Miracle-dz/UniFAR-FTUs huggingface dataset:
An overview of tecovirimat for smallpox treatment and expanded anti-orthopoxvirus applications

ABSTRACT Introduction Tecovirimat (TPOXX®; ST-246) was approved for the treatment of symptomatic smallpox by the USFDA in July of 2018 and has been stockpiled by the US government for use in a smallpox outbreak. While there has not been a reported case of smallpox since 1978 it is still considered a serious bioterrorism threat. Areas covered A brief history of smallpox from its proposed origins as a human disease through its eradication in the late 20th century is presented. The current smallpox threat and the current public health response plans are described. The discovery, and development of tecovirimat through NDA submission and subsequent approval for treatment of smallpox are discussed. Google Scholar and PubMed were searched over all available dates for relevant publications. Expert opinion Approval of tecovirimat to treat smallpox represents an important milestone in biosecurity preparedness. Incorporating tecovirimat into the CDC smallpox response plan, development of pediatric liquid and intravenous formulations, and approval for post-exposure prophylaxis would provide additional health security benefit. Tecovirimat shows broad efficacy against orthopoxviruses in vitro and in vivo and could be developed for use against emerging orthopoxvirus diseases such as monkeypox, vaccination-associated adverse events, and side effects of vaccinia oncolytic virus therapy.
Succession, environmental fluctuations, and stability in experimentally manipulated microalgal communities

Periphytic algae were experimentally manipulated over a 20-week period to evaluate the influence of environmental fluctuations and community age on succession and community stability. Environmental fluctuations were generated by periodically transferring artificial substrata between stations in an oligotrophic lake during 9 or 10 weeks. Developing communities exposed to induced fluctuations of two- and four-week periods did not track the fluctuations. Instead, succession was slowed and followed a trajectory intermediate between those of unmanipulated control communities representing the two extremes of the fluctuation cycles. The fluctuations favored the growth of some early successional taxa while strongly suppressing the growth of at least one late successional taxon (.)
Confronting the controversy: interleukin-6 and the COVID-19 cytokine storm syndrome

The concept of coronavirus disease 2019 (COVID-19)-related cytokine storm syndrome (COVID-CSS) emerged early in the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic to explain why some patients exposed to this virus become critically ill with acute respiratory distress syndrome, multi-organ failure, and death. A seminal study from Wuhan, China reported higher serum concentrations of inflammatory cytokines in patients requiring critical care compared to those with milder disease, and the authors postulated that “cytokine storm was associated with disease severity” [1]. Hypercytokinaemic immune dysregulation in COVID-19 is known as cytokine storm syndrome. Interleukin-6 levels ≥80 pg·mL−1 predict an increased risk of respiratory failure and death, and immunomodulatory therapy is an area of urgent investigation. https://bit.ly/3jq3uJ4
Oral mucosal lesions in patients with SARS-CoV-2 infection. Report of four cases. Are they a true sign of COVID-19 disease?

BACKGROUND Vesiculobullous and macular lesions in the oral mucosa have been reported in patients positive for SARS-CoV-2 infection. Nonetheless, the significance and physiopathology of oral manifestations have not been clearly established in the clinical progression or outcome of the infection. AIM To describe the clinico-pathological oral mucosal lesions in four patients with confirmed SARS-CoV-2 infection. METHODS AND RESULTS Four patients with COVID-19 disease and confirmed by polymerase chain reaction (PCR) presented angina bullosa hemorragica-like lesion, vascular disorder, and nonspecific stomatitis, one patient with histological analysis demonstrated perivascular reactive lymphocitic infliltrate, focal capillary thrombosis, and hemorrhage. According to the discrimination of other local and systemic conditions and the synchronous onset of oral and systemic symptoms, the diagnosis of oral lesions probably associated with COVID-19 was established. CONCLUSION Infection with SARS-CoV-2 may result in oral manifestations with various clinical presentations, which presumably support the hypothesis of thrombi formation and vasculitis; nevertheless, these findings need more evidence and a long-term follow up of patients to accurately establish the significance of the oral mucosa affection in the COVID-19 disease.
Branched-Chain Amino Acid Fortification Does Not Restore Muscle Protein Synthesis Rates following Ingestion of Lower- Compared with Higher-Dose Mycoprotein.

BACKGROUND We have shown that ingesting a large bolus (70 g) of the fungal-derived, whole food mycoprotein robustly stimulates muscle protein synthesis (MPS) rates. OBJECTIVE The aim of this study was to determine if a lower dose (35 g) of mycoprotein enriched with branched-chain amino acids (BCAAs) stimulates MPS to the same extent as 70 g of mycoprotein in resistance-trained young men. METHODS Nineteen men [aged 22 ± 1 y, BMI (kg/m2): 25 ± 1] took part in a randomized, double-blind, parallel-group study. Participants received primed, continuous infusions of l-[ring-2H5]phenylalanine and ingested either 70 g mycoprotein (31.5 g protein; MYCO; n = 10) or 35 g BCAA-enriched mycoprotein (18.7 g protein: matched on BCAA content; ENR; n = 9) following a bout of unilateral resistance exercise. Blood and bilateral quadriceps muscle samples were obtained before exercise and protein ingestion and during a 4-h postprandial period to assess MPS in rested and exercised muscle. Two- and 3-factor ANOVAs were used to detect differences in plasma amino acid kinetics and mixed muscle fractional synthetic rates, respectively. RESULTS Postprandial plasma BCAA concentrations increased more rapidly and to a larger degree in ENR compared with MYCO. MPS increased with protein ingestion (P ≤ 0.05) but to a greater extent following MYCO (from 0.025% ± 0.006% to 0.057% ± 0.004% · h-1 in rested muscle, and from 0.024% ± 0.007% to 0.072% ± 0.005% · h-1 in exercised muscle; P < 0.0001) compared with ENR (from 0.031% ± 0.003% to 0.043% ± 0.005% · h-1 in rested muscle, and 0.027% ± 0.005% to 0.052% ± 0.005% · h-1 in exercised muscle; P < 0.01) ingestion. Postprandial MPS rates were greater in MYCO compared with ENR (P < 0.01). CONCLUSIONS The ingestion of lower-dose BCAA-enriched mycoprotein stimulates resting and postexercise MPS rates, but to a lesser extent compared with the ingestion of a BCAA-matched 70-g mycoprotein bolus in healthy young men. This trial was registered at clinicaltrials.gov as 660065600.
Developing a clinically relevant radiosensitizer for temozolomide-resistant gliomas

The prognosis for patients with glioblastoma (GB) remains grim. Concurrent temozolomide (TMZ) radiation—the cornerstone of glioma control—extends the overall median survival of GB patients by only a few months over radiotherapy alone. While these survival gains could be partly attributed to radiosensitization, this benefit is greatly minimized in tumors expressing O6-methylguanine DNA methyltransferase (MGMT), which specifically reverses O6-methylguanine lesions. Theoretically, non-O6-methylguanine lesions (i.e., the N-methylpurine adducts), which represent up to 90% of TMZ-generated DNA adducts, could also contribute to radiosensitization. Unfortunately, at concentrations attainable in clinical practice, the alkylation capacity of TMZ cannot overwhelm the repair of N-methylpurine adducts to efficiently exploit these lesions. The current therapeutic application of TMZ therefore faces two main obstacles: (i) the stochastic presence of MGMT and (ii) a blunted radiosensitization potential at physiologic concentrations. To circumvent these limitations, we are developing a novel molecule called NEO212—a derivatization of TMZ generated by coupling TMZ to perillyl alcohol. Based on gas chromatography/mass spectrometry and high-performance liquid chromatography analyses, we determined that NEO212 had greater tumor cell uptake than TMZ. In mouse models, NEO212 was more efficient than TMZ at crossing the blood-brain barrier, preferentially accumulating in tumoral over normal brain tissue. Moreover, in vitro analyses with GB cell lines, including TMZ-resistant isogenic variants, revealed more potent cytotoxic and radiosensitizing activities for NEO212 at physiologic concentrations. Mechanistically, these advantages of NEO212 over TMZ could be attributed to its enhanced tumor uptake presumably leading to more extensive DNA alkylation at equivalent dosages which, ultimately, allows for N-methylpurine lesions to be better exploited for radiosensitization. This effect cannot be achieved with TMZ at clinically relevant concentrations and is independent of MGMT. Our findings establish NEO212 as a superior radiosensitizer and a potentially better alternative to TMZ for newly diagnosed GB patients, irrespective of their MGMT status.
Growth, carcass traits, immunity and oxidative status of broilers exposed to continuous or intermittent lighting programs

Objective An experiment was conducted to investigate the continuous and intermittent lighting program effects on terms of the productive performance, carcass traits, blood biochemical parameters, innate immune and oxidative status in broiler chicks. Methods A total of 600 Cobb-500 one day old chicks were randomly allocated into six equal groups (100 chicks per treated group with five replicates of 20 chicks each) based on lighting program; 22 continuous lighting (22 C), 11 h lighting+1 darkness twice daily (11 L/1 D), 20 h continuous lighting (20 C), 5 h lighting+1 darkness four times daily (5 L/1 D), 18 h continuous lighting (18 C) and the final group subjected for 3 h lighting+1 h darkness six times daily (3 L/1 D). The experimental period lasted 42 days. Results Compared with those under the intermittent light program, broiler chicks exposed to continuous lighting for 22 h had significant improvement in live body weight and carcass (dressing and breast percentage) measured traits. Though reducing lighting hours significantly reduced feed intake and feed conversion ratio values. Different lighting programs revealed no significant effect on all blood biochemical parameters. Oxidative stress and innate immunity parameters significantly enhance by reducing lighting hours (3L/1D). Conclusion The findings suggest that reducing lighting hours up to 3L/1D would be more useful in enhancing feed efficiency, innate immunity, and oxidative status compared with continuous lighting programs on broilers.
Spring Declines in Microtus pennsylvanicus and the Role of Steroid Hormones

Spring declines are a common feature of small mammal demography. We tested the hypothesis that meadow voles from populations experiencing severe spring declines should exhibit severe stress responses as indicated by high free corticosterone levels. Three populations in southern Ontario were live-trapped intensively in the spring of 1985, all animals were bled each time, and measurements of total corticosterone, corticosterone-binding globulin (CBG), and total androgen (testosterone and dihydrotestosterone) were obtained by radioimmunoassay
Fetal Maintenance and Its Evolutionary Significance in the Amphibia: Gymnophiona

The oviducts of several species of caecilians are modified for maintenance of fetal development through metamorphosis. Nutrition is provided by secretions from epithelial cells of the duct. Nutritional demands on the parent are great. I t is concluded that the species-specific fetal dentition is functional in obtaining nutrition in the oviduct, in contrast to previous suggestions. This mode of viviparity is found in members of three of the four families of caecilians. Several species of amphibians are known to retain developing young in their oviducts and to give birth to fully metamorphosed juveniles. The majority of such amphibian species belong to the order Gymnophiona-the blind, limbless, elongate caecilians of the tropics. Several aspects of the reproductive biology of caecilians are correlated with the ability to bear living young. Members of all caecilian species practice internal fertilization and have a number of morphological and behavioral modifications to facilitate it (Barrio, 1969; Wake, 1968, 1970, 1972); females produce relatively few, but large and yolky eggs (Wake, 1968); oviducts are capable of great distention and of secretory activity (Wake, 1970). Study of the morphology of oviducts of pregnant and non-pregnant adult females and the way developing young are maintained in the oviducts, as well as analysis of the developmental morphology of the fetuses, has produced some new ideas about the mechanism of viviparity in caecilians. In addition, i t has necessitated review of previous ideas about caecilian fetal growth and nutrition. Morphology o f the Oviduct. -The gross morphology of the oviduct of several species, both viviparous and oviparous, has been described (Parker, 1956; Wake, 1970). A specimen of Dermophis mexicanus has more extensive epithelial proliferation than seen in other species. Three 'columns' of epithelium, one ventral, two lateral, f i l l the lumen of the duct, except for the space occupied by fetuses. The six 25 mm fetuses have gills, but yolk appears to be resorbed, or nearly so. General comments about the microanatomy of the ducts of two viviparous species, Gymnopis multiplicata and Scolecomorphus kirk i i were also presented by Wake ( 1970). Material is now available representing the non-pregnant Gymnopis multiplicata oviduct, pregnant and non-pregnant Dermophis, and the pregnant and non-pregnant ducts of Typhlonectes compressicauda. These agree in general with the descriptions by Parker (1956) and Wake (1970). In non-pregnant females of both species the duct is slender, 1-3 mm in external diameter. Projections of connective tissue and capillaries covered with epithelium fi l l the lumen of the duct. The histology of the oviduct has been examined in more detail in order to consider the characteristics of the epithelium, especially the secretory cells of pregnant females. The epithelium is a single cell layer thick, and virtually all cells are ciliated. Nuclei are large; the 1977 JOURNAL OF HERPETOLOGY 11(4):379-386 (379)
Morphologic evolution of recent small sub-cortical infarcts and adjacent white matter in the basal ganglia in a Chinese cohort

Abstract Background Data on the evolution of recent small sub-cortical infarcts are limited, especially in the Chinese. Previous studies have reported a large heterogeneity in cavitation and infarct location; therefore, the present study assessed the morphology of small sub-cortical infarcts in the basal ganglia in a Chinese cohort. Methods Patients who had experienced a recent, single, small sub-cortical infarct in the basal ganglia and received at least one follow-up magnetic resonance imaging (MRI) scan were retrospectively identified from January 2014 to June 2018. Time to follow-up imaging, baseline infarct size, vascular risk factors, and other clinical data, as well as the morphologic changes of the index infarct and surrounding white matter were recorded. Demographic, clinical and MRI characteristics were respectively compared among three groups (white matter hyper-intensitie [WMH] vs. cavitation vs. absent) and between with and without new WMH formation groups. In addition, logistic regression analyses were performed in investigating the determinate independent predictors for new WMH formation. Results Seventy-eight subjects were included with a median follow-up time of 304 days (range: 124–552 days). We found a significant reduction in infarct size at follow-up: 46 of 78 (59.0%) infarctions showed some degree of cavitation, 19 of 78 (24.4%) index lesions resembled non-cavitated WMH, and 13 of 78 (16.7%) infarcts had disappeared at follow-up MRI. No factors were found to be associated with differential outcomes of the infarcts. In addition, 8 of 78 (10.3%) patients demonstrated new WMH formation surrounding the index infarct; white matter progression (odds ratio = 15.95, 95% confidence interval = 1.65–153.99; P = 0.017) was an independent risk factor of new WMH formation. Conclusions More than half of the small sub-cortical infarcts in the basal ganglia progressed to cavities, demonstrating that these infarcts can be reduced and go undetected. The presence of new WMH around the infarct may be indicative of the worsening progression of cerebral small vessel diseases. Additionally, white matter progression is an independent risk factor, which may be a potential therapeutic target.
Claudin-1 Leads to Strong Formation of Tight Junction in Cultured Mouse Lung Microvascular Endothelial Cells

We aimed to examine paracellular barrier function in cultured mouse lung microvascular endothelial cells (LMECs). The transcellular resistance of LMEC monolayers yielded an electrical resistance of approximately 19 Ω × cm2 at days 6 - 7 in culture when the cells reached confluence, and paracellular permeable clearance of sodium fluorescein was the lowest on day 6 in culture, suggesting the formation of tight junctions (TJs) in cultured LMECs. Moreover, the expression of TJ-associated proteins, occludin, claudin-1 and -4 and zonula occludents 1 (ZO-1) was detected in LMECs at day 6 in culture. However, mRNAs of occludin, claudin-1 and -4 and ZO-1 were already expressed on day 1 after culture, and large variations were absent in the mRNA levels of occludin, claudin-4 and ZO-1 between days 1 and 7 in culture, when the level of each mRNA on day 1 in culture was used as a basal level. However, the claudin-1 mRNA level gradually increased up to approximately 7-fold on day 7 in culture over the basal level. These results indicate that the drastic increase in the mRNA expression level of claudin-1 leads to the strong formation of TJs.
Tissue turnover within grass-clover mixed swards grazed by sheep. Methodology for calculating growth, senescence and intake fluxes

1. A sustainable, low-input land use might be achieved by the use of grazed grass-legume mixtures. However, maintaining the species balance has proven to be difficult, especially as grazing provides differential defoliation and regrowth. Since changes in the sward botanical composition can be ascribed to species differences in growth, senescence or intake, a method that yields independent estimates of these three fluxes for both components of a grazed grass-legume mixture is needed. 2. The objective of this paper is to present and assess such a detailed tissue turnover method based on non-destructive measurements of individually marked population units. This method was applied during two spring and summer growing seasons to a ryegrass-clover mixture continuously or rotationally grazed by sheep and is assessed using these experimental results. 3. Defoliation was measured on grazed population units (i.e. grass tillers; elongated and axillary shoot growing points of clover). To calculate the growth rate of defoliated leaves, a sample of ungrazed leaves of each defoliation status (with or without previous defoliation) was used. Additionally, for clover, a sample of ungrazed leaves of each 'botanical number' was also required. The mean extension rates of leaves that underwent defoliation during an observed period, and of leaves that did not, was not significantly different during the preceding period. 4. The estimates of the mixture growth flux varied by less than 10 and 17% when the mean values of the gravimetric coefficients and of the density of the population units, respectively, were increased by one standard deviation. The net recruitment of new population units led to an underestimation of the growth flux by 8 and 5% with grass and clover, respectively. 5. The method was partially validated, by comparing independent estimates of the mean dry-weight of the population units, based either on tissue turnover or on destructive measurements. For vegetative tillers and elongated clover growing points, both estimates were highly correlated with no significant bias. 6. Although this method is labour intensive, it yields reliable estimates of the growth, intake and senescence fluxes, at three different levels (square metre, population unit and plant part). Hence, a better understanding of the impacts of herbivory on the grass-legume balance in a grazed mixture can be gained.
A Genetic Window on Sardinian Native Horse Breeds through Uniparental Molecular Systems

Simple Summary The horse is a mammalian species showing a high variation among maternal lineages but a limited variability in the paternal inheritance. The female phylogenetic history is commonly investigated by analyzing the maternally transmitted mitochondrial DNA (mtDNA), while the male perspective is provided by the paternally inherited portion of the Y chromosome (NRY). Here we explored the variation of both non-recombining genetic systems in three horse breeds present in Sardinia: Giara, Sarcidano, and Sardinian Anglo-Arab. The analysis of 34 stallions revealed three differentially distributed NRY types: (i) the first and most ancestral one is typical of Sarcidano; (ii) the second is well represented in Giara and seems to derive from Neapolitan/Oriental stallions; (iii) the third confirms the Thoroughbred influence in the Sardinian Anglo-Arab breed. By extending the analysis to 178 mtDNAs, we observed a common maternal origin for Giara and Sarcidano. Contrarily, the outlier behavior of the Sardinian Anglo-Arab is due to its higher mitochondrial variability, testifying for multiple maternal lineages in its current population. Our preliminary findings highlight the importance of a parallel molecular screening of NRYs and mtDNAs to reconstruct both paternal and maternal phylogenetic histories and to fully evaluate the extent of autochthonous genetic resources in the island. Abstract Sardinia, an island located to the west of Italy in the Mediterranean Sea, boasts three native horse breeds: Giara, Sarcidano, and Sardinian Anglo-Arab. Here, we have investigated for the first time three loci of the non-recombining region of the Y chromosome (NRY) in 34 stallions from these breeds and performed a phylogenetic analysis of the maternal relationships among 178 previously published mitochondrial control regions. We found that the current NRY diversity of Sardinian horse breeds is linked to three haplotypes (HT), all identified within Sarcidano. Each breed showed a typical HT: HT1 (ancestral) was the most represented in Sarcidano, HT2 (Neapolitan/Oriental wave) in Giara, and HT3 (Thoroughbred wave) in Sardinian Anglo-Arab. The specificity of each haplotype suggests the influence of independent breeding strategies and the effect of genetic drift in each Sardinian population. The female counterpart, extended to 178 horses, showed a low genetic variability and a common maternal origin for Giara and Sarcidano. The higher variability of the Sardinian Anglo-Arab indicates multiple mare lineages in its current population. Further genetic analyses will be crucial to understand the paternal history of male horses, preserve the endangered mares’ and stallions’ lineages, and improve the enhancement of autochthonous genetic resources on this island.