Miracle-dz/UniFAR-FTUs huggingface dataset:
Therapy of Small Cell Lung Cancer (SCLC) with a Topoisomerase-I–inhibiting Antibody–Drug Conjugate (ADC) Targeting Trop-2, Sacituzumab Govitecan

Purpose: We evaluated a Trop-2–targeting antibody conjugated with SN-38 in metastatic small cell lung cancer (mSCLC) patients. Experimental Design: Sacituzumab govitecan was studied in patients with pretreated (median, 2; range, 1–7) mSCLC who received either 8 or 10 mg/kg i.v. on days 1 and 8 of 21-day cycles. The primary endpoints were safety and objective response rate (ORR); duration of response, progression-free survival (PFS), and overall survival (OS) were secondary endpoints. Results: Sixty percent of patients showed tumor shrinkage from baseline CTs. On an intention-to-treat basis (N = 50), the ORR was 14% (17% for the 10-mg/kg group); the median response duration, 5.7 months; the clinical benefit rate (CBR ≥4 months), 34%; median PFS, 3.7 months; and median OS, 7.5 months. There was a suggested improvement in PR, CBR, and PFS with sacituzumab govitecan in second-line patients who were sensitive to first-line therapy, but no difference between first-line chemosensitive versus chemoresistant patients in the overall population. There was a statistically significant higher OS in those patients who received prior topotecan versus no topotecan therapy in a small subgroup. Grade ≥3 adverse events included neutropenia (34%), fatigue (13%), diarrhea (9%), and anemia (6%). Trop-2 tumor staining was not required for patient selection. No antibodies to the drug conjugate or its components were detected on serial blood collections. Conclusions: Sacituzumab govitecan appears to have a safe and effective therapeutic profile in heavily pretreated mSCLC patients, including those who are chemosensitive or chemoresistant to first-line chemotherapy. Additional studies as a monotherapy or combination therapy are warranted. Clin Cancer Res; 23(19); 5711–9. ©2017 AACR.
Immunological profile and aspects of immunotherapy in type 1 diabetes

Background We have previously shown that two injections of 20 mu g alum-formulated glutamic acid decarboxylase 65 (GAD(65)) (GAD-alum; Diamyd (R)) in children with recent-onset type 1 diabetes lead to preservation of residual insulin secretion. In vitro cytokine production at the 15 months follow-up indicated immunomodulation. In the present study, we took advantage of peripheral blood mononuclear cells, cryopreserved during early follow-ups, to investigate whether the immunomodulatory effect of GAD-alum was apparent earlier after treatment, preceding the changes previously reported at 15 months. Methods Peripheral blood mononuclear cells from 70 type 1 diabetic children, randomly assigned GAD-alum (n = 35) or placebo (n = 35), that had been frozen at baseline (n = 27) and after 1 (n = 58), 3 (n = 67) and 9 (n = 66) months, were stimulated in vitro with GAD(65), tyrosine phosphatase-like protein IA-2 peptide, insulin peptide, GAD-alum, alum formulation or phytohaemagglutinin. Interleukin (IL)-5, -6, -10, -12, -13, -17, tumour necrosis factor and interferon-gamma were measured in cell supernatants and serum samples using Luminex. Expression of FOXP3 and transforming growth factor-beta was determined by real-time reverse transcription polymerase chain reaction. Results Already 1 month after the first injection, GAD(65)-induced IL-5 and IL-13 together with FOXP3 were enhanced in GAD-alum-treated patients compared to those with placebo. The in vitro response at 3 and 9 months was characterized by a broader range of cytokines in the treated group. Notably, only the T-helper 2-associated cytokines IL-5 and IL-13 together with FOXP3 increased continuously over time. Conclusions Treatment with GAD-alum in type 1 diabetic children induced an early T-helper 2 immune enhanced response to GAD(65), followed by a wider spectrum of cytokines at 3 and 9 months. Copyright (C) 2010 John Wiley a Sons, Ltd.
Correlation between the Functional and Histological Staging of Oral Submucous Fibrosis

Aims: To correlate the functional and histological staging of oral submucous fibrosis. Materials and Methods: The study group consisted of 50 subjects who were clinically and histologically diagnosed as oral submucous fibrosis. Functional and histological staging were divided into four groups, as group I to IV. Results: The 50 subjects were in the age range of 12-57 years, out of 13 (26%) subjects in functional stage I, 5 and 8 subjects were in histological Group I and II respectively; 18 (36%) subjects in functional stage III, 5 and 13 were in histological group II and III respectively. Conclusion: Statistical analysis with Chi-square test showed highly significant with P value < 0.001.
UBC-Nepal Expedition: acute alterations in sympathetic nervous activity do not influence brachial artery endothelial function at sea level and high altitude.

Evidence indicates that increases in sympathetic nervous activity (SNA), and acclimatization to high altitude (HA), may reduce endothelial function as assessed by brachial artery flow-mediated dilatation (FMD); however, it is unclear whether such changes in FMD are due to direct vascular constraint, or consequential altered hemodynamics (e.g., shear stress) associated with increased SNA as a consequence of exposure to HA. We hypothesized that 1) at rest, SNA would be elevated and FMD would be reduced at HA compared with sea-level (SL); and 2) at SL and HA, FMD would be reduced when SNA was acutely increased, and elevated when SNA was acutely decreased. Using a novel, randomized experimental design, brachial artery FMD was assessed at SL (344 m) and HA (5,050 m) in 14 participants during mild lower-body negative pressure (LBNP; -10 mmHg) and lower-body positive pressure (LBPP; +10 mmHg). Blood pressure (finger photoplethysmography), heart rate (electrocardiogram), oxygen saturation (pulse oximetry), and brachial artery blood flow and shear rate (Duplex ultrasound) were recorded during LBNP, control, and LBPP trials. Muscle SNA was recorded (via microneurography) in a subset of participants (n = 5). Our findings were 1) at rest, SNA was elevated (P < 0.01), and absolute FMD was reduced (P = 0.024), but relative FMD remained unaltered (P = 0.061), at HA compared with SL; and 2) despite significantly altering SNA with LBNP (+60.3 ± 25.5%) and LBPP (-37.2 ± 12.7%) (P < 0.01), FMD was unaltered at SL (P = 0.448) and HA (P = 0.537). These data indicate that acute and mild changes in SNA do not directly influence brachial artery FMD at SL or HA.NEW & NOTEWORTHY The role of the sympathetic nervous system on endothelial function remains unclear. We used lower-body negative and positive pressure to manipulate sympathetic nervous activity at sea level and high altitude and measured brachial endothelial function via flow-mediated dilation. We found that acutely altering sympathetic nervous activity had no effect on endothelial function.
Use of garenoxacin: a new generation antibiotic for surgical infections

Background: The management of skin and skin structure infections (SSSI) still continues to be global challenge. USFDA has given strong recommendation for adequate empirical antibiotic coverage to avoid further complication of the wounds. Wound complications, especially in the diabetic population, patients with low immunity remains a big challenge though other factors like site of the wound, age of the patients also play an important role. Methods: A retrospective observational study was conducted to analyze clinical utility of garenoxacin for surgical prophylaxis. A total of 100 patients, 30 patients with diabetic foot and 70 patients with post-surgical intraabdominal wounds who were prescribed garenoxacin 2×200 mg as stat dose prophylactically. Swab culture from the wound slough and drain tube samples were sent for culture/sensitivity on day 0, day 5, and day 7. Wound healing was evaluated by estimating slough discharge, size of the wound, vascularity, and overall healing. They were categorized as treatment failure group, when sough/drain-discharge reduction was ≤50%, improved if sough/drain-discharge reduction was 50-75% and cure when sough/drain-discharge reduction was 75-100%. Results: The healthy granulation tissue was observed post 7 days therapy of garenoxacin 2×200 mg in diabetic foot ulcer (DFU) patients when administered empirically before surgical debridement. In patients with post-operative infectious intraabdominal wounds, the most common isolated organisms were Enterococcus, Acinetobacter and Klebsiella . Post garenoxacin therapy used as switch therapy empirically for 5 days resulted in 100% sterile culture. While evaluating slough/drain-discharge in DFU patients, 84% patients showed cure and 16% showed improvement at the end of day 7 and in patients with post-operative infectious intra-abdominal wounds cure was observed in 86% patients showed cure and 14% patient showed improvement. No side effects were reported during the study. Conclusions: Administration of garenoxacin used as empirical therapy for surgical prophylaxis and as switch therapy in patients with DFU s and post-surgical infectious wounds for the period of 5-7 days has been found effective indicating its wide spectrum of action.
Classification of Airflow Limitation Based on z‐Score Underestimates Mortality in Patients with Chronic Obstructive Pulmonary Disease

&NA; Rationale: Global Lung Function Initiative recommends reporting lung function measures as z‐score, and a classification of airflow limitation (AL) based on this parameter has recently been proposed. Objectives: To evaluate the prognostic capacity of the AL classifications based on z‐score or percentage predicted of FEV1 in patients with chronic obstructive pulmonary disease (COPD). Methods: A cohort of 2,614 patients with COPD recruited outside the hospital setting was examined after a mean (± SD) of 57 ± 13 months of follow‐up, totaling 10,322 person‐years. All‐cause mortality was analyzed, evaluating the predictive capacity of several AL staging systems. Measurements and Main Results: Based on Global Initiative for Chronic Obstructive Lung Disease guidelines, 461 patients (17.6%) had mild, 1,452 (55.5%) moderate, 590 (22.6%) severe, and 111 (4.2%) very severe AL. According to z‐score classification, 66.3% of patients remained with the same severity, whereas 23.7% worsened and 10.0% improved. Unlike other staging systems, patients with severe AL according to z‐score had higher mortality than those with very severe AL (increase of risk by 5.2 and 3.9 times compared with mild AL, respectively). The predictive capacity for 5‐year survival was slightly higher for FEV1 expressed as percentage of predicted than as z‐score (area under the curve: 0.714‐0.760 vs. 0.649‐0.708, respectively). A severity‐dependent relationship between AL grades by z‐score and mortality was only detected in patients younger than age 60 years. Conclusions: In patients with COPD, the AL classification based on z‐score predicts worse mortality than those based on percentage of predicted. It is possible that the z‐score underestimates AL severity in patients older than 60 years of age with severe functional impairment.
Bundled Payment and Care of Acute Stroke: What Does it Take to Make it Work?

With nearly 800 000 strokes occurring a year, stroke remains the leading cause of disability and the fourth most common cause of death in the United States.1 Stroke also imposes an enormous economic burden, including long-term care costs and productivity losses. Total direct medical stroke-related costs to US economy are projected to triple from $71.6 billion in 2012 to $184.1 billion in 2030.1 Although treatment for acute stroke is generally not vividly effective, the type and quality of stroke care can effect outcomes. Appropriate and prompt use of tissue-type plasminogen activator, reducing risk of acute medical complications, such as deep vein thrombosis, prophylaxis, and prevention of aspiration, secondary prevention, such as anticoagulation for atrial fibrillation, and early institution of aggressive rehabilitation can have substantial impacts on survival and disability.1,2 Moreover, given the high cost of disabling strokes, even care that is modestly effective in reducing functional loss can be highly cost-effective.3 Evidence suggests we could treat patients with acute stroke more effectively and at lower cost. A review showed large variation in patient-level cost of strokes (between 2 and 4-fold difference) across hospitals that is not explained by improved process of care or clinical outcomes.4 Other studies found similar wide cost variation.5–7 Substantial variation also exists in clinical outcomes of stroke patients that is unexplained by patient and hospital characteristics.8 Programs such as Get-With-The Guidelines have documented that systematic improvements in stroke care are possible.9 The high variation in costs of stroke and outcomes reflects not only the complex nature of the process of treating and managing stroke patients but also points to inefficiencies in the process of care. It has been argued that these inefficiencies are partly attributable to the current payment system, which is mostly based on …
Versican Promotes Tumor Progression, Metastasis and Predicts Poor Prognosis in Renal Carcinoma

The proteoglycan versican (VCAN) promotes tumor progression and enhances metastasis in several cancers; however, its role in clear cell renal cell carcinoma (ccRCC) remains unknown. Recent evidence suggests that VCAN is an important target of chromosomal 5q gain, one of the most prevalent genetic abnormalities in ccRCC. Thus, we investigated whether VCAN expression is associated with the pathogenesis of ccRCC. VCAN expression was analyzed using three RCC and normal kidney cell lines as well as a clinical cohort of 84 matched ccRCC and normal renal tissues. Functional analyses on growth and progression properties were performed using VCAN-depleted ccRCC cells. Microarray expression profiling was employed to investigate the target genes and biologic pathways involved in VCAN-mediated ccRCC carcinogenesis. ccRCC had elevated VCAN expression in comparison with normal kidney in both cell lines and clinical specimens. The elevated expression of VCAN was significantly correlated with metastasis (P < 0.001) and worse 5-year overall survival after radical nephrectomy (P = 0.014). In vitro, VCAN knockdown significantly decreased cell proliferation and increased apoptosis in Caki-2 and 786-O cells, and this was associated with alteration of several TNF signaling–related genes such as TNFα, BID, and BAK. Furthermore, VCAN depletion markedly decreased cell migration and invasion which correlated with reduction of MMP7 and CXCR4. These results demonstrate that VCAN promotes ccRCC tumorigenesis and metastasis and thus is an attractive target for novel diagnostic, prognostic, and therapeutic strategies. Implications: This study highlights the oncogenic role of VCAN in renal cell carcinogenesis and suggests that this gene has therapeutic and/or biomarker potential for renal cell cancer. Mol Cancer Res; 15(7); 884–95. ©2017 AACR.
Ki-67 expression in pericoronal tissues of impacted mandibular third molars

The study was performed to histologically and immunohistochemically evaluate soft tis¬sue pathologic changes in pericoronal epithelial tissues of impacted mandibular third molars that did not exhibit pathologic pericoronal radiolucency and to clarify the role of Ki-67 expression for separation between healthy follicle and dentigerous cyst. Fifty pericoronal tissues associated with completely impacted mandibular third molars were submitted for histologic examination by each of 2 pathologists after surgical tooth re¬moval was performed. Biopsy samples were fixed in 10% buffered neutral formalin solu¬tion and embedded in paraffin blocks. Sections (4-6 μm) were obtained from the paraffin block and to evaluate the expression of Ki-67 sections were immunostained anti-Ki-67 primary antibody and streptavidin-biotin complex system. The incidence of normal tis¬sue of a dental follicle was 22%, and the incidence of dentigerous cyst was 52%, and the incidence of chronic nonspecific inflammatory tissue was 26%. Ki-67 expression was positive in 19 of 26 lining epithelia in cystic specimens, in 4 of 13 chronic nonspecific inflammatory tissue specimens, and in 0 of 11 healthy follicular specimens. These find¬ings suggest that the majority of cystic specimens demonstrated proliferative activity, therefore the incidence of dentigerous cyst associated with impacted third molar teeth is high and proliferative marker may be played a role in diagnosis of dentigerous cyst as¬sociated with radiographically normal third molar impactions. J. Exp. Clin. Med., 2012; 29:9-12
Arenas of Drug Transactions: Adolescent Cannabis Transactions in England—Social Supply

The issue of the social supply of illicit drugs is an important one because it delineates a separate category of “dealing,” whereby friends supply or facilitate supply to other friends. Supply of this nature has been argued to be sufficiently different to “dealing proper” to justify a different criminal justice approach in relation to it. This has been argued to be particularly true regarding social supply among young people who use substances such as cannabis. This research involved interviews with 192 cannabis users in six (three rural, three urban) locations in England. Most were exclusively cannabis users. Nearly half (45%) had been involved in some form of supply, and 78% reported sharing their cannabis with others. Nearly all supply events were between friends within a close age range. The findings suggest that there is little contact by young cannabis users to the wider drug market and that it may be better to understand this activity as taking place in an “arena of transaction” rather than seeing it as an extension of the normally conceived drug market. We argue that there is sufficient difference within this arena of transaction from the wider drug market for most activity there to be dealt with less punitively by the criminal justice system.
Whole grain and body weight changes in apparently healthy adults: a systematic review and meta-analysis of randomized controlled studies.

BACKGROUND Whole grains have received increased attention for their potential role in weight regulation. A high intake has been associated with smaller weight gain in prospective cohort studies, whereas the evidence from randomized controlled studies has been less consistent. OBJECTIVE We assessed the effects of whole-grain compared with non-whole-grain foods on changes in body weight, percentage of body fat, and waist circumference by using a meta-analytic approach. DESIGN We conducted a systematic literature search in selected databases. Studies were included in the review if they were randomized controlled studies of whole-grain compared with a non-whole-grain control in adults. A total of 2516 articles were screened for eligibility, and relevant data were extracted from 26 studies. Weighted mean differences were calculated, and a metaregression analysis was performed by using the whole-grain dose (g/d). RESULTS Data from 2060 participants were included. Whole-grain intake did not show any effect on body weight (weighted difference: 0.06 kg; 95% CI: -0.09, 0.20 kg; P = 0.45), but a small effect on the percentage of body fat was seen (weighted difference: -0.48%; 95% CI: -0.95%, -0.01%; P = 0.04) compared with that for a control. An examination of the impact of daily whole-grain intake could predict differences between groups, but there was no significant association (β = -0.0013 kg × g/d; 95% CI: -0.011, 0.009 kg × g/d). CONCLUSIONS Whole-grain consumption does not decrease body weight compared with control consumption, but a small beneficial effect on body fat may be present. The relatively short duration of intervention studies (≤16 wk) may explain the lack of difference in body weight and fat. Discrepancies between studies may be caused by differences in study design.
Endothelial Cell–Specific FGD5 Involvement in Vascular Pruning Defines Neovessel Fate in Mice

Background— New vessel formation contributes to organ development during embryogenesis and tissue repair in response to mechanical damage, inflammation, and ischemia in adult organisms. Early angiogenesis includes formation of an excessive primitive network that needs to be reorganized into a secondary vascular network with higher hierarchical structure. Vascular pruning, the removal of aberrant neovessels by apoptosis, is a vital step in this process. Although multiple molecular pathways for early angiogenesis have been identified, little is known about the genetic regulators of secondary network development. Methods and Results— Using a transcriptomics approach, we identified a new endothelial specific gene named FYVE, RhoGEF, and PH domain–containing 5 (FGD5) that plays a crucial role in vascular pruning. Loss- and gain-of-function studies demonstrate that FGD5 inhibits neovascularization, indicated by in vitro tube-formation, aortic-ring, and coated-bead assays and by in vivo coated-bead plug assays and studies in the murine retina model. FGD5 promotes apoptosis-induced vaso-obliteration via induction of the hey1-p53 pathway by direct binding and activation of cdc42. Indeed, FGD5 correlates with apoptosis in endothelial cells during vascular remodeling and was linked to rising p21CIP1 levels in aging mice. Conclusion— We have identified FGD5 as a novel genetic regulator of vascular pruning by activation of endothelial cell–targeted apoptosis.
Study of pattern related to side effects and removal of IUCD usage

Background: An effective contraception is the only way to stop this population explosion. There are too advantages and side effects associated with the IUCD, But most of side effects are effectively controlled by proper selection of clients and counseling process. Objective: To know the pattern of side effects and reason for removal among beneficiaries. Methods: A cross sectional study was conducted in 400 beneficiaries selected using systematic random sampling. Study sites included both urban and rural area. Data was entered and analyzed using MS excel sheet. Results: In this study maximum client 348 (87%) belonged to age group of 21 to 30 years. 47 (11.8%) clients were illiterate and 285 (71.3%) clients were unemployed/housewife. Most common side effect was pain with heavy bleeding in 30.6% clients, pain in 23.8% clients and pain with light spotting in 18.4% clients. Most common reasons for removal were pain with heavy bleeding in 42.6% clients while 10 (12.8%) clients removed due to husband’s insistence. Conclusions: After ICUD insertion 36.8% clients had side effect. Pain with heavy bleeding, pain with light spotting and only pain are the most common type of side effects. Removal of ICUD was 19.25%. Most common reason for removal was pain with heavy bleeding.