Miracle-dz/UniFAR-FTUs huggingface dataset:
PB28, the Sigma-1 and Sigma-2 Receptors Modulator With Potent Anti–SARS-CoV-2 Activity: A Review About Its Pharmacological Properties and Structure Affinity Relationships

These unprecedented times have forced the scientific community to gather to face the COVID-19 pandemic. Efforts in diverse directions have been made. A multi-university team has focused on the identification of the host (human) proteins interacting with SARS-CoV-2 viral proteins, with the aim of hampering these interactions that may cause severe COVID-19 symptoms. Sigma-1 and sigma-2 receptors surprisingly belong to the “druggable” host proteins found, with the pan-sigma receptor modulator PB28 displaying the most potent anti–SARS-CoV-2 activity in in vitro assays. Being 20-fold more active than hydroxychloroquine, without cardiac side effects, PB28 is a promising antiviral candidate worthy of further investigation. Our research group developed PB28 in 1996 and have thoroughly characterized its biological properties since then. Structure–affinity relationship (SAfiR) studies at the sigma receptor subtypes were also undertaken with PB28 as the lead compound. We herein report our knowledge of PB28 to share information that may help to gain insight into the antiviral action of this compound and sigma receptors, while providing structural hints that may speed up the translation into therapeutics of this class of ligands.
Correlation Between the COVID-19 Respiratory Triage Score and SARS-COV-2 PCR Test

Background: COVID-19 clinical presentation is usually non-specific and includes commonly encountered symptoms like fever, cough, nausea, and vomiting. It has been reported that COVID-19 patients can potentially transmit the disease to others before developing symptoms. Thus, extensive surveillance and screening of individuals at risk of the disease is required to limit SARS-COV-2 spread. The COVID-19 respiratory triage score has been used for patient screening. We aimed to determine its diagnostic performance characteristics, which have not been adequately studied before. Methodology: This is a retrospective observational study involving all patients screened for COVID-19 at a tertiary care facility. Patients were tested using nasopharyngeal swab for SARS-COV-2 PCR. The Saudi CDC COVID-19 respiratory triage score was measured for all subjects. The sensitivity, specificity, positive predictive value, and negative predicted value of COVID-19 respiratory triage score were measured with reference to SARS-COV-2 PCR test. Multivariate regression analysis was done to identify factors that can predict a positive SARS-COV-2 PCR test. Result: A total of 1,435 subjects were included. The COVID-19 respiratory triage score provided a marginal diagnostic performance with a receiver-operating characteristics (ROC) area under the curve value of 0.60 (95% CI: 0.57–0.64). A triage score of 5 provided the best cut-off value for the combined sensitivity and specificity. Clinical characteristics that independently predicted positive COVID-19 PCR test include male sex (adjusted OR: 1.47; p = 0.034), healthcare workers and their family members (adjusted OR: 1.99; 95%; p = 0.016), fever (adjusted OR: 2.98; p < 0.001), and moderate disease severity (adjusted OR: 5; p < 0.001). Conclusion: The current COVID-19 respiratory triage score has marginal diagnostic performance characteristics. Its performance can improve by including additional predictors to the respiratory symptoms in order to avoid missing COVID-19 patients with atypical presentation and to limit unnecessary SARS-COV-2 PCR testing.
Protected Areas and Endemic Freshwater Fishes of the Cape Fold Ecoregion: Missing the Boat for Fish Conservation?

Freshwater systems and their associated biodiversity are among the most threatened ecosystems globally. The greatest threats to freshwater fishes are the introduction and spread of non-native species, pollution, habitat degradation and loss, and overexploitation. While many regions across the world contain extensive networks of protected areas, these are largely ineffective for protecting riverine systems and their biodiversity. This is because they were designed with the aim of prioritising conservation of terrestrial biodiversity, with limited or no consideration for aquatic systems. The Cape Fold Ecoregion, located within the Western and Eastern Cape Provinces of South Africa, is home to the highest percentage of threatened freshwater fishes in the country. The region has an extensive protected area network that protects a wide array of ecosystems, but limited information exists on the role of protected areas in conserving the endemic freshwater fish fauna of this region. This study evaluated the value of protected areas for protection of freshwater fishes in the Western Cape Province by setting species conservation targets and then intersecting species distribution data with protected area polygons. Conservation targets were set to protect the minimum viable population required for long-term persistence, with a minimum of 10 subpopulations as a target. This, along with other factors such as population viability and protected area effectiveness was used to determine whether a species was effectively protected by the current protected area network. Species were classified into one of four categories; (1) “well protected,” (2) “moderately protected,” (3) “poorly protected,” and (4) “not protected. ” Our results indicate that the majority of native fishes are inadequately protected within the current protected area network in the province. This is mainly a result of the linear nature of riverine ecosystems that exposes them to impacts and threats that emanate from outside of the protected area. These limitations are not unique to the CFE, and our findings have broader implications as they highlight the need for integrating both the riverine and terrestrial ecosystems in the design, expansion and management of protected areas. This will enhance and maximise conservation and protection of riverine systems and their unique biodiversity.
The Elephant in the Lab (and Field): Contamination in Aquatic Environmental DNA Studies

The rapid evolution of environmental (e)DNA methods has resulted in knowledge gaps in smaller, yet critical details like proper use of negative controls to detect contamination. Detecting contamination is vital for confident use of eDNA results in decision-making. We conducted two literature reviews to summarize (a) the types of quality assurance measures taken to detect contamination of eDNA samples from aquatic environments, (b) the occurrence, frequency and attribution (i.e., putative sources) of unexpected amplification in these quality assurance samples, and (c) how results were interpreted when contamination occurred. In the first literature review, we reviewed 156 papers and found that 91% of targeted and 73% of metabarcoding eDNA studies reported inclusion of negative controls within their workflows. However, a large percentage of targeted (49%) and metabarcoding (80%) studies only reported negative controls for laboratory procedures, so results were potentially blind to field contamination. Many of the 156 studies did not provide critical methodological information and amplification results of negative controls. In our second literature review, we reviewed 695 papers and found that 30 targeted and 32 metabarcoding eDNA studies reported amplification of negative controls. This amplification occurred at similar proportions for field and lab workflow steps in targeted and metabarcoding studies. These studies most frequently used amplified negative controls to delimit a detection threshold above which is considered significant or provided rationale for why the unexpected amplifications did not affect results. In summary, we found that there has been minimal convergence over time on negative control implementation, methods, and interpretation, which suggests that increased rigor in these smaller, yet critical details remains an outstanding need. We conclude our review by highlighting several studies that have developed especially effective quality assurance, control and mitigation methods.
Rapid Transmission of a Hyper-Virulent Meningococcal Clone Due to High Effective Contact Numbers and Super Spreaders

Rapid transmission, a critical contributory factor in outbreaks of invasive meningococcal disease, requires naïve populations of sufficient size and intermingling. We examined genomic variability and transmission dynamics in a student population subject to an 11-fold increase in carriage of a hypervirulent Neisseria meningitidis serogroup W ST-11 clone. Phylogenetic clusters, mutation and recombination rates were derived by bioinformatic analyses of whole-genome sequencing data. Transmission dynamics were determined by combining observed carriage rates, cluster sizes and distributions with simple SIS models. Between 9 and 15 genetically-distinct clusters were detected and associated with seven residential halls. Clusters had low mutation accumulation rates and infrequent recombination events. Modeling indicated that effective contacts decreased from 10 to 2 per day between the start and mid-point of the university term. Transmission rates fluctuated between 1 and 4% while the R(t) for carriage decreased from an initial rate of 47 to 1. Decreases in transmission values correlated with a rise in vaccine-induced immunity. Observed carriage dynamics could be mimicked by populations containing 20% of super spreaders with 2.3-fold higher effective contact rates. We conclude that spread of this hypervirulent ST-11 meningococcal clone depends on the levels of effective contacts and immunity rather than genomic variability. Additionally, we propose that super-spreaders enhance meningococcal transmission and that a 70% MenACWY immunization level is sufficient to retard, but not fully prevent, meningococcal spread in close-contact populations.
Transcriptome Profiling Provides Insights Into Potential Antagonistic Mechanisms Involved in Chaetomium globosum Against Bipolaris sorokiniana

Chaetomium globosum Kunze is recognized as a potential biocontrol fungus against spot blotch of wheat caused by Bipolaris sorokiniana. Its molecular mechanism of biocontrol activity and the biosynthetic pathways involved have not been yet elucidated. Here, global transcriptome profiling of C. globosum strain Cg2 during interaction with B. sorokiniana isolate BS112 using RNA-seq was performed in order to gain insights into the potential mechanisms of antagonism. The Illumina HiSeq platform (2 × 150 bp) yielded an average of 20–22 million reads with 50–58% GC. De novo assembly generated 45,582 transcripts with 27,957 unigenes. Transcriptome analysis displayed distinct expression profiles in the interaction (Cg2–BS112), out of which 6,109 unique differentially expressed genes were present. The predominant transcripts classified as genes involved in “catalytic activity” constituted 45.06%, of which 10.02% were associated with “hydrolytic activity” (GO:0008152), and similarly, in the biological process, 29.18% of transcripts were involved in “metabolic activity” (GO:0004096 and GO:0006979). Heat map and cluster categorization suggested an increase in the expression levels of genes encoding secondary metabolites like polyketide synthase (GO:0009058), S-hydroxymethyl glutathione dehydrogenase (GO:0006069), terpene cyclase (EC 4.2.3.-), aminotran_1_2 domain-containing protein (GO:0009058), and other hydrolytic CAZYmes such as the glycosyl hydrolase (GH) family (GH 13, GH 2, GH 31, and GH 81; GO:0005975), cellulase domain-containing protein, chitinases, β-1, 3-glucanases (GO:0004565), glucan endo-1,3-beta-glucanase (GO:0052861), and proteases (GO:0004177). The obtained RNA-seq data were validated by RT-qPCR using 20 randomly chosen genes, showing consistency with the RNA-seq results. The present work is worldwide the first effort to unravel the biocontrol mechanism of C. globosum against B. sorokiniana. It generated a novel dataset for further studies and facilitated improvement of the gene annotation models in the C. globosum draft genome.
Paclitaxel Plus Platinum Neoadjuvant Chemotherapy Followed by Surgery Versus Primary Surgery in Locally Advanced Cervical Cancer—A Propensity Score Matching Analysis

Objective To compare the efficacy and safety of neoadjuvant chemotherapy followed by surgery (NACTS) and primary surgery (PS) in locally advanced cervical cancer (LACC). Methods LACC (stage IB2/IIA2, FIGO 2009) patients who accepted NACTS or PS in the Cancer Hospital of the Chinese Academy of Medical Sciences from 2007 to 2017 were enrolled, and a database was established. A 1:1 ratio propensity score matching (PSM) was performed for the NACTS group and PS group according to pretreatment characteristics. After PSM, the clinicopathological features and prognosis between the matched groups were compared. Results Of 802 cases in the database, 639 met the inclusion criteria, with 428 received paclitaxel plus platinum NACTS, and 211 received PS. After PSM, the two groups had comparable pretreatment characteristics, with 190 cases in each group. In the NACTS group, the operation parameters were similar to the PS group except for the longer operation time (median 255 min vs. 239 min, P = 0.007); pathological intermediate-risk factors including tumor diameter (P < 0.001) and LVSI(+) (P < 0.001) were significantly decreased; fewer patients were with ≥2 intermediate-risk factors (10.5 vs. 53.2%, P < 0.001) so that the rate of adjuvant radiotherapy was reduced (54.2 vs. 70.0%, P = 0.002). DFS and OS were similar between the NACTS group and PS group (P > 0.05). However, for patients with tumor diameter ≥5 cm or SCC ≥5 ng/ml, DFS of the NACTS group was significantly prolonged (P = 0.016, P = 0.007). Conclusion Paclitaxel plus platinum neoadjuvant chemotherapy can reduce adjuvant radiotherapy by decreasing pathological risk factors. Patients with tumor diameter ≥5 cm or SCC ≥5 ng/ml may obtain survival benefits.
Prevalence and Related Factors of Insomnia Among Chinese Medical Staff in the Middle and Late Stage of COVID-19

Background: The outbreak of novel coronavirus disease (COVID-19) has brought serious psychological pressure to people, especially medical health staff. At present, there are few studies on insomnia and related factors of medical health staff in the middle and late stage of the epidemic of COVID-19. Therefore, the purpose of this study was to investigate the prevalence of insomnia and its related risk factors among medical workers in China in the middle and later stage of COVID-19 epidemic, as well as the relationship between insomnia and psychological resilience. Methods: From February 14 to March 29, 2020, a cross-sectional survey was conducted among 606 medical staff in China through Ranxing Technology's “SurveyStar” network platform. All subjects were assessed with the Insomnia Severity Index (ISI) and simplified Chinese version of Connor-Davidson Resilience scale (CD-RISC-10). Results: In the middle and later stages of the COVID-19 outbreak, the incidence of insomnia among medical staff was 32.0%. Compared with non-insomnia group, the insomnia group had younger age, lower education level, longer daily working hours and less psychological resilience. In addition, the prevalence of insomnia was higher in medical staff with a history of somatic diseases. The severity of insomnia of Chinese medical staff was associated with age, education level, daily working hours, psychological resilience and somatic diseases. Conclusions: Our study shows that nearly 1/3 of Chinese medical workers suffer from insomnia nearly a month after the COVID-19 outbreak. Compared with the general population, medical staff who are working with COVID are more prone to insomnia. Risk factors for insomnia include younger age, lower education level, longer working hours per day, and physical illness. The tenacious dimension of psychological resilience is a protective factor for insomnia.
Pilot Study on the Reliability of the Coach's Eye: Identifying Talent Throughout a 4-Day Cadet Judo Camp

A typical assumption found in talent identification literature is that different coaches, given the same athletes and circumstances, will identify the same subset of athletes as “talented”. However, while coaches play a major role during talent identification in practical sport settings, there is limited empirical research exploring the processes which underpin this. The purpose of this study was to explore the reliability of “the coach's eye” during the assessment of talent in a group of athletes. Specifically, this project compared inter-coach agreement between nine judo coaches (ages 35.8 ± 10.6 years) with varying levels of experience (12.9 ± 8.9 years) in the evaluation of 24 talented cadet judo athletes (13–15 years) at seven timepoints throughout a 4-day development training camp. Without discussion of their scores with other coaches, coaches provided a single score representing each athlete's “potential for future performance” on an 11-point Likert scale at each timepoint. Scores from each coach were converted into rankings from 1 to 24 to create a normalized scale to facilitate comparison of athletes. Based on their rankings at each timepoint, athletes were placed into one of three evenly distributed groups (high, medium, and low rank). Inter-coach agreement at each timepoint was determined by the number of coaches who ranked each athlete in the same group, categorized at three levels: 50, 75 or 100% agreement. Overall results showed that at completion of the camp, coaches reached 100% agreement on only two athletes, both of whom were in the high rank group. When inter-coach agreement was set at 50%, 15 athletes (62.5%) were placed into like groups. The first timepoint at which coaches were able to differentiate between the majority of athletes was Timepoint 3 (end of day 2). The findings suggest that, in isolation, coaches do not agree on the talent or potential of athletes. This indicates that the “coach's eye” is subjective and variable, and, given the same context, there is poor inter-coach agreement in the identification of talented athletes. In turn, these findings may have significant implications for both future talent identification research and athlete selection processes by sport organizations.
Interannual Variability in the Thermal Habitat of Alexandrium catenella in the Bay of Fundy and the Implications of Climate Change

Globally, harmful algal blooms (HABs) are an increasing problem. In the Gulf of Maine and Bay of Fundy, blooms of the toxic dinoflagellate Alexandrium catenella are annually recurrent phenomena. As this region is one of the most rapidly warming areas of the global ocean, an improved understanding of the mechanisms driving the initiation of local A. catenella blooms, their interannual variability and the implications of future climate change is critical to local monitoring strategies and marine resources management. A 27-year (1988–2014) time series of weekly A. catenella cell counts from the Bay of Fundy and concurrent satellite-measured sea surface temperature, freshwater discharge from the St. John River and wind-driven turbulence are compared to assess their relationship to variability in bloom phenology metrics. The mean thermal habitat associated with early detection of A. catenella is 6.5 ± 1.6°C, whereas that of bloom initiation averages 9.2 ± 1.5°C. Both thermal habitats for A. catenella are trending earlier over the study period. Bloom initiations that precede the arrival of the thermal habitat mean (occur in colder water) are associated with higher spring freshwater discharge and are generally weaker blooms. Increased spring freshwater discharge is also associated with earlier bloom initiation and earlier maximum concentration dates. No significant relationship was observed with the strength of wind-driven mixing. Removal of the mean thermal seasonal cycle shows that surface temperature anomalies have a strong negative relationship to the bloom phenology metrics and arrival of thermal habitat: warmer years are linked to earlier arrival of thermal habitats (∼12 days °C–1) and earlier detection and bloom initiation dates (∼33 days °C–1). Using these relationships and present trends in Bay of Fundy surface temperature warming over the period 1982–2019, we project the arrival dates of bloom thermal habitat and bloom phenology metrics out to the middle of this century. Based on current rates of sea surface temperature change, bloom phenology metrics (e.g., bloom initiation, early detection), can be expected to shift 1–2 months earlier in the season by mid-century. Such changes in the phenology of A. catenella blooms will need to be incorporated into both monitoring strategies and forecasting models for the region.
Systems View of Deconditioning During Spaceflight Simulation in the PlanHab Project: The Departure of Urine 1 H-NMR Metabolomes From Healthy State in Young Males Subjected to Bedrest Inactivity and Hypoxia

We explored the metabolic makeup of urine in prescreened healthy male participants within the PlanHab experiment. The run-in (5 day) and the following three 21-day interventions [normoxic bedrest (NBR), hypoxic bedrest (HBR), and hypoxic ambulation (HAmb)] were executed in a crossover manner within a controlled laboratory setup (medical oversight, fluid and dietary intakes, microbial bioburden, circadian rhythm, and oxygen level). The inspired O2 (FiO2) fraction next to inspired O2 (PiO2) partial pressure were 0.209 and 133.1 ± 0.3 mmHg for the NBR variant in contrast to 0.141 ± 0.004 and 90.0 ± 0.4 mmHg (approx. 4,000 m of simulated altitude) for HBR and HAmb interventions, respectively. 1H-NMR metabolomes were processed using standard quantitative approaches. A consensus of ensemble of multivariate analyses showed that the metabolic makeup at the start of the experiment and at HAmb endpoint differed significantly from the NBR and HBR endpoints. Inactivity alone or combined with hypoxia resulted in a significant reduction of metabolic diversity and increasing number of affected metabolic pathways. Sliding window analysis (3 + 1) unraveled that metabolic changes in the NBR lagged behind those observed in the HBR. These results show that the negative effects of cessation of activity on systemic metabolism are further aggravated by additional hypoxia. The PlanHab HAmb variant that enabled ambulation, maintained vertical posture, and controlled but limited activity levels apparently prevented the development of negative physiological symptoms such as insulin resistance, low-level systemic inflammation, constipation, and depression. This indicates that exercise apparently prevented the negative spiral between the host’s metabolism, intestinal environment, microbiome physiology, and proinflammatory immune activities in the host.
Physiological and Pathological Roles of Mammalian NEK7

NEK7 is the smallest NIMA-related kinase (NEK) in mammals. The pathological and physiological roles of NEK7 have been widely reported in many studies. To date, the major function of NEK7 has been well documented in mitosis and NLRP3 inflammasome activation, but the detailed mechanisms of its regulation remain unclear. This review summarizes current advances in NEK7 research involving mitotic regulation, NLRP3 inflammasome activation, related diseases and potential inhibitors, which may provide new insights into the understanding and therapy of the diseases associated with NEK7, as well as the subsequent studies in the future.