Miracle-dz/UniFAR-FTUs huggingface dataset:
The risk factors of residual lesions and recurrence of the high-grade cervical intraepithelial lesions (HSIL) patients with positive-margin after conization

Abstract The aim of this study was to illuminate risks factors of residual lesions, and recurrence of the high-grade cervical intraepithelial lesions (HSIL) patients with positive margin who underwent cervical conization. A retrospective cohort study of 218 patients with positive margin after conization, including cold knife conization (CKC) and loop electrosurgical excisional procedure (LEEP), and follow-up from 2013 through 2016. The diagnosis of residual disease and recurrence were established and confirmed by biopsy. We evaluate the correlations among residual rate, recurrence rate, and clinical parameters, such as age, menopausal status, gravity, parity, glandular involvement, thinprep cytologic test (TCT), and human papillomavirus (HPV) results. We also detect the difference between CKC and LEEP. There was statistical difference between the positive margin rate of CKC group and LEEP regarding the surgery methods (5.8% and 12.09% separately, P < .001). Residual disease was found in 53.66% cases where 41 patients received second surgery after conization. Besides, age (P = .027), menopausal status (P = .006), and HPV infection (P = 0.018) were significantly associated with residual lesion. Among 177 cases with histopathologic follow-up, 15.91% women relapsed from 4 to 27 months. As for recurrence we found it was more frequent with HPV infection and glandular involvement (P < .001). TCT was also an independent factor in patients with recurrence of lesion. No evidence shows difference between CKC and LEEP for recurrence rate (P = .918). The factors related to rate of residual lesion were age, menopausal status, and HPV infection. HPV infection, TCT, and glandular involvement were associated with HSIL recurrence. LEEP was as effective as CKC with regard to recurrence rate. Further large-scale studies are needed to confirm our findings.
PLP1 Mutations in Patients with Multiple Sclerosis: Identification of a New Mutation and Potential Pathogenicity of the Mutations

PLP1 is located on the X-chromosome and encodes myelin proteolipid protein (PLP), the most abundant protein in central nervous system myelin. Generally, point mutations in PLP1 result in X-linked dysmyelinating disorders, such as Pelizaeus-Merzbacher disease (PMD) or spastic paraplegia type 2 (SPG2). However, several case studies have identified patients with missense point mutations in PLP1 and clinical symptoms and signs compatible with a diagnosis of multiple sclerosis (MS). To investigate if PLP1 mutations occur relatively frequently in MS, we sequenced the coding regions of PLP1 in 22 female MS patients who had developed disease after the age of 40 and in 42 healthy women, and identified a missense mutation in exon 2 of PLP1 resulting in a Leu30Val mutation in the protein in one of the MS patients. mCherry-tagged plasmids containing wild type or mutant PLP1 sequences of PLP, including two known PMD/SPG2-related mutations as positive controls, were constructed and transfected into Cos-7 cells. In comparison with cells transfected with wild type PLP1, all mutations caused significant accumulation of PLP in the endoplasmic reticulum of the cells and induction of the unfolded protein response—a mechanism that leads to apoptosis of cells expressing mutant proteins. Additionally, in silico analysis of the binding of peptides containing the Leu30Val mutation to the human leukocyte antigen (HLA) molecules carried by the patient harboring this mutation suggested that the mutation could produce several novel immunogenic epitopes in this patient. These results support the idea that mutations in myelin-related genes could contribute to the development of MS in a small proportion of patients.
Sexual health of young people with perinatal HIV and HIV negative young people in England

As adolescents with perinatal HIV (PHIV) survive into adulthood, gaining insight into sexual behaviour and risk-taking is important. Between 2013–2015, 296 PHIV aged 13–21 years and 96 HIV negative affected adolescents (13–23 years) were recruited to the Adolescents and Adults Living with Perinatal HIV (AALPHI) cohort in England. Sexual health data were collected through computer-assisted self-interview questionnaires. Quality of life and household deprivation were also measured. T-tests compared means, and χ2 proportions; logistic regression examined predictors of ever having sex. 120(41%) PHIV and 31(32%) HIV- young people were male, 254(86%) and 70(73%) were black, median age 16 [IQR 15,18] and 16 [14,18] years respectively. 77(26%) PHIV had a previous AIDS diagnosis. 93(32%) PHIV and 38(40%) HIV- had ever had sex; median number of partners was 3 [1,6] and 4 [1,6] respectively. 54 (41%) of 131 young people who were sexually active reported not always using condoms, including 32% (30/93) of PHIV. In multivariable analysis, older age, male sex, worse deprivation score, worse quality of life, and alcohol and/or drugs were associated with ever having sex, but not HIV status. 12/30 PHIV reporting unprotected sex had at least one HIV viral load ≥200c/ml in the previous 12 months. Age at first sex and number of sexual partners were similar among PHIV and HIV-, and comparable to normative data. In conclusion, small numbers of PHIV reported condomless sex with a detectable viral load, which could result in HIV transmission, indicating the need for targeted sexual health and ART adherence interventions for young people with perinatal HIV.
Knockdown of CLDN6 inhibits cell proliferation and migration via PI3K/AKT/mTOR signaling pathway in endometrial carcinoma cell line HEC-1-B

Backgroud Dysregulation of claudin-6 (CLDN6) expression in cancers has been widely documented. However, no study has reported a complete mechanistic understanding of CLDN6 regulation and function in endometrial carcinoma (EC) progression. In the current study, we aimed to assess the expression and biological functions of CLDN6 in EC. Methods Firstly, the expression level of CLDN6 in EC was measured based on The Cancer Genome Atlas (TCGA) database. Then, qRT-PCR and western blotting were implemented to detect the expression levels of CLDN6 in 82 pairs of EC tissues and corresponding non-tumor tissues, as well as EC cell line HEC-1B. After knockdown of CLDN6, with the attempt to assess whether CLDN6 reduction had positive effects on the cell proliferation, clone formation, invasion and migration abilities of HLC-1Bs, cell counting kit-8 (CCK-8) assay (24, 48, 72 and 96 hours post-transfection), clone experiment, and invasion and migration assays were conducted. Through western blotting analysis, CLDN6-mediated phosphatidylinositol 3-kinase (PI3K) pathway was evaluated. Results Based on the data of TCGA database, clinical patients and cell line HEC-1B, CLDN6 was up-regulated in EC compared with normal. Univariate as well as multivariate COX analysis indicated that CLDN6 expression can act as an independent prognostic factor for overall survival of EC. Further, knockdown of CLDN6 significantly inhibited HEC-1B cell proliferation, suppressed the colony numbers of HEC-1-B cells, and restrained the invasive and migratory ability of HEC-1-B cells. Importantly, through western blot analysis, we found that inhibition of CLDN6 remarkably decreased p-AKT, p-PI3K, and mTOR expression level in EC HEC-1B cell line. Conclusion Our data underscore the significance of CLDN6 in EC progression, and CLDN6 is a new candidate oncogene in EC. Our findings propose that targeting CLDN6 might offer future clinical utility in EC.
3D Printing of PLA/clay Nanocomposites: Influence of Printing Temperature on Printed Samples Properties

In this study, the possibility of using a layered silicate-reinforced polylactic acid (PLA) in additive manufacturing applications was investigated. In particular, the aim of this work was to study the influence of printing temperature in the 3D printing process of PLA/clay nanocomposites. For this reason, two PLA grades (4032D and 2003D, D-isomer content 1.5 and 4, respectively) were melt-compounded by a twin screw extruder with a layered silicate (Cloisite 30B) at 4 wt %. Then, PLA and PLA/clay feedstock filaments (diameter 1.75 mm) were produced using a single screw extruder. Dog-bone and prismatic specimens were 3D printed using the FDM technique at three different temperatures, which were progressively increased from melting temperature (185–200–215 °C for PLA 4032D and 165–180–195 °C for PLA 2003D). PLA and PLA/clay specimens were characterized using thermogravimetric analysis (TGA), dynamic mechanical analysis (DMA), differential scanning calorimetry (DSC), and tensile tests. Moreover, the morphology of the 3D printed specimens was investigated using optical microscopy and contact angle measurements. The different polymer matrix and the resulting nanocomposite morphology strongly influenced 3D printed specimen properties. DMA on PLA/clay filaments reported an increase in storage modulus both at ambient temperature and above the glass transition temperature in comparison to neat PLA filaments. Furthermore, the presence of nanoclay increased thermal stability, as demonstrated by TGA, and acted as a nucleating agent, as observed from the DSC measurements. Finally, for 3D printed samples, when increasing printing temperature, a different behavior was observed for the two PLA grades and their nanocomposites. In particular, 3D printed nanocomposite samples exhibited higher elastic modulus than neat PLA specimens, but for PLA 4032D+C30B, elastic modulus increased at increasing printing temperature while for PLA 2003D+C30B slightly decreased. Such different behavior can be explained considering the different polymer macromolecular structure and the different nanocomposite morphology (exfoliated in PLA 4032D matrix and intercalated in PLA 2003D matrix).
Safety and Tolerability of Overdosed Artificial Tears by Abraded Rabbit Corneas

Abstract Purpose: Preservative-free cationic emulsion-based artificial tear (AT) is an innovative eye drop based on the Novasorb® technology with cetalkonium chloride (CKC) as the cationic agent. The cationic emulsion Cationorm is designed for the management of mild-to-moderate dry eye disease (DED) patients that present cornea epithelium alterations. The aim of the present study was to evaluate the safety and tolerability of overdosed ATs by altered corneal epithelium in vivo and assess the usefulness of the ex vivo eye irritation test (EVEIT) as a predictive alternate toxicity test method. Methods: The experimental procedure, treatment duration, and instillation frequency closely mimic in vivo the ex vivo protocol described by Pinheiro et al. and discussed in the Discussion and Conclusion section of this article. Two to 3-month-old female New Zealand white rabbits, n = 6 per group, were treated with ATs (21 instillations/day over 3 days) following corneal abrasion. Corneal fluorescein staining, in vivo confocal microscopy (IVCM), and slit lamp examinations were performed to assess corneal epithelium recovery and the ocular tolerability of the overdosed ATs. Results: All abraded eyes experienced almost complete epithelium recovery within 3 days following treatments with Cationorm, Optive, Vismed, and Saline. Benzalkonium chloride (BAK, 0.02%) treatment resulted in 82.4% reepithelialization. IVCM data illustrated corneal epithelium normal recovery. Acute local tolerability of the overdosed ATs was confirmed using Draize and McDonald–Shadduck's test scales. Conclusions: The different ATs were demonstrated to be well tolerated by abraded corneas in vivo, and the extreme overdosing regimen did not hamper the wound healing process of the rabbit eye in comparison to saline. These data did not confirm the ones obtained with the nonvalidated ex vivo eye irritation test.
Eating disorder symptomatology and body mass index are associated with readers' expectations about character behavior: Evidence from eye‐tracking during reading

OBJECTIVE Many theories have been put forward suggesting key factors underlying the development and maintenance of eating disorders, such as: unhealthy food-related cognitive biases, negative body attitude, and perfectionism; however, underlying cognitive processes associated with eating disorder symptomatology remain unclear. We used eye-tracking during reading as a novel implicit measure of how these factors may relate to eating disorder symptomatology. METHOD In two experiments, we monitored women's eye movements while they read texts in which the characters' emotional responses to food-, body image-, and perfectionism-related scenarios were described. Participants' eating disorder symptomatology was then assessed. RESULTS Both studies suggest that moment-to-moment processing of characters' emotional responses to perfectionism-, and to a lesser extent, body image-related information was associated with participants' eating disorder symptomatology, thus supporting theories in which these factors are key to developing and maintaining eating disorders. Interestingly, the moment-to-moment processing of characters' emotional responses to food-related scenarios was not related to eating disorder symptomatology. DISCUSSION These findings provide novel insights into cognitive processes underlying eating disorder symptomatology, as well as demonstrating the utility of more natural implicit measures.
Immunomodulatory Effects of the Nutraceutical Garlic Derivative Allicin in the Progression of Diabetic Nephropathy

Diabetic nephropathy (DN) is presently the primary cause of chronic kidney disease and end-stage renal disease (ESRD). It has been suggested that inflammation and oxidative stress, in addition to or in concert with the metabolic changes, plays an important role in the maintenance and progression of the disease. Therefore, attenuating or blocking these mechanisms may be a therapeutic target to delay the progression of the disease. Diallyl thiosulfinate (allicin), a compound derived from garlic, inhibits free radical formation, increases glutathione synthesis and decreases the levels of proinflammatory molecules in vitro. This research aimed to assess the effect of allicin on oxidative stress and inflammation-induced diabetes. Animals were divided into control and diabetes (streptozotocin 50 mg/kg i.p.), and maintained for 30 days. After 30 days, the group of diabetic animals was subdivided into diabetes and allicin-treated diabetes (16 mg/kg/day oral gavage). The three experimental groups were maintained for another month. We analyzed the status of renal function, oxidative stress and proinflammatory cytokines. The untreated diabetic group showed hyperglycemia and increased diuresis, creatinine clearance, proteinuria, glycosuria and urinary excretion of N-acetyl-β-d-glucosaminidase (NAG), as well as increased oxidative stress and the expression of interleukin 1β (IL-1β), IL-6, nuclear factor kappa beta (NFκβ) and transforming growth factor-β1 (TGF-β1) in plasma and kidney. In contrast, the inhibitor of NFκβ (Iκβ) is decreased in the cortex. It has been demonstrated that the allicin treatment decreases hyperglycemia, polyuria, and NAG excretion. The oxidative stress and proinflammatory cytokines were also reduced by the allicin treatment. In conclusion, allicin delays the progression of diabetic nephropathy through antioxidant and anti-inflammatory mechanisms.
Identification of a strawberry NPR-like gene involved in negative regulation of the salicylic acid-mediated defense pathway

Hormonal modulation plays a central role in triggering various resistant responses to biotic and abiotic stresses in plants. In cultivated strawberry (Fragaria x ananassa), the salicylic acid (SA)-dependent defense pathway has been associated with resistance to Colletotrichum spp. and the other pathogens. To better understand the SA-mediated defense mechanisms in strawberry, we analyzed two strawberry cultivars treated with SA for their resistance to anthracnose and gene expression profiles at 6, 12, 24, and 48 hr post-treatment. Strawberry genes related to SA biosynthesis, perception, and signaling were identified from SA-responsive transcriptomes of the two cultivars, and the induction of 17 candidate genes upon SA treatment was confirmed by qRT-PCR. Given the pivotal role of the non-expressor of pathogenesis-related (NPR) family in controlling the SA-mediated defense signaling pathway, we then analyzed NPR orthologous genes in strawberry. From the expression profile, FaNPRL-1 [ortholog of FvNPRL-1 (gene20070 in F. vesca)] was identified as an NPR-like gene significantly induced after SA treatment in both cultivars. With a conserved BTB/POZ domain, ankyrin repeat domain, and nuclear localization signal, FvNPRL-1 was found phylogenetically closer to NPR3/NPR4 than NPR1 in Arabidopsis. Ectopic expression of FvNPRL-1 in the Arabidopsis thaliana wild type suppressed the SA-mediated PR1 expression and the resistance to Pseudomonas syringae pv. tomato DC3000. Transient expression of FvNPRL-1 fused with green fluorescent protein in Arabidopsis protoplasts showed that SA affected nuclear translocation of FvNPRL-1. FvNPRL-1 likely functions similar to Arabidopsis NPR3/NPR4 as a negative regulator of the SA-mediated defense.
Food Reward and Distance Influence the Foraging Pattern of Stingless Bee, Heterotrigona itama

Beekeeping with stingless bee provides new opportunities to improve the incomes of many households in Malaysia through the sale of honey and other bee products. While Heterotrigona itama is one of the most commonly cultured species of stingless bees, its behavior is not very well understood. Hence, we conducted this study to investigate the behavior of H. itama in exploiting food sources by ascertaining the nectar sugar concentration preferred by the bee. We also aimed to determine the preferred distance of food source from the beehive. Our results suggest that H. itama prefers high sugar concentrations of 35% and above, and most of the bees preferred to forage close to their hive to collect food. We discuss how nectar concentration, food distance, and abiotic factors influence the number of bees exploiting food sources and the overall foraging pattern of H. itama.
Changes in the morphology of corneal endothelial cells in young myopic adults after 6 months of wearing soft contact lenses: a Malaysian perspective

Purpose Soft contact lens wear is most frequently associated with morphologic changes in corneal endothelial cells, but the data are scarce in Asians. This study aimed to evaluate changes in corneal endothelial cell morphology after 6 months of wearing soft hydrogel contact lenses (SH) in young myopic adults living in Kuala Lumpur. Patients and methods Forty-eight subjects were included in the study, 24 were fitted with SH contact lenses (A) and the rest were prescribed with glasses (B). Refraction was conducted subjectively and standard contact lens fitting protocol was followed. Corneal endothelial cell morphology (endothelial cell density, ECD; coefficient of variation, COV; cells’ hexagonality, HEX; and central corneal thickness, CCT) was evaluated using specular microscope. Data were collected at baseline and after 6 months of lens wear. Results Mean age of all subjects was 21.23±1.30 years. All results are shown at baseline and 6 months, respectively. Mean refraction for A was –2.16±0.97 diopter sphere (DS) and –2.05±1.03 DS (P=0.49); for B was –2.72±1.51 DS and –2.73±1.51 DS (P=0.58). Mean ECD (cell/mm2) for A: 3104.19±237.30 and 3107.23±237.51 (P=0.07); for B: 3011.56±227.95 and 2983.83±244.55 (P=0.33). COV (%) for A: 46.52±8.63 and 48.53±10.65 (P=0.06); for B: 46.93±9.31 and 46.14±10.65 (P=0.88). HEX (%) for A: 46.21±10.12 and 45.15±10.01 (P=0.08); for B: 46.21±10.12 and 45.15±10.01 (P=0.12). CCT (µm) for A: 520.33±0.04 and 525.70±0.05 (P=0.41); for B: 532.00±0.04 µm and 530.00±0.05 µm (P=0.40). Conclusion This study found no significant change in corneal endothelial cell morphology after 6 months of wearing SH contact lenses. This is probably due to better oxygen permeability of the contact lens material, good compliance, and short wearing period.
A model predicting short-term mortality in patients with advanced liver cirrhosis and concomitant infection

Abstract Infection is a common cause of death in patients with advanced cirrhosis. We aimed to develop a predictive model in Child–Turcotte–Pugh (CTP) class C cirrhotics hospitalized with infection for optimizing treatment and improving outcomes. Clinical information was retrospectively abstracted from 244 patients at Tianjin Third Central Hospital, China (cohort 1). Factors associated with mortality were determined using logistic regression. The model for predicting 90-day mortality was then constructed by decision tree analysis. The model was further validated in 91 patients at Mayo Clinic, Rochester, MN (cohort 2) and 82 patients at Seoul St. Mary's Hospital, Korea (cohort 3). The predictive performance of the model was compared with that of the CTP, model for end-stage liver disease (MELD), MELD-Na, Chronic Liver Failure–Sequential Organ Failure Assessment, and the North American consortium for the Study of End-stage Liver Disease (NACSELD) models. The 3-month mortality was 58%, 58%, and 54% in cohort 1, 2, and 3, respectively. In cohort 1, respiratory failure, renal failure, international normalized ratio, total bilirubin, and neutrophil percentage were determinants of 3-month mortality, with odds ratios of 16.6, 3.3, 2.0, 1.1, and 1.03, respectively (P < .05). These parameters were incorporated into the decision tree model, yielding area under receiver operating characteristic (AUROC) of 0.804. The model had excellent reproducibility in the U.S. (AUROC 0.808) and Korea cohort (AUROC 0.809). The proposed model has the highest AUROC and best Youden index of 0.488 and greatest overall correctness of 75%, compared with other models evaluated. The proposed model reliably predicts survival of advanced cirrhotics with infection in both Asian and U.S. populations.
Do More Recent Born Generations of Older Adults Have Stronger Grip? A Comparison of Three Cohorts of 66- to 84-Year-Olds in the Tromsø Study

Abstract Background Evidence pertaining to whether more recent born generations of adults reaching old age have better physical capability than previous generations is scarce and inconclusive. We aimed to investigate birth cohort differences in grip strength. Methods The study comprised 5,595 individuals from the Tromsø study waves in 1994/1995, 2007/2008, and 2015/2016. Grip strength (bar) was measured using a Martin vigorimeter, and compared across three birth cohorts of 66- to 84-year-olds (born in: 1910–1929, 1923–1942, 1931–1949), as well as within narrower age bands to ensure nonoverlapping cohorts. Linear regression was applied, adjusted for age, education, smoking, physical activity, height, and weight. Results Grip strength increased across birth cohorts, and the increase was similar within narrower age bands and across genders. Overall, the increase in sex-adjusted mean grip strength when comparing the first and latest born cohorts, born 21 years apart, was 0.06 bar (95% CI 0.04, 0.07). Higher educational levels, and greater height and weight in the most recent born cohort explained 48% of this difference, while reduced smoking and physical inactivity in more recent born cohorts had little impact. Conclusions Our findings suggest higher grip strength in more recent birth cohorts of older Norwegian adults, which can be partly attributed to higher education and greater height. This difference corresponded to a 5-year difference in grip strength; more recent born generations of 80-year-olds, therefore, have similar mean grip strength as 75-year-olds born one generation earlier.