Miracle-dz/UniFAR-FTUs huggingface dataset:
Macular vascular density at the superficial capillary plexus using the optical coherence tomography angiography

Purpose The aim of this study was to assess the effects of age, gender, axial length and retinal thickness on the vascular density in a normal population using the Optovue optical coherence tomography angiography (OCT-A). Methods A total of 209 eyes of 209 healthy subjects were scanned using the OCT-A on an outpatient basis. Patients were 20–75 years of age. The built-in software covered a 3×3 mm circle centered at the macula. The circle was divided into five sectors: a 1 mm central foveal circle and an upper, lower, nasal and temporal sector each spanning 1–3 mm away from the central circle. The vascular density (VD) at the superficial capillary plexus was measured, which spanned from the inner limiting membrane to the inner plexiform layer. Results The fovea was the least dense area (32.5%±5.9%), and the temporal area was the densest (52.4%± 4.4%). Similarly, the fovea was the thinnest part of the retina (237.8±20.7 µm); however, the nasal sector was the thickest (308.5±15.1 µm). We found a correlation of the retinal thickness (r=0.541, P<0.001) with VD only at the fovea. Similarly, males had a greater density at the fovea (P=0.002). All regions significantly and negatively correlated with age even after adjusting for axial length. The age sees a decline in the density after the fifth decade where the variability also seems to increase. Conclusion This study provides normative data for the Pakistani population. Additionally, it demonstrates that VD is affected by the retinal thickness at the fovea and the density begins to decline after the fifth decade.
Predictors of treatment response for cognitive behaviour therapy for prolonged grief disorder

ABSTRACT Background: Prolonged grief disorder (PGD) causes significant impairment in approximately 7% of bereaved people. Although cognitive behaviour therapy (CBT) has been shown to effectively treat PGD, there is a need to identify predictors of treatment non-response. Methods: PGD patients (N = 80) were randomly allocated to receive 10 weekly two-hour group CBT sessions and (a) four individual sessions of exposure therapy or (b) CBT without exposure. PGD was assessed by self-report measures at baseline, post-treatment (N = 61), and six-months (N = 56) after treatment. Results: Post-treatment assessments indicated that greater reduction in grief severity relative to pretreatment levels was associated with being in the CBT/Exposure condition, and lower baseline levels of self-blame and avoidance. At follow-up, greater grief symptom reduction was associated with being in the CBT/Exposure condition and lower levels of avoidance. Conclusions: These patterns suggest that strategies that target excessive self-blame and avoidance during treatment may enhance response to grief-focused cognitive behaviour therapy.
Introduction of the Exocelinacasuarina-group, with a key to its representatives and descriptions of 19 new species from New Guinea (Coleoptera, Dytiscidae, Copelatinae)

Abstract Nineteen new species of Exocelina Broun, 1886 from New Guinea are described herein: E.adelbertensissp. n. , E.ambuasp. n. , E.bewanisp. n. , E.cyclopssp. n. , E.ibalimisp. n. , E.kekisp. n. , E.kumulensissp. n. , E.mendiensissp. n. , E.menyamyasp. n. , E.okapasp. n. , E.piusisp. n. , E.pseudofumesp. n. , E.pseudopusillasp. n. , E.pusillasp. n. , E.simasp. n. , E.simbaiensissp. n. , E.simbaijimisp. n. , E.sumokedisp. n. , and E.yoginofisp. n. All of them, together with five already described species, have been united into the newly defined casuarina-group, a polyphyletic complex of related species with similar shape of the median lobe and paramere setation. An identification key to all known species of the group is provided, and important diagnostic characters (habitus, color, male protarsomeres 4–5, median lobes, and parameres) are illustrated. Data on the distribution of the species are given, showing that most of the species occur in the central, mountain part of Papua New Guinea.
Lower rotational inertia and larger leg muscles indicate more rapid turns in tyrannosaurids than in other large theropods

Synopsis Tyrannosaurid dinosaurs had large preserved leg muscle attachments and low rotational inertia relative to their body mass, indicating that they could turn more quickly than other large theropods. Methods To compare turning capability in theropods, we regressed agility estimates against body mass, incorporating superellipse-based modeled mass, centers of mass, and rotational inertia (mass moment of inertia). Muscle force relative to body mass is a direct correlate of agility in humans, and torque gives potential angular acceleration. Agility scores therefore include rotational inertia values divided by proxies for (1) muscle force (ilium area and estimates of m. caudofemoralis longus cross-section), and (2) musculoskeletal torque. Phylogenetic ANCOVA (phylANCOVA) allow assessment of differences in agility between tyrannosaurids and non-tyrannosaurid theropods (accounting for both ontogeny and phylogeny). We applied conditional error probabilities a(p) to stringently test the null hypothesis of equal agility. Results Tyrannosaurids consistently have agility index magnitudes twice those of allosauroids and some other theropods of equivalent mass, turning the body with both legs planted or pivoting over a stance leg. PhylANCOVA demonstrates definitively greater agilities in tyrannosaurids, and phylogeny explains nearly all covariance. Mass property results are consistent with those of other studies based on skeletal mounts, and between different figure-based methods (our main mathematical slicing procedures, lofted 3D computer models, and simplified graphical double integration). Implications The capacity for relatively rapid turns in tyrannosaurids is ecologically intriguing in light of their monopolization of large (>400 kg), toothed dinosaurian predator niches in their habitats.
Proinflammatory Role of Angiotensin II in the Aorta of Normotensive Mice

Angiotensin II plays important functions in cardiovascular system mediating actions leading to inflammatory responses such as activation of VSMC in order to produce ROS, inflammatory cytokines, chemokines, and adhesion molecules. Changes in angiotensin II production could stimulate the recruitment and activation of myeloid cells initiating local inflammatory response without effect on BP. We aimed to verify if angiotensin II induces an inflammatory response in the aorta and if it correlates with variations in BP. C57Bl/6 mice treated with saline solution (0.9%, control group) or angiotensin II (30ng/kg, Ang II group) were used. BP and HR levels were measured. Immunohistochemistry for IL1-β, TGF-β, iNOS, CD45, and α-actin was performed in the aorta. BP and HR do not change. A biphasic response was observed both for IL1-β and TGF-β expression and also for the presence of CD45 positive cells, with an acute increase (between 30 and 60 minutes) and a second increase, between 24 and 48 hours. Positive staining for iNOS increased in the earlier period (30 minutes) in perivascular adipose tissue and in a longer period (48 hours) in tunica adventitia. Immunoblotting to α-actin showed no alterations, suggesting that the applied dose of angiotensin II does not alter the aortic VSMCs phenotype. The results suggest that angiotensin II, even at doses that do not alter BP, induces the expression of inflammatory markers and migration of inflammatory cells into the aorta of normotensive mice. Thus, angiotensin II may increase the propensity to develop a cardiovascular injury, even in normotensive individuals.
A 'bump-&-hole' approach for engineering allele-selective inhibition of the BET bromodomains

Chemical tools can be used to investigate the function of proteins and their importance to biological processes and disease. This approach has many advantages over classical genetic tools, but requires compounds with high selectivity for their targets. When single-target selectivity cannot be achieved through normal means it can be engineered through the development of orthogonal protein:ligand pairs, wherein target proteins are mutated and an existing ligand is modified to become mutant-selective. An ideal model for this engineered, allele-specific chemical genetic work is the BET family of bromodomains – 8 closely related, and structurally conserved, epigenetic acetyl-lysine reader domains that so far has defied single-bromodomain inhibition. The Alessio Ciulli lab has previously designed a proof-of-concept ‘bump-&-hole’ system to selectively target these bromodomains by mutating a conserved leucine to an alanine (L/A mutation) and adding an ethyl bump to an existing inhibitor scaffold (ET compound). This system was promising, but required optimisation of the mutation and modified compound before it could be used to answer biological questions. Here the L/A mutation is replaced with a more conservative leucine/valine (L/V) mutation, which is shown to be significantly more functional with regards to acetylated chromatin binding and downstream gene expression. Simultaneously, a large number of new modifications were incorporated into a library of bumped compounds, which were then screened for their selectivity for L/V BET bromodomains (over WT). This lead to the selection of ‘9-ME-1’ as the preferred L/V-selective compound. This optimised BET bump-&-hole system was validated through a number of cellular assays. By repurposing some of these cellular assays the bump-&-hole system was then used to answer biological questions – specifically the relative importance of different BET bromodomains to BET protein function. These results, in connection to recent advances in the literature, provides evidence for a new model of how the BET bromodomains work together to drive downstream gene expression. Finally, the need to use CRISPR/Cas9 gene-editing technology to generate L/Vmutant cell-lines was identified, and an attempt was made to knock-in the L/V mutation to the first bromodomain of BRD4 in a cancer cell-line.
PAK1 Expression in Pancreatic Cancer: Clinicopathological Characteristics and Prognostic Significance

Background: Improvement of the management of pancreatic cancer requires a better understanding of the genetic and molecular changes responsible for the development of the disease. The family of p21-activated kinases (PAKs) and especially PAK1 appears to mediate many cellular processes that contribute to the development and progression of pancreatic cancer, but the clinical relevance of PAK1 expression with the disease still remains unclear. Aim of the study was to assess the clinical value and the potential prognostic significance of PAK1 in pancreatic adenocarcinoma. Methods: We investigated the relationship between the PAK1 expression and the clinical and histopathologic characteristics of pancreatic cancer patients and the potential significance of PAK1 on survival. We examined tissue samples from 51 patients operated for pancreatic cancer. PAK1 expression was investigated with immunohistochemistry and correlated to clinicopathological parameters. Results: PAK1 was detected in all tumor samples and high expression was found in most patients. High PAK1 expression was also associated with younger age and well-differentiated tumors, but no association was found between PAK1 expression and Tumor-Node-Metastasis stage as well as deceased or alive status on follow-up. Moderate to high PAK1 expression favored higher 6-month and 1-year survival and low PAK1 expression 2-year survival but without statistical significance. Conclusions Our results indicate that PAK1 could potentially be used as a prognostic marker in pancreatic cancer. Further studies could clarify whether utilization of PAK1 in therapeutic protocols for the treatment of pancreatic cancer will render them more effective.
Vitamin D3 and Dental Caries in Children with Growth Hormone Deficiency

Vitamin D deficiency is a common risk factor for multifactorial diseases, and it seems to be associated with growth hormone deficiency (GHD). Vitamin D could prevent dental caries. The goal of this study was to identify whether there is an association between hormonal therapy with growth hormone (GH), vitamin D3 supplementation, vitamin D3 levels, and the occurrence of caries among children affected by GHD. The study group consisted of patients from the Department of Endocrinology and Diabetology of the University Paediatric Hospital at the Medical University of Lublin treated with recombinant human GH for pituitary GHD. It was conducted between October 2014 and June 2015. The study group included 121 children and adolescents aged 6 to 18 years, with 56 children from rural areas and 65 from urban areas. The study group was stratified by the area of residence. We found the statistically significant impact of vitamin D3 concentration on the average value of the DMFT (decayed, missed, and filled teeth) index and its component—DT (decayed teeth), which was noted in subjects from rural areas. Among patients from urban areas, we found a statistically significant correlation between duration of therapy and the DMFT index. An increase in duration of GH therapy by 10 months leads to a mean increase in DMFT index by 0.70. Based on multiple regression analysis, we developed the following model: value of DT = 3.10 − 0.73∗category of vitamin D3 concentration − 0.07∗duration of supplementation (in months). In this model, variables with a significant impact on the value of DT in the group of patients from rural areas include time of vitamin D3 supplementation and category of vitamin D3 concentration. Greater emphasis should be placed on promoting vitamin D3 as a potentially effective agent reducing the number of dental caries, especially among patients with GHD.
LATS1/2 kinases trigger self-renewal of cancer stem cells in aggressive oral cancer

Cancer stem cells (CSCs), which play important roles in tumor initiation and progression, are resistant to many types of therapies. However, the regulatory mechanisms underlying CSC-specific properties, including self-renewal, are poorly understood. Here, we found that LATS1/2, the core Hippo pathway-kinases, were highly expressed in the oral squamous cell carcinoma line SAS, which exhibits high capacity of CSCs, and that depletion of these kinases prevented SAS cells from forming spheres under serum-free conditions. Detailed examination of the expression and activation of LATS kinases and related proteins over a time course of sphere formation revealed that LATS1/2 were more highly expressed and markedly activated before initiation of self-renewal. Moreover, TAZ, SNAIL, CHK1/2, and Aurora-A were expressed in hierarchical, oscillating patterns during sphere formation, suggesting that the process consists of four sequential steps. Our results indicate that LATS1/2 trigger self-renewal of CSCs by regulating the Hippo pathway, the EMT, and cell division.
ARssist: augmented reality on a head-mounted display for the first assistant in robotic surgery

In robot-assisted laparoscopic surgery, the first assistant (FA) is responsible for tasks such as robot docking, passing necessary materials, manipulating hand-held instruments, and helping with trocar planning and placement. The performance of the FA is critical for the outcome of the surgery. The authors introduce ARssist, an augmented reality application based on an optical see-through head-mounted display, to help the FA perform these tasks. ARssist offers (i) real-time three-dimensional rendering of the robotic instruments, hand-held instruments, and endoscope based on a hybrid tracking scheme and (ii) real-time stereo endoscopy that is configurable to suit the FA's hand–eye coordination when operating based on endoscopy feedback. ARssist has the potential to help the FA perform his/her task more efficiently, and hence improve the outcome of robot-assisted laparoscopic surgeries.
Studies of the Chemical Reactivity of a Series of Rhodanine Derivatives by Approaches to Quantum Chemistry

This theoretical chemical reactivity study was conducted using the Density Functional Theory (DFT) method, at computational level B3LYP/6-31G (d). It involved a series of six (06) 5-arylidene rhodanines and allowed to predict the chemical reactivity of these compounds. DFT global chemical reactivity descriptors (HOMO and LUMO energies, chemical hardness, softness, electronegativity) were examined to predict the relative stability and reactivity of rhodanin derivatives. Thus, the compound 6 which has an energy gap between the orbitals of ΔEgap = 3.004 eV is the most polarizable, the most reactive, the least stable, the best electron donor and the softest molecule. Calculation of the local indices of reactivity as well as dual descriptors revealed that the sulfur heteroatom of the Rhodanine ring is the privileged site of electrophilic attack in a state of sp3 hybridization and privileged site of nucleophilic attack in a state of sp2 hybridization.
Performance and Return to Sport After Hip Arthroscopic Surgery in Major League Baseball Players

Background: Femoroacetabular impingement (FAI) is a common cause of hip pain that may lead to decreased performance in Major League Baseball (MLB) players. Purpose: To determine the (1) return-to-sport (RTS) rate in MLB players after hip arthroscopic surgery for FAI; (2) postoperative career length, innings pitched (IP) (pitchers), and plate appearances (PA) (position players); (3) preoperative and postoperative performance; and (4) postoperative performance compared with control players matched by position, age, years of experience, and performance. Study Design: Cohort study; Level of evidence, 3. Methods: MLB athletes who underwent hip arthroscopic surgery for FAI and matched controls were identified. Demographic and performance data were collected. RTS was defined as playing in at least 1 MLB game after surgery. Continuous variables of each group were compared using a 2-tailed paired-samples Student t test for normally distributed data. The chi-square test was used to analyze categorical data. The Bonferroni correction was used to control for multiple comparisons, with statistical significance defined by a P value of ≤. 007. Results: A total of 50 players (57 surgeries) were analyzed (mean age, 30.4 ± 3.9 years; mean MLB experience at the time of surgery, 7.0 ± 4.6 years). Pitchers (31 surgeries; 54.4%) represented the largest proportion of players analyzed. Of these players, 42 (47 surgeries; 82.5%) were able to RTS at a mean of 8.3 ± 4.1 months. The overall 1-year MLB career survival rate of players undergoing FAI surgery was 78.9%. Players in the control group were in MLB a similar number of years (4.0 ± 2.9 years) to players who underwent surgery (3.3 ± 2.4 years) (P > .007). There was no significant decrease in IP or PA per season after surgery (P > .007). There was no significant difference in performance for pitchers and nonpitchers compared with matched controls after surgery (P > .007). Conclusion: The RTS rate for MLB athletes after hip arthroscopic surgery for FAI was high. There were similar IP, PA, and career lengths postoperatively compared with preoperatively and with matched controls. There was no significant difference in performance for pitchers and nonpitchers compared with matched controls after surgery.
Effect of Hydroethanolic Extract of Nigella sativa L. on Skin Wound Healing Process in Diabetic Male Rats

Background: The aim of this study was to investigate the effect of hydroethanolic Nigella sativa L. extract on skin wound healing in diabetic male rats. Methods This experimental study was conducted on 49 male Wistar rats weighing 220–250 g divided into 7 groups of 7 each: control (nondiabetic untreated), sham (nondiabetic eucerin-treated), nondiabetic phenytoin (1%)-treated, diabetic untreated, and three diabetic groups treated independently with phenytoin 1%, hydroethanolic N. sativa extracts 20% or 40%. Diabetes was induced with 60 mg/kg streptozosin in one administration. After anesthesia, 2 × 1 cm2 wounds were made on the rats’ backs and each group was administered with its own respective treatment until the wounds were healed completely. Tissue specimens were prepared for histological examinations. The areas of the wounds were measured every 3 days. The data were analyzed by ANOVA and Tukey's post-hoc test. Results: The mean duration of wound healing was 27 and 24 days for diabetic untreated and diabetic phenytoin-treated groups, respectively. Wounds were healed completely in nondiabetic untreated, sham, and nondiabetic phenytoin-treated groups on days 23, 24, and 21, respectively. The shortest duration of wound healing was seen in diabetic N. sativa extract (40%)-treated group (15 days) followed by diabetic N. sativa (20%)-treated group (18 days). These two groups were found to have the lowest mean wound area during the study with a significant difference from mean wound area in the controls (P < 0.05). Conclusions: N. sativa extract significantly promoted wound healing in diabetic rats in comparison with control groups. Although the beneficial mechanism of the promotion of wound healing was not specifically studied, it is believed that the anti-inflammatory and antimicrobial properties of N. sativa would contribute to this enhanced wound healing.
Human Embryonic Stem Cells Acquire Responsiveness to TRAIL upon Exposure to Cisplatin

Tumor necrosis factor-related apoptosis-inducing ligand—TRAIL—is a protein operating as a ligand capable of inducing apoptosis particularly in cancerously transformed cells, while normal healthy cells are typically nonresponsive. We have previously demonstrated that pluripotent human embryonic stem cells (hESC) are also refractory to TRAIL, even though they express all canonical components of the death receptor-induced apoptosis pathway. In this study, we have examined a capacity of DNA damage to provoke sensitivity of hESC to TRAIL. The extent of DNA damage, behavior of molecules involved in apoptosis, and response of hESC to TRAIL were investigated. The exposure of hESC to 1 μM and 2 μM concentrations of cisplatin have led to the formation of 53BP1 and γH2AX foci, indicating the presence of double-strand breaks in DNA, without affecting the expression of proteins contributing to mitochondrial membrane integrity. Interestingly, cisplatin upregulated critical components of the extrinsic apoptotic pathway—initiator caspase 8, effector caspase 3, and the cell death receptors. The observed increase of expression of the extrinsic apoptotic pathway components was sufficient to sensitize hESC to TRAIL-induced apoptosis; immense cell dying accompanied by enhanced PARP cleavage, processing of caspase 8, and full activation of caspase 3 were all observed after the treatment combining cisplatin and TRAIL. Finally, we have demonstrated the central role of caspase 8 in this process, since its downregulation abrogated the sensitizing effect of cisplatin.