Miracle-dz/UniFAR-FTUs huggingface dataset:
Opportunities for biomaterials to address the challenges of COVID‐19

Abstract The coronavirus disease 2019 (COVID‐19) pandemic has revealed major shortcomings in our ability to mitigate transmission of infectious viral disease and provide treatment to patients, resulting in a public health crisis. Within months of the first reported case in China, the virus has spread worldwide at an unprecedented rate. COVID‐19 illustrates that the biomaterials community was engaged in significant research efforts against bacteria and fungi with relatively little effort devoted to viruses. Accordingly, biomaterials scientists and engineers will have to participate in multidisciplinary antiviral research over the coming years. Although tissue engineering and regenerative medicine have historically dominated the field of biomaterials, current research holds promise for providing transformative solutions to viral outbreaks. To facilitate collaboration, it is imperative to establish a mutual language and adequate understanding between clinicians, industry partners, and research scientists. In this article, clinical perspectives are shared to clearly define emerging healthcare needs that can be met by biomaterials solutions. Strategies and opportunities for novel biomaterials intervention spanning diagnostics, treatment strategies, vaccines, and virus‐deactivating surface coatings are discussed. Ultimately this review serves as a call for the biomaterials community to become a leading contributor to the prevention and management of the current and future viral outbreaks.
Understanding metabolism related differences in ocular efficacy of MGV354

Abstract MGV354 was being developed as a novel ocular therapy for lowering of intraocular pressure, a key modifiable risk factor for glaucoma. MGV354 is an activator of soluble guanylate cyclase, an enzyme known to be involved in the regulation of IOP. MGV354 has been shown to robustly lower IOP over 24 h after a single topical ocular drop in rabbit and monkey pharmacology models. However, MGV354 failed to produce similar results in patients with ocular hypertension or open-angle glaucoma. With an objective of explaining the lack of efficacy in the clinic, we attempted to study whether human metabolism was significantly different from animal metabolism. The present study documents the investigation of metabolism of MGV354 in an effort to understand potential differences in biotransformation pathways of MGV354 in rabbits, monkeys, and humans. Overall twenty-six metabolites, formed via oxidative and conjugative pathways, were identified in vitro and in vivo. In vitro hepatic metabolism was qualitatively similar across species, with minor but distinct differences. There were no observable interspecies differences in the hepatic and ocular metabolism of MGV354. Although ocular metabolism was not as extensive as hepatic, the results do not explain the lack of efficacy of MGV354 in clinical studies.
Clinical neurophysiology and cerebrospinal liquor analysis to detect Guillain‐Barré syndrome and polyneuritis cranialis in COVID‐19 patients: A case series

We report a case series of five patients affected by SARS‐CoV‐2 who developed neurological symptoms, mainly expressing as polyradiculoneuritis and cranial polyneuritis in the 2 months of COVID‐19 pandemic in a city in the northeast of Italy. A diagnosis of Guillain‐Barré syndrome was made on the basis of clinical presentation, cerebrospinal fluid analysis, and electroneurography. In four of them, the therapeutic approach included the administration of intravenous immunoglobulin (0.4 g/kg for 5 days), which resulted in the improvement of neurological symptoms. Clinical neurophysiology revealed the presence of conduction block, absence of F waves, and in two cases a significant decrease in amplitude of compound motor action potential compound muscle action potential (cMAP). Four patients presented a mild facial nerve involvement limited to the muscles of the lower face, with sparing of the forehead muscles associated to ageusia. In one patient, taste assessment showed right‐sided ageusia of the tongue, ipsilateral to the mild facial palsy. In three patients we observed albuminocytological dissociation in the cerebrospinal fluid, and notably, we found an increase of inflammatory mediators such as the interleukin‐8. Peripheral nervous system involvement after infection with COVID‐19 is possible and may include several signs that may be successfully treated with immunoglobulin therapy.
Neurocognitive development and capabilities in boys with 49,XXXXY syndrome

49,XXXXY was previously associated with profound to severe intellectual deficits. However, prior research papers on the cognitive profiles of this population were confounded by small samples sizes, wide age spreads, and incomplete histories of testosterone replacement therapy. This study is the first comprehensive, international investigation of the neurocognitive aspects of 49,XXXXY, and the potential effects of biological treatment on this profile. Sixty‐seven boys from infancy to 11 years of age were enrolled in this longitudinal study, with the majority of boys postnatally diagnosed though chromosomal analysis. These boys received a comprehensive neurocognitive evaluation tailored to specific language‐based deficits and cognitive challenges. Results revealed higher neurocognitive capacities, both verbally and nonverbally, than previously reported in this disorder. Infant boys with 49,XXXXY who received early hormonal therapy (EHT) had significantly higher scores on the cognitive domain of the Bayley Scales of Infant Development than untreated infants (p = .013). In addition, treated school‐aged participants had significantly better scaled scores than untreated boys in form completion (p = .042), a task that requires deductive reasoning, on nonverbal testing on the Leiter International Performance Scales. This study indicates greater cognitive capacities with a wide range of abilities in the child with 49,XXXXY, thus warranting further investigation to identify and understand the critical influences on the etiology and the variability of those capacities.
Computational discovery of small drug-like compounds as potential inhibitors of SARS-CoV-2 main protease

Abstract A computational approach to in silico drug discovery was carried out to identify small drug-like compounds able to show structural and functional mimicry of the high affinity ligand X77, potent non-covalent inhibitor of SARS-COV-2 main protease (MPro). In doing so, the X77-mimetic candidates were predicted based on the crystal X77-MPro structure by a public web-oriented virtual screening platform Pharmit. Models of these candidates bound to SARS-COV-2 MPro were generated by molecular docking, quantum chemical calculations and molecular dynamics simulations. At the final point, analysis of the interaction modes of the identified compounds with MPro and prediction of their binding affinity were carried out. Calculation revealed 5 top-ranking compounds that exhibited a high affinity to the active site of SARS-CoV-2 MPro. Insights into the ligand − MPro models indicate that all identified compounds may effectively block the binding pocket of SARS-CoV-2 MPro, in line with the low values of binding free energy and dissociation constant. Mechanism of binding of these compounds to MPro is mainly provided by van der Waals interactions with the functionally important residues of the enzyme, such as His-41, Met-49, Cys-145, Met-165, and Gln-189 that play a role of the binding hot spots assisting the predicted molecules to effectively interact with the MPro active site. The data obtained show that the identified X77-mimetic candidates may serve as good scaffolds for the design of novel antiviral agents able to target the active site of SARS-CoV-2 MPro. Communicated by Ramaswamy H. Sarma
NPC1 as a Modulator of Disease Severity and Viral Entry of Sars-CoV-2.

The COVID-19 plague is hitting mankind. Several viruses, including SARS-CoV-1, MERS-CoV, EBOV, and SARS-CoV-2, use the endocytic machinery to enter the cell. Genomic variants in NPC1, which encodes for the endolysosomal Niemann-Pick type C1 protein, restricts the host-range of viruses in bats and susceptibility to infections in humans. Lack of NPC1 and its pharmacological suppression inhibits many viral infections including SARS-CoV-1 and Type I Feline Coronavirus Infection. Antiviral effects of NPC1-inhibiting drugs for COVID-19 treatment should be explored.
Value of laboratory results in addition to vital signs in a machine learning algorithm to predict in-hospital cardiac arrest: A single-center retrospective cohort study

Background Although machine learning-based prediction models for in-hospital cardiac arrest (IHCA) have been widely investigated, it is unknown whether a model based on vital signs alone (Vitals-Only model) can perform similarly to a model that considers both vital signs and laboratory results (Vitals+Labs model). Methods All adult patients hospitalized in a tertiary care hospital in Japan between October 2011 and October 2018 were included in this study. Random forest models with/without laboratory results (Vitals+Labs model and Vitals-Only model, respectively) were trained and tested using chronologically divided datasets. Both models use patient demographics and eight-hourly vital signs collected within the previous 48 hours. The primary and secondary outcomes were the occurrence of IHCA in the next 8 and 24 hours, respectively. The area under the receiver operating characteristic curve (AUC) was used as a comparative measure. Sensitivity analyses were performed under multiple statistical assumptions. Results Of 141,111 admitted patients (training data: 83,064, test data: 58,047), 338 had an IHCA (training data: 217, test data: 121) during the study period. The Vitals-Only model and Vitals+Labs model performed comparably when predicting IHCA within the next 8 hours (Vitals-Only model vs Vitals+Labs model, AUC = 0.862 [95% confidence interval (CI): 0.855–0.868] vs 0.872 [95% CI: 0.867–0.878]) and 24 hours (Vitals-Only model vs Vitals+Labs model, AUC = 0.830 [95% CI: 0.825–0.835] vs 0.837 [95% CI: 0.830–0.844]). Both models performed similarly well on medical, surgical, and ward patient data, but did not perform well for intensive care unit patients. Conclusions In this single-center study, the machine learning model predicted IHCAs with good discrimination. The addition of laboratory values to vital signs did not significantly improve its overall performance.
Substitution of parts of aerobic training by resistance training lowers fasting hyperglycemia in individuals with metabolic syndrome.

We sought to determine the effects of substituting parts of aerobic training (AT) by resistance training (RT) on metabolic syndrome (MetS) factors. MetS patients (56±7 years old; BMI 33±5 kg·m-2 and 3.9±0.8 MetS factors) were randomized to undergo one of the following isocaloric, 16-week long exercise programs: i) cycling 4 bouts of 4-min at 90% of HRmax followed by 3 sets of 12 repetitions of 3 lower limb free-weight exercises (HIIT+RT group; n=33), ii) cycling 5 bouts of 4-min at 90% of HRmax (HIIT+HIIT group; n=33) or iii) no exercise control group (CONT group; n=21). We measured the evolution of all five MetS components (Z-score), cardiorespiratory fitness (VO2max), leg strength and power (leg press 1RM and countermovement jump (CMJ)), fasting blood glucose (FG), insulin (FI) and insulin resistance (HOMA2). Both training groups improved VO2max similarly (170±310 and 190±210 mLO2·min-1; P<0.001) and Z-score (-0.12±0.29 and -0.12±0.31 for HIIT+RT and HIIT+HIIT, respectively; P<0.02). However, only HIIT+RT improved CMJ (P=0.002) and leg press 1RM above the HIIT+HIIT group (21% vs 6%; P<0.001). Furthermore, FG only decreased in the HIIT+RT group (5%; P=0.026, time x group). Our findings suggest that substitution of part of HIIT by leg RT, improves glucose control in MetS individuals. Bullets Points: •Most studies addressing the efficacy of endurance vs resistance training are not matched by energy expenditure. •We found that substituting 20% of aerobic training with resistance training reduces hyperglycemia in MetS individuals. •Thus, training recommendations to regain glycemic control in MetS individuals should include resistance training.
Factors Affecting the Metabolizable Energy Content of Poultry Feeds 2. Variability in the M.E. Values Attributed to Samples of Tallow, and Undegummed Soybean Oil

Abstract AKNOWLEDGE of the available energy content of poultry feeds is essential if the most economical rations are to be formulated. The question arises as to which method of describing available energy is to be employed. Practical difficulties, associated with the excretion of both feces and urine via a common cloaca, prevent the derivation of precise digestibility data. Axelsson (1939) and Halnan (1951) have argued strongly against the use of net energy values, and Titus (1955), Davidson et al. (1957) and Hill and Anderson (1958) have found productive energy data to be unsatisfactory. It is, therefore, understandable why many poultry nutritionists have turned to the evaluation of feeds in terms of metabolizable energy (M.E.). It is possible that M.E. values are subject to certain intrinsic errors although there is little published evidence to either support or refute this hypothesis. Matterson et al. (1958) have demonstrated that the M.E. value for a …
Psychometric properties of the Italian version of the Interpersonal Needs Questionnaire-15 (INQ-15-I).

OBJECTIVE The Interpersonal Needs Questionnaire (INQ-15) is a self-report measure of thwarted belongingness and perceived burdensomeness, two constructs associated with suicidal ideation. The objective of the current study was to translate the INQ-15 from English to Italian (INQ-15-I) and to test its factor structure, reliability, and validity in Italian samples. METHOD We examined (a) whether the components of the hypothesized two-factor measurement model are invariant across a community sample (N = 510) and a clinical sample (N = 259); (b) the relations between the INQ-15-I factors and measures of depression (Beck Depression Inventory-II), hopelessness (Beck Hopelessness Scale), and suicidal ideation (Beck Scale for Suicide Ideation); (c) the reliability and psychometric properties of the INQ-15-I. RESULTS Results from multigroup confirmatory factor analyses supported the adequacy of the two-factor model to represent thwarted belongingness and perceived burdensomeness. The model is invariant across community and clinical groups, showing excellent fit. The two INQ-15-I scales measure highly intercorrelated constructs. Both significantly correlate with depression, hopelessness, and suicidal ideation, and correlations are high in the clinical sample. CONCLUSION The INQ-15-I is a valid and reliable measure of thwarted belongingness and perceived burdensomeness. Implications for research, assessment, and intervention in suicidal ideation are discussed.
A long-read RNA-seq approach to identify novel transcripts of very large genes

RNA-seq is widely used for studying gene expression, but commonly used sequencing platforms produce short reads that only span up to two exon junctions per read. This makes it difficult to accurately determine the composition and phasing of exons within transcripts. Although long-read sequencing improves this issue, it is not amenable to precise quantitation, which limits its utility for differential expression studies. We used long-read isoform sequencing combined with a novel analysis approach to compare alternative splicing of large, repetitive structural genes in muscles. Analysis of muscle structural genes that produce medium (Nrap: 5 kb), large (Neb: 22 kb), and very large (Ttn: 106 kb) transcripts in cardiac muscle, and fast and slow skeletal muscles identified unannotated exons for each of these ubiquitous muscle genes. This also identified differential exon usage and phasing for these genes between the different muscle types. By mapping the in-phase transcript structures to known annotations, we also identified and quantified previously unannotated transcripts. Results were confirmed by endpoint PCR and Sanger sequencing, which revealed muscle-type-specific differential expression of these novel transcripts. The improved transcript identification and quantification shown by our approach removes previous impediments to studies aimed at quantitative differential expression of ultralong transcripts.
CENP-B creates alternative epigenetic chromatin states permissive for CENP-A or heterochromatin assembly

ABSTRACT CENP-B binds to CENP-B boxes on centromeric satellite DNAs (known as alphoid DNA in humans). CENP-B maintains kinetochore function through interactions with CENP-A nucleosomes and CENP-C. CENP-B binding to transfected alphoid DNA can induce de novo CENP-A assembly, functional centromere and kinetochore formation, and subsequent human artificial chromosome (HAC) formation. Furthermore, CENP-B also facilitates H3K9 (histone H3 lysine 9) trimethylation on alphoid DNA, mediated by Suv39h1, at ectopic alphoid DNA integration sites. Excessive heterochromatin invasion into centromere chromatin suppresses CENP-A assembly. It is unclear how CENP-B controls such different chromatin states. Here, we show that the CENP-B acidic domain recruits histone chaperones and many chromatin modifiers, including the H3K36 methylase ASH1L, as well as the heterochromatin components Suv39h1 and HP1 (HP1α, β and γ, also known as CBX5, CBX1 and CBX3, respectively). ASH1L facilitates the formation of open chromatin competent for CENP-A assembly on alphoid DNA. These results indicate that CENP-B is a nexus for histone modifiers that alternatively promote or suppress CENP-A assembly by mutually exclusive mechanisms. Besides the DNA-binding domain, the CENP-B acidic domain also facilitates CENP-A assembly de novo on transfected alphoid DNA. CENP-B therefore balances CENP-A assembly and heterochromatin formation on satellite DNA. Summary: The acidic domain of CENP-B facilitates assembly of various proteins at centromeric satellite DNA, including HP1 and ASH1L. CENP-B controls centromere epigenetic status.
Factors influencing dystocia and prediction of dystocia in Angus heifers selected for yearling growth rate

Data on 914 Angus heifers and their calves that had been selected for yearling growth rate (from birth to 1 year of age) were used to (i) evaluate the effect of dystocia on subsequent cow and calf performance, (ii) identify factors influencing dystocia, and (iii) develop and validate equations for predicting dystocia. Records on heifers born in the high, control, and low growth selection lines from 1975 to 1990 and their calves were used. Calving was classified as normal (no assistance), with a code of 0, or difficult (requiring assistance), with a code of 1. The incidence of dystocia was 4.5%, 9.7%, and 6.2% in the high, control, and low lines, respectively, with the difference between the high and control lines being significant (P < 0.05). Dystocia resulted in a significant reduction in calf survival to weaning (97% for normal v. 85% for difficult calvings). Of all the calving and pre-calving traits studied, the ratio of calf birth weight to heifer weight accounted for the highest variation in dystocia in the control (19.6%), low (15.2%), and high (5.4%) lines. The total variation explained by models generated by stepwise regression and discriminant analyses ranged from 5.4% to 36.8%. Prediction equations developed by discriminant analysis using traits measured prior to calving had high accuracy of predicting normal calvings (72.6%–90.3%), when tested on independent data sets. However, the sensitivity (ability to identify those heifers having difficult birth) of the equations was low (0%–40%). These results imply that the approach to be used to reduce dystocia and minimise its effects is to develop an overall management strategy involving both planning of mate selection at joining and supervision at calving.
Epicardial Adipose Tissue and Reactive Oxygen Species 42

Epicardial adipose tissue (EAT), one of a number of distinct fat depots within the body, is the adipose tissue located on the surface of the heart. EAT is located mainly around the epicardial coronary vessels but is also present on the myocardial surface from which it can extend into the heart to be interspersed with myocardial muscle fibers. EAT serves a number of important physiologic functions but its capacity to generate reactive oxygen species (ROS) is significantly more than subcutaneous adipose tissue probably due to an increased expression of two of the main components of NADPH namely gp91 phox and p47phox. mRNA expression for several enzymes involved in oxidative stress namely Glutathione S-transferase P (GSTP1), protein disulfide isomerase (PDIA1) and phosphoglcerate mutase 1 (PGAM1) are present in EAT and are greater in EAT than in subcutaneous fat. The thickness and volume of epicardial fat is significantly greater in patients with coronary artery disease compared to persons without coronary artery disease (CAD). Several lines of evidence support
When do adolescents feel loved? A daily within-person study of parent-adolescent relations.

Feeling loved has many benefits, but research is limited on how daily behaviors of one person in a relationship shape why someone else feels more or less loved from day to day. The parent-adolescent relationship is a primary source of love. We expected parent-reported warmth and conflict would explain daily fluctuations in how loved adolescents reported feeling. In a sample of 151 families (adolescent MAge = 14.60; 61.6% female) over a 21-day period, we used multilevel models to disentangle within-family (daily variability) and between-family (average levels) parent-reported daily warmth and conflict in relation to adolescents' daily reports about how loved they were feeling. Findings indicated adolescents in families with higher parent-reported warmth across days and higher adolescent-reported closeness with parents felt more loved by their parents, on average. At a within-person level, we found considerable day-to-day variability in how loved adolescents reported feeling that was partially explained by meaningful variability in both parent-reported warmth and conflict across days. On days when parents reported more warmth than usual and less conflict than usual, adolescents reported feeling more loved. Further, a significant within-day interaction indicated that the importance of days' parent warmth was greater on high conflict days, but when parents directed more warmth toward their adolescents, the difference between high- and low-conflict days was negligible. Theoretical implications for studying daily emotional love in parent-youth relationships and suggestions for parenting interventions that focus on daily practices of parent warmth are discussed. (PsycInfo Database Record (c) 2020 APA, all rights reserved).