Miracle-dz/UniFAR-FTUs huggingface dataset:
Ambulatory Blood Pressure Monitoring to Predict Response to Renal Denervation: A Post Hoc Analysis of the RADIANCE-HTN SOLO Study.

Renal denervation (RDN) is effective in lowering blood pressure (BP) in patients with hypertension. The issue remains how to best identify potential responders. Ambulatory BP monitoring may be useful. Baseline nighttime systolic BP (SBP) ≥136 mm Hg and its variability (SD) ≥12 mm Hg in DENER-HTN trial or 24-hour heart rate ≥73.5 bpm in SPYRAL HTN-OFF MED Trial were shown to predict the BP response to RDN. We applied these criteria to the patients with hypertension in the sham-controlled RADIANCE-HTN SOLO trial to predict the BP response to ultrasound RDN at 2 months while patients were maintained off medications. BP responders were defined as: clinical with 24-hour SBP <130 mm Hg (RDN: 22/64 versus sham: 7/58); meaningful with 24-hour SBP reduction ≥10 mm Hg (RDN: 24/64, sham: 7/58); and extreme with 24-hour SBP reduction above mean+2 SD of the SBP decrease in the sham group, that is, ≥16.5 mm Hg (RDN: 10/64 versus sham: 2/58). The predictive criteria reported above were tested for sensitivity, specificity, and positive and negative predictive values. The predictive value varied according to the definition of response, with the clinical definition being strongly influenced by regression to the mean. Baseline nighttime SBP and its variability, especially when combined, offered good specificity (>90% irrespective of definition) but low sensitivity (from 9.1% to 30% depending on the definition) to predict responders; the heart rate criterion had insufficient predictive value. This analysis suggests the potential role of nighttime SBP and its variability to predict BP response to RDN in patients with hypertension. Registration: URL: https://www.clinicaltrials. gov; Unique identifier: NCT02649426.
Structure and dynamics of membrane protein in SARS-CoV-2

Abstract SARS-CoV-2 membrane (M) protein performs a variety of critical functions in virus infection cycle. However, the expression and purification of membrane protein structure is difficult despite tremendous progress. In this study, the 3 D structure is modeled followed by intensive validation and molecular dynamics simulation. The lack of suitable homologous templates (>30% sequence identities) leads us to construct the membrane protein models using template-free modeling (de novo or ab initio) approach with Robetta and trRosetta servers. Comparing with other model structures, it is evident that trRosetta (TM-score: 0.64; TM region RMSD: 2 Å) can provide the best model than Robetta (TM-score: 0.61; TM region RMSD: 3.3 Å) and I-TASSER (TM-score: 0.45; TM region RMSD: 6.5 Å). 100 ns molecular dynamics simulations are performed on the model structures by incorporating membrane environment. Moreover, secondary structure elements and principal component analysis (PCA) have also been performed on MD simulation data. Finally, trRosetta model is utilized for interpretation and visualization of interacting residues during protein-protein interactions. The common interacting residues including Phe103, Arg107, Met109, Trp110, Arg131, and Glu135 in the C-terminal domain of M protein are identified in membrane-spike and membrane-nucleocapsid protein complexes. The active site residues are also predicted for potential drug and peptide binding. Overall, this study might be helpful to design drugs and peptides against the modeled membrane protein of SARS-CoV-2 to accelerate further investigation. Communicated by Ramaswamy H. Sarma Graphical Abstract
Monoatomic Layer Electronics Constructed by Graphene and Boron Nitride Nanoribbons

A new and simple kind of heterostructure nanoelectronics, which are free of metal electrodes, is constructed by a boron nitride nanoribbon (BNNR) seamlessly connected between two pieces of graphene nanoribbons (GNRs). The electron transport properties of devices based on such GNR-BNNR-GNR heterostructures are systematically investigated. The effects of vacancy, chirality, width, and boundary of nanoribbons on the electron transport properties of these devices are discussed. Energy gaps over 1 eV are observed in the electron transmission spectra of devices composed of these heterojunctions, indicating their pronounced field effect transistor (FET) characters. Removing hydrogen atoms at the boron edge of zigzag BNNR can result in 100% electron spin polarization in the GNR-BNNR-GNR FET. This study has implications for developing high-performance monatomic layer nanoelectronics with simple heterojunctions.
Digital Eye Strain Epidemic amid COVID-19 Pandemic – A Cross-sectional Survey

ABSTRACT Purpose: There has been an enormous increase in the use of gadgets for online classes and entertainment during the COVID-19 pandemic. This study aimed to estimate the prevalence of digital eye strain (DES), describe the pattern of gadget usage, and analyse the risk factors for DES. Methods: This online survey analysed 941 responses from students of online classes (688), teachers of online classes (45), and general population (208). A pre-validated questionnaire was used to calculate the DES score. Non-parametric tests of medians were used to compare the median DES score, Chi-square test to compare categorical variables, and binary logistic regression to find the predictors of DES. Results: The prevalence of eye strain was higher among students taking online classes compared to the general public (50.6% vs 33.2%; χ2 = 22.5, df = 1, p < .0001). There was an increase in screen time during the pandemic compared to pre-pandemic time. The DES score was highest among students attending online classes (p < .0001), in those with eye diseases (p = .001), greater screen time (p = <0.0001), screen distance <20 cm (p = .002), those who used gadgets in dark (p = .017) and those who took infrequent/no breaks (p = .018). The DES scores were proportional to the increase in the number of hours of gadget usage during the pandemic. Conclusion: There is a need to educate people about limiting overall screen exposure and ergonomic methods of screen viewing. Efforts from policymakers to reduce the duration of online classes for students and online work hours for professionals are warranted to control this epidemic of eye strain.
Deep Learning in Drug Design: Protein-Ligand Binding Affinity Prediction

Computational drug design relies on the calculation of binding strength between two biological counterparts especially a chemical compound, i.e., a ligand, and a protein. Predicting the affinity of protein-ligand binding with reasonable accuracy is crucial for drug discovery, and enables the optimization of compounds to achieve better interaction with their target protein. In this paper, we propose a data-driven framework named DeepAtom to accurately predict the protein-ligand binding affinity. With 3D Convolutional Neural Network (3D-CNN) architecture, DeepAtom could automatically extract binding related atomic interaction patterns from the voxelized complex structure. Compared with the other CNN based approaches, our light-weight model design effectively improves the model representational capacity, even with the limited available training data. We carried out validation experiments on the PDBbind v.2016 benchmark and the independent Astex Diverse Set. We demonstrate that the less feature engineering dependent DeepAtom approach consistently outperforms the other baseline scoring methods. We also compile and propose a new benchmark dataset to further improve the model performances. With the new dataset as training input, DeepAtom achieves Pearson's R=0.83 and RMSE=1.23 <inline-formula><tex-math notation="LaTeX">$pK$</tex-math><alternatives><mml:math><mml:mrow><mml:mi>p</mml:mi><mml:mi>K</mml:mi></mml:mrow></mml:math><inline-graphic xlink:href="rezaei-ieq1-3046945.gif"/></alternatives></inline-formula> units on the PDBbind v.2016 core set. The promising results demonstrate that DeepAtom models can be potentially adopted in computational drug development protocols such as molecular docking and virtual screening.
Reduced top‐down attentional control in adolescents with generalized anxiety disorder

Generalized anxiety disorder (GAD) can significantly impair quality of life and is associated with a relatively poor long‐term prognosis. Anxiety disorders are often associated with hyper‐responsiveness to threat, perhaps coupled with impaired executive functioning. However, GAD, particularly adolescent GAD, has been the focus of little functional neuroimaging work compared to other anxiety disorders. Here, we examine the neural association of adolescent GAD with responsiveness to threat and response control.
Differentially expressed genes associated with disease severity in siblings with cystic fibrosis

Cystic fibrosis (CF) is an autosomal recessive disease caused by CFTR gene mutations. Despite having the same mutation, CF patients may demonstrate clinical variability in severity and prognosis of the disease. In this study, we aimed to determine differentially expressed genes between mild and severe siblings with same genotype. We performed targeted real‐time polymerase chain reaction based transcriptomic analysis of nasal epithelial cells obtained from two families with two siblings with Class II mutations (F508del/F508del) and (F508del/G85E), one family with three siblings with Class IV mutation (I1234V/I1234V). In severe siblings with Class II mutations, TNFRSF11A, KCNE1, STX1A, SLC9A3R2 were found to be up regulated. CXCL1, CFTR, CXCL2 were found to be down regulated. In the severe sibling with Class IV mutation; mainly genes responsible from complement and coagulation system were identified. Comparison of CF patients to non‐CF control; showed that ICAM1 was up regulated whereas EZR, TNFRSF1A, HSPA1A were down regulated in patients. As a result of this study, differentially expressed genes responsible for clinical severity among affected siblings carrying the same mutation were identified. The results will provide an opportunity for the development of novel target molecules for treatment of disease.
Pupillary and Attentional Responses to Infant Facial Expressions in Mothers Across Socioeconomic Variations.

Maternal responses to infant facial expressions were examined in two socioeconomically diverse samples of South African mothers (Study I, N = 111; and Study II, N = 214; age: 17-44 years) using pupil and gaze tracking. Study I showed increased pupil response to infant distress expressions in groups recruited from private as compared to public maternity clinics, possibly reflecting underlying differences in socioeconomic status (SES) across the groups. Study II, sampling uniformly low-SES neighborhoods, found increased pupil dilation and faster orientation to expressions of infant distress, but only in the highest income group. These results are consistent with maternal physiological and attentional sensitivity to infant distress cues but challenge the universality of this sensitivity across socioeconomic diversity.
Microclimate structures communities, predation and herbivory in the High Arctic

Abstract In a warming world, changes in climate may result in species‐level responses as well as changes in community structure through knock‐on effects on ecological interactions such as predation and herbivory. Yet, the links between these responses at different levels are still inadequately understood. Assessing how microclimatic conditions affect each of them at local scales provides information essential for understanding the consequences of macroclimatic changes projected in the future. Focusing on the rapidly changing High Arctic, we examine how a community based on a common resource species (avens, Dryas spp.), a specialist insect herbivore (Sympistis zetterstedtii) and natural enemies of lepidopteran herbivores (parasitoids) varies along a multidimensional microclimatic gradient. We ask (a) how parasitoid community composition varies with local abiotic conditions, (b) how the community‐level response of parasitoids is linked to species‐specific traits (koino‐ or idiobiont life cycle strategy and phenology) and (c) whether the effects of varying abiotic conditions extend to interaction outcomes (parasitism rates on the focal herbivore and realized herbivory rates). We recorded the local communities of parasitoids, herbivory rates on Dryas flowers and parasitism rates in Sympistis larvae at 20 sites along a mountain slope. For linking community‐level responses to microclimatic conditions with parasitoid traits, we used joint species distribution modelling. We then assessed whether the same abiotic variables also affect parasitism and herbivory rates, by applying generalized linear and additive mixed models. We find that parasitism strategy and phenology explain local variation in parasitoid community structure. Parasitoids with a koinobiont strategy preferred high‐elevation sites with higher summer temperatures or sites with earlier snowmelt and lower humidity. Species of earlier phenology occurred with higher incidence at sites with cooler summer temperatures or later snowmelt. Microclimatic effects also extend to parasitism and herbivory, with an increase in the parasitism rates of the main herbivore S. zetterstedtii with higher temperature and lower humidity, and a matching increase in herbivory rates. Our results show that microclimatic variation is a strong driver of local community structure, species interactions and interaction outcomes in Arctic ecosystems. In view of ongoing climate change, these results predict that macroclimatic changes will profoundly affect arctic communities.
Ileocolocolic intussusception with multiple internal abdominal herniations complicated by multiple colonic perforations: an enigma

A 55-year-old gentleman presented with complaints of alteration of bowel habits for the past 2 months, the passage of blood-mixed mucus per rectum for about 10 days and multiple episodes of bilious vomiting associated with colicky pain and persistent abdominal distention for 2 days. General physical examination was marked by the presence of tachycardia, tachypnoea and signs of dehydration. His abdomen was distended, with visible ‘step ladder-pattern’ of bowel peristalsis, mildly tender with the absence of guarding or rigidity. Per-rectal examination revealed ballooning of the rectum with a smooth-surfaced, bilobed mass hanging from the top into the lumen like a ‘bell-clapper’, and associated with a bloody-mucinous discharge. His sigmoidoscopy revealed a large, freely mobile, mass hanging from the proximal colon into the rectum and obstructing the lumen at 10 cm from the anal verge. Contrast-enhanced computed tomography scan of the abdomen demonstrated the presence of massive intussusception into rectosigmoid with evidence of a 7.5 × 5 cm sized fat-containing lesion in rectum at the tip of intussusception having a centrally enhancing solid component (Fig. 1). Emergency exploratory laparotomy revealed small bowel proximal to the site of intussusception dilated and congested. The terminal ileum, caecum, ascending colon and proximal half of the transverse colon had telescoped into the distal part of the colon, reaching up to the proximal rectum. Few jejunal loops herniated through mesocolon of the descending colon to lie in the left paracolic gutter and anterior to the left kidney (left paraduodenal herniation). A couple of jejunal loops herniated through distal half of the
Exploring the origin and regulatory role of mast cells in asthma

Purpose of review Mast cells have previously been thought to function solely as effector cells in asthma but more recent studies have indicated that mast cells may play a more central role in propagating and regulating lower airway inflammation in asthma. Recent findings Initial studies have found increased numbers of mast cell progenitors (MCPs) in the peripheral blood of patients with asthma and these cells could contribute to the increased number of progenitors identified in the airways of patients with asthma. There are unique subpopulations of mast cells within the asthmatic airway, which are characterized by their physical location and distinguished by their expression profile of mast cell proteases. Intraepithelial mast cells are tightly associated with type-2 (T2) inflammation but additional studies have suggested a role for anti-mast cell therapies as a treatment for T2-low asthma. Mast cells have recently been shown to closely communicate with the airway epithelium and airway smooth muscle to regulate lower airway inflammation and airway hyperresponsiveness. Summary Recent studies have better illuminated the central role of mast cells in regulating lower airway inflammation and airway hyperresponsiveness.
Documenting the course of loss of control over eating prior to, during and after pregnancy among women with pre-pregnancy overweight and obesity.

OBJECTIVE Loss of control over eating (LOC) is common among women, particularly those with overweight and obesity (OV/OB), and predicts weight gain. Given the importance of understanding weight and eating behaviors during pregnancy, we sought to characterize LOC across pregnancy and the postpartum period among women with pre-pregnancy OV/OB. METHODS Pregnant women (N = 257; 28.44 ± 5.48 years old) with self-reported OV/OB prior to pregnancy were interviewed using a pregnancy-adapted version of the Eating Disorder Examination (EDE-PV). Pre-pregnancy LOC was retrospectively assessed during the first trimester and then prospectively assessed monthly throughout pregnancy and postpartum over the course of seven assessments. RESULTS Rates of LOC were significantly higher during pregnancy compared to prior to ( χ 1 2 =44.845, p < .01) and after ( χ 1 2 =36.379, p < .01) pregnancy, with 37% (n = 95) of women reporting ≥1 LOC episode during pregnancy. LOC during pregnancy was associated with higher likelihood of LOC postpartum. Higher age (OR = 1.084, p = .04) and identifying as a minority (OR = 0.344, p = .02) was associated with greater likelihood of experiencing LOC during pregnancy only. DISCUSSION LOC during pregnancy is common among women with pre-pregnancy OV/OB, suggesting that screening and intervention for LOC during pregnancy may be warranted. Future research is necessary to examine the relationship between LOC during pregnancy and maternal and infant health outcomes.
Indicators of Secretory Activation in Mothers of Preterm Very Low Birth Weight Infants

Background Inconsistent information exists regarding indicators of secretory activation in mothers delivering very low birth weight infants. Research aims To compare time to the onset of secretory activation using three separate indicators. A secondary aim examined the association between indicators of secretory activation and milk production. Methods Indicators of secretory activation included maternal perception, volume attainment (production of ≥ 20 mL in two consecutive expression sessions) and biomarkers (sodium and lactose) obtained at volume attainment. Milk production was measured on Days 1–7 and then weekly for 6 weeks. Results In 69 mothers of infants born ≤ 32 weeks’ gestation and < 1500 g, we found no correlation in time to secretory activation between indicators. Earlier volume attainment was associated with increased milk production on Days 1–7, 14, 21, and 28 (all p < .007). Participants who exhibited both normal lactose and sodium levels produced more milk on Days 28 and 42 (p = .028 and .011), those with only normal lactose levels produced more on Day 42 (p = .026) and those with only normal sodium levels on Day 28 (p = .036). Earlier secretory activation by volume attainment was associated with increased expression frequency during Days 2–5 (all p < .014) and participants with normal biomarkers expressed more frequently during Days 2–5 (all p < .020). Conclusion Mothers of very low birth weight infants are at risk for delayed secretory activation, which may decrease their milk production. Frequent expression during the first 5 days postpartum may promote earlier secretory activation. Valid methods of determining secretory activation are necessary to develop interventions promoting earlier secretory activation.
Transition metal complexes with Schiff-base ligands: 4-aminoantipyrine based derivatives–a review

The survey highlights structural properties and biological studies of transition metal complexes derived from 4-aminoantipyrine. The most important results of extensive studies (syntheses, spectral, magnetic, redox, structural characteristics, antimicrobial and DNA cleavage) of the metal complexes with heterocyclic Schiff bases of 4-aminoantipyrine with some aldehydes and oximes are reviewed.
Targeting BCL‐2 with venetoclax and dexamethasone in patients with relapsed/refractory t(11;14) multiple myeloma

Venetoclax (Ven) is a selective small‐molecule inhibitor of BCL‐2 that exhibits antitumoral activity against MM cells with t(11;14) translocation. We evaluated the safety and efficacy of Ven and dexamethasone (VenDex) combination in patients with t(11;14) positive relapsed/refractory (R/R) multiple myeloma (MM). This open‐label, multicenter study had two distinct phases (phase one [P1], phase two [P2]). Patients in both phases received VenDex (oral Ven 800 mg/day + oral Dex 40 mg [20 mg for patients ≥75 years] on days 1, 8, and 15, per 21–day cycle). The primary objective of the P1 VenDex cohort was to assess safety and pharmacokinetics. Phase two further evaluated efficacy with objective response rate (ORR) and very good partial response or better. Correlative studies explored baseline BCL2 (BCL‐2) and BCL2L1 (BCL‐XL) gene expression, cytogenetics, and recurrent somatic mutations in MM. Twenty and 31 patients in P1 and P2 with t(11;14) positive translocation received VenDex. P1/P2 patients had received a median of 3/5 lines of prior therapy, and 20%/87% were refractory to daratumumab. Predominant grade 3/4 hematological adverse events (AEs) with ≥10% occurrence included lymphopenia (20%/19%), neutropenia (15%/7%), thrombocytopenia (10%/10%), and anemia (5%/16%). At a median follow‐up of 12.3/9.2 months, ORR was 60%/48%. The duration of response estimate at 12 months was 50%/61%, and the median time to progression was 12.4/10.8 months. In biomarker evaluable patients, response to VenDex was independent of concurrent del(17p) or gain(1q) and mutations in key oncogenic signaling pathways, including MAPK and NF‐kB. VenDex demonstrated efficacy and manageable safety in heavily‐pre‐treated patients with t(11;14) R/R MM.