Miracle-dz/UniFAR-FTUs huggingface dataset:
Impact of Basic Lymphedema Management and Antifilarial Treatment on Acute Dermatolymphangioadenitis Episodes and Filarial Antigenaemia

Background: A major factor in the progression of lymphedema is acute dermatolymphangioadenitis (ADLA). Aims To study ADLA episodes and antigenaemia in patients with different grades of filarial lymphedema at pre- and two years post-treatment. Setting and Design: A prospectively conducted study from May 2008 through May 2010. Patients and Methods: Forty five patients complaining of limb swelling with present or past history of limb redness suggestive of ADLA attacks were included. Patients were clinically examined for lymphedema grading, detection of potential entry points and diagnosis of microfilaraemia. Wuchereria bancrofti antigen titer was estimated by “Trop-Ag W. Bancrofti” ELISA kit. Basic lymphedema management and treatment with antifilarial drugs were applied. Statistical Analysis Mann–Whitney test and Chi-square test were used. Results: The number of ADLA attacks in the pretreatment period, ranged from one to three per year. Mean duration of the attacks was 3.87±0.79 days. Entry points were detected in 82% of cases. The study revealed statistical significance between extension and grade of lymphedema and number of ADLA attacks per year (P=0.018 and 0.022, respectively). Microfilaraemia was detected in four cases and positive filarial antigenaemia were detected in 29 patients (64.4). The number of ADLA attacks per year significantly decreased from the pre-treatment period (mean: 2.05±0.560) to be 1.23±0.706 after one year and 0.89±0.575 after two years post treatment. There was a significant decrease in the mean antigen titer one year and two years after treatment. Conclusion: Basic lymphedema management is effective for controlling ADLA attacks in areas where lymphatic filariasis is endemic.
Functional Characterization of Evolutionarily Divergent 4-Coumarate:Coenzyme A Ligases in Rice1[W][OA]

4-Coumarate:coenzyme A ligase (4CL; EC 6.2.1.12) is a key enzyme in the phenylpropanoid metabolic pathways for monolignol and flavonoid biosynthesis. 4CL has been much studied in dicotyledons, but its function is not completely understood in monocotyledons, which display a different monolignol composition and phenylpropanoid profile. In this study, five members of the 4CL gene family in the rice (Oryza sativa) genome were cloned and analyzed. Biochemical characterization of the 4CL recombinant proteins revealed that the rice 4CL isoforms displayed different substrate specificities and catalytic turnover rates. Among them, Os4CL3 exhibited the highest turnover rate. No apparent tissue-specific expression of the five 4CLs was observed, but significant differences in their expression levels were detected. The rank in order of transcript abundance was Os4CL3 > Os4CL5 > Os4CL1 > Os4CL4 > Os4CL2. Suppression of Os4CL3 expression resulted in significant lignin reduction, shorter plant growth, and other morphological changes. The 4CL-suppressed transgenics also displayed decreased panicle fertility, which may be attributed to abnormal anther development as a result of disrupted lignin synthesis. This study demonstrates that the rice 4CLs exhibit different in vitro catalytic properties from those in dicots and that 4CL-mediated metabolism in vivo may play important roles in regulating a broad range of biological events over the course of rice growth and development.
Regulation of apoptotic potassium currents by coordinated zinc‐dependent signalling

Oxidant‐liberated intracellular Zn2+ regulates neuronal apoptosis via an exocytotic membrane insertion of Kv2.1‐encoded ion channels, resulting in an enhancement of voltage‐gated K+ currents and a loss of intracellular K+ that is necessary for caspase‐mediated proteolysis. In the present study we show that an N‐terminal tyrosine of Kv2.1 (Y124), which is a known target of Src kinase, is critical for the apoptotic current surge. Moreover, we demonstrate that Y124 works in concert with a C‐terminal serine (S800) target of p38 mitogen‐activated protein kinase (MAPK) to regulate Kv2.1‐mediated current enhancement. While Zn2+ was previously shown to activate p38, we show here that this metal inhibits cytoplasmic protein tyrosine phosphatase ɛ (Cyt‐PTPɛ), which specifically targets Y124. Importantly, a point mutation of Y124 to a non‐phosphorylatable residue or over‐expression of Cyt‐PTPɛ protects cells from injury. Kv2.1‐encoded channels thus regulate neuronal survival by providing a converging input for two Zn2+‐dependent signal transduction cascades.
Epidermal Growth Factor Receptor (EGFR)-mediated Positive Feedback of Protein-tyrosine Phosphatase ϵ (PTPϵ) on ERK1/2 and AKT Protein Pathways Is Required for Survival of Human Breast Cancer Cells*

Background: To investigate the functional role of PTPϵ in human breast cancer cell lines. Results: PTPϵ was up-regulated in human breast cancer cells in an EGFR- and ERK1/2-dependent manner. PTPϵ displayed a positive role in survival of human breast cancer cells. Conclusion: PTPϵ generates a positive feedback regulatory loop required for survival of human breast cancer cells. Significance: PTPϵ could be a putative target in breast cancer treatment. Increased tyrosine phosphorylation has been correlated with human cancer, including breast cancer. In general, the activation of tyrosine kinases (TKs) can be antagonized by the action of protein-tyrosine phosphatases (PTPs). However, in some cases PTPs can potentiate the activation of TKs. In this study, we have investigated the functional role of PTPϵ in human breast cancer cell lines. We found the up-regulation and activation of receptor PTPϵ (RPTPϵ) in MCF-7 cells and MDA-MB-231 upon PMA, FGF, and serum stimulation, which depended on EGFR and ERK1/2 activity. Diminishing the expression of PTPϵ in human breast cancer cells abolished ERK1/2 and AKT activation, and decreased the viability and anchorage-independent growth of the cells. Conversely, stable MCF-7 cell lines expressing inducible high levels of ectopic PTPϵ displayed higher activation of ERK1/2 and anchorage-independent growth. Our results demonstrate that expression of PTPϵ is up-regulated and activated in breast cancer cell lines, through EGFR, by sustained activation of the ERK1/2 pathway, generating a positive feedback regulatory loop required for survival of human breast cancer cells.
Irinotecan plus cisplatin compared with etoposide plus cisplatin for extensive small-cell lung cancer.

BACKGROUND Irinotecan hydrochloride, a topoisomerase I inhibitor, is effective against small-cell lung cancer. In a phase 2 study of irinotecan plus cisplatin in patients with extensive small-cell lung cancer, there was a high response rate and a promising median survival time. METHODS We conducted a multicenter, randomized, phase 3 study in which we compared irinotecan plus cisplatin with etoposide plus cisplatin in patients with extensive (metastatic) small-cell lung cancer. RESULTS The planned size of the study population was 230 patients, but enrollment was terminated early because an interim analysis found a statistically significant difference in survival between the patients assigned to receive irinotecan and cisplatin and those assigned to receive etoposide and cisplatin; as a result, only 154 patients were enrolled. The median survival was 12.8 months in the irinotecan-plus-cisplatin group and 9.4 months in the etoposide-plus-cisplatin group (P=0.002 by the unadjusted log-rank test). At two years, the proportion of patients surviving was 19.5 percent in the irinotecan-plus-cisplatin group and 5.2 percent in the etoposide-plus-cisplatin group. Severe or life-threatening myelosuppression was more frequent in the etoposide-plus-cisplatin group than in the irinotecan-plus-cisplatin group, and severe or life-threatening diarrhea was more frequent in the irinotecan-plus-cisplatin group than in the etoposide-plus-cisplatin group. CONCLUSIONS Irinotecan plus cisplatin is an effective treatment for metastatic small-cell lung cancer.
Pilot Study for Managing Complex Chronic Care Medicaid Patients With Diabetes Using a Mobile Health Application Achieves “Triple Aim” Improvement in a Primary Care Setting

IN BRIEF Cost-effective innovations to improve health and health care in patients with complex chronic diseases are urgently needed. Mobile health (mHealth) remote monitoring applications (apps) are a promising technology to meet this need. This article reports on a study evaluating patients’ use of a tablet device with an mHealth app and a cellular-enabled glucose meter that automatically uploaded blood glucose values to the app. Improvements were observed across all three components of the Patient Protection and Affordable Care Act’s “triple aim. ” Self-rated wellness and numerous quality-of-care metrics improved, billed charges and paid claims decreased, but no changes in clinical endpoints were observed.
Plasma luteinizing hormone and progesterone in the adult female pig during the oestrous cycles, late pregnancy and lactation, and after ovariectomy and pentobarbitone treatment.

In a series of experiments on female miniature pigs, the pattern of plasma LH and progesterone levels during the oestrous cycle, late pregnancy and lactation and after ovariectomy were characterized, and the effect of pentobarbitone treatment was tested. The preovulatory surge of LH occurred in seven out of eight animals between 00.00 and 12.0 h on day 0 of the oestrous cycle (day 1 of standing heat). Plasma progesterone strated to decline 8 days before oestrus and reached its lowest value 5 days before the preovulatory LH peak. Increases in progesteron concentration were already noticeable 48 h after the LH surge. During late pregnancy, parturition and lactation, plasma LH was low and showed only minor fluctuations, while plasma progesterone declined 4 to 5 days before parturition. Both hormones remained at low levels throughout lactation. Three weeks before parturition increases in LH were always followed by an increase in progesterone. This dependency was greatly diminished immediately before delivery. Four to 12 days after weaning the animals came into oestrus which was followed by an increase in LH and later an increase in progesterone concentrations. Ovariectomy during dioestrus resulted in a steady increase in plasma LH levels of 35-39 days. Ovariectomy caused abortion if performed on day 100 of pregnancy. It was followed by a rapid increase of plasma LH concentration. Normal parturition (around day 115) and lactation took place when animals were spayed on day 112 of pregnancy. In this case, plasma LH levels remained even lower than before ovariectomy as long as lactation was maintained. Immediately after weaning a rapid increase in the normal postovariectomy pattern of LH secretion was observed. Pentobarbitone anaesthesia (30-35 mg/kg body wt, initial dose), during pro-oestrusoestrus, for less than 5 h had no effect on the preovulatory LH increase. However, pentobarbitone anaesthesia for more than 6 h inhibitied the LH peak and ovulation if the animal was under deep anaesthesia before 24.00 h on the day before oestrus. Pentobarbitone treatment of ovariectomized pigs resulted in a clear decrease in LH levels 40 min after a single i.v. dose.
Apolipoprotein C-III and hepatic triglyceride-rich lipoprotein production

Purpose of review A strong positive correlation between plasma apolipoprotein (apo) C-III and triglyceride concentrations has been invariably observed in human and animal studies. The hypertriglyceridemic effect of apo C-III has been conventionally explained by its extracellular roles in inhibiting lipolysis catalysed by lipoprotein lipase and attenuating triglyceride-rich lipoprotein clearance through receptor-dependent and/or independent mechanisms. However, recent experimental evidence suggests that apo C-III may also play an intracellular role in promoting hepatic triglyceride-rich lipoprotein production. Recent findings Kinetic studies with humans and genetically modified mice have shown that apo C-III is linked with increased production of triglyceride-rich lipoproteins, such as very-low-density lipoprotein 1 (VLDL1). Mutational studies on human apo C-III variants (originally identified in humans with hypotriglyceridemia or hyperalphalipoproteinemia) provide the structure–function analysis of human apo C-III, demonstrating that loss-of-function mutations within human apo C-III impair the assembly and secretion of triglyceride-rich VLDL1 under lipid-rich conditions. Summary The current review summarizes recent experimental evidence for an intrahepatic role of human apo C-III in promoting mobilization and utilization of triglyceride during VLDL1 assembly/secretion. Understanding mechanisms by which hepatic apo C-III expression is regulated under insulin resistance and diabetic conditions will lead to better and more rational strategies for the prevention and treatment of diabetic hypertriglyceridemia that is closely related to premature atherosclerosis.
Pathological nature of renal tumors - does size matter?

Introduction: We examined the relationship between the size and nature of renal masses in term of malignant potential, histological grading, pathological staging and presence of necrosis and sarcomatoid changes. Materials and Methods: Retrospectively, we reviewed 323 consecutive nephrectomies between 2000 and 2010. Final pathology was correlated with tumour size. The renal tumours were stratified into three groups according to the largest diameter, defined as 4 cm or smaller, greater than 4 cm to 7 cm, and greater than 7 cm. We recorded the proportion of benign tumours, tumour grade and stage, presence of necrosis and sarcomatoid change. Results: Small renal masses ≤4 cm (SRMs) were more likely to be localised to the kidney (90%) and of lower histological grade (75%). The proportion of benign tumours in SRMs (15%) was higher than other two groups with the majority of benign tumours being oncocytomas. There was a statistically significant trend with greater necrosis and sarcomatoid change for the large size group. Conclusions: SRMs are likely to be low grade and organ confined with little or no adverse pathological features. There is increased likelihood of benignity in SRTs with the majority of benign tumours being oncocytomas.
Psychosocial Dysfunction in Children and Adolescents With Eosinophilic Esophagitis

Objective: Children with eosinophilic esophagitis (EoE) experience daily challenges related to coping with symptoms and the psychosocial effect of this chronic disease. The aim of this study was to identify features of psychosocial dysfunction experienced by children with EoE who were evaluated in a tertiary care program. Methods: We performed a retrospective review of EoE patients and their families’ psychosocial evaluations performed in a tertiary care EoE program. Consecutive evaluations were analyzed to document reports of patients’ disease-related pain/discomfort; feeding/appetite symptoms; sleep, social, and school problems; depression, anxiety; and overall psychological adjustment. Results: Sixty-four patients received psychosocial evaluation during an 18-month period and were analyzed. Sixty-nine percent of children evaluated experienced some form of psychosocial problems, including social difficulties (64%), anxiety (41%), sleep difficulties (33%), depression (28%), and school problems (26%). Adjustment problems were identified in 44% of the sample. Older children experienced more adjustment difficulties than younger children (P = 0.05). Sleep disturbances and feeding problems predominated in the younger children. Anxious behavior and depressive feelings increased with age. Children with gastrostomy tubes (G-tubes) had more social, school, and psychological adjustment problems than those without. Conclusions: The majority of children with EoE who underwent health and behavior evaluation in a tertiary care program experienced psychosocial adjustment and coping problems. Evaluation and management by mental health professionals would likely benefit a majority of patients with this chronic disease.
Prognostic impact and initial recurrence site of lymphovascular and visceral pleural invasion in surgically resected stage I non-small-cell lung carcinoma.

OBJECTIVES This study aimed to analyse and validate the prognostic impact and effect of the initial recurrence site of lymphovascular and visceral pleural invasion (VPI) on survival outcomes for Stage I non-small-cell lung carcinoma (NSCLC). METHODS We retrospectively reviewed 433 patients undergoing resection of Stage I NSCLC. The relationship between the clinicopathological background and the pathological variables, lymphovascular invasion (LVI) and VPI, was evaluated by univariate and multivariate analyses. RESULTS Lymphovascular and VPI was observed in 41 and 45 patients, respectively. On univariate analysis, the presence of LVI was associated with a significant decrease in relapse-free survival (RFS) (P < 0.001) and overall survival (OS) (P < 0.001). The RFS of the patients of Stage IB with LVI was worse than the RFS of those of Stage IIA (T2aN1 and T2bN0)/IIB (T3N0), and similar to the RFS of those of Stage IIB (T2bN1). The presence of VPI was also associated with a significant decrease in RFS (P < 0.001) and OS (P = 0.01). On multivariate analysis, LVI was found to be an independent predictor of both decreased RFS and decreased OS. However, VPI was not an independent predictor of both. Recurrence was seen in 68 patients. As an initial recurrence site, distant recurrence was seen in 32 patients and local recurrence, in 36. The proportion of local recurrence was significantly higher in the patients with VPI than in those without VPI compared with between the patients with LVI and those without LVI. CONCLUSIONS We propose that LVI and/or VPI may be a candidate marker to determine adjuvant therapy or a more careful follow-up for these patients.
Factors influencing exposure of children to major hazards on family farms.

On family farms, parents are usually knowledgeable of high-risk activities, yet they allow their children to be active participants in (or bystanders to) hazardous work for reasons not well-documented. A two-phase descriptive study, based on the theory of planned behavior and using mail survey research methods, was carried out to understand factors that influence parents' decisions to expose children to major hazards on family farms. A representative sample of 1,255 Wisconsin dairy farm fathers provided data about factors that influence their decisions to expose children younger than 14 years to risks of injury. Multivariate analyses revealed that attitudes, subjective norms, and perceived control accounted for up to three-fourths of the variance in fathers' behavioral intentions. Fathers' attitudes were stronger predictors of behavioral intentions than subjective norms (i.e., perceived social pressure) or perceived control. Grandparents and mothers exerted a limited influence. Other groups, such as health care providers, 4-H, Future Farmers of America, and insurers, exerted only a modest influence on fathers' feelings of social pressure. Few demographic characteristics of the family or farm were predictive of fathers' intentions to expose children to hazards.
Pael‐R is accumulated in Lewy bodies of Parkinson's disease

We examined the distribution of Pael‐R, a newly identified substrate for Parkin, in Parkinson's disease (PD) and multiple system atrophy (MSA). Pael‐R, Parkin, α‐synuclein, and ubiquitin accumulated in Lewy bodies (LBs) and neurites. Pael‐R was localized in the core of LBs. Parkin and α‐synuclein accumulated in the halo, neuronal cell bodies, and processes. These findings potentially suggest the involvement of Pael‐R in LB formation, and protection role of Parkin in Pael‐R‐mediated neurotoxicity in PD. The absence of Pael‐R and Parkin in glial cytoplasmic inclusions (GCIs) in MSA implies a distinct pathway involved in the formation of LBs and GCIs. Ann Neurol 2004
The Design of Child Restraint System (CRS) Labels and Warnings Affects Overall CRS Usability

A study was conducted that assessed the effectiveness of different child restraint system (CRS) label/warning designs on users' installation performance. Forty-eight paid participants installed a convertible CRS in a vehicle, and two child test dummies in a CRS, using one of four label conditions. The label conditions were: (1) no labels, (2) the manufacturer's labels that were already affixed to the CRS (“Current”), (3) labels that were designed according to a combination of the current U.S. regulations concerning CRS labels and recently proposed changes to these regulations (“Proposed”), and (4) labels that were designed according to human factors principles and guidelines, and that were based on a hierarchical behavioral task analysis (“Optimal”). Results demonstrated that, overall, the Optimal labels resulted in higher usability ratings and better task performance. This indicates that labels designed using human factors and task analyses that identify critical task information requirements for label features will result in increased user compliance with instructions, higher usability, and improved task performance. Surprisingly, having no labels on the CRS resulted in better installation performance than when either the Current or the Proposed label conditions were used. This indicates that label design can decrease task performance; the actual physical design of a CRS may be just as critical as label content in the installation choices provided to the user. Collectively, results suggest that implementation of the proposed changes to the U.S. regulations concerning CRS labeling would likely not result in increased performance or usability compared to existing manufacturer labels that follow the current guidelines. In order to achieve significantly better ease-of-use and task performance, it would be necessary to implement features of the Optimal label condition.
Panel Models with Two Threshold Variables: The Case of Financial Constraints

We develop threshold estimation methods for panel data models with two threshold variables and individual fixed specific effects covering short time periods. In the static panel data model, we propose least squares estimation of the threshold and regression slopes using fixed effects transformations; while in the dynamic panel data model, we propose maximum likelihood estimation of the threshold and slope parameters using first difference transformations. In both models, we propose to estimate the threshold parameters sequentially. We apply the methods to a 15-year sample of 565 U.S. firms to test whether financial constraints affect investment decisions.