Miracle-dz/UniFAR-FTUs huggingface dataset:
Prognostication in oncology

Prognostication involves formulation and communication about the expected course of the disease and is unique in surgical oncology because of the need to incorporate patient, procedural, and cancer‐related factors. Several tools and techniques are available to assist physicians in formulating prognosis on the basis of these factors. Use of established communication techniques are effective in discussing prognosis. In situations with prognostic uncertainty, use of the best case/worst case/most likely case or time‐limited trial of therapy can be helpful.
Drugging the Small GTPase Pathways in Cancer Treatment: Promises and Challenges

Small GTPases are a family of low molecular weight GTP-hydrolyzing enzymes that cycle between an inactive state when bound to GDP and an active state when associated to GTP. Small GTPases regulate key cellular processes (e.g., cell differentiation, proliferation, and motility) as well as subcellular events (e.g., vesicle trafficking), making them key participants in a great array of pathophysiological processes. Indeed, the dysfunction and deregulation of certain small GTPases, such as the members of the Ras and Arf subfamilies, have been related with the promotion and progression of cancer. Therefore, the development of inhibitors that target dysfunctional small GTPases could represent a potential therapeutic strategy for cancer treatment. This review covers the basic biochemical mechanisms and the diverse functions of small GTPases in cancer. We also discuss the strategies and challenges of inhibiting the activity of these enzymes and delve into new approaches that offer opportunities to target them in cancer therapy.
Motor learning enhanced by combined motor imagery and noninvasive brain stimulation is associated with reduced short‐interval intracortical inhibition

Motor imagery (MI) improves motor skill learning, which is further enhanced when MI is paired with primary motor cortex transcranial brain stimulation or with electrical stimulation of the peripheral median nerve. Applying both stimulation types (here with 25 ms intervals) is called paired associative stimulation (PAS25). The final primary motor cortex output is determined by combined excitatory and intracortical inhibitory circuits, and reducing the latter is associated with enhanced synaptic transmission and efficacy. Indeed, short‐interval intracortical inhibition (SICI) inhibits motor evoked potentials (MEPs), and motor learning has been associated with decreased SICI and increased cortical excitability. Here, we investigated whether cortical excitability and SICI are altered by PAS25 applied after MI‐induced modulation of motor learning.
Effects of Anti-Glaucoma Prostaglandin Ophthalmic Solutions on Cultured Human Corneal Epithelial Cells

ABSTRACT Purpose: We compare the cytotoxicity of anti-glaucoma prostaglandin ophthalmic solutions on human corneal epithelial cells and elucidate mechanisms of toxicity. Methods: Cell viability was examined using MTS assay, and morphological changes of the cells were observed. Induction of necrosis/apoptosis was measured by colorimetric caspase assay. The production of Reactive oxygen species (ROS) and release of cytokines were analyzed using 2ʹ, 7ʹ-dichlorodihydrofluorescein diacetate and bead-based indirect immunofluorescent assay, respectively. Results: Xalatan, Lumigan 0.01%, and Lumigan 0.03% decreased cell viability and induced morphological changes. Xalatan and Lumigan 0.01% induced necrosis. Xalatan, Lumigan 0.01%, Lumigan 0.03%, and Taflotan stimulated ROS production. Travatan and Lumigan 0.03% increased concentrations of Interleukin (IL)-6 and IL-8 in culture media. Conclusions: Xalatan and Lumigan 0.01% ophthalmic solutions demonstrated potent cytotoxicity compared with Lumigan 0.03%, Travatan, Taflotan, and Taflotan UD. Taflotan UD, compared to Taflotan 0.0015%, induced less oxidative stress and apoptotic signalling. The cytotoxicity might be partly associated with benzalkonium chloride.
Corticosteroid Action in the Brain: The Potential of Selective Receptor Modulation

Glucocorticoid hormones have important effects on brain function in the context of acute and chronic stress. Many of these are mediated by the glucocorticoid receptor (GR). GR has transcriptional activity which is highly context-specific and differs between tissues and even between cell types. The outcome of GR-mediated transcription depends on the interactome of associated coregulators. Selective GR modulators (SGRMs) are a class of GR ligands that can be used to activate only a subset of GR-coregulator interactions, thereby giving the possibility to induce a unique combination of agonistic and antagonistic GR properties. We describe SGRM action in animal models of brain function and pathology, and argue for their utility as molecular filters, to characterize context-specific GR interactome and transcriptional activity that are responsible for particular glucocorticoid-driven effects in cognitive processes such as memory consolidation. The ultimate objective of this approach is to identify molecular processes that are responsible for adaptive and maladaptive effects of glucocorticoids in the brain.
Variation of Fungal Metabolites in Sorghum Malts Used to Prepare Namibian Traditional Fermented Beverages Omalodu and Otombo

Sorghum malts, which are important ingredients in traditional fermented beverages, are commonly infected by mycotoxigenic fungi and mycotoxins may transfer into the beverages, risking consumers’ health. Liquid chromatography–tandem mass spectrometry was used to determine variation of fungal metabolites in 81 sorghum malts processed for brewing of Namibian beverages, otombo (n = 45) and omalodu (n = 36). Co-occurrence of European Union (EU)-regulated mycotoxins, such as patulin, aflatoxins (B1, B2, and G2), and fumonisins (B1, B2, and B3) was detected in both malts with a prevalence range of 2–84%. Aflatoxin B1 was quantified in omalodu (44%) and otombo malts (14%), with 20% of omalodu malts and 40% of otombo malts having levels above the EU allowable limit. Fumonisin B1 was quantified in both omalodu (84%) and otombo (42%) malts. Emerging mycotoxins, aflatoxin precursors, and ergot alkaloids were quantified in both malts. Notably, 102 metabolites were quantified in both malts, with 96% in omalodu malts and 93% in otombo malts. An average of 48 metabolites were quantified in otombo malts while an average of 67 metabolites were quantified in omalodu malts. The study accentuates the need to monitor mycotoxins in sorghum malts intended for brewing and to determine their fate in the beverages.
Fine-Scale Characterization of Genomic Structural Variation in the Human Genome Reveals Adaptive and Biomedically Relevant Hotspots

Genomic structural variants (SVs) are distributed nonrandomly across the human genome. These “hotspots” have been implicated in critical evolutionary innovations, as well as serious medical conditions. However, the evolutionary and biomedical features of these hotspots remain incompletely understood. In this study, we analyzed data from 2,504 genomes from the 1000 Genomes Project Consortium and constructed a refined map of 1,148 SV hotspots in human genomes. By studying the genomic architecture of these hotspots, we found that both nonallelic homologous recombination and non-homologous mechanisms act as mechanistic drivers of SV formation. We found that the majority of SV hotspots are within gene-poor regions and evolve under relaxed negative selection or neutrality. However, we found that a small subset of SV hotspots harbor genes that are enriched for anthropologically crucial functions, including blood oxygen transport, olfaction, synapse assembly, and antigen binding. We provide evidence that balancing selection may have maintained these SV hotspots, which include two independent hotspots on different chromosomes affecting alpha and beta hemoglobin gene clusters. Biomedically, we found that the SV hotspots coincide with breakpoints of clinically relevant, large de novo SVs, significantly more often than genome-wide expectations. As an example, we showed that the breakpoints of multiple large de novo SVs, which lead to idiopathic short stature, coincide with SV hotspots. As such, the mutational instability in SV hotpots likely enables chromosomal breaks that lead to pathogenic structural variation formations. Our study contributes to a better understanding of the mutational landscape of the genome and implicates both mechanistic and adaptive forces in the formation and maintenance of SV hotspots.
Treatment of patients with recurrent epithelial ovarian cancer for whom platinum is still an option.

BACKGROUND Ovarian cancer remains the most deadly gynecologic cancer with the majority of patients relapsing within 3 years of diagnosis. Traditional treatment paradigms linked to platinum sensitivity or resistance are currently being questioned in the setting of new diagnostic methods and treatment options. DESIGN Authors carried out review of the literature on key topics in treatment of recurrent epithelial ovarian cancer (EOC) when platinum is still an option; including secondary surgical cytoreduction, chemotherapy, novel treatment options, and maintenance therapy. A treatment algorithm is proposed. RESULTS Molecular characterization of EOC is critical to help guide treatment decisions. The role of secondary cytoreductive surgery is currently being evaluated with results from Gynecologic Oncology Group (GOG) 213 and anticipated results from DESKTOP III clinical trials. Chemotherapy backbone has remained relatively unchanged but utilizing non-platinum-based regimens is under investigation. In addition, maintenance therapy with anti-angiogenic therapy and Poly (ADP-ribose) Polymerase (PARP) inhibitors has emerged as the standard of care. Novel combinations, including immunotherapy and anti-angiogenesis agents, may further change the current landscape. CONCLUSIONS The treatment of recurrent EOC is rapidly changing. Clinical trial design will need to continue to evolve as many novel therapies move to the upfront setting. Ultimately, the treatment of patients with recurrent EOC must incorporate individual patient and tumor factors.
Hedgehog Signaling Regulates Taste Organs and Oral Sensation: Distinctive Roles in the Epithelium, Stroma, and Innervation

The Hedgehog (Hh) pathway has regulatory roles in maintaining and restoring lingual taste organs, the papillae and taste buds, and taste sensation. Taste buds and taste nerve responses are eliminated if Hh signaling is genetically suppressed or pharmacologically inhibited, but regeneration can occur if signaling is reactivated within the lingual epithelium. Whereas Hh pathway disruption alters taste sensation, tactile and cold responses remain intact, indicating that Hh signaling is modality-specific in regulation of tongue sensation. However, although Hh regulation is essential in taste, the basic biology of pathway controls is not fully understood. With recent demonstrations that sonic hedgehog (Shh) is within both taste buds and the innervating ganglion neurons/nerve fibers, it is compelling to consider Hh signaling throughout the tongue and taste organ cell and tissue compartments. Distinctive signaling centers and niches are reviewed in taste papilla epithelium, taste buds, basal lamina, fibroblasts and lamellipodia, lingual nerves, and sensory ganglia. Several new roles for the innervation in lingual Hh signaling are proposed. Hh signaling within the lingual epithelium and an intact innervation each is necessary, but only together are sufficient to sustain and restore taste buds. Importantly, patients who use Hh pathway inhibiting drugs confront an altered chemosensory world with loss of taste buds and taste responses, intact lingual touch and cold sensation, and taste recovery after drug discontinuation.
Functional and Aesthetic Interplay Between the Platysma and Masseter Muscles.

4. KYTHERA Biopharmaceuticals, Inc. KYTHERA Biopharmaceuticals Announces US Availability of KYBELLA(TM)—First FDA-Approved Injectable Treatment for “Double Chin”—Through KYBELLA(TM) Trained Physicians. GlobeNewswire News Room; 2015. Available from: https://www. globenewswire.com/news-release/2015/06/19/745915/0/ en/KYTHERA-Biopharmaceuticals-Announces-US-Availability-ofKYBELLA-TM-First-FDA-Approved-Injectable-Treatment-forDouble-Chin-Through-KYBELLA-TM-Trained-Physicians.html. Accessed July 13, 2019.
The use of stromal vascular fraction (SVF), platelet-rich plasma (PRP) and stem cells in the treatment of osteoarthritis: an overview of clinical trials

Abstract Osteoarthritis (OA) is a major cause of disability across the world, which its prevalence is relatively high in elder population. Current accepted therapies such as exercise, anti-inflammatory drugs and intra-articular inoculation of corticosteroids are aimed at controlling symptoms in the affected patients. Surgical options including arthroplasty, osteotomy and joint replacement are other choices of treatment, which are invasive and can be applied in case of failure of conventional therapies. In the last few decades, efforts to treat musculoskeletal diseases are being increasingly focused on regenerative cellular therapies. Stromal vascular fraction (SVF), which obtained from adipose tissue, contains a variety of cells include mesenchymal stem cells (MSCs) and has shown to be effective in cartilage repair. Autologous blood products such as platelet-rich plasma (PRP) act as an adjuvant of surgical treatment and its intra-articular delivery has shown beneficial effects for OA treatment. Given the efficacy of such treatment approaches in OA, this paper discusses both preclinical and clinical evidence with major focus on clinical trials.
Prenatal Inflammation Dampens Neurogenesis and Enhances Serotonin Transporter Expression in the Hippocampus of Adult Female Rats

Background/Aims: Prenatal exposure to lipopolysaccharide (LPS) dampens hippocampal neurogenesis. This effect is associated with increased anxiety-like behavior in adult offspring. Furthermore, blocking serotonin transporters (SERT) promotes adult neurogenesis. Previous studies were performed largely in males. Therefore, we explored the impact of prenatal LPS on neurogenesis, SERT expression in the hippocampus, and anxiety-like behavior in female rats during prepubertal and adulthood stages. Materials and Methods: Timed pregnant rats were injected with either saline or LPS (100 µg/kg, i.p.) on gestational days 15, 17, and 19. Newly born neurons were monitored by immunohistochemistry, and anxiety-like behavior was monitored using the elevated plus maze and open-field test. SERT expression in the hippocampus was assessed by Western blot and immunofluorescence. Results: Prenatal LPS led to reduced hippocampal neurogenesis in adult but not in prepubertal female offspring. This reduced neurogenesis was associated with enhanced hippocampal expression of SERT protein. However, there was no significant impact of prenatal LPS on anxiety-like behavior. Conclusions: Prenatal LPS-induced reduction in neurogenesis was dissociated from anxiety-like behavior in adult female rats. Furthermore, the long-lasting impact of prenatal LPS on neurogenesis in female offspring was age-dependent.
Diffusion-weighted Magnetic Resonance Imaging for Predicting Response to Chemoradiation Therapy for Head and Neck Squamous Cell Carcinoma: A Systematic Review

Objective To systematically review the evaluation of the diagnostic accuracy of pre-treatment apparent diffusion coefficient (ADC) and change in ADC during the intra- or post-treatment period, for the prediction of locoregional failure in patients with head and neck squamous cell carcinoma (HNSCC). Materials and Methods Ovid-MEDLINE and Embase databases were searched up to September 8, 2018, for studies on the use of diffusion-weighted magnetic resonance imaging for the prediction of locoregional treatment response in patients with HNSCC treated with chemoradiation or radiation therapy. Risk of bias was assessed by using the Quality Assessment Tool for Diagnostic Accuracy Studies-2. Results Twelve studies were included in the systematic review, and diagnostic accuracy assessment was performed using seven studies. High pre-treatment ADC showed inconsistent results with the tendency for locoregional failure, whereas all studies evaluating changes in ADC showed consistent results of a lower rise in ADC in patients with locoregional failure compared to those with locoregional control. The sensitivities and specificities of pre-treatment ADC and change in ADC for predicting locoregional failure were relatively high (range: 50–100% and 79–96%, 75–100% and 69–95%, respectively). Meta-analytic pooling was not performed due to the apparent heterogeneity in these values. Conclusion High pre-treatment ADC and low rise in early intra-treatment or post-treatment ADC with chemoradiation, could be indicators of locoregional failure in patients with HNSCC. However, as the studies are few, heterogeneous, and at high risk for bias, the sensitivity and specificity of these parameters for predicting the treatment response are yet to be determined.
Electrospun nanofiber mesh with fibroblast growth factor and stem cells for pelvic floor repair.

Surgical outcome following pelvic organ prolapse (POP) repair needs improvement. We suggest a new approach based on a tissue-engineering strategy. In vivo, the regenerative potential of an electrospun biodegradable polycaprolactone (PCL) mesh was studied. Six different biodegradable PCL meshes were evaluated in a full-thickness abdominal wall defect model in 84 rats. The rats were assigned into three groups: (1) hollow fiber PCL meshes delivering two dosages of basic fibroblast growth factor (bFGF), (2) solid fiber PCL meshes with and without bFGF, and (3) solid fiber PCL meshes delivering connective tissue growth factor (CTGF) and rat mesenchymal stem cells (rMSC). After 8 and 24 weeks, we performed a histological evaluation, quantitative analysis of protein content, and the gene expression of collagen-I and collagen-III, and an assessment of the biomechanical properties of the explanted meshes. Multiple complications were observed except from the solid PCL-CTGF mesh delivering rMSC. Hollow PCL meshes were completely degraded after 24 weeks resulting in herniation of the mesh area, whereas the solid fiber meshes were intact and provided biomechanical reinforcement to the weakened abdominal wall. The solid PCL-CTGF mesh delivering rMSC demonstrated improved biomechanical properties after 8 and 24 weeks compared to muscle fascia. These meshes enhanced biomechanical and biochemical properties, demonstrating a great potential of combining tissue engineering with stem cells as a new therapeutic strategy for POP repair. © 2019 Wiley Periodicals, Inc. J Biomed Mater Res Part B: 00B: 000-000, 2019.
Hepatocellular Carcinoma: Texture Analysis of Preoperative Computed Tomography Images Can Provide Markers of Tumor Grade and Disease-Free Survival

Objective To investigate the usefulness of computed tomography (CT) texture analysis (CTTA) in estimating histologic tumor grade and in predicting disease-free survival (DFS) after surgical resection in patients with hepatocellular carcinoma (HCC). Materials and Methods Eighty-one patients with a single HCC who had undergone quadriphasic liver CT followed by surgical resection were enrolled. Texture analysis of tumors on preoperative CT images was performed using commercially available software. The mean, mean of positive pixels (MPP), entropy, kurtosis, skewness, and standard deviation (SD) of the pixel distribution histogram were derived with and without filtration. The texture features were then compared between groups classified according to histologic grade. Kaplan-Meier and Cox proportional hazards analyses were performed to determine the relationship between texture features and DFS. Results SD and MPP quantified from fine to coarse textures on arterial-phase CT images showed significant positive associations with the histologic grade of HCC (p < 0.05). Kaplan-Meier analysis identified most CT texture features across the different filters from fine to coarse texture scales as significant univariate markers of DFS. Cox proportional hazards analysis identified skewness on arterial-phase images (fine texture scale, spatial scaling factor [SSF] 2.0, p < 0.001; medium texture scale, SSF 3.0, p < 0.001), tumor size (p = 0.001), microscopic vascular invasion (p = 0.034), rim arterial enhancement (p = 0.024), and peritumoral parenchymal enhancement (p = 0.010) as independent predictors of DFS. Conclusion CTTA was demonstrated to provide texture features significantly correlated with higher tumor grade as well as predictive markers of DFS after surgical resection of HCCs in addition to other valuable imaging and clinico-pathologic parameters.
Pulmonary fibrosis: “idiopathic” is not “cryptogenic”

The writer makes a powerful plea for clarity of thought based on clarity of language, arguing from the Socratic maxim that “the beginning of wisdom is the definition of terms”. This etymological perspective is extremely apposite because the distinction between “cryptogenic” and “idiopathic” disease is seminal in the ongoing idiopathic pulmonary fibrosis (IPF) terminology debate. The additional argument advanced by Professor Cottin for retention of the term “idiopathic pulmonary fibrosis” is highly persuasive http://ow.ly/n05630nVCZd
Comparison of heated humidiﬁed high‐flow nasal cannula flow rates (1‐L·kg·min−1 vs 2‐L·kg·min −1) in the management of acute bronchiolitis

We aimed to compare the heated humidiﬁed high‐ﬂow nasal cannula (HHHFNC) flow rate of 1‐L·kg·min−1 (1 L) with 2‐L·kg·min −1 (2 L) in patients with severe bronchiolitis presenting to the pediatric emergency department.
Development and evaluation of doxorubicin self nanoemulsifying drug delivery system with Nigella Sativa oil against human hepatocellular carcinoma

Abstract Objective The development of self nano emulsifying co-delivery system of doxorubicin and Nigella sativa oil for potentiating the anticancer effects against HepG2 cell lines. Materials and methods SNEDDS were formulated by using Labrafil and N. sativa oil (3:2% w/w), Kolliphor RH40 (15% w/w), glycerol (5% w/w) as oil phase, surfactant and co-surfactant while deionized water (75% v/v) used as an aqueous phase. Optimized SNEDDS was evaluated for drug release and in vitro anticancer efficacy in liver cancer (HepG2) cell line. Results and discussion The selected formulation (F6) has a mean particle size of 79.7 nm with PDI 0.098 and the minimum viscosity of 16.42 cps with % transmittance of 1.332 with maximum drug release of 96.968% in 32 h as compared to DOX alone. Stability data showed stable emulsion in both 250C and -40C. F6 showed improved efficacy in HepG2 cells by cytotoxicity, showed significant results p<. 05 with 2.5 μg/ml of (inhibitory concentration) IC50. Conclusion The overall study displayed that co-delivery of DOX and Nigella sativa oil in the form of SNEDDS may be an efficient carrier for further in vivo studies using oral delivery in human hepatocellular carcinoma in mammals. Graphical Abstract