Miracle-dz/UniFAR-FTUs huggingface dataset:
The First Berberine-Based Inhibitors of Tyrosyl-DNA Phosphodiesterase 1 (Tdp1), an Important DNA Repair Enzyme

A series of berberine and tetrahydroberberine sulfonate derivatives were prepared and tested against the tyrosyl-DNA phosphodiesterase 1 (Tdp1) DNA-repair enzyme. The berberine derivatives inhibit the Tdp1 enzyme in the low micromolar range; this is the first reported berberine based Tdp1 inhibitor. A structure–activity relationship analysis revealed the importance of bromine substitution in the 12-position on the tetrahydroberberine scaffold. Furthermore, it was shown that the addition of a sulfonate group containing a polyfluoroaromatic moiety at position 9 leads to increased potency, while most of the derivatives containing an alkyl fragment at the same position were not active. According to the molecular modeling, the bromine atom in position 12 forms a hydrogen bond to histidine 493, a key catalytic residue. The cytotoxic effect of topotecan, a clinically important topoisomerase 1 inhibitor, was doubled in the cervical cancer HeLa cell line by derivatives 11g and 12g; both displayed low toxicity without topotecan. Derivatives 11g and 12g can therefore be used for further development to sensitize the action of clinically relevant Topo1 inhibitors.
Risk factors for myocardial injury in patients with coronavirus disease 2019 in China

In patients with coronavirus disease 2019 (COVID‐19), the involvement of the cardiovascular system significantly relates to poor prognosis. However, the risk factors for acute myocardial injury have not been sufficiently studied. Thus, we aimed to determine the characteristics of myocardial injury and define the association between routine blood markers and cardiac troponin I, in order to perform a predictive model.
Adolescent diet and physical activity in the context of economic, social and nutrition transition in rural Maharashtra, India: a qualitative study.

OBJECTIVE To explore the perceptions of adolescents and their caregivers on drivers of diet and physical activity in rural India in the context of ongoing economic, social and nutrition transition. DESIGN A qualitative study comprising eight focus group discussions (FGD) on factors affecting eating and physical activity patterns, perceptions of health and decision-making on food preparation. SETTING Villages approximately 40-60 km from the city of Pune in the state of Maharashtra, India. PARTICIPANTS Two FGD with adolescents aged 10-12 years (n 20), two with 15- to 17- year-olds (n 18) and four with their mothers (n 38). RESULTS Dietary behaviour and physical activity of adolescents were perceived to be influenced by individual and interpersonal factors including adolescent autonomy, parental influence and negotiations between adolescents and caregivers. The home food environment, street food availability, household food security and exposure to television and digital media were described as influencing behaviour. The lack of facilities and infrastructure was regarded as barriers to physical activity as were insufficient resources for public transport, safe routes for walking and need for cycles, particularly for girls. It was suggested that schools take a lead role in providing healthy foods and that governments invest in facilities for physical activity. CONCLUSIONS In this transitioning environment, that is representative of many parts of India and other Lower Middle Income Countries (LMIC), people perceive a need for interventions to improve adolescent diet and physical activity. Caregivers clearly felt that they had a stake in adolescent health, and so we would recommend the involvement of both adolescents and caregivers in intervention design.
Congenital Cytomegalovirus Infection: Update on Diagnosis and Treatment

Congenital cytomegalovirus (cCMV) infection is the most common congenital viral infection and is the leading non-genetic cause of sensorineural hearing loss (SNLH) and an important cause of neurodevelopmental disabilities. The risk of intrauterine transmission is highest when primary infection occurs during pregnancy, with a higher rate of vertical transmission in mothers with older gestational age at infection, while the risk of adverse fetal effects significantly increases if fetal infection occurs during the first half of pregnancy. Despite its prevalence and morbidity among the neonatal population, there is not yet a standardized diagnostic test and therapeutic approach for cCMV infection. This narrative review aims to explore the latest developments in the diagnosis and treatment of cCMV infection. Literature analysis shows that preventive interventions other than behavioral measures during pregnancy are still lacking, although many clinical trials are currently ongoing to formulate a vaccination for women before pregnancy. Currently, we recommend using a PCR assay in blood, urine, and saliva in neonates with suspected cCMV infection. At present, there is no evidence of the benefit of antiviral therapy in asymptomatic infants. In the case of symptomatic cCMV, we actually recommend treatment with oral valganciclovir for a duration of 12 months. The effectiveness and tolerability of this therapy option have proven effective for hearing and neurodevelopmental long-term outcomes. Valganciclovir is reserved for congenitally-infected neonates with the symptomatic disease at birth, such as microcephaly, intracranial calcifications, abnormal cerebrospinal fluid index, chorioretinitis, or sensorineural hearing loss. Treatment with antiviral drugs is not routinely recommended for neonates with the mildly symptomatic disease at birth, for neonates under 32 weeks of gestational age, or for infants more than 30 days old because of insufficient evidence from studies. However, since these populations represent the vast majority of neonates and infants with cCMV infection and they are at risk of developing late-onset sequelae, a biomarker able to predict long-term sequelae should also be found to justify starting treatment and reducing the burden of CMV-related complications.
Genetic studies on growth, conformation and feed consumption traits in growth and feed efficiency line of broilers

The present investigation was carried out to study the genetic parameters in two lines viz., growth and feed efficiency line of red Cornish which were under gone to selection of 10 generations for their respective traits. In the light of experiment conducted, growth line has superiority over feed efficiency line with respect to body weight at different ages. Conformation traits viz., shank length, keel bone length and breast angle seem to be more or less similar in both the sexes of growth and feed efficiency line. The differences among the hatches did not show any definite trend. The weight gain and feed efficiency measured during 5–8 weeks in growth line has an edge over the feed efficiency line in all the sexes and hatches. The heritabilities computed for the traits studied were low to moderate in magnitude. Most of the genetic and phenotypic correlations between growth and conformation traits were positive and highly significant. Similar trend was observed for feed consumption traits in both lines.
Regression Networks for Neurophysiological Indicator Evaluation in Practicing Motor Imagery Tasks

Motor Imagery (MI) promotes motor learning in activities, like developing professional motor skills, sports gestures, and patient rehabilitation. However, up to 30% of users may not develop enough coordination skills after training sessions because of inter and intra-subject variability. Here, we develop a data-driven estimator, termed Deep Regression Network (DRN), which jointly extracts and performs the regression analysis in order to assess the efficiency of the individual brain networks in practicing MI tasks. The proposed double-stage estimator initially learns a pool of deep patterns, extracted from the input data, in order to feed a neural regression model, allowing for infering the distinctiveness between subject assemblies having similar variability. The results, which were obtained on real-world MI data, prove that the DRN estimator fosters pre-training neural desynchronization and initial training synchronization to predict the bi-class accuracy response, thus providing a better understanding of the Brain–Computer Interface inefficiency of subjects.
Progressive Lung Injury, Inflammation and Fibrosis in Rats following Inhalation of Sulfur Mustard.

Sulfur mustard (SM) inhalation causes debilitating pulmonary injury in humans which progresses to fibrosis. Herein, we developed a rat model of SM toxicity which parallels pathological changes in the respiratory tract observed in humans. SM vapor inhalation caused dose (0.2 - 0.6 mg/kg) related damage to the respiratory tract within 3 d of exposure. At 0.4 - 0.6 mg/kg, ulceration of the proximal bronchioles, edema and inflammation were observed, along with a proteinaceous exudate containing inflammatory cells in alveolar regions. Time course studies revealed that the pathologic response was biphasic. Thus, changes observed at 3 d post-SM were reduced at 7 d - 16 d; this was followed by more robust aberrations at 28 d, including epithelial necrosis and hyperplasia in the distal bronchioles, thickened alveolar walls, enlarged vacuolated macrophages, and interstitial fibrosis. Histopathologic changes were correlated with biphasic increases in BAL cell and protein content and PCNA expression. Proinflammatory proteins RAGE, HMGB1, and MMP-9 also increased in a biphasic manner following SM inhalation, along with SP-D. TNFα and iNOS, inflammatory proteins implicated in mustard lung toxicity, and the proinflammatory/profibrotic protein, Gal-3, were upregulated in alveolar macrophages and in bronchiolar regions at 3 d and 28 d post-SM. Inflammatory changes in the lung were associated with oxidative stress, as reflected by increased expression of HO-1. These data demonstrate a similar pathologic response to inhaled SM in rats and humans suggesting that this rodent model can be used for mechanistic studies and for the identification of efficacious therapeutics for mitigating toxicity.
Genetic variation and inter-trait correlations in Eucalyptus globulus base population trials in Argentina

Genetic variation and inter-trait correlations were examined in a base population of Eucalyptus globulus established on four sites in Argentina. The genetic material included 223 open pollinated seed lots from 11 Australian localities and 52 open pollinated and control pollinated seed lots from European and South American land races. Survival, growth, bark thickness, tree form, transition to adult foliage and Pilodyn penetration were addressed, at different ages up to 4 years. Average single site individual narrow-sense heritabilities were low for forking (0.03), survival (0.05) and form (0.10); intermediate for growth (0.27) and relative bark thickness (0.32); and high for Pilodyn penetration (0.48) and transition to adult foliage (0.60). There was strong positive genetic correlations between growth and other traits were not statistically significant (Pilodyn penetration -0.04, fork 0.06, proportion of adult foliage 0.06, bark thickness -0.02. Correlations amongst subrace effects were generally consistent with the family within subrace genetic correlations, but to some extent lower and less significant. Other estimates of genetic parameters reported for E. globulus were generally consistent with the present study. The limitations on parameter estimates from open pollinated progeny trials are discussed.
Development, structure, and protein composition of reptilian claws and hypotheses of their evolution

Here, we review the development, morphology, genes, and proteins of claws in reptiles. Claws likely form owing to the inductive influence of phalangeal mesenchyme on the apical epidermis of developing digits, resulting in hyperproliferation and intense protein synthesis in the dorsal epidermis, which forms the unguis. The tip of claws results from prevalent cell proliferation and distal movement along most of the ungueal epidermis in comparison to the ventral surface forming the subunguis. Asymmetrical growth between the unguis and subunguis forces beta‐cells from the unguis to rotate into the apical part of the subunguis, sharpening the claw tip. Further sharpening occurs by scratching and mechanical wearing. Ungueal keratinocytes elongate, form an intricate perimeter and cementing junctions, and remain united impeding desquamation. In contrast, thin keratinocytes in the subunguis form a smooth perimeter, accumulate less corneous beta proteins (CBPs) and cysteine‐poor intermediate filament (IF)‐keratins, and desquamate. In addition to prevalent glycine–cysteine–tyrosine rich CBPs, special cysteine‐rich IF‐keratins are also synthesized in the claw, generating numerous SS bonds that harden the thick and compact corneous material. Desquamation and mechanical wear at the tip ensure that the unguis curvature remains approximately stable over time. Reptilian claws are likely very ancient in evolution, although the unguis differentiated like the outer scale surface of scales, while the subunguis might have derived from the inner scale surface. The few hair‐like IF‐keratins synthesized in reptilian claws indicate that ancestors of sauropsids and mammals shared cysteine‐rich IF‐keratins. However, the number of these keratins remained low in reptiles, while new types of CBPs function to strengthen claws.
Prevalence, Determinants, and Effects of Food Insecurity among Middle Eastern and North African Migrants and Refugees in High-Income Countries: A Systematic Review

Issues related to poverty and income inequality in high-income countries have led to food insecurity among some population groups, such as migrants and refugees. While there are some studies on the experience of some migrant groups (and other subpopulations), little is known about food security among Middle Eastern and African migrants and refugees. This systematic review identified the prevalence of food insecurity and its effects among Middle Eastern and North African (MENA) migrants and refugees in high-income countries. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were followed in this systematic review. Four databases, namely MEDLINE (Ovid), Embase (Ovid), CINAHL (EBSCO), and PubMed were searched. Three studies met the inclusion criteria, all of which were conducted in USA: two among Sudanese migrant families, and one among Somali refugee women. The rates of reported food insecurity ranged from 40% to 71% and were significantly higher than for the general population. Food insecurity was associated with acculturation and socio-economic factors. Food insecurity adversely impacts the health of MENA migrants and refugees, creating economic implications for individuals, families, the broader community in which they now live, and for governments.
Overexpressing Runx2 of BMSCs improve the repairment of knee cartilage defects.

BACKGROUND Recruitment of gene modify bone marrow mesenchymal stem cells (BMSCs) has been considered an alternative to single cell injection in articular cartilage repair. PURPOSE The aim of this study was to investigate the effect whether of runt-related transcription factor 2(Runx2) overexpression bone marrow mesenchymal stem cells in vivo could improve the quality of repaired tissue of a knee cartilage defect in a rabbit model. METHODS Thirty-two New Zealand rabbits were randomly divided into four groups.The blank group (Con) don't received anything, the model group (Mo) was administered saline, the simple stem cell group (MSCs) received MSCs injection, the Runx2 transfection group (R-MSCs) received Runx2 overexpression MSCs injection. After adapting to the environment for a week, a 5 mm diameter cylindrical osteochondral defect was created in the center of medial femoral condyle. Cell and saline injections are performed in the first and third weeks after surgery. The cartilage repair was evaluated by macroscopically and microscopically at 4 and 8 weeks. RESULTS Macroscopically, defects were filled and surfaces were smoother in the MSCs groups than in the Mo group at 4 weeks. Microscopically, the R-MSCs group showed coloration similar to surrounding normal articular cartilage tissue at 8weeks in masson trichrome staining. The COL-Ⅱ, SOX9 and Aggrecan mRNA expression of MSCs was enhanced at 4 weeks compared with R-MSCs, then the expression reduced at 8 weeks, but was still higher than Mo group level (P<0.05). The western blot examination revealed that the COL-Ⅱand SOX9 expression of MSCs was higher than R-MSCs at 4 weeks, then the expression reduced at 8 weeks, but was still higher than Mo level (P<0.05). The IL-1β content in joint fluid also revealed that cartilage repair with R-MSCs was better than that with MSCs at 8 weeks (P<0.05). CONCLUSIONS The R-MSCs group showed cellular morphology and arrangement similar to surrounding normal articular cartilage tissue, Runx2 overexpression of MSCs resulted in overall superior cartilage repair as compared with MSCs at 8 weeks.
Effect of paclobutrazol on growth and flowering in rose cv. Gruss-an-Teplitz.

Paclobutrazol at 40 mg a.i./plant significantly reduced length of primary shoot and increased number of primary and secondary shoots per plant and fresh and dry weight of flowers per plant. However, 20 mg paclobutrazol/plant conspicuously reduced plant height and increased number of flowers per plant. It is interesting to note that all the treated plants with paclobutrazol delayed flowering. Various doses of paclobutrazol failed to exert any striking effect on diameter of primary shoot and days taken to bud appearance.
Surface Roughness Influence on Néel-, Crosstie, and Bloch-Type Charged Zigzag Magnetic Domain Walls in Nanostructured Fe Films

Charged magnetic domain walls have been visualized in soft magnetic nanostructured Fe thin films under both static and dynamic conditions. A transition in the core of these zigzagged magnetic walls from Néel-type to Bloch-type through the formation of crosstie walls has been observed. This transition in charged zigzagged walls was not previously shown experimentally in Fe thin films. For film thicknesses t < 30 nm, Néel-type cores are present, while at t ≈ 33 nm, walls with crosstie cores are observed. At t > 60 nm, Bloch-type cores are observed. Along with the visualization of these critical parameters, the dependence on the film thickness of the characteristic angle and length of the segments of the zigzagged walls has been observed and analyzed. After measuring the bistable magneto-optical behavior, the values of the wall nucleation magnetic field and the surface roughness of the films, an energetic fit to these nucleation values is presented.
Mutational characteristics determined using circulating tumor DNA analysis in triple‐negative breast cancer patients with distant metastasis

Dear editor, Breast cancer has been considered as the most commonmalignancy and the leading cause of death in women worldwide [1]. Triple-negative breast cancer (TNBC) accounts for 10%-20% of breast cancers, which are characterized by the absence of estrogen receptor (ER), progesterone receptor (PR), and amplification of human epidermal growth factor receptor 2 (HER2) [2]. TNBC is well known for its rapid progressiveness, high rate of distant organ recurrence, and poor prognosis. Metastasis remains the major cause of death for patients with TNBCs. Up to date, the only direct treatment for metastatic TNBCs is chemotherapy, which has been challenged by tumor heterogeneity and drug resistance. Lack of effective targeted therapy for metastatic TNBCs impels researchers to focus on discovering potentially actionable targets through mutational profiling. Although next-generation sequencing (NGS) has shown valuable benefits in oncology, its use in metastatic TNBC demands attentions. On one hand, in view of cellular heterogeneity, the genomic profiles of tissue biopsies might not be representative for lethal tumors. There exists trauma, pain, and other safety issues when obtaining metastatic tissues in clinical practices, since metastatic TNBCs frequently involve distant organs including the liver, lungs, bones, or brain. Recently, circulating
A scoping review of psychoeducational interventions for people after transient ischemic attack and minor stroke

ABSTRACT Background Psychoeducation can provide information and support to cope with the physical and emotional effects of a health condition. This scoping review aimed to identify the evidence regarding psychoeducational interventions for people after a Transient Ischemic Attack (TIA) and minor stroke. Methods This review was conducted in accordance with the PRISMA Extension for Scoping Reviews. Three electronic databases (MEDLINE, Embase, PsycINFO) were searched for articles on interventions related to psychoeducational support post-TIA and minor/mild stroke. Search retrieved 3722 articles. Three reviewers independently screened titles, abstracts, full-texts, and extracted data for included studies. Study quality was assessed using the JADAD scale. TIDieR checklist was used to describe interventions. Results Fifteen RCTs were included. Twelve studies were of high quality (JADAD score ≥2), two were of low quality. A total of 1500 participants were recruited across studies. Definition of TIA and minor stroke was unclear, leading to the exclusion of several studies. Various interventions were included, including education/psychoeducation (n = 4); exercise and lifestyle advice (n = 3); telephone-based education/counseling (n = 3); secondary prevention education (n = 1); motivational interviewing (n = 2); self-management (n = 2). Interventions were inconsistently described, with information missing about who delivered it and tailoring. Conclusions Definitions of stroke severity are not adequately reported. There are a variety of interventions including education about a range of stroke-specific topics. Many interventions are not adequately described, thus making it difficult to determine if the aim was to provide information or support post-TIA/minor stroke. There is a need for an in-depth systematic review to develop a clear definition of psychoeducation.