Miracle-dz/UniFAR-FTUs huggingface dataset:
High Weight Loss during Radiation Treatment Changes the Prognosis in Under-/Normal Weight Nasopharyngeal Carcinoma Patients for the Worse: A Retrospective Analysis of 2433 Cases

Background Although weight loss is common in nasopharyngeal carcinoma (NPC) patients receiving radiotherapy, the prognostic influence of weight loss and its impact modified by body mass index (BMI) are still unclear. Methods 2433 NPC patients receiving radical radiotherapy at Sun Yat-sen University Cancer Center from November, 2000 to December, 2004 were enrolled. Weight change during radiation treatment was categorized into high weight loss (HWL) and low weight loss (LWL). The associations of HWL with overall survival (OS) and disease-specific survival (DSS) were analyzed by Cox regression. Results Among underweight patients, HWL was independently associated with poor OS (hazard ratio [HR], 2.06; 95% CI 1.36–3.11) and DSS (HR, 2.27; 95% CI 1.38–3.73), as compared with LWL, after adjusting for covariates. In normal weight patients, the impact of HWL on OS (HR, 1.47; 95% CI 1.19–1.80) and DSS (HR, 1.59; 95% CI 1.24–2.03) was moderate. Among overweight/obese patients, no significant association between HWL and OS (HR, 1.22; 95% CI 0.95–1.55), or DSS (HR, 1.23; 95% CI 0.93–1.64) was found. Conclusion Except for overweight/obese patients, high weight loss during radiation treatment was independently associated with poor survival in NPC. This impact was more prominent in the underweight patient group.
Impaired Intracellular Trafficking of Adeno-Associated Virus Type 2 Vectors Limits Efficient Transduction of Murine Fibroblasts

ABSTRACT Although adeno-associated virus type 2 (AAV) has gained attention as a potentially useful alternative to the more commonly used retrovirus- and adenovirus-based vectors for human gene therapy, efficient gene transfer and transgene expression by AAV vectors require that the following two obstacles be overcome. First, the target cell must express the receptor and the coreceptor for AAV infection, and second, the cell must allow for viral second-strand DNA synthesis. We now describe a third obstacle, impaired intracellular trafficking of AAV to the nucleus, which results in the lack of transgene expression in murine fibroblasts which do express the AAV receptor and the coreceptor and which are permissive for viral second-strand DNA synthesis. We document that AAV vectors bind efficiently and gain entry successfully into NIH 3T3 cells, but trafficking into the nucleus is significantly impaired in these cells. In contrast, viral trafficking to the nucleus in cells known to be efficiently transduced by AAV vectors is both rapid and efficient. The demonstration of yet another obstacle in AAV-mediated gene transfer has implications for the optimal use of these vectors in human gene therapy.
Randomized, controlled clinical trial of zinc supplementation to prevent immunological failure in HIV-infected adults.

BACKGROUND Adequate zinc is critical for immune function; however, zinc deficiency occurs in >50% of human immunodeficiency virus (HIV)-infected adults. We examined the safety and efficacy of long-term zinc supplementation in relation to HIV disease progression. METHODS A prospective, randomized, controlled clinical trial was conducted involving 231 HIV-infected adults with low plasma zinc levels (<0.75 mg/L), who were randomly assigned to receive zinc (12 mg of elemental zinc for women and 15 mg for men) or placebo for 18 months. The primary end point was immunological failure. HIV viral load and CD4(+) cell count were determined every 6 months. Questionnaires, pill counts, and plasma zinc and C-reactive protein levels were used to monitor adherence to study supplements and antiretroviral therapy. Intent-to-treat analysis used multiple-event analysis, treating CD4(+) cell count <200 cells/mm(3) as a recurrent immunological failure event. Cox proportional hazard models and the general-linear model were used to analyze morbidity and mortality data. RESULTS Zinc supplementation for 18 months reduced 4-fold the likelihood of immunological failure, controlling for age, sex, food insecurity, baseline CD4(+) cell count, viral load, and antiretroviral therapy (relative rate, 0.24; 95% confidence interval, 0.10-0.56; P<.002). Viral load indicated poor control with antiretroviral therapy but was not affected by zinc supplementation. Zinc supplementation also reduced the rate of diarrhea by more than half (odds ratio, 0.4; 95% confidence interval, 0.183-0.981; P=.019), compared with placebo. There was no significant difference in mortality between the 2 groups. CONCLUSIONS This study demonstrated that long-term (18-month) zinc supplementation at nutritional levels delayed immunological failure and decreased diarrhea over time. This evidence supports the use of zinc supplementation as an adjunct therapy for HIV-infected adult cohorts with poor viral control. Trial registration. ClinicalTrials.gov identifier: NCT00149552.
Effectiveness of physical therapy treatment of clearly defined subacromial pain: a systematic review of randomised controlled trials

Aim To summarise the current evidence regarding the effectiveness of physical therapy on pain, function and range of motion in individuals with subacromial pain syndrome (SAPS). Design Systematic review. Data sources PubMed, Web of Science, CINAHL, Cochrane, Embase, Lilacs, Ibecs and Scielo databases. Eligibility criteria for selecting studies Randomised controlled trials (RCTs) investigating physical therapy modalities for SAPS on pain, function/disability or range of motion were included. Results 64 high-quality RCTs were included. Exercise therapy provided high evidence of being as effective as surgery intervention and better than no treatment or placebo treatment to improve pain, function and range of motion in the short, mid and long terms. The combination of mobilisation and exercises provided high evidence to decrease pain and improve function in the short term. There is limited evidence for improvements on the outcomes with the isolated application of manual therapy. High level of evidence was synthesised regarding the lack of beneficial effects of physical resources such as low-level laser, ultrasound and pulsed electromagnetic field (PEMF) on pain, function or range of motion in the treatment of SAPS. There is limited evidence for microwave diathermy and transcutaneous electrical nerve stimulation. There is moderate evidence to no benefits with taping in the short term. Effects of diacutaneous fibrolysis and acupuncture are not well established yet. Conclusions Exercise therapy should be the first-line treatment to improve pain, function and range of motion. The addition of mobilisations to exercises may accelerate reduction of pain in the short term. Low-level laser therapy, PEMF and taping should not be recommended.
Synthesis of power efficient multitone signals with flat amplitude spectrum

It is shown that, generally, any binary or polyphase sequence belonging to a pair of complementary sequences can be used to construct the initial phases of tones forming a multitone signal with the crest factor less than or equal to 6 dB. The previously proposed Shapiro-Rudin sequences are representatives of a much larger family of binary Golay complementary sequences. Numerical investigations show that the values of the crest factors obtained by applying complementary sequences (binary or polyphase) are between 5 and 6 dB, regardless of the number of tones. >
Strength of different Krackow stitch configurations using high-strength suture.

The purpose of the present study concerning high-strength sutures was to determine whether increasing the number of locking loops with different size sutures or decreasing the suture size with increased suture strands would have any influence on the strength of Achilles tendon repair. A total of 32 fresh bovine Achilles tendon specimens were randomly assigned to 4 groups. For 3 of the groups, 1 suture was used (no. 2 or no. 5 FiberWire™ with 2 or 4 Krackow locking loops). For the fourth group, 2 sutures (2-0 FiberWire™) with 2 locking loops were used. After repair, the study groups underwent cyclic loading (0 to 200 N, 200 cycles) and then underwent tension to failure in a testing machine. Cyclic elongation, peak to peak displacement, ultimate load, stiffness, and failure mode were recorded for each specimen. The tendon width and thickness were measured in all specimens. The mean width, thickness, cyclic displacement, load to failure, and pull-out stiffness showed no differences among the 4 groups. The cyclic peak to peak displacements (0.01 ± 0.01 mm) were smallest with the no. 5 suture with 4 locking loops (p < .05), with no failure during cyclic loading, unlike in the other groups. In the group with 2-0 suture with 4 strands and 2 locking loops, 6 failed during cyclic loading. The number of locking loops used might have had an influence on the strength of the Krackow suture configuration using the larger diameter, high-strength sutures. However, decreasing the suture diameter, with a simultaneous increase in the number of strands, failed to improve the initial strength of the repair.
Improvements in indicators of diabetes-related health status among first nations individuals enrolled in a community-driven diabetes complications mobile screening program in Alberta, Canada.

OBJECTIVE The goal of Screening for Limb, I-Eye, Cardiovascular, and Kidney complications of diabetes (SLICK) is to reduce the burden of diabetes among Alberta First Nations individuals. By analyzing the longitudinal results of SLICK over a six-year time span, our purpose was to examine both baseline diabetes-related health status and whether subsequent improvements occurred. METHODS Diabetes complications screening, diabetes education, and community-based care were provided by mobile clinics which traveled to 43 Alberta First Nations communities biannually. Body mass index (BMI), waist circumference, hemoglobin A1c (HbA1c), total cholesterol and blood pressure, as well as the presence of foot and kidney abnormalities were assessed among 2102 unique subjects with diabetes. Mean values of diabetes health indicators at baseline and subsequent visits for returning subjects were compared. Secular trends were sought by examining trends in mean baseline health indicators per year. RESULTS High baseline rates of obesity, poor HbAlc concentrations, hypercholesterolemia, hypertension, foot abnormalities and kidney damage were observed. Significant improvements in BMI, blood pressure, total cholesterol and HbA1c concentrations were identified (p < 0.01) in returning subjects. Similarly, significant decreasing secular trends in total cholesterol and HbA1c concentrations were observed (p < 0.01). At baseline, females had a higher prevalence of obesity and abnormal waist circumference (p < 0.05); however, males had more inadequate HbA1c concentrations (>8.4%), hypercholesterolemia, hypertension, foot abnormalities and kidney damage (p < 0.05). DISCUSSION Despite worrisome baseline clinical characteristics, diabetes-related health appears to be improving modestly in Alberta First Nations individuals.
Analysis of Mice Lacking DNaseI Hypersensitive Sites at the 5′ End of the IgH Locus

The 5′ end of the IgH locus contains a cluster of DNaseI hypersensitive sites, one of which (HS1) was shown to be pro-B cell specific and to contain binding sites for the transcription factors PU.1, E2A, and Pax5. These data as well as the location of the hypersensitive sites at the 5′ border of the IgH locus suggested a possible regulatory function for these elements with respect to the IgH locus. To test this notion, we generated mice carrying targeted deletions of either the pro-B cell specific site HS1 or the whole cluster of DNaseI hypersensitive sites. Lymphocytes carrying these deletions appear to undergo normal development, and mutant B cells do not exhibit any obvious defects in V(D)J recombination, allelic exclusion, or class switch recombination. We conclude that deletion of these DNaseI hypersensitive sites does not have an obvious impact on the IgH locus or B cell development.
The hypothalamic-pituitary-thyroid axis in subjects with subclinical thyroid diseases: the impact of the negative feedback mechanism.

OBJECTIVE To evaluate the hypothalamus-pituitary-thyroid (HPT) axis in patients with subclinical thyroid dysfunction recently reported to have either symptoms or organ involvements with potential morbidity, in order to better differentiate these patients with respect to controls. PATIENTS Sixtythree patients with subclinical hyperthyroidism (HyperT), 178 normal subjects (EuT) and 106 patients with subclinical hypothyroidism (HypoT) were enrolled; the groups presented normal thyroid hormone (FT4, FT3) levels and, respectively, reduced (HyperT), normal (EuT) and increased (HypoT) TSH levels. The negative feedback was simultaneously evaluated by multiple linear regression. RESULTS The mean TSH, FT4 and FT3 levels were significantly different in the three groups. The negative correlation between thyroid hormones (FT4 and FT3) and TSH secretion was significant (p<0.001 in HyperT; p<0.01 in EuT; p<0.000001 in HypoT group). FT4 mostly contributed to the negative correlation with TSH. The normal ranges of TSH values was accurately defined on the basis of the regression equation in the EuT group, due to the combining influence of both thyroid hormones (FT3 and FT4). No patient of the HyperT or HypoT group fell inside the range of estimated values of the normal group. CONCLUSIONS The HPT axis in patients with subclinical hyper- and hypo-thyroidism is significantly modified with respect to normal subjects. The status of the axis, as evaluated by the relationship between the three hormones (FT4, FT3, TSH) together considered, is characteristic of the normal or pathologic condition. A reliable method based on the regression analysis is proposed to correctly evaluate the status of the HPT axis.
Selecting Sequences of Items via Submodular Maximization

Motivated by many real world applications such as recommendations in online shopping or entertainment, we consider the problem of selecting sequences of items. In this paper we introduce a novel class of utility functions over sequences of items, strictly generalizing the commonly used class of submodular set functions. We encode the sequential dependencies between items by a directed graph underlying the utility function. Classical algorithms fail to achieve any constant factor approximation guarantees on the problem of selecting sequences of bounded length with maximum utility. We propose an efficient algorithm for this problem that comes with strong theoretical guarantees characterized by the structural properties of the underlying graph. We demonstrate the effectiveness of our algorithm in synthetic and real world experiments on a movie recommendation dataset.
Dynamics of cAMP-dependent protein kinase.

B. N-Terminus/C-Terminus 2253 1. N-Terminal Tail 2253 2. C-Terminal Tail 2257 C. Signal Integration Motifs 2257 1. C Helix 2258 2. Activation Loop 2258 3. F Helix 2258 D. Dynamics 2259 1. Fluorescence Anisotropy 2259 2. Molecular Dynamic Simulations 2260 III. Inhibitors of the Catalytic Subunit 2260 A. Protein Kinase Inhibitor 2260 B. Regulatory Subunits 2262 1. cAMP-Binding Domains 2263 2. Overall Structure and Dynamics 2265 IV. A-Kinase Anchoring Proteins 2266 V. Future Directions and Challenges 2266 A. Small-Angle Scattering 2266 B. Hydrogen/Deuterium (H/D) Exchange:Mass Spectrometry 2267
Pancreatic β Cell Mass Death

Type two diabetes (T2D) is a challenging metabolic disorder for which a cure has not yet been found. Its etiology is associated with several phenomena, including significant loss of insulin-producing, beta cell (β cell) mass via progressive programmed cell death and disrupted cellular autophagy. In diabetes, the etiology of β cell death and the role of mitochondria are complex and involve several layers of mechanisms. Understanding the dynamics of those mechanisms could permit researchers to develop an intervention for the progressive loss of β cells. Currently, diabetes research has shifted toward rejuvenation and plasticity technology and away from the simplified approach of hormonal compensation. Diabetes research is currently challenged by questions such as how to enhance cell survival, decrease apoptosis and replenish β cell mass in diabetic patients. In this review, we discuss evidence that β cell development and mass formation are guided by specific signaling systems, particularly hormones, transcription factors, and growth factors, all of which could be manipulated to enhance mass growth. There is also strong evidence that β cells are dynamically active cells, which, under specific conditions such as obesity, can increase in size and subsequently increase insulin secretion. In certain cases of aggressive or advanced forms of T2D, β cells become markedly impaired, and the only alternatives for maintaining glucose homeostasis are through partial or complete cell grafting (the Edmonton protocol). In these cases, the harvesting of an enriched population of viable β cells is required for transplantation. This task necessitates a deep understanding of the pharmacological agents that affect β cell survival, mass, and function. The aim of this review is to initiate discussion about the important signals in pancreatic β cell development and mass formation and to highlight the process by which cell death occurs in diabetes. This review also examines the attempts that have been made to recover or increase cell mass in diabetic patients by using various pharmacological agents.
Who Are the Bright Children? The Cultural Context of Being and Acting Intelligent

In the United States as well as in much of the developed world, many of us tend to take for granted that children who do well on teacher-made and standardized tests are intelligent. But different cultures have different views of intelligence, so which children are considered intelligent may vary from one culture to another. Moreover, the acts that constitute intelligent behavior may vary from one culture to another. Whether teachers take into account the differences in conceptions of who is intelligent and who acts intelligently can also affect how well students learn. This article describes how culture influences what constitutes intelligence, intelligent acts, and intelligent teaching.
Acute hemorrhagic leukoencephalitis in patients with acute myeloid leukemia in hematologic complete remission.

The authors describe the cases of three patients affected by acute myeloid leukemia, in complete remission, who rapidly developed neurologic symptoms leading to death. Neither clinical characteristics, nor radiological or microbiological procedures, allowed an etiological diagnosis of the neurologic syndrome. Post-mortem examination of the brain showed both macroscopic and microscopic findings compatible with acute hemorrhagic leukoencephalitis. The difficulty in distinguishing this entity from other CNS disease-related complications (e.g. leukemia infiltration, drug toxicity, hemorrhages) should not lead to an underestimation of the true incidence of this complication. We believe that with more attention to the possibility of this complication there would probably be both a greater possibility of collecting clinical informations about the real impact of this dramatic disease and a stronger hope of finding the right treatment for it.
IBAL: A Probabilistic Rational Programming Language

In a rational programming language, a program specifies a situation faced by an agent; evaluating the program amounts to computing what a rational agent would believe or do in the situation. This paper presents IBAL, a rational programming language for probabilistic and decision-theoretic agents. IBAL provides a rich declarative language for describing probabilistic models. The expression language allows the description of arbitrarily complex generative models. In addition, IBAL’s observation language makes it possible to express and compose rejective models that result from conditioning on the observations. IBAL also integrates Bayesian parameter estimation and decisiontheoretic utility maximization thoroughly into the framework. All these are packaged together into a programming language that has a rich type system and built-in extensibility. This paper presents a detailed account of the syntax and semantics of IBAL, as well as an overview of the implementation.
Isolation and Functional Analysis of Arabidopsis Stress-Inducible NAC Transcription Factors That Bind to a Drought-Responsive cis-Element in the early responsive to dehydration stress 1 Promoterw⃞

The MYC-like sequence CATGTG plays an important role in the dehydration-inducible expression of the Arabidopsis thaliana EARLY RESPONSIVE TO DEHYDRATION STRESS 1 (ERD1) gene, which encodes a ClpA (ATP binding subunit of the caseinolytic ATP-dependent protease) homologous protein. Using the yeast one-hybrid system, we isolated three cDNA clones encoding proteins that bind to the 63-bp promoter region of erd1, which contains the CATGTG motif. These three cDNA clones encode proteins named ANAC019, ANAC055, and ANAC072, which belong to the NAC transcription factor family. The NAC proteins bound specifically to the CATGTG motif both in vitro and in vivo and activated the transcription of a β-glucuronidase (GUS) reporter gene driven by the 63-bp region containing the CATGTG motif in Arabidopsis T87 protoplasts. The expression of ANAC019, ANAC055, and ANAC072 was induced by drought, high salinity, and abscisic acid. A histochemical assay using PNAC-GUS fusion constructs showed that expression of the GUS reporter gene was localized mainly to the leaves of transgenic Arabidopsis plants. Using the yeast one-hybrid system, we determined the complete NAC recognition sequence, containing CATGT and harboring CACG as the core DNA binding site. Microarray analysis of transgenic plants overexpressing either ANAC019, ANAC055, or ANAC072 revealed that several stress-inducible genes were upregulated in the transgenic plants, and the plants showed significantly increased drought tolerance. However, erd1 was not upregulated in the transgenic plants. Other interacting factors may be necessary for the induction of erd1 in Arabidopsis under stress conditions.
Toxicities of the anti-PD-1 and anti-PD-L1 immune checkpoint antibodies.

Immune checkpoint antibodies that augment the programmed cell death protein 1 (PD-1)/PD-L1 pathway have demonstrated antitumor activity across multiple malignancies, and gained recent regulatory approval as single-agent therapy for the treatment of metastatic malignant melanoma and nonsmall-cell lung cancer. Knowledge of toxicities associated with PD-1/PD-L1 blockade, as well as effective management algorithms for these toxicities, is pivotal in order to optimize clinical ef ﬁ cacy and safety. In this article, we review selected published and presented clinical studies investigating single-agent anti-PD-1/PD-L1 therapy and trials of combination approaches with other standard anticancer therapies, in multiple tumor types. We summarize the key adverse events reported in these studies and their management algorithms.