Miracle-dz/UniFAR-FTUs huggingface dataset:
Protection of CTGF Antibody Against Diabetic Nephropathy in Mice Via Reducing Glomerular β‐Catenin Expression and Podocyte Epithelial‐Mesenchymal Transition

Despite substantial progress in medical care, the morbidity rate of diabetic nephropathy (DN) remains high in patients with diabetes. Evidence suggests that connective tissue growth factor (CTGF) induced podocyte injury may contribute to DN and CTGF inhibition could reduce albuminuria. However, to date the mechanisms involved in the effect of CTGF on podocyte injury have not been fully understood. The aim of this study is to investigate the effects of therapeutic CTGF antibody on glomerular β‐catenin expression and podocyte epithelial‐mesenchymal transition (EMT) in diabetic mice. C57BL/6J mice were randomly divided into three groups as the following: the control, DN, and DN treated by CTGF antibody group. DN was induced by a single intraperitoneal injection of streptozotocin and then CTGF antibody was administrated three times per week for 8 weeks. Urinary albumin excretion, mesangial proliferation and matrix deposition, and β‐catenin expression in glomeruli at mRNA and protein level were all increased in DN mice compared to that in the control. Besides, the development of EMT in podocytes from diabetic mice, demonstrated by the downregulation of nephrin and upregulation of desmin in glomeruli, was detected. Furthermore, blocking CTGF by specific antibody reduced albuminuria, prevented the overexpression of CTGF, as well as β‐catenin, in glomeruli and subsequently ameliorated podocyte EMT in DN mice. In summary, this study suggested that CTGF antibody protected podocytes against injury in DN mice by reducing β‐catenin overexpression and preventing podocyte EMT, which might provide new insight into the mechanism of CTGF inhibition in the treatment of DN. J. Cell. Biochem. 118: 3706–3712, 2017. © 2017 Wiley Periodicals, Inc.
Hair cortisol concentrations exhibit a positive association with salivary cortisol profiles and are increased in obese prepubertal girls

Abstract Cortisol, a key mediator of the stress response, has been associated with obesity and metabolic syndrome manifestations as early as in childhood. Scalp hair cortisol has been proposed as a reliable index of long-term circulating cortisol. We aimed to investigate whether obese prepubertal girls have higher scalp hair cortisol than normal-weight controls and whether hair cortisol levels are correlated with salivary cortisol concentrations in these groups. In this cross-sectional study, 25 obese girls and 25 normal-weighted, age-matched girls were enrolled. Anthropometric evaluation, blood chemistry and salivary cortisol measurements were performed, and body mass index (BMI) and areas under the curve with respect to ground (AUCg) were calculated. Hair cortisol determination was performed with liquid chromatography–tandem mass spectrometry. Both hair cortisol concentrations and salivary cortisol AUCs were higher in the obese than the normal-weight girls (p < .001 and p = .002, respectively). A positive correlation between hair cortisol and BMI Z-score was found (rho = .327, p = .025), while hair cortisol correlated positively with salivary cortisol AUCg (rho = .3, p = .048). We conclude that obese prepubertal girls have higher hair and salivary cortisol concentrations than their age-matched lean counterparts. Hair cortisol assessment seems to be a sensitive method of evaluating systemic cortisol exposure, which is supported by our finding that hair cortisol is associated with salivary concentrations of the hormone. Lay Summary: Cortisol is the key hormone of the stress response. Childhood obesity has been associated with cortisol production dysregulation. Our findings suggest a positive association between obesity in prepubertal girls and elevated cortisol concentrations, measured in saliva and hair.
Enhanced Antitumor Effects of Epidermal Growth Factor Receptor Targetable Cetuximab-Conjugated Polymeric Micelles for Photodynamic Therapy

Nanocarrier-based delivery systems are promising strategies for enhanced therapeutic efficacy and safety of toxic drugs. Photodynamic therapy (PDT)—a light-triggered chemical reaction that generates localized tissue damage for disease treatments—usually has side effects, and thus patients receiving photosensitizers should be kept away from direct light to avoid skin phototoxicity. In this study, a clinically therapeutic antibody cetuximab (C225) was conjugated to the surface of methoxy poly(ethylene glycol)-b-poly(lactide) (mPEG-b-PLA) micelles via thiol-maleimide coupling to allow tumor-targetable chlorin e6 (Ce6) delivery. Our results demonstrate that more C225-conjugated Ce6-loaded polymeric micelles (C225-Ce6/PM) were selectively taken up than Ce6/PM or IgG conjugated Ce6/PM by epidermal growth factor receptor (EGFR)-overexpressing A431 cells observed by confocal laser scanning microscopy (CLSM), thereby decreasing the IC50 value of Ce6-mediated PDT from 0.42 to 0.173 μM. No significant differences were observed in cellular uptake study or IC50 value between C225-Ce6/PM and Ce6/PM groups in lower EGFR expression HT-29 cells. For antitumor study, the tumor volumes in the C225-Ce6/PM-PDT group (percentage of tumor growth inhibition, TGI% = 84.8) were significantly smaller than those in the Ce6-PDT (TGI% = 38.4) and Ce6/PM-PDT groups (TGI% = 53.3) (p < 0.05) at day 21 through reduced cell proliferation in A431 xenografted mice. These results indicated that active EGFR targeting of photosensitizer-loaded micelles provides a possible way to resolve the dose-limiting toxicity of conventional photosensitizers and represents a potential delivery system for PDT in a clinical setting.
Total Diet Score as a valid method of measuring diet quality among older adults.

BACKGROUND AND OBJECTIVES This study aimed to determine the accuracy of a diet quality measurement tool, the Total Diet Score (TDS) using two validation methods; firstly the TDS calculated from a food frequency questionnaire (FFQ) was compared to the TDS calculated from weighed food records (WFRs); secondly the TDS was compared to a number of dietary biomarkers. METHODS AND STUDY DESIGN Data were collected from a population based cohort study located in the Blue Mountains region of Sydney, Australia. To compare dietary assessment tools, a sub sample of 75 subjects (aged 63 to 83 years) completed the FFQ and three, four-day WFRs at baseline. Fasting blood samples were collected from 2897 subjects at the first follow up in 1997-1999. TDS scores were calculated from both WFRs and FFQs. Methods to compare FFQ TDS scores to WFR TDS scores included paired t-tests, Pearson correlations, Bland-Altman plots, joint classification quartiles and weighted kappa scores. Linear regression analyses were used to assess the relationship between TDS and biomarkers. RESULTS No significant mean difference was found between FFQ TDS and WFRs TDS (p=0.63) with a significant positive correlation seen between the two methods (r=0.75, p<0001). The Bland-Altman method found no linear trend between the differences and means of TDS scores between the FFQ and WFR (p=0.38). A significant trend for higher serum vitamin B-12, serum folate, homocysteine and lower total cholesterol was found with increasing TDS. CONCLUSIONS These findings suggest that the TDS is a useful tool for assessing diet quality in an older population.
The effect of carbon irradiation is associated with greater oxidative stress in mouse intestine and colon relative to γ-rays

Abstract Carbon irradiation due to its higher biological effectiveness relative to photon radiation is a concern for toxicity to proliferative normal gastrointestinal (GI) tissue after radiotherapy and long-duration space missions such as mission to Mars. Although radiation-induced oxidative stress is linked to chronic diseases such as cancer, effects of carbon irradiation on normal GI tissue have not been fully understood. This study assessed and compared chronic oxidative stress in mouse intestine and colon after different doses of carbon and γ radiation, which are qualitatively different. Mice (C57BL/6J) were exposed to 0.5 or 1.3 Gy of γ or carbon irradiation, and intestinal and colonic tissues were collected 2 months after irradiation. While part of the tissues was used for isolating epithelial cells, tissue samples were also fixed and paraffin embedded for 4 µm thick sections as well as frozen for biochemical assays. In isolated epithelial cells, reactive oxygen species and mitochondrial status were studied using fluorescent probes and flow cytometry. We assessed antioxidant enzymes and nicotinamide adenine dinucleotide phosphate (NADPH) oxidase activity in tissues and formalin-fixed tissue sections were stained for 4-hydroxynonenal, a lipid peroxidation marker. Data show that mitochondrial deregulation, increased NADPH oxidase activity, and decreased antioxidant activity were major contributors to carbon radiation-induced oxidative stress in mouse intestinal and colonic cells. When considered along with higher lipid peroxidation after carbon irradiation relative to γ-rays, our data have implications for functional changes in intestine and carcinogenesis in colon after carbon radiotherapy as well as space travel.
Comparative Efficacy and Tolerability of 5-Loxin® and Aflapin® Against Osteoarthritis of the Knee: A Double Blind, Randomized, Placebo Controlled Clinical Study

Aflapin® is a novel synergistic composition derived from Boswellia serrata gum resin (Indian Patent Application No. 2229/CHE/2008). Aflapin is significantly better as an anti-inflammatory agent compared to the Boswellia extracts presently available in the market. A 90-day, double-blind, randomized, placebo-controlled study was conducted to evaluate the comparative efficacy and tolerability of 5-Loxin® and Aflapin® in the treatment of osteoarthritis (OA) of the knee (Clinical trial registration number: ISRCTN80793440). Sixty OA subjects were included in the study. The subjects received either 100 mg (n=20) of 5-Loxin® or 100 mg (n=20) of Aflapin® or a placebo (n=20) daily for 90 days. Each patient was evaluated for pain and physical functions by using the standard tools (visual analog scale, Lequesne's Functional Index, and Western Ontario and McMaster Universities Osteoarthritis Index) at the baseline (day 0), and at days 7, 30, 60 and 90. A battery of biochemical parameters in serum, urine and hematological parameters in citrated whole blood were performed to assess the safety of 5-Loxin® and Aflapin® in OA subjects. Fifty seven subjects completed the study. At the end of the study, both 5-Loxin® and Aflapin conferred clinically and statistically significant improvements in pain scores and physical function scores in OA subjects. Interestingly, significant improvements in pain score and functional ability were recorded as early as 7 days after initiation of the study in the treatment group supplemented with 100 mg Aflapin. Corroborating the improvements in pain scores in treatment groups, our in vitro studies provide evidences that Aflapin® is capable of inhibiting cartilage degrading enzyme MMP-3 and has the potential to regulate the inflammatory response by inhibiting ICAM-1. Aflapin® and 5-Loxin® reduce pain and improve physical functions significantly in OA subjects. Aflapin exhibited better efficacy compared to 5-Loxin®. In comparison with placebo, the safety parameters were almost unchanged in the treatment groups. Hence both 5-Loxin® and Aflapin® are safe for human consumption.
Automating Optimization of Reconfigurable Designs

We present Automatic Reconfigurable Design Efficient Global Optimization (ARDEGO), a new algorithm based on the existing Efficient Global Optimization (EGO) methodology for automating optimization of reconfigurable designs targeting Field-Programmable Gate Array (FPGA) technology. It is a potentially disruptive design approach: instead of manually improving designs repeatedly but without understanding the design space as a whole, ARDEGO users follow a novel approach that: (a) automates the manual optimization process, significantly reducing optimization time and (b) does not require the user to calibrate or understand the inner workings of the algorithm. We evaluate ARDEGO using two case studies: financial option pricing and seismic imaging.
Coming out in STEM: Factors affecting retention of sexual minority STEM students

LGBQ college students are 7% less likely than heterosexuals to persist in STEM after 4 years versus switching to a non-STEM field. Using a national longitudinal survey data set from the Higher Education Research Institute, this study tested whether students who identified as a sexual minority (for example, lesbian, gay, bisexual, or queer) were more or less likely to persist after 4 years in science, technology, engineering, and mathematics (STEM) fields, as opposed to switching to a non-STEM program, compared to their heterosexual peers. A multilevel regression model controlling for various experiences and characteristics previously determined to predict retention in STEM demonstrated that, net of these variables, sexual minority students were 7% less likely to be retained in STEM compared to switching into a non-STEM program. Despite this finding, sexual minority STEM students were more likely to report participating in undergraduate research programs, and the gender disparity in STEM retention appears to be reversed for sexual minority STEM students.
The impact of 27-hydroxycholesterol on endometrial cancer proliferation

Endometrial cancer (EC) is the most common gynaecological malignancy. Obesity is a major risk factor for EC and is associated with elevated cholesterol. 27-hydroxycholesterol (27HC) is a cholesterol metabolite that functions as an endogenous agonist for Liver X receptor (LXR) and a selective oestrogen receptor modulator (SERM). Exposure to oestrogenic ligands increases risk of developing EC; however, the impact of 27HC on EC is unknown. Samples of stage 1 EC (n = 126) were collected from postmenopausal women undergoing hysterectomy. Expression of LXRs (NR1H3, LXRα; NR1H2, LXRβ) and enzymes required for the synthesis (CYP27A1) or breakdown (CYP7B1) of 27HC were detected in all grades of EC. Cell lines originating from well-, moderate- and poorly-differentiated ECs (Ishikawa, RL95, MFE 280 respectively) were used to assess the impact of 27HC or the LXR agonist GW3965 on proliferation or expression of a luciferase reporter gene under the control of LXR- or ER-dependent promoters (LXRE, ERE). Incubation with 27HC or GW3965 increased transcription via LXRE in Ishikawa, RL95 and MFE 280 cells (P < 0.01). 27HC selectively activated ER-dependent transcription (P < 0.001) in Ishikawa cells and promoted proliferation of both Ishikawa and RL95 cells (P < 0.001). In MFE 280 cells, 27HC did not alter proliferation but selective targeting of LXR with GW3965 significantly reduced cell proliferation (P < 0.0001). These novel results suggest that 27HC can contribute to risk of EC by promoting proliferation of endometrial cancer epithelial cells and highlight LXR as a potential therapeutic target in the treatment of advanced disease.
An outbreak of atypical mycobacterial port site infections in a newly established medical college & hospital of West-Bengal : A preventable nuisance

Introduction: Laparoscopic surgery (LS) has multiple advantages like less pain, rapid healing and early ambulation. Yet, port site infection is an emerging nuisance. Early onset port site infections (PSIs) are usually caused by non-fastidious microbes and are easily preventable or treatable with conventional antimicrobial therapy following a culture and sensitivity testing. However, the late-onset PSIs are mostly caused by the Mycobacterium spp. and if not managed properly, tend to become chronic non healing lesions leading to neutralize the benefits of LS. Objectives: To determine the microbial aetiology of late onset PSIs at our institution, to assess the intramural infection rate of such PSIs and to observe the sterilization protocols followed for LS in General Surgery operation theatre (GSOT) & suggest amendments (if required) to combat these port site infections. Material & Methods: The study was conducted on 192 post LS patients (undergoing laparoscopic surgery for various indications) from January 2016 to June 2017 at the GSOT of our hospital. All these patients were observed for PSIs during post-operative follow-up for six months. Simultaneously, various ongoing sterilization and disinfection activities in the GSOT were scrutinized. Aspirated pus or swab taken from the port site wounds were processed for microscopy, culture (aerobic, anaerobic, mycobacterial and fungal cultures) and Cartridge Based Nucleic Acid Amplification Test (CB-NAAT) for Mycobacterium tuberculosis. Cultured bacterial colonies from Lowenstein Jensen (LJ) media were subjected to Ziehl-Neelsen (ZN) and auramine staining followed by light and fluorescent microscopy respectively for presence of acid fast bacilli (AFB) and tested with immunochromatographic lateral flow rapid assay for detecting MPT64 TB antigen. Results: All detected PSIs were caused by rapid growing atypical mycobacteria. Intramural infection rate of mycobacterial PSI was 14.53% in 2016. No such occurrence was noted in December 2016 and in the 1 st half of 2017. Amendments included in sterilization and disinfection protocols in mid-November 2016 played the key role in remission and further prevention of the concerned nosocomial outbreak of atypical mycobacterial late onset PSIs in our institution. Conclusion: Nosocomial menace like late onset PSI is controllable by inculcating optimum protocols for proper sterilization of laparoscopic instruments.
Precuneus Is a Functional Core of the Default-Mode Network

Efforts to understand the functional architecture of the brain have consistently identified multiple overlapping large-scale neural networks that are observable across multiple states. Despite the ubiquity of these networks, it remains unclear how regions within these large-scale neural networks interact to orchestrate behavior. Here, we collected functional magnetic resonance imaging data from 188 human subjects who engaged in three cognitive tasks and a resting-state scan. Using multiple tasks and a large sample allowed us to use split-sample validations to test for replication of results. We parceled the task-rest pairs into functional networks using a probabilistic spatial independent components analysis. We examined changes in connectivity between task and rest states using dual-regression analysis, which quantifies voxelwise connectivity estimates for each network of interest while controlling for the influence of signals arising from other networks and artifacts. Our analyses revealed systematic state-dependent functional connectivity in one brain region: the precuneus. Specifically, task performance led to increased connectivity (compared to rest) between the precuneus and the left frontoparietal network (lFPN), whereas rest increased connectivity between the precuneus and the default-mode network (DMN). The absolute magnitude of this effect was greater for DMN, suggesting a heightened specialization for resting-state cognition. All results replicated within the two independent samples. Our results indicate that the precuneus plays a core role not only in DMN, but also more broadly through its engagement under a variety of processing states.
Analysis of Fission Products on the AGR-1 Capsule Components

The components of the AGR-1 irradiation capsules were analyzed to determine the retained inventory of fission products in order to determine the extent of in-pile fission product release from the fuel compacts. This includes analysis of (i) the metal capsule components, (ii) the graphite fuel holders, (iii) the graphite spacers, and (iv) the gas exit lines. The fission products most prevalent in the components were Ag-110m, Cs 134, Cs 137, Eu-154, and Sr 90, and the most common location was the metal capsule components and the graphite fuel holders. Gamma scanning of the graphite fuel holders was also performed to determine spatial distribution of Ag-110m and radiocesium. Silver was released from the fuel components in significant fractions. The total Ag-110m inventory found in the capsules ranged from 1.2×10 2 (Capsule 3) to 3.8×10 1 (Capsule 6). Ag-110m was not distributed evenly in the graphite fuel holders, but tended to concentrate at the axial ends of the graphite holders in Capsules 1 and 6 (located at the top and bottom of the test train) and near the axial center in Capsules 2, 3, and 5 (in the center of the test train). The Ag-110m further tended to be concentrated around fuelmore » stacks 1 and 3, the two stacks facing the ATR reactor core and location of higher burnup, neutron fluence, and temperatures compared with Stack 2. Detailed correlation of silver release with fuel type and irradiation temperatures is problematic at the capsule level due to the large range of temperatures experienced by individual fuel compacts in each capsule. A comprehensive Ag 110m mass balance for the capsules was performed using measured inventories of individual compacts and the inventory on the capsule components. For most capsules, the mass balance was within 11% of the predicted inventory. The Ag-110m release from individual compacts often exhibited a very large range within a particular capsule. « less
Oral clefts: a review of the cases and our experience at a single institution.

OBJECTIVE To identify the frequency of different types of oral clefts and presence of known risk factors among patients. METHODS The retrospective review of 292 patients, presenting with oral clefts between 1992 and 2011, was conducted at the Aga Khan University Hospital, Karachi. A pre-designed questionnaire was used to collect details, including demographics, type of cleft, presence of known risk factors, surgical details, and follow-up visits. SPSS 16 was used for data analysis. Chi-square test and analysis of variance was used: whenever applicable. RESULTS Of the total, 168 (57-53%) patients had cleft lip with or without cleft palate, and 124 (42.5%) had cleft palate alone. The most common defect was left-sided complete cleft lip and palate and midline incomplete cleft palate in the two groups respectively. Consanguinity among the parents was found to be the most common risk factor (n = 50; 17.1%). Median age of repair was 4 months for cleft lip and 10 months for cleft palate in the first group. For the other group, the median age of primary repair was 13 months. First-week follow-up after surgery was 50% (n = 84) for the lip repair, and 65% (n = 81) for palate repair. CONCLUSION Our review revealed that most patients had cleft lip with or without cleft palate (CL/P). The most common risk factor was consanguinity among parents. Delay in seeking care, low follow-up rates after surgical repair of the anomaly and lack of involvement of speech therapist and orthodontist was observed.