Miracle-dz/UniFAR-FTUs huggingface dataset:
Immuno‐oncology gene expression profiling of formalin‐fixed and paraffin‐embedded clear cell renal cell carcinoma: Performance comparison of the NanoString nCounter technology with targeted RNA sequencing

Inflammatory gene signatures are currently being explored as predictive biomarkers for immune checkpoint blockade, and particularly for the treatment of renal cell cancers. From a diagnostic point of view, the nCounter analysis platform and targeted RNA sequencing are emerging alternatives to microarrays and comprehensive transcriptome sequencing in assessing formalin‐fixed and paraffin‐embedded (FFPE) cancer samples. So far, no systematic study has analyzed and compared the technical performance metrics of these two approaches. Filling this gap, we performed a head‐to‐head comparison of two commercially available immune gene expression assays, using clear cell renal cell cancer FFPE specimens. We compared the nCounter system that utilizes a direct hybridization technology without amplification with an NGS assay that is based on targeted RNA‐sequencing with preamplification. We found that both platforms displayed high technical reproducibility and accuracy (Pearson coefficient: ≥0.96, concordance correlation coefficient [CCC]: ≥0.93). A density plot for normalized expression of shared genes on both platforms showed a comparable bi‐modal distribution and dynamic range. RNA‐Seq demonstrated relatively larger signaling intensity whereas the nCounter system displayed higher inter‐sample variability. Estimated fold changes for all shared genes showed high correlation (Spearman coefficient: 0.73). This agreement is even better when only significantly differentially expressed genes were compared. Composite gene expression profiles, such as an interferon gamma (IFNg) signature, can be reliably inferred by both assays. In summary, our study demonstrates that focused transcript read‐outs can reliably be achieved by both technologies and that both approaches achieve comparable results despite their intrinsic technical differences.
Simultaneous Versus Delayed Resection for Initially Resectable Synchronous Colorectal Cancer Liver Metastases

Supplemental Digital Content is available in the text Objective: To answer whether synchronous colorectal cancer liver metastases (SLM) should be resected simultaneously with primary cancer or should be delayed. Summary Background Data: Numerous studies have compared both strategies. All were retrospective and conclusions were contradictory. Methods: Adults with colorectal cancer and resectable SLM were randomly assigned to either simultaneous or delayed resection of the metastases. The primary outcome was the rate of major complications within 60 days following surgery. Secondary outcomes included overall and disease-free survival. Results: A total of 105 patients were recruited. Eighty-five patients (39 and 46 in the simultaneous- and delayed-resection groups, respectively) were analyzed. The percentage of major perioperative complications did not differ between groups (49% and 46% in the simultaneous- and delayed-resection groups, respectively, adjusted OR 0.84, 95% CI 0.35–2.01; P = 0.70, logistic regression). Complications rates were 28% and 13% (P = 0.08, χ2 test) at colorectal site and 15% and 17% (P = 0.80, χ2 test) at liver site, in simultaneous- and delayed-resection groups, respectively. In the delayed-resection group, 8 patients did not reach the liver resection stage, and this was due to disease progression in 6 cases. After 2 years, overall and disease-free survival tended to be improved in simultaneous as compared with delayed-resection groups (P = 0.05), a tendency which persisted for OS after a median follow-up of 47 months. Conclusions: Complication rates did not appear to differ when colorectal cancer and synchronous liver metastases are resected simultaneously. Delayed resection tended to impair overall survival.
Wide Stromal Mapping Using an Anterior Segment Optical Coherence Tomography

Purpose To quantify and assess the reproducibility of the corneal stromal thickness profiles captured by the SD-OCT. Secondly, we correlated the zonal thicknesses to the age, gender and axial length. Methods We included 227 normal eyes of 227 patients with a maximum hypermetropia of +5 and myopia of –6 diopters (D). Subjects with an intraocular pressure exceeding 22 mm Hg, evidence of cataract formation, history of ophthalmic surgery or disease were excluded. Lastly, reproducibility was evaluated in a subset of 50 participants by means of an identical scan protocol repeated by 2 different OCT operators. Results Stromal values were consistently thicker in the peripheral cornea (p<0.001). Age was negatively correlated with approximately every sector of the stroma with notable exceptions of the center (r=0.117, p=0.088) and the superior inner (r=0.057, 0.409), middle (r=0.086, p=0.209) and outer locations (r=0.120, p=0.079). There was no statistical significance in most sectors when looking at the axial length, gender and K1/K2. This method was highly reproducible in terms of both the ICC and COV. Conclusion Corneal stromal mapping is highly reproducible and shows a negative correlation to age. Additionally, the periphery of the stroma is consistently thicker to the center. Other variables like gender and axial length show no relationship to the corneal stroma.
Recent progress in treating advanced prostate cancer.

PURPOSE OF REVIEW Summarize recent advances in the treatment of advanced prostate cancer. RECENT FINDINGS Recent randomized data suggest a survival advantage to early use of novel androgen receptor inhibitors in combination with androgen deprivation therapy both in the setting of hormone-sensitive metastatic prostate cancer and nonmetastatic castration-resistant disease. While ongoing analyses examine optimal sequencing of existing agents for treatment of advanced prostate cancer, additional research focuses on expanding treatment options through development of novel genomically targeted therapies, antibody-drug conjugates, and immune therapy combinations. SUMMARY In this review, we summarize the recent data supporting the early use of novel androgen receptor inhibitors in advanced prostate cancer and aim to also frame how these drugs may fit within the existing context of docetaxel and abiraterone. We present recent series examining sequencing of approved therapies while searching for predictive biomarkers. Finally, we examine trials evaluating novel agents that target certain biological pathways to highlight the likely future directions for progress in the clinical management of advanced prostate cancer.
Goodyschle A, a new butenolide with significant BchE inhibitory activity from Goodyera schlechtendaliana

Abstract Goodyschle A (1), a new butenolide, was isolated from the whole grass of Goodyera schlechtendaliana, an orchidaceous edible medicinal plant. The structure of the new compound was elucidated by 1 D and 2 D NMR experiments in addition to HRESIMS analyses. Compound 1 was evaluated for its bioactivities including cytotoxic activity against human gastric cancer (SGC-7901) and human hepatocellular carcinoma (HepG2) cell lines, inhibitory activity on acetylcholinesterase (AChE) and butyrylcholinesterase (BChE), and DPPH radical scavenging activity. As a result, compound 1 showed potent BChE inhibitory activity (IC50 value = 6.88 ± 1.63 μM), moderate DPPH radical scavenging activity (IC50 value = 16.25 ± 0.21 μM), and slight AChE inhibitory and cytotoxic activities. These findings suggest that compound 1 is worthy for further investigations in terms of its selective BChE inhibitory activity. Graphical Abstract
Myriocin‐induced adaptive laboratory evolution of an industrial strain of Saccharomyces cerevisiae reveals its potential to remodel lipid composition and heat tolerance

The modification of lipid composition allows cells to adjust membrane biophysical properties in response to changes in environmental temperature. Here, we use adaptive laboratory evolution (ALE) in the presence of myriocin, a sphingolipid (SLs) biosynthesis inhibitor, to remodel the lipid profile of an industrial yeast strain (LH) of Saccharomyces cerevisiae. The approach enabled to obtain a heterogeneous population (LHev) of myriocin‐tolerant evolved clones characterized by its growth capacity at high temperature. Myriocin exposure also caused tolerance to soraphen A, an inhibitor of the acetyl‐CoA carboxylase Acc1, the rate‐limiting enzyme in fatty acid de novo production, supporting a change in lipid metabolism during ALE. In line with this, characterization of two randomly selected clones, LH03 and LH09, showed the presence of lipids with increased saturation degree and reduced acyl length. In addition, the clone LH03, which displays the greater improvement in fitness at 40°C, exhibited higher SL content as compared with the parental strain. Analysis of the LH03 and LH09 genomes revealed a loss of chromosomes affecting genes that have a role in fatty acid synthesis and elongation. The link between ploidy level and growth at high temperature was further supported by the analysis of a fully isogenic set of yeast strains with ploidy between 1N and 4N which showed that the loss of genome content provides heat tolerance. Consistent with this, a thermotolerant evolved population (LH40°) generated from the parental LH strain by heat‐driven ALE exhibited a reduction in the chromosome copy number. Thus, our results identify myriocin‐driven evolution as a powerful approach to investigate the mechanisms of acquired thermotolerance and to generate improved strains.
Ultrasensitive fluorescent detection of pesticides in real sample by using green carbon dots

Pesticides, widely used in modern agriculture, could potentially cause environmental pollution and affect human lives. Hence, the development of a highly sensitive sensing element to detect pesticide residues is crucial for food safety and ecosystem protection. Optical methods based on fluorescence properties provide an ideal approach for screening and quantification of these compounds in different medias including water, plant, and nutritional products. The development of fluorescence emitting carbon dot-based sensors for monitoring pesticides has attracted great attention in recent years. In comparison to other fluorophores, carbon dots have more promising optical features, higher quantum yields and better biocompatibility. This article aims to present a novel fluorescent sensing method of diazinon, glyphosate, and amicarbazone using plant-based carbon dots. A comprehensive characterization of carbon dots obtained from cauliflower was performed by methods including UV-visible, FTIR spectroscopy, fluorometry, AFM, DLS, and zeta sizer. Following this step, carbon dots were used to detect pesticides. The fluorescence quenching property of carbon dots has been utilized to identify detection limit of 0.25, 0.5, and 2 ng ml-1 for diazinon, amicarbazone, and glyphosate, respectively. Also, real sample study revealed that the detection of pesticides accompanied by our developed nano-sensor is repeatable and accurate. According to carbon dots specificity determination, the prepared nano sensor does not have the potential to identify “bromacil” and “dialen super” pesticides but the other three mentioned pesticides are detectable. The results confirm that synthesized green carbon dots are well qualified for application in food safety and environmental monitoring.
Twelve tips for organising speed mentoring events for healthcare professionals at small or large-scale venues

Abstract Mentors play a critical role in the development of professionals, influencing their job satisfaction, career aspirations and evolving professional identity. A variety of mentoring models exist, each with distinct benefits and challenges. Speed mentoring, based on the concept of speed dating, provides mentees with opportunities to meet multiple mentors over a short time and pose focussed career development questions. At large-scale events such as the annual AMEE (Association for Medical Education in Europe) meeting, speed mentoring sessions can successfully connect aspiring, novice and mid-career educators with international educational leaders to facilitate transfer of valuable insights for professional growth. For some mentors and mentees, this might spur ongoing communications or even longitudinal relationships. In this paper, we aim to provide strategies for planning and implementing speed mentoring events, combining insights gained from the literature and our experience of organising speed mentoring at the 2019 AMEE meeting in Vienna. These tips will be useful to a variety of professionals planning to organise speed mentoring initiatives.
Comparison of the pain-reducing effects of EMLA cream and of lidocaine tape during arteriovenous fistula puncture in patients undergoing hemodialysis: A multi-center, open-label, randomized crossover trial

Arteriovenous fistula puncture pain is a serious problem for patients undergoing dialysis and a good indication for topical anesthetics. No previous study has compared lidocaine/prilocaine cream (EMLA) with lidocaine tape for pain relief during arteriovenous fistula puncture in patients undergoing maintenance hemodialysis. To this end, we conducted a multicenter randomized crossover study including 66 patients (mean age, 65.8 years; males, 57.6%) undergoing maintenance hemodialysis thrice/week. Subjects were assigned to Sequence EL (EMLA administration followed by lidocaine, with 1-week wash-out) or Sequence LE (reverse administration, first lidocaine then EMLA). All subjects completed the study. At each puncture site, 1 g EMLA (25 mg lidocaine + 25 mg prilocaine) or one sheet of lidocaine tape (18 mg lidocaine) was applied 1 h or 30 min prior to arteriovenous fistula puncture, respectively. The primary endpoint was puncture pain relief, which was measured using a 100-mm visual analog scale. The secondary endpoints included quality of life, which was measured by SF-36, and safety. EMLA produced a 10.1-mm greater visual analog scale improvement than lidocaine tape (P = 0.00001). However, there was no statistically significant difference in the quality of life between the two groups, and no significant carryover/period effect was observed in any analysis. Further, no drug-related adverse events were observed. Taken together, these results suggest that EMLA cream is superior to lidocaine tape for the relief of arteriovenous fistula puncture pain in patients undergoing maintenance hemodialysis. Trial registration: University Hospital Medical Information Network Clinical Trials Registry (UMIN000027885).
Culture, Sun Exposure and Vitamin D Deficiency in Benghazi Libya

Background: Vitamin D is produced from sunlight exposure through ultraviolet B radiation of the skin. Several factors affect sunlight exposure include time of day, seasonal variation, lower absorption of vitamin D due to dark skin color, sunscreen use, clothing and coverage for cultural or religious reasons along with behavioral attitudes. There is a dearth of studies looking into socio-cultural and behavioral reasons for vitamin D deficiency in the Middle East particularly in Libya. The aim of this study was to identify sun exposure and cultural influences on vitamin D status among patients attending three out patient clinics in Benghazi. Methods: A cross-sectional sample of 287 subjects who were attending three polyclinics in Benghazi. 258 females, and 29 males. Data on participants’ attitudes and behaviors in relation to sun exposure, cultural and skin tone preference were collected using interviews and questionnaires. Results: Duration of sun exposure, use of sun block, wearing long sleeves, believing lighter skin is more attractive than darker and feeling unhappy if the sun made the skin darker were all significantly different between different serum vitamin D level groups and predicted lower vitamin D levels. Vitamin D deficiency was 76.1%, insufficiency was 15.2% and Vitamin D sufficiency was 8.7% in our study. Conclusion: Culture, attitudes and sun exposure behavior could be major contributing factors to the observed high prevalence of VDD in this study. Circulating concentrations of 25(OH)D was significantly lower in subjects with less sun exposure and in those exhibiting negative attitudes toward sunlight. A more accurate measure for culture, behavior and knowledge and sun exposure in a controlled environment is needed to confirm these findings.
Ridge Augmentation Using β-Tricalcium Phosphate and Biphasic Calcium Phosphate Sphere with Collagen Membrane in Chronic Pathologic Extraction Sockets with Dehiscence Defect: A Pilot Study in Beagle Dogs

This study was conducted to comparatively examine spontaneous healing versus ridge augmentation, in surgically-created dehiscence defects, associated with chronic pathology in dogs. Mandibular second, third and fourth premolars (P2, P3 and P4) were hemi-sectioned, and a dehiscence defect was created at the mesial root, while a groove was made on the buccal area from the top of the teeth to the bottom of the defect, exposing the dental pulp. The mesial roots of P2, P3 and P4 were extracted 1 month after the induction of the dehiscence defect with chronic pathology. Three teeth were randomly allocated to these experimental groups: (i) spontaneous healing without any bone graft (Control group: C); (ii) ridge augmentation with β-tricalcium phosphate (β-TCP) granules (Test 1 group: T1); and (iii) ridge augmentation with 60% hydroxyapatite (HA) and 40% β-TCP microspheres (Test 2 group: T2). Postmortem histopathologic examination showed significant between-group differences in C and T1 and C and T2 in bone volume/tissue volume in qualitative micro-computed tomography (CT) analysis, as well as significant intergroup differences in the coronal area at 4 and 12 weeks. The composition of connective tissue and mineralized bone in C and T1 were higher than in T2 at 4 weeks of healing, whereas the composition of mineralized bone was higher in T2 than in T1 at 12 weeks of healing. Biphasic calcium phosphate, composed of 60% HA and 40% β-TCP microsphere (i) potentially prevented marked osteoclastic resorption and (ii) promoted ridge preservation in the extraction socket with the dehiscence defect and chronic pathology.
Soft and Stretchable Thermoelectric Generators Enabled by Liquid Metal Elastomer Composites.

Stretchable thermoelectric generators (TEGs) capable of harvesting electrical energy from body heat in cold weather conditions have the potential to make wearable electronics and robotic systems more lightweight and portable by reducing their dependency on on-board batteries. However, progress depends on the integration of soft conductive materials for robust electrical wiring and thermal management. The use of thermally conductive soft elastomers is especially important for conforming to the body, absorbing body heat, and maintaining a temperature gradient between the two sides of the TEG in order to generate power. Here, we introduce a soft-matter TEG architecture composed of electrically and thermally conductive liquid metal embedded elastomer (LMEE) composites with integrated arrays of n-type and p-type Bi2Te3 semiconductors. The incorporation of LMEE as a multifunctional encapsulating material allows for the seamless integration of 100 thermoelectric semiconductor elements into a simplified material layup that has dimensions of 41.0×47.3×3.0mm. These stretchable thermoelectric devices generate voltages of 59.96mV at Δ10C, 130mV at Δ30C, and 278.6mV and power measurements of 86. 6µW/cm^2 at Δ60C. Moreover, they do not electrically or mechanically fail when stretched to strains above 50%, making them well-suited for energy harvesting in soft electronics and wearable computing applications.
Movement Therapy of the Upper Extremities with a Robotic Ball in Stroke Patients: Results of a Randomized Controlled Crossover Study

Abstract Background Stroke is associated with motor impairments of the upper extremities. The defining goal of rehabilitation is independent execution of activities of daily living. New therapy procedures use different hardware components to implement digital therapy contents. These can be useful complements to established therapy protocols. Objectives The aim of this study was to examine the effect of movement therapy with a robotic ball on motor function parameters in stroke patients. Materials and Methods 25 patients (60.0±10.0 years, 172.5±13.8 cm, 79.5±13.8 kg, 89.8±72.6 months post-stroke) took part in this crossover study. The intervention and control periods comprised 12 weeks each. Training with the robotic ball was done in addition to standard therapy two times a week for 45 min each. Different game activities were carried out with the help of a tablet and a smartphone. Results Isometric grip strength improved by 4.5±3.6 kg (p=0.000), and unilateral dexterity increased by 7.5±6.3 successful tries (p=0.000) in the round block test. The self-reported disabilities of the arm, shoulder and hand were assessed using the QuickDASH questionnaire and showed improvements by 12.4±13.0 points (p=0.001). Conclusions Additional therapy using the robotic ball improved upper extremity motor function and self-perceived health status in chronic stroke patients. However, performance stagnated when standard therapy was implemented alone. Moderately affected patients seem to benefit the most. The presence of very severe motor or cognitive symptoms led, in part, to some dropouts. The results need to be verified using larger patient populations.
Leishmanicidal phenolic compounds derived from Dalbergia cultrata

Abstract Leishmaniasis is a protozoan tropical infection that is estimated to be more than 0.3 million new cases occur annually worldwide. A novel phenolic compound, cultratin A (1), was isolated as a leishmanicidal constituent from the timber of Dalbergia cultrata, along with three known neoflavanoids (2, 3, 4), two benzofurans (5, 6), and two phenolic compounds (7, 8). Their structures were determined using spectral methods. Among them, a new compound (1) and 4-(S)-methoxydalbergione (2) showed effective leishmanicidal activities (IC50: 2.0 and 2.6 μM, respectively), while compound 8 showed moderate activity (IC50: 11 μM). The cytotoxicity of compounds 1 and 2 was also weaker than that of the other compounds. Graphical Abstract