Miracle-dz/UniFAR-FTUs huggingface dataset:
Construction of a novel predictive nomogram for difficult procedure of endoscopic submucosal dissection for colorectal neoplasms

Abstract Objectives To determine the predictors of difficult colorectal endoscopic submucosal dissection (ESD) and to develop a preoperative predictive model for difficult colorectal ESD procedures. Methods Colorectal neoplasms intended to be resected by ESD in our center between August 2013 and February 2019 were retrospectively enrolled. An ESD procedure which took more than 30 min, failed to remove the lesions en bloc or converted to surgery was defined as difficulty. Logistic regression analysis was conducted to find out the predictors of difficult ESD. A nomogram integrating independent predictors was developed and validated with respect to its discrimination, calibration and clinical application, using the receiver operating characteristic (ROC) curve, calibration plot and decision curve analysis (DCA), respectively. Results A total of 368 colorectal neoplasms in 355 patients were included. The independent predictors for difficult colorectal ESD were size ≥2 cm (odds ratio [OR] = 6.102, p < .001), positive non-lifting sign (OR = 6.569, p = .005), lesions located in left colon (OR = 2.475, p = .036) or rectum (OR = 2.183, p = .048), laterally spreading tumors (LSTs) (OR = 2.501, p = .008) and less colorectal ESD experience (≤20 cases) (OR = 2.3091, p = .028). The nomogram model incorporating the above predictors performed well in both of the training and validation sets (area under the cure [AUC] = 0.786 and 0.784, respectively). DCA demonstrated the clinical benefit of the nomogram was superior to that of each independent predictor alone. Conclusions The nomogram incorporating tumor size, location, morphology, non-lifting sign and ESD experience of operator can be conveniently used to facilitate the preoperative prediction of difficult colorectal ESD.
In Vitro Assessment of the Cell Metabolic Activity, Cytotoxicity, Cell Attachment, and Inflammatory Reaction of Human Oral Fibroblasts on Polyetheretherketone (PEEK) Implant–Abutment

The purpose of this research is to compare the cytotoxicity of polyetheretherketone (PEEK) and polyetherketoneketone (PEKK) with conventional dental implant–abutment materials, namely titanium alloy (Ti-6Al-4V) and yttria-stabilized tetragonal zirconia polycrystal (Y-TZP), to evaluate the cell metabolic activity, cytotoxicity, and inflammation potential of human oral fibroblasts (HOF) on these materials. Disk-shaped specimens were designed and prepared via a dental computer-aided manufacturing technology system. Surface topography, roughness, and free energy were investigated by atomic force microscope and contact angle analyzer; cell metabolic activity and cytotoxicity by MTT assay; and morphological changes by scanning electron microscopy (SEM). The effect of pro-inflammatory gene expression was evaluated by RT-qPCR. The obtained data were analyzed with one-way analysis of variance and post-hoc Tukey’s honest significant difference tests. PEEK and PEKK exhibited higher submicron surface roughness (0.04 μm) and hydrophobicity (>80°) than the control. Although the cell activity of PEEK was lower than that of Ti-6Al-4V and Y-TZP for the first 24 h (p < 0.05), after 48 h there was no difference (p > 0.05). According to the cell cytotoxicity and the pro-inflammatory cytokine gene expression assays, there was no difference between the materials (p > 0.05). SEM observations indicated that HOF adhered poorly to PEKK but properly to Ti-6Al-4V, Y-TZP, and PEEK. PEEK and PEKK show comparable epithelial biological responses to Ti-6Al-4V and Y-TZP as implant–abutment materials. Between the two polymeric materials, the PEEK surface, where the HOF showed better cell metabolic activity and cytotoxicity, was a more promising implant–abutment material.
Pancreatic Lineage Specifier PDX1 Increases Adhesion and Decreases Motility of Cancer Cells

Simple Summary A possible way to inhibit tumor cells migration could be strengthening adhesion between tumor and stromal cells in primary solid tumors. Expanding on our previous findings, we have shown that ectopic expression of the pancreatic lineage specifier PDX1 reduces the migration potential of pancreatic cancer cells by increasing their adhesiveness and reducing the sensitivity to TGFβ1-induced epithelial-mesenchymal transition. We observed decreased expression levels of genes associated with promoting cell migration and increased expression of genes negatively affecting cell motility. Our study highlights a potential window for the PDX1 therapeutic application as an antimetastatic agent at the initial stages of cancer development. Abstract Intercellular interactions involving adhesion factors are key operators in cancer progression. In particular, these factors are responsible for facilitating cell migration and metastasis. Strengthening of adhesion between tumor cells and surrounding cells or extracellular matrix (ECM), may provide a way to inhibit tumor cell migration. Recently, we demonstrated that PDX1 ectopic expression results in the reduction of pancreatic cancer line PANC-1 cell motility in vitro and in vivo, and we now provide experimental data confirming the hypothesis that suppression of migration may be related to the effect of PDX1 on cell adhesion. Cell migration analyses demonstrated decreased motility of pancreatic Colo357 and PANC-1 cell lines expressing PDX1. We observed decreased expression levels of genes associated with promoting cell migration and increased expression of genes negatively affecting cell motility. Expression of the EMT regulator genes was only mildly induced in cells expressing PDX1 during the simulation of the epithelial-mesenchymal transition (EMT) by the addition of TGFβ1 to the medium. PDX1-expressing cancer cell lines showed increased cell adhesion to collagen type I, fibronectin, and poly-lysine. We conclude that ectopic expression of PDX1 reduces the migration potential of cancer cells, by increasing the adhesive properties of cells and reducing the sensitivity to TGFβ1-induced EMT.
The Critical Role of Coping Strategies in Moderating Loneliness and Quality of Life: Parallel and Unique Processes among Transgender and Heterosexual Cisgender People in Pakistan

Groups marginalized and/or isolated by minority status—including transgender individuals—are at significant risk for loneliness and diminished quality of life (QoL), effects that can be mitigated to some extent by coping styles. In this study, we examined the relationships among coping styles, loneliness, and QoL outcomes in a marginalized but understudied gender minority group, namely, 200 transgender individuals living in communities in an emerging/developing non-Western geo-cultural region of South-Central Asia (Pakistan), comparing them against a reference group of 100 heterosexual cisgender individuals. Results indicated strong relationships among coping styles, loneliness, and QoL in both transgender and cisgender groups. Moderating variable analysis revealed that coping skills—whether adaptive or maladaptive—help explain differences in loneliness and QoL not only between trans- and cis-gender individuals, but also within just the transgender group. The implications of these findings for intervention strategies to improve QoL among transgender populations are discussed, with reference to both the specific context within Pakistan and the larger context of transgender marginalization within many developing/emerging countries.
Incidence and Characteristics of Intraocular Lens Dislocation after Phacoemulsification: An Eight-Year, Nationwide, Population-Based Study

Background: We investigate the incidence and characteristics of IOL dislocation among the pseudophakic population after phacoemulsification. Methods: National data were collected from the health claims recorded with the Health Insurance Review and Assessment Service of South Korea from 2009 to 2016. Pseudophakic patients aged 40 years or older were included. The incidence estimates of phacoemulsification and IOL dislocation were analyzed, and the cumulative probabilities of IOL dislocation among the pseudophakic population and general population were calculated as a proportion. Results: Of 51,307,821 total subjects, 25,271,917 of whom were aged 40 years or older, 3,906,071 cataract cases in 2,650,104 pseudophakic patients were identified, and 72,309 patients experienced IOL dislocation. The cumulative probability was 2.73% per person and 1.85% per surgery among patients 40 years of age or older. The eight-year incidence rate for IOL dislocation in the pseudophakic population aged 40 years or older was 7671 per 1,000,000 person-years (95% CI: 7616–7727), including 10,341 cases in men and 5814 in women. Incidence peaked in the seventh decade of life for cataract surgery but in the fifth decade of life for IOL dislocation. The cumulative probability of IOL dislocation after phacoemulsification was approximately 2%, and the incidence rate was about 7000 per 1,000,000 pseudophakic patients. Conclusions: There was a significantly higher incidence of IOL dislocation among young males, even though the higher incidence of cataract surgery was observed among older females. These estimates of the nationwide, population-based incidence of IOL dislocation can help increase understanding of the population vulnerable to IOL dislocation.
Childhood Socioeconomic Position, Adult Educational Attainment and Health Behaviors: The Role of Psychological Capital and Health Literacy

Socioeconomic circumstances during childhood and adulthood are known to negatively affect health promoting behaviors. On the other hand, psychological capital (PsyCap) and health literacy are positively associated with these lifestyle behaviors. We, therefore, reasoned that PsyCap and health literacy might “buffer” the negative influences of socioeconomic circumstances on health-promoting behaviors. Method: We measured subjective childhood socioeconomic position (SEP) and adult educational attainment (as a proxy for adult socioeconomic circumstances), health literacy, PsyCap, and health behaviors (fruits and vegetables consumption, exercise, and sweets and cookies consumption) in a sample of N = 150 individuals (mean age 34.98 years, 66.7% female). Results: Bootstrapped mediation analyses including PsyCap and health literacy as parallel mediators revealed that: (I) The relationship between childhood SEP and (a) fruits and vegetables consumption and (b) exercise was mediated by PsyCap, and (II) the relationship between adult educational attainment and (a) fruits and vegetables consumption and (b) exercise was mediated by PsyCap and health literacy. We found no significant effects for consumption of sweets and cookies. Conclusion: These results suggest that larger studies are warranted that confirm the potential of PsyCap and health literacy in mitigating the negative effects of lower SEP on health behaviors and health outcomes.
Large Granular Lymphocytic Leukemia: From Immunopathogenesis to Treatment of Refractory Disease

Simple Summary Large Granular Lymphocytic Leukemia (LGLL) is a clonal disorder of cytotoxic T-cells. Because of the variety of clinical presentations ranging from the mere presence of lymphocytosis to cytopenias and autoimmune conditions, this rare lymphoma may require treatment to control such manifestations. Although first-line treatments are more established, refractory cases are often managed based on the experience of the attending physician. Herein, we review the pathways involved in the pathogenesis of LGLL, including refractory cases, inferring clues as to the potentially actionable targets. Abstract Large Granular Lymphocyte Leukemia (LGLL) is a rare, chronic lymphoproliferative disorder of effector cytotoxic T-cells, and less frequently, natural killer (NK) cells. The disease is characterized by an indolent and often asymptomatic course. However, in roughly 50% of cases, treatment is required due to severe transfusion-dependent anemia, severe neutropenia, or moderate neutropenia with associated recurrent infections. LGLL represents an interesting disease process at the intersection of a physiological immune response, autoimmune disorder, and malignant (clonal) proliferation, resulting from the aberrant activation of cellular pathways promoting survival, proliferation, and evasion of apoptotic signaling. LGLL treatment primarily consists of immunosuppressive agents (methotrexate, cyclosporine, and cyclophosphamide), with a cumulative response rate of about 60% based on longitudinal expertise and retrospective studies. However, refractory cases can result in clinical scenarios characterized by transfusion-dependent anemia and severe neutropenia, which warrant further exploration of other potential targeted treatment modalities. Here, we summarize the current understanding of the immune-genomic profiles of LGLL, its pathogenesis, and current treatment options, and discuss potential novel therapeutic agents, particularly for refractory disease.
A Standardized Prospective Memory Evaluation of the Effects of COVID-19 Confinement on Young Students

The restriction imposed worldwide for limiting the spread of coronavirus disease 2019 (COVID-19) globally impacted our lives, decreasing people’s wellbeing, causing increased anxiety, depression, and stress and affecting cognitive functions, such as memory. Recent studies reported decreased working memory (WM) and prospective memory (PM), which are pivotal for the ability to plan and perform future activities. Although the number of studies documenting the COVID-19 effects has recently blossomed, most of them employed self-reported questionnaires as the assessment method. The main aim of our study was to use standardized tests to evaluate WM and PM in a population of young students. A sample of 150 female psychology students was recruited online for the administration of two self-reported questionnaires that investigated psychological wellbeing (DASS-21), prospective, and retrospective memory (PRMQ). Subjects were also administered two standardized tests for WM (PASAT) and PM (MIST). We found increased anxiety, depression, and stress and decreased PM as measured by self-reports. The perceived memory failures agreed with the results from the standardized tests, which demonstrated a decrease in both WM and PM. Thus, COVID-19 restriction has strongly impacted on students’ mental health and memory abilities, leaving an urgent need for psychological and cognitive recovery plans.
1 Pre-treatment sTNFR1 and HGF levels predict toxicity and overall survival after 90 Y radioembolization: potential novel application of biomarkers for personalized management of hepatotoxicity

Liver function Pretreatment blood cytokine levels are biomarkers for prediction of toxicity and survival after external beam radiation therapy. We hypothesized that cytokines may also predict outcomes after radioembolization, enabling a biomarker-driven personalized approach to treatment. Methods: Pre-therapy blood samples from patients enrolled on a prospective protocol evaluating 90 Y radioembolization for management of intrahepatic malignancy were analyzed for two cytokines selected based on prior studies in stereotactic body radiotherapy (SBRT), soluble tumor necrosis factor receptor 1 (sTNFR1) and hepatocyte growth factor (HGF), via enzyme-linked immunosorbent assay (ELISA), and key dosimetric parameters were derived from post-treatment 90 Y PET/CT imaging. Toxicity was defined as a change in albumin-bilirubin score (ALBI) from baseline to follow up [3-6-month post-treatment (ΔALBI)]. Associations of cytokine levels, dose metrics, and baseline liver function with toxicity and overall survival were assessed. Results: Data from 43 patients treated with 90 Y radioembolization for primary [48.8% (21/43)] or secondary [51.2% (22/43)] malignancy were assessed. Examined dose metrics and baseline liver function were not associated with liver toxicity; however, levels of sTNFR1 (p=0.045) and HGF (p=0.005) were associated with liver toxicity in univariate models. Cytokines were the only predictors of toxicity in multivariable models including dose metrics and prior liver directed therapy. sTNFR1 (HR 12.3; CI 3.5-42.5, p<0.001) and HGF (HR 7.5; CI 2.4-23.1, p<0.001) predicted overall survival, and findings were similar when models were controlled for absorbed dose and presence of metastatic disease. Conclusions: Pretreatment cytokine levels predict liver toxicity and overall survival. These pathways can be targeted with available drugs, an advantage over previously studied dose metrics and liver function tests. Interventions directed at the TNF alpha axis should be considered in future studies for prevention of liver toxicity, and HGF should be explored further to determine whether its elevation drives toxicity or indicates ongoing liver regeneration after prior injury.
Antioxidant Procedure Improve Olive Cuttings Rooting During The Cool Season

Olive tree (Olea europaea L.) consider one of the most important economic resources and diet for the Mediterranean region (Leone et al., 2015), which produce 98% of the olive oil production worldwide (IOC, 2019). Olive oil consumption and demand is increasing due to balanced fatty acid composition and antioxidant properties (IOC, 2019). Also, olive tree is a widely distributed in arid areas for ramified root system and special leaf structure (Tanasijevica et al., 2014). High quality transplants are necessary to success in fruit production. Vegetative propagation of olive via rooting leafy cuttings is widely used (Hartmann et al., 2002 and Fabbri et al., 2004), which considered easy, inexpensive, fast and appropriate for mass plant propagation. The greatest effect on rooting achieved by Auxins (Eid et al., 2018). IBA (indole butyric acid) is the most auxin used for rooting of olive cuttings (Hussein at al., 2017 and Shiri et al., 2019), therefore, the results found vary a lot according to the dosage, the cultivar, the period of rooting, the substrate and the type of cutting among other factors. C temperature during winter season consider an environmental constrains for root and shoot development of olive cuttings. This experiment was carried out during two seasons (2018/19 and 2019/20) to study the rooting ability of ‘Coratina’, ‘Picual’ and ‘Manzanillo’ olive cultivars in addition to study the effect of supplementary intermittent application of IBA and antioxidant (1:1 ascorbic and citric acid) at 100, 200, 300ppm three times after cuttings planting on their rooting behavior during cold winter. The results showed that, ‘Coratina’ olive cultivar recorded the highest significant rooting percent success (75.86 &74.73%) and root number compared to ‘Picual’ and ‘Manzanillo’ cultivar. While, ‘Manzanillo’ cultivar recorded the lowest rooting percent, root number and root length. Antioxidant at 300ppm recorded the highest rooting percent 74.44 & 73.78%, root number and root length. Concerning the interaction effect, the highest significant rooting percent 94.67 & 96.00% and root number was achieved by ‘Coratina’ olive cultivar treated with 300 ppm antioxidant. While, the highest root length recorded by ‘Coratina’ cultivar with100ppm IBA and the highest leaves number recorded by ‘Manzanillo’ cultivar under 100 ppm antioxidant. It can be concluded that, ‘Coratina’ olive cultivar was more suitable for winter season propagation. Also, supplementary application of 300ppm antioxidant was more effective in olive cuttings propagating, while 300ppm IBA had negative effects.
Variable Molecular Weight Polymer Nanoparticles for Detection and Hyperthermia-Induced Chemotherapy of Colorectal Cancer

Simple Summary The purpose of this work was to evaluate the development of polymer-based nanoparticles that can both generate heat and be used for fluorescence detection. The nanoparticles were used against luminescent colorectal cancer cells that were either sensitive or resistant to the chemotherapy drug, oxaliplatin. The fluorescence of the nanoparticles indicates that they are internalized within the cells for heat generation. Mild heating makes oxaliplatin-resistant cancer cells responsive to chemotherapy, and the nanoparticle-induced hyperthermia causes cell death in a few minutes, compared to classical bulk heating, which takes a few hours. Changes in the luminescence of the cancer cells can be used to determine the thermal dose induced by the nanoparticles, which may be correlated with the cell viability and therapeutic response. Abstract Oxaliplatin plays a significant role as a chemotherapeutic agent for the treatment of colorectal cancer (CRC); however, oxaliplatin-resistant phenotypes make further treatment challenging. Here, we have demonstrated that rapid (60 s) hyperthermia (42 °C), generated by the near-infrared stimulation of variable molecular weight nanoparticles (VMWNPs), increases the effectiveness of oxaliplatin in the oxaliplatin-resistant CRC cells. VMWNP-induced hyperthermia resulted in a higher cell death in comparison to cells exposed to chemotherapy at 42 °C for 2 h. Fluorescence from VMWNPs was observed inside cells, which allows for the detection of CRC. The work further demonstrates that the intracellular thermal dose can be determined using cell luminescence and correlated with the cell viability and response to VMWNP-induced chemotherapy. Mild heating makes oxaliplatin-resistant cancer cells responsive to chemotherapy, and the VMWNPs-induced hyperthermia can induce cell death in a few minutes, compared to classical bulk heating. The results presented here lay the foundation for photothermal polymer nanoparticles to be used for cell ablation and augmenting chemotherapy in drug-resistant colorectal cancer cells.
Piezoelectric Microvibration Mitigates Estrogen Loss-Induced Osteoporosis and Promotes Piezo1, MicroRNA-29a, and Wnt3a Signaling in Osteoblasts

Biophysical stimulation alters bone-forming cell activity, bone formation and remodeling. The effect of piezoelectric microvibration stimulation (PMVS) intervention on osteoporosis development remains uncertain. We investigated whether 60 Hz, 120 Hz, and 180 Hz PMVS (0.05 g, 20 min/stimulation, 3 stimulations/week for 4 consecutive weeks) intervention affected bone integrity in ovariectomized (OVX) mice or osteoblastic activity. PMVS (120 Hz)-treated OVX mice developed fewer osteoporosis conditions, including bone mineral density loss and trabecular microstructure deterioration together with decreased serum resorption marker CTX-1 levels, as compared to control OVX animals. The biomechanical strength of skeletal tissue was improved upon 120 Hz PMVS intervention. This intervention compromised OVX-induced sparse trabecular bone morphology, osteoblast loss, osteoclast overburden, and osteoclast-promoting cytokine RANKL immunostaining and reversed osteoclast inhibitor OPG immunoreactivity. Osteoblasts in OVX mice upon PMVS intervention showed strong Wnt3a immunoreaction and weak Wnt inhibitor Dkk1 immunostaining. In vitro, PMVS reversed OVX-induced loss in von Kossa-stained mineralized nodule formation, Runx2, and osteocalcin expression in primary bone-marrow stromal cells. PMVS also promoted mechanoreceptor Piezo1 expression together with increased microRNA-29a and Wnt3a expression, whereas Dkk1 rather than SOST expression was repressed in MC3T3-E1 osteoblasts. Taken together, PMVS intervention promoted Piezo1, miR-29a, and Wnt signaling to upregulate osteogenic activity and repressed osteoclastic bone resorption, delaying estrogen deficiency-induced loss in bone mass and microstructure. This study highlights a new biophysical remedy for osteoporosis.