Miracle-dz/UniFAR-FTUs huggingface dataset:
Probing the active site of deubiquitinase USP30 with non-canonical tryptophan analogues.

Methanosarcina mazei pyrrolysyl-tRNA synthetase (PylRS) and its cognate tRNA have been evolved to generate genetically encoded non-canonical amino acids (ncAAs). Use of tryptophan (Trp) analogs with pyrrole ring modification for their spatial and polarity tuning in enzyme activity and substrate specificity is still limited. Herein, we report the application of an evolved PylRS, FOWRS2, for efficient incorporation of five Trp analogues into the deubiquitinase USP30 to decipher the role of W475 for di-ubiquitin selectivity. Structures of the five FOWRS-C/Trp analogue complexes at 1.7-2.5 Å resolution showed multiple ncAA binding modes. The W475 near the USP30 active site was replaced with Trp analogues and the effect on the activity as well as the selectivity towards di-ubiquitin linkage types was examined. It was found that the Trp analogue with a formyl group attached to the nitrogen atom of indole ring led to improved activity of USP30 likely due to enhanced polar interactions, and that another Trp analogue, 3-benzothienyl-L-alanine, induced a unique K6-specificity. Collectively, genetically encoded non-canonical Trp analogues by evolved PylRS•tRNA^Pyl pair unravel the spatial role of USP30-W475 in its di-ubiquitin selectivity.
P3 amplitude reductions are associated with shared variance between internalizing and externalizing psychopathology.

P3 amplitude reductions, commonly elicited in oddball paradigms, have been associated with both internalizing (e.g., depression and anxiety) and externalizing problems (e.g., substance use, aggression, and impulsivity). Recent factor analytic models have focused on the shared variance between internalizing and externalizing problems as a potentially important separable psychopathology construct (a general psychopathology factor, or p-factor). To assess neurophysiological markers of this shared variance, we examined P3 amplitude to target and novel stimuli in an undergraduate sample with a range of internalizing and externalizing problems. Participants (N = 125) completed a rotated heads visual oddball paradigm, with IAPS pictures serving as infrequent novel stimuli. Results replicated P3 amplitude reduction relative to both target and novel stimuli separately for internalizing and externalizing problems, and found that the shared variance across internalizing and externalizing was significantly related to lower P3 amplitude to novels, targets, and a factor score of target and novel P3 measures. The present results are consistent with the interpretation that a general or shared problem behavior factor accounts for much of the associations between reduced P3 amplitude and internalizing and externalizing problems.
Evaluation of a New Criterion for Detecting Prion Disease With Diffusion Magnetic Resonance Imaging.

Importance Early diagnosis is a requirement for future treatment of prion diseases. Magnetic resonance imaging (MRI) with diffusion-weighted images and improved real-time quaking-induced conversion (RT-QuIC) in cerebrospinal fluid (CSF) have emerged as reliable tests. Objectives To assess the sensitivity and specificity of diffusion MRI for the diagnosis of sporadic Creutzfeldt-Jakob disease (sCJD) with a new criterion (index test) of at least 1 positive brain region among the cortex of the frontal, parietal, temporal, and occipital lobes; the caudate; the putamen; and the thalamus. Design, Setting, and Participants This diagnostic study with a prospective and a retrospective arm was performed from January 1, 2003, to October 31, 2018. MRIs were collected from 1387 patients with suspected sCJD consecutively referred to the National Prion Disease Pathology Surveillance Center as part of a consultation service. Intervention Magnetic resonance imaging. Four neuroradiologists blinded to the diagnosis scored the MRIs of 200 randomly selected patients. One neuroradiologist scored the MRIs of all patients. Main Outcomes and Measures Sensitivity and specificity of the index test compared with currently used criteria and CSF diagnostic (improved RT-QuIC, 14-3-3, and tau CSF tests). Results A total of 872 patients matched the inclusion criteria (diffusion MRI and autopsy-confirmed diagnosis), with 619 having sCJD, 102 having other prion diseases, and 151 having nonprion disease. The primary analysis included 200 patients (mean [SD] age, 63.6 [12.9] years; 100 [50.0%] male). Sensitivity of the index test of 4 neuroradiologists was 90% to 95% and superior to sensitivity of current MRI criteria (69%-76%), whereas specificity was 90% to 100% and unchanged. Interrater reliability of the 4 neuroradiologists was high (κ = 0.81), and individual intrarater reliability was excellent (κ ≥0.87). The sensitivity of the index test of 1 neuroradiologist for 770 patients was 92.1% (95% CI, 89.7%-94.1%) and the specificity was 97.4% (95% CI, 93.4%-99.3%) compared with a sensitivity of 69.8% (95% CI, 66.0%-73.4%; P < .001) and a specificity of 98.0% (95% CI, 94.3%-99.6%; P > .99) according to the current criteria. For 88 patients, index test sensitivity (94.9%; 95% CI, 87.5%-98.6%) and specificity (100%; 95% CI, 66.4%-100%) were similar to those of improved RT-QuIC (86.1% [95% CI, 76.5%-92.8%] and 100% [95% CI, 66.4%-100%], respectively). Lower specificities were found for 14-3-3 and tau CSF tests in 452 patients. Conclusions and Relevance In this study, the diagnostic performance of diffusion MRI with the new criterion was superior to that of current standard criteria and similar to that of improved RT-QuIC. These results may have important clinical implications because MRI is noninvasive and typically prescribed at disease presentation.
Calcipotriol/betamethasone dipropionate formulations for psoriasis: an overview of the options and efficacy data

ABSTRACT Introduction Psoriasis is a very common chronic inflammatory skin disease affecting up to 3% of the general population with 75% of the psoriasis subjects being affected by a mild form of disease. Hence, topical therapy is the most frequent employed treatment in psoriasis also because it can be easily combined with systemic therapy. In this context, calcipotriol/betamethasone dipropionate (Cal/BD) fixed-dose association represents the first-line treatment due to its efficacy and once-daily application. Different Cal/BD formulations, such as ointment, gel (topical suspension), and aerosol foam, are approved by US Food and Drug Administration. Areas covered For this review, relevant English literature (trials, real-life studies, case series, and reviews) regarding Cal/BD different formulations efficacy in psoriasis was searched for through to 28 January 2020. The following database were consulted: PubMed, Embase, the Cochrane Library, Google Scholar, EBSCO, and clinicaltrials.gov. Expert opinion Cal/BD formulations are efficacious treatment for psoriasis. Cal/BD aerosol foam shows a higher efficacy compared to Cal/BD ointment or gel formulations, appearing as a game-changer in psoriasis therapy not only for mild disease but also for moderate psoriasis as well as in selected severe cases in combination with systemic treatments.
Impact of Pain, Opioids, and the Mu-opioid Receptor on Progression and Survival in Patients With Newly Diagnosed Stage IV Pancreatic Cancer

Supplemental Digital Content is available in the text. Objectives: Pancreatic adenocarcinoma is frequently associated with pain requiring opioid therapy. Opioids, however, have been implicated in causing tumor progression, ultimately shortening survival. We examined the impact of pain, opioid use, and the mu-opioid receptor (MOP-R) expression in tumor tissue on progression-free survival and overall survival of patients with metastatic pancreatic cancer. Methods: We identified 103 patients with metastatic pancreatic adenocarcinoma receiving chemotherapy and abstracted data from Tumor Registry, in addition to pain, opioid exposure, carbohydrate antigen 19-9 values, survival, and imaging response. MOP-R expression was evaluated using an immunohistochemistry assay. The association of variables with progression-free survival and overall survival was analyzed in univariate and multivariate models. Results: Patients with low opioid use (<5 mg oral morphine equivalent/d) survived longer than patients with high opioid (HO) use (≥5 mg oral morphine equivalent/d) (median overall survival of 315 vs. 150 d; hazard ratio [HR]=1.79; 95% confidence interval [CI]: 1.13, 2.84). This effect persisted on multivariate models (adjusted HR=2.76; 95% CI: 1.39, 5.48). Low opioid patients tended to respond better to treatment than HO patients, based on carbohydrate antigen 19-9. Patients with low MOP-R expression had longer median survival (230 vs. 193 d), though the HR was not significant (1.15; 95% CI: 0.71, 1.88). Baseline pain was not associated with outcomes. Conclusion: In patients with metastatic pancreatic adenocarcinoma, HO use is associated with decreased survival, but the severity of baseline pain and MOP-R expression score in tumor tissue does not correlate with clinical outcomes.
Bacterial Growth on and Penetration of the Shell Membranes of the Hen's Egg

Commonly occurring contaminants of rotten eggs multiplied in a buffered solution of mineral salts containing intact shell membranes. Aeromonas liquefaciens, a nonpigmented pseudomonad, and sometimes a proteolytic strain of a Cloaca sp. caused the membranes to lose their pink colour. This was associated with a marked increase in the turbidity of the suspending medium and with the appearance of substances which reacted with Nessler's reagent and ninhydrin. These changes were not seen after growth of Proteus vulgaris, Alcaligenes faecalis, Pseudomonas fluorescens or non-proteolytic strains of Cloaca spp. No differences were noted in the rate of penetration of the shell and shell membranes by these two groups.
Molecular Mechanisms of Insulin Resistance in the Polycystic Ovary Syndrome

Although the clinical association between dis­ orders of carbohydrate metabolism and signs of androgen excess has long been appreciated (for a review see Dunaif), it was not until the mid-1970s that a distinct syndrome of insulin-resistant diabetes mellitus and virilization (Type A syndrome) was described by Kahn and colleagues. Over the next decade, it became generally appreciated that hyperandrogenism was common to several other rare syn­ dromes of extreme insulin resistance, such as lipotrophic diabetes, leprechaunism, and, when it developed in premenopausal women, the Type B syndrome, characterized by antibodies against the insulin re­ ceptor. These observations, taken together with the recognition that the common hyperandrogenic dis­ order, the polycystic ovary syndrome (PCOS), was also associated with hyperinsulinemia, led to the development of the hypothesis that insulin might be a regulator of ovarian androgen production. Alter­ natively, it was also suggested that androgens might affect insulin action, resulting in hyperinsulinemia. As is described in other articles in this issue, potential biologic bases for insulin action on an­ drogen production have been identified (e.g., by acting through the ovarian insulin-like growth factor-I [IGF-I] receptor). In several of the rare syndromes of extreme insulin resistance and hyperandrogenism, mutations in the insulin receptor gene have been found to cause the insulin resistance. This suggests that insulin resistance precedes, and perhaps causes hyperandrogenism. If intrinsic (i.e., genetic) defects in insulin action were also found in PCOS, this would support the hypothesis that insulin resistance plays a role in the development of hyperandrogen­ ism rather than vice versa. Thus, determining the mechanisms of insulin resistance in PCOS should help clarify the nature of the association between hyperinsulinemia and hyperandrogenism. More­ over, women with PCOS have insulin resistance of the same magnitude as individuals with noninsulindependent diabetes mellitus (NIDDM) (Fig. 1), and PCOS has been shown to be a major risk factor for the development of NIDDM. Thus, investigating the pathogenesis of glucose intolerance in PCOS will provide insight into a common cause of NIDDM. Insulin acts via its specific cell surface receptor (Fig. 2) (for review see Kahn and White). The insu­ lin receptor is a glycoprotein that is a heterotetramer made of two α-subunits and two β-subunits, analo­ gous to the IGF-I receptor. Each αβ dimer is the product of a single gene and, after synthesis and processing, it assembles with another αβ dimer to which it is linked by disulfide bonds. The α-subunits are extracellular and contain the insulin binding domain. The β-subunits span the cell membrane and project intracellularly. The cytoplasmic domain of the β-subunit is an enzyme, a protein tyrosine kinase. Insulin binds to the α-subunit transmitting a sig­ nal to the β-subunit, probably via conformational
Feminist-Informed Protective Factors for Subthreshold Eating Disorders

Despite knowledge that the larger sociocultural context contributes to the development of eating disorders, few studies have examined protective factors for women with subthreshold eating disorders. Using feminist-informed constructivist grounded theory methodology, 15 women (ages 18–25 years) with subthreshold eating disorders were interviewed. Results suggest that participants spoke of their subthreshold eating disorders in an externalized way and used protective factors to guide decision making toward their preferred values. A grounded theory model was developed to illustrate this process. Protective factors included (a) people who provide emotional and tangible support, (b) support people who challenge the eating disorder, (c) personal sense of agency, and (d) community activism and involvement. Participants experiencing subthreshold eating disorders demonstrated a capacity to distinguish their own thoughts and values from those of the “eating disorder voice,” and protective factors facilitated this process. Implications for future research and practice are discussed.
Factors Affecting the Biology of Telenomus isis (Polaszek) (Hymenoptera: Scelionidae), an Egg Parasitoid of Cereal Stem Borers in West Africa

Abstract This study aimed at an assessment of the potential of the egg parasitoid Telenomus isis (Polaszek) as a biological control agent of cereal stem borers. Therefore, the effects of temperature, host species, host age, and time of host deprivation on the development and the reproductive potential of T. isis were studied in the laboratory. By use of linear regression and a modified Logan model and with eggs of the noctuid Sesamia calamistis Hampson as hosts, the lower and upper thresholds for development were estimated at 13.1 and 36°C, respectively, and the optimal temperature for development was 31°C. Female T. isis had no measurable preoviposition period, and the oviposition period ranged from 3 to 5 days. Approximately 66% of the total lifetime complement of eggs of T. isis were produced within 6 h after emergence. Average total lifetime fecundity was 61.1 and 82.1 eggs per female at 21 and 28°C, respectively. Longevity of adult females was 17.1 days at 21°C and 5.2 days at 30°C. Host acceptance and suitability were tested, using nine lepidopteran borer species. Only the noctuids S. calamistis, Sesamia poephaga (Tam & Bowden), Sesamia botanephaga (Tam & Bowden), and Busseola fusca (Fuller) were successfully attacked by T. isis. Parasitism and emergence did not differ among those species, but the sex ratio (expressed as proportion of female progeny) was significantly lower on S. calamistis. An increase of the host age from 1 to 4 days significantly reduced mean parasitism from 56.7 to 23.5%. Parasitoid emergence rates and sex ratio did not vary among 1-, 2-, or 3-day-old host eggs, but both parameters were significantly lower on 4-day-old eggs. With increasing duration of host deprivation from 0 to 17 days, longevity increased from 8.5 to 18.5 days, whereas average lifetime fecundity decreased from 81.2 to 40.5 eggs per female, respectively, indicating resorption of eggs. The results are discussed and compared with life table parameters of the ubiquitous egg parasitoid Telenomus busseolae (Gahan).
Chemical composition of selected take-away dishes consumed in Saudi Arabia

Ten common take‐away dishes from Saudi Arabia restaurants were analysed for energy value, selected minerals, fatty acids and cholesterol. Wide variations in the composition and nutritive value were evident among the various take‐away dishes. Moisture, carbohydrate, fat. protein, crude fiber and ash contents ranged from 43.5–57.5. 9.8–35.4, 9.4–25.0. 5.9–15.6. 0.15–0.76 and 0.70 to 2.9% respectively. Food energy values ranged from 987 to 1413 KJ (235–336 cal) per 100g. Sodium, potassium and calcium were the predominant major minerals (ranges from 71.7–484.6, 54–271 and 2.17–47.44 mg/100g respectively). Iron, magnesium, zinc and copper contents also varied widely. Oleic. palmitic, linoleic and stearic were the predominant fatty acids. The polyunsatu‐rated:monounsaturated:saturated fatty acid ratios as well as the P:S ratios were generally not compatible with recommended values. Cholesterol contents ranged between 3.82–20.5 mg/100g.
MUCILAGE-PRODUCING CELLS IN THE SEED COAT OF PLANTAGO OVATA: DEVELOPMENTAL FINE STRUCTURE,

A B S T R A C T As the ovule of Plantago ovata matures into a seed its epidermal cells are transformed from undifferentiated parenchyma to thin-walled containers of almost pure mucilage. During this process the volume of the cells increases 60-80 fold, and the protoplast degenerates to a remnant. Rapid cell expansion begins with pollination and is accompanied by an increase in the size of the nucleus and nucleolus, a change in the random arrangement of ribosomes, a decrease in the thickness of cell walls, and synthesis of starch. Deposition of mucilage inside vacuoles and between the plasma membrane and cell wall accompanies a marked increase in the number and size of Golgi vesicles. Histochemical evidence using the thiocarbohydrazide-osmium vapor method shows polysaccharide to be present within Golgi vesicles while they are still attached to the Golgi apparatus. Mucilage deposition is associated with further cell expansion, separation of the protoplast from the cell wall, fusion of vacuoles and extra protoplasmic space, and the disappearance of starch. TIIE OUTERMOST CELL LAYER of the seed in the genus Plantago contains little but mucilage. The seed-produced polysaccharides of several Plantago
Coccomyxa parasitica sp. nov. (Coccomyxaceae, Chlorococcales), a parasite of giant scallops in Newfoundland

Coccomyxa parasitica sp. nov. (Coccomyxaceae; Chlorococcales) is described as a parasite of the marine giant scallop, Placopecten magellanicus Gmelin, from Newfoundland, Canada. Cells occur in colonies distributed through various host organs, but especially in the mantle fold. Cell morphology is highly variable, although characterised by the possession of a distinct hyaline tip which is reduced or absent in culture. Pyrenoids are lacking, 1–3 parietal chloroplasts occur and the cell wall lacks cellulose. Reproduction is by 2, 4 or 8 autospores in the host, and by 2, 4, 8 or 16 autospores in culture. Sexual reproduction is lacking. Pigment analysis reveals the predominance of chlorophyll a, with chlorophyll b, α- and β-carotene and neoxanthin also present. The parasitism is regarded as at best facultative, although free-living C. parasitica is at present not known.
The association between metabolically healthy obesity and risk of cancer: A systematic review and meta‐analysis of prospective cohort studies

The risk of cancer among adults with metabolically healthy obesity (MHO) has not yet been established. We systematically searched from inception to 15 March 2020. We included prospective cohort studies that compared participants with MHO and participants with metabolically healthy non‐obesity (MHNO) for incidence of any type of cancer. Benign tumors, cancer mortality or cancer prognosis were not in the scope of our analysis. The Newcastle–Ottawa Scale was used for quality assessment. Ultimately, eight studies with a total of 12 542 390 participants were included. The pooled meta‐analysis using random effect model showed participants with MHO demonstrated a significantly increased risk of developing cancer (odds ratio [OR], 1.14; 95% confidence interval [CI], 1.05 to 1.23; and I2 = 39%) than those with MHNO. The subgroup analysis revealed a higher pooled estimate (OR, 1.17; 95% CI, 1.01–1.35; and I2 = 56%) in comparison with metabolically healthy normal weight. No evidence of effect modification by age, sex, ethnicity, smoking, sample size or length of follow‐up was found. In conclusion, the present study reports a positive association between MHO and cancer incidence. All individuals with obesity, even in the absence of metabolic dysfunction, should be encouraged to lose weight.
Adverse Outcomes in Pregnant Women Hospitalized with Respiratory Syncytial Virus Infection: A Case-Series.

We identified 10 women hospitalized with RSV infection during pregnancy. Diagnoses included pneumonia/atelectasis (five), respiratory failure (two), and sepsis (two). Six had obstetrical complications during hospitalization, including one induced preterm birth. One required intensive care unit admission and mechanical ventilation. Four infants had complications at birth.
Spatial covariation in survival rates of northeast pacific chum salmon

Abstract Using indices of survival rate (residuals from stock-recruitment relationships) across four decades, we examined the spatial patterns of covariation among 40 wild and 27 hatchery stocks of chum salmon Oncorhynchus keta from 15 geographical regions in Washington, British Columbia, and Alaska. We found strong evidence of positive covariation among spawner-to-recruit survival rates of wild stocks within regions and between certain adjacent regions (e.g., correlations from 0.3 to 0.7) but little evidence of covariation between stocks of distant regions (e.g., separated by 1,000 km or more). Similarly, for hatchery stocks from Washington, British Columbia, and southeast Alaska, positive covariation in the indices of fry-to-recruit survival rate occurred only within regions and between certain adjacent regions. These patterns suggest that important environmental processes affecting interannual variation in spawner-to-recruit survival rates of chum salmon operate at local or regional spatial scales rath.
GENETIC IMPROVEMENT AND COCOA YIELDS IN GHANA

This paper documents the yield gains attributable to the breeding and distribution of new cocoa varieties in Ghana, using data from a 2002 survey of 192 fields in the country's key cocoa producing regions. We find that planting the more recently-released varieties is associated with at least 42% higher yields, and that genetic improvement accounts for much but not all of the observed correlation between tree age and cocoa yield. Fertilizer use is also very important, being associated with 19% higher cocoa yield per 50 kg bag of fertilizer. We find no evidence that varieties differ in their response to fertilizer, pesticide use or labour, and no evidence of a decline in the yield advantage of new varieties over the 17-year age span observed in the sample.