrogate for SARS‐CoV‐2. Bacteriophage phi6 was exposed to increasing doses of low irradiance (~0.5 mW cm−2) 405‐nm light while suspended in SM buffer and artificial human saliva at low (~103–4 PFU mL−1) and high (~107–8 PFU mL−1) seeding densities, to determine system efficacy for SARS‐CoV‐2 inactivation and establish the influence of biologically relevant suspension media on viral susceptibility. Complete/near‐complete (≥99.4%) inactivation was demonstrated in all cases, with significantly enhanced reductions observed in biologically relevant media (P < 0.05). Doses of 43.2 and 172.8 J cm−2 were required to achieve ~3 log10 reductions at low density, and 97.2 and 259.2 J cm−2 achieved ~6 log10 reductions at high density, in saliva and SM buffer, respectively: 2.6–4 times less dose was required when suspended in saliva compared to SM buffer. Comparative exposure to higher irradiance (~50 mW cm−2) 405‐nm light indicated that, on a per unit dose basis, 0.5 mW cm−2 treatments were capable of achieving up to 5.8 greater log10 reductions with up to 28‐fold greater germicidal efficiency than that of 50 mW cm−2 treatments. These findings establish the efficacy of low irradiance 405‐nm light systems for inactivation of a SARS‐CoV‐2 surrogate and demonstrate the significant enhancement in susceptibility when suspended in saliva, which is a major vector in COVID‐19 transmission.