Miracle-dz/UniFAR-FTUs huggingface dataset:
Single Particle Tracking Confirms That Multivalent Tat Protein Transduction Domain-induced Heparan Sulfate Proteoglycan Cross-linkage Activates Rac1 for Internalization*

The mechanism by which HIV-1-Tat protein transduction domain (TatP) enters the cell remains unclear because of an insufficient understanding of the initial kinetics of peptide entry. Here, we report the successful visualization and tracking of TatP molecular kinetics on the cell surface with 7-nm spatial precision using quantum dots. Strong cell binding was only observed with a TatP valence of ≥8, whereas monovalent TatP binding was negligible. The requirement of the cell-surface heparan sulfate (HS) chains of HS proteoglycans (HSPGs) for TatP binding and intracellular transport was demonstrated by the enzymatic removal of HS and simultaneous observation of two individual particles. Multivalent TatP induces HSPG cross-linking, recruiting activated Rac1 to adjacent lipid rafts and thereby enhancing the recruitment of TatP/HSPG to actin-associated microdomains and its internalization by macropinocytosis. These findings clarify the initial binding mechanism of TatP to the cell surface and demonstrate the importance of TatP valence for strong surface binding and signal transduction. Our data also shed light on the ability of TatP to exploit the machinery of living cells, using HSPG signaling to activate Rac1 and alter TatP mobility and internalization. This work should guide the future design of TatP-based peptides as therapeutic nanocarriers with efficient transduction.
The relationship between sexual dimorphism in human faces and fluctuating asymmetry

Previous studies have found both support and lack of support for a positive relationship between masculinity and symmetry, two putative signs of mate quality, in male faces. We re–examined this relationship using an explicit measure of facial fluctuating asymmetry, as well as other measures of asymmetry, and measures of facial masculinity/femininity. We also used ratings of these traits for faces. Further, we examined the relationship between facial sexual dimorphism and body asymmetry. We found no significant correlations between facial masculinity and any of our measures of asymmetry or ratings of symmetry in males. Facial femininity was not consistently associated with facial symmetry in females, but was associated with body symmetry. Therefore, for females, but not males, facial femininity and body symmetry may reflect similar aspects of mate quality. We also examined the relationships between trait ratings and measurements. Our results provide validation of our ability to measure aspects of asymmetry that are perceived to be symmetrical, and aspects of sexual dimorphism that are perceived as feminine in females and masculine in males.
The Earnings Announcement Return Cycle

Stocks earn significantly negative abnormal returns before earnings announcements and positive after them. This "earnings announcement return cycle" (EARC) is unrelated to the earnings announcement premium, and it is a feature of stocks widely covered by analysts. Analysts' forecasts follow the same pattern as returns: analysts' forecasts become more optimistic after an earnings announcement and more pessimistic as the next one draws near. We attribute one-half of the earnings announcement return cycle to this optimism cycle. The EARC may stem from mispricing: both the return and optimism patterns are stronger among high-uncertainty and difficult-to-arbitrage stocks, and the EARC strategy is more profitable on days when it would accommodate larger amounts of arbitrage capital.
The Physical, Behavioral, and Psychosocial Consequences of Internet Use in College Students

The purposes of this study were to identify the physical, behavioral, and psychosocial consequences of Internet use in undergraduate college students; and to evaluate whether time, social norms, and adopter category predict the consequences of Internet use. Rogers' model for studying consequences of innovation was adapted for this study. A descriptive, correlational design was used. Convenience sampling yielded 293 undergraduate students who answered the online survey. Consequences of Internet use were assessed with the researcher-developed instrument, the Internet Consequences Scale (ICONS). Mean scores on the behavioral and psychosocial subscales of the ICONS indicated positive consequences of Internet use, while the physical consequences subscale revealed negative consequences. Multiple regression analyses revealed a small, but significant, amount of variance in consequences of Internet use that could be explained by time, social norms, and adopter category, thus supporting the adapted model for the study of consequences of Internet use in college students.
Intralesional Lymphokine-activated Killer Cells as Adjuvant Therapy for Primary Glioblastoma

Despite recent advances, median survival for patients with resectable glioblastoma multiforme (GBM) is only 12 to 15 months. We previously observed minimal toxicity and a 9.0-month median survival after treatment with intralesional autologous lymphokine-activated killer (LAK) cells in 40 patients with recurrent GBM. In this study, GBM patients were treated with adjuvant intralesional LAK cells. Eligible patients had completed primary therapy for GBM without disease progression. LAK cells were produced by incubating autologous peripheral blood mononuclear cells with interleukin-2 for 3 to 7 days and then placed into the surgically exposed tumor cavity by a neurosurgeon. The 19 men and 14 women had a median age of 57 years. Prior therapy included surgical resection (97%), partial brain irradiation (97%), γ knife radiosurgery (97%), and temozolomide chemotherapy (70%). Median time from diagnosis to LAK cell therapy was 5.3 months (range: 3.0 to 11.1 mo). LAK cell treatment was well tolerated; average length of hospitalization was 3 days. At the time of this analysis, 27 patients have died; the median survival from the date of original diagnosis is 20.5 months with a 1-year survival rate of 75%. In subset analyses, superior survival was observed for patients who received higher numbers of CD3+/CD16+/CD56+ (T-LAK) cells in the cell products, which was associated with not taking corticosteroids in the month before leukopheresis. Intralesional LAK cell therapy is safe and the survival sufficiently encouraging to warrant further evaluation in a randomized phase 2 trial of intralesional therapies with LAK or carmustine-impregnated wafers.
The role of sex on VARC outcomes following transcatheter aortic valve implantation with both Edwards SAPIEN™ and Medtronic CoreValve ReValving System® devices: the Milan registry.

AIMS To assess outcomes after transcatheter aortic valve implantation (TAVI) according to sex, with the two available valves and four recognised delivery approaches. METHODS AND RESULTS VARC outcomes are reported according to sex for 305 high-risk patients consecutively treated in our centre, via available access routes utilising the Edwards SAPIEN™/SAPIEN™ XT or the Medtronic CoreValve ReValving System® devices. Three hundred and five patients underwent TAVI: 52.1% male and 47.9% female. Females had a smaller body surface area (1.84±0.16 m² vs. 1.70±0.16 m²; p<0.001) and aortic annulus (24.4±1.6 mm vs. 22.6±1.7 mm; p<0.001) with increased symptoms (NYHA Class III/IV 61.6% vs. 73.6%; p=0.026). Conversely, men had more comorbidities: diabetes mellitus (35.2% vs. 21.9%; p=0.010), chronic kidney disease (41.8% vs. 23.3%; p=0.001), chronic obstructive pulmonary disease (45.3% vs. 30.1%; p=0.006) and previous myocardial infarction (28.3% vs. 14.4%; p=0.003). Thirty-day mortality was 4.7% with no difference between groups. There was a trend for females to develop more major vascular complications (11.9% vs. 19.9%; p=0.058). Notably, females required more blood transfusion (38.4% vs. 50.0%; p=0.041). No differences were observed in device success (92.5%; p=0.667), combined safety endpoint (61.8%; p=0.211) or combined efficacy endpoint (72.0%; p=0.889). CONCLUSIONS Female sex was a predictor of major vascular complications with females requiring more transfusion. No differences were noted amongst patients undergoing TAVI in composite safety and efficacy endpoints according to sex.
[Are SPA therapy and pulsed electromagnetic field therapy effective for chronic neck pain? Randomised clinical trial First part: clinical evaluation].

OBJECTIVES The purpose of this study was to compare SPA therapy (ST) with pulsed electromagnetic field (PEMF) therapy in chronic neck pain. MATERIALS AND METHODS Inclusion criteria were age between 18 and 80 years, neck pain of more than 3 months' duration and pain score>30 mm on a visual analog scale (VAS). Exclusion criteria were contraindication to ST or PEMF. The protocol was approved by the ethics committee of Grenoble Hospital. Randomisation to the ST (n=44) and PEMF groups (n=42) was blinded. The main outcome measure was number of improved patients at 6 months in each group. A patient was considered improved if pain score decreased by more than 20%. Secondary measures were score on the Copenhagen and MOS SF-36 scales. Evaluation and intent-to-treat analysis were also blinded. RESULTS Patients' preferences were for PEMF. At 6 months, in the PEMF group, 33 patients were improved, 5 not improved and 4 lost to follow-up. In the ST group, 24 patients were improved, 14 not improved and 6 lost to follow-up, for significantly greater improvement in the PEMF than ST group (p=0.02). Significant improvement was seen in both groups in terms of pain score, Copenhagen scale score and score on some dimensions of the MOS SF-36 survey. CONCLUSION PEMF seems to be superior to standard ST without massage in control of neck pain. The difference between groups, although perhaps biased, seem to suggest the importance of our conclusions.
A comprehensive utility-based system of activity-travel scheduling options modelling (CUSTOM) for worker's daily activity scheduling processes

This paper presents a comprehensive utility-based system of activity-travel scheduling options modelling (CUSTOM) and applies it to simulate workers’ daily activity-travel demand. CUSTOM uses a random utility maximizing econometric approach for jointly modelling activity-type choices, time expenditure choices and location choices. It considers the depleting time budgets as activity-travel scheduling progresses along with shrinking potential path areas (PPAs) for activity location choices. For prototype application, the model is estimated on a sample of workers and students taken from the 2011 household travel survey of the National Capital Region (NCR) of Canada. A validation exercise is performed and it is demonstrated that CUSTOM can accurately predict activity-travel behaviour. Differential travel time sensitivity is identified and it is revealed that people are more sensitive to auto travel time than transit or non-motorized travel times. Changes in choice randomness, time expenditure choices .
Adherence to current guidelines for chronic obstructive pulmonary disease (COPD) among patients treated with combination of long-acting bronchodilators or inhaled corticosteroids

Background To estimate the potential cost savings by following the current Global Initiative for Chronic Obstructive Lung Disease (GOLD) guideline recommendations in patients being treated for chronic obstructive pulmonary disease (COPD) with the combination of long-acting β2-agonist (LABA), long-acting muscarinic antagonist (LAMA) or inhaled corticosteroids (ICS). Methods The Geisinger Health System (GHS) database was utilized to identify subjects between January 1, 2004 to March 12, 2007. The index date was based on the first prescription of a LAMA plus LABA, LAMA plus LABA/ICS, or LABA plus ICS. Patients were included in the study if they: had a COPD diagnosis; had data representative of treatment 12 months prior to and 12 months post index date; were 40 years of age or over; had no prior diagnosis for asthma; and had pulmonary function test (PFT) data. We examined the baseline characteristics of these patients along with their healthcare resource utilization. Based on PFT data within 30 days of the index date, a subgroup was classified as adhering or non-adhering to GOLD guidelines. Results A total of 364 subjects could be classified as adhering or non-adherent to current GOLD guidelines based on their PFT results. The adherent subgroup received COPD medications consistent with current GOLD guidelines. Of the LAMA plus LABA cohort, 25 patients adhered and 39 patients were non-adherent to current GOLD guidelines. In the cohort of LABA plus ICS, 74 patients were adherent and 180 patients non-adherent to current GOLD guidelines. In the cohort of LAMA plus LABA/ICS, 21 patients were adherent and 25 patients non-adherent to current GOLD guidelines. GOLD adherence was associated with mean total cost of all services savings of $5,889 for LAMA plus LABA, $3,330 for LABA + ICS, and $10,217 for LAMA plus LABA/ICS cohorts. Conclusion Staging of COPD with a PFT and adherence to current GOLD guidelines was associated with lower costs in subjects with moderate to severe COPD. Appropriate use of LAMA plus LABA, LABA plus ICS, and LAMA plus LABA/ICS has economic as well as clinical benefits for patients and payers.
Immunological and virological response to antiretroviral treatment in migrant and native men and women in Western Europe; is benefit equal for all?

The aim of the study was to evaluate differences in immunovirological response to combination antiretroviral therapy (cART) in migrant and native men and women within a European collaboration of HIV cohorts Collaboration of Observational HIV Epidemiological Research in Europ (COHERE) in EuroCoord, 2004–2013.
Phenotype-genotype correlation in eight Chinese 17alpha-hydroxylase/17,20 lyase-deficiency patients with five novel mutations of CYP17A1 gene.

CONTEXT P450c17 deficiency (17OHD), caused by mutation in CYP17A1 gene, is characterized by severe hypertension-hypokalemia, sexual infantilism in females, and pseudohermaphroditism in males. We investigated eight Chinese 17OHD patients with five novel mutations of CYP17A1 gene and analyzed phenotype-genotype correlation in a patient with regular menses and seven others with classic presentations by in vitro expression and computer modeling. OBJECTIVE The objective of the study was to explore the phenotype-genotype correlation in patients with subtle and classic manifestations. SUBJECTS AND METHODS Eight patients with 17OHD from seven families were diagnosed according to clinical manifestations and basal hormone assays. The CYP17A1 gene was amplified and sequenced. Haplotyping analysis was performed to determine a common ancestor for those subjects with a frequent mutation 1517_1525del. In vitro enzymatic activities assay and computer modeling were used to analyze the phenotype-genotype correlation. RESULTS Five novel CYP17A1 mutations, homozygous D487_F489del (1517_1525del) and F453S, combined compound Y329K and 1047del, P434L and V310_W313del, and R416C and D487_F489del were identified. Haplotyping showed that 1517_1525del might be inherited from a common ancestor. Compared with the mutations in patients with classical manifestations, F453S in the patient with regular menses, occasional hypertension, and hypokalemia showed a partially reduced 17alpha-hydroxylase (29% of those of wild type) and a minor protein conformational change. CONCLUSION The clinical manifestations in patients with 17OHD correlate with CYP17A1 mutations and enzymatic activities by in vitro enzyme assay and computer modeling. F453S mutation results in partially reduced enzymatic activities and a subtle phenotype. The prevalent mutation 1517_1525del in Chinese 17OHD patients might be a founder effect.
The Negative Predictive Value of Clinical Examination With or Without Anesthesia Versus Magnetic Resonance Imaging for Parametrial Infiltration in Cervical Cancer Stages IB1 to IIA

Objective This study aimed to compare the negative predictive value (NPV) of clinical examination with or without anesthesia and magnetic resonance imaging (MRI) in identifying patients with cervical carcinoma without parametrial infiltration. Methods This retrospective cohort study was conducted at the Academic Medical Center in Amsterdam. The medical files of 203 patients diagnosed with cervical cancer stages IB1-IIA, who underwent surgical treatment between January 1, 2003, and January 31, 2011, were reviewed. We compared clinical International Federation of Gynecology and Obstetrics staging and MRI during the staging procedure. The results were compared with the parametrial status by surgical-pathological investigation, which was considered to be the reference standard. Results Based on the surgical-pathological findings, 16.7% of the patients treated surgically had parametrial infiltration. For parametrial infiltration, examination under anesthesia (EUA) had an NPV of 65.3% and MRI of 76.9%, respectively. We found no significant difference between these NPVs. Conclusions Examination under anesthesia and MRI are equal in identifying cervical cancer patients without parametrial infiltration with a tendency for MRI to perform better than EUA. When outpatient clinical staging is considered inconclusive, pretreatment staging may be limited to MRI. In these cases, EUA seems to have no additional value.
Effectiveness of screening for risk of medical emergencies in the elderly.

STUDY OBJECTIVE UK government policy mandates the introduction of 'intermediate care services' to reduce emergency admissions to hospital from the population aged 75 years or more. We evaluated one of these initiatives-the Keep Well At Home (KWAH) Project-in a West London Primary Care Trust. DESIGN KWAH involves a two-phase screening process, including a home visit by a community nurse. We employed cohort methods to determine whether KWAH resulted in fewer emergency attendances and admissions to hospital in the target population, from October 1999 to December 2002. RESULTS estimated levels of coverage in the two phases of screening were 61 and 32%, respectively. The project had not maintained records of which additional health and social care services had been delivered following screening. The rates of emergency admissions to hospital in the 9 months before screening were similar in practices that did and did not join the project (rate ratio (RR) = 1.05; 95% CI 0.95-1.17), suggesting absence of volunteer bias. Over the first 37 months of the project, there was no significant impact on either attendances at Accident & Emergency departments (RR = 1.02; 95% CI 0.97-1.06) or emergency admissions of elderly patients (RR = 0.98; 95% CI 0.93-1.05). CONCLUSION the KWAH Project has been ineffective in reducing emergency admissions among the elderly. Significant questions arise in relation to selection of the screening instruments, practicality of achieving higher coverage of the eligible population, and creation of a new postcode lottery.
Examining the theoretical–empirical inconsistency on stationarity of shipping freight rate

ABSTRACT As market price, shipping freight rates should in theory be stationary, but most empirical tests have found them to be non-stationary. To examine the causes of this theoretical–empirical inconsistency, we investigate the sensitivities of the stationarity of shipping freight rates from two perspectives: sample length and sample window. Longer samples are found not sufficient to make them stationary. Instead, sample windows separated by structural breaks are tested as stationary. Moreover, freight rates are found to have entered into a new phase since the 2008 financial crisis. This study contributes to the literature on the stationarity of shipping freight rates by providing an explanation for the theoretical–empirical inconsistency.
Biophysical studies in polymer therapeutics: the interactions of anionic and cationic PAMAM dendrimers with lipid monolayers

Abstract Understanding how polymers interact with biological membranes is important for the development of polymer-based therapeutics and wider biomedical applications. Here, biophysical methods (surface pressure measurements, external reflection FTIR) have been used to investigate the interaction between PAMAM dendrimers (Generation 5 or 4.5) and anionic (DPPG) or zwitterionic (DPPC) model membranes. We observed a concentration-dependent binding behaviour of both PAMAM species to both model membranes; however, equivalent levels of penetration into DPPC monolayers required approximately 10-fold higher dendrimer concentrations than for penetration into DPPG monolayers. Overall, the anionic PAMAM G4.5 showed a slightly better penetration ability which could be caused by repulsive forces towards the lipid layers. In comparison, increasing concentration of cationic PAMAM G5 leads to saturation of adsorption at the anionic lipid surface before penetration into the lipid layer likely driven by electrostatic attraction. Our studies also showed that physiologically relevant concentrations of sodium chloride (144 mM) decreased PAMAM penetration into DPPG monolayers but did not significantly affect the dendrimer–DPPC interaction. These results provide an insight into the mechanism of interaction between charged dendritic polymers with a lipid interface and show that the nature of such interactions are affected by lipid headgroup, dendrimer charge and solution salinity.
Adherence to a Community-based Exercise Program Is a Strong Predictor of Improved Back Pain Status in Older Adults: An Observational Study

ObjectivesTo identify factors that were predictive of improved pain status among older adults with chronic back pain participating in the Adaptive Physical Activity (APA) program and to identify factors that were predictive of adherence to APA. MethodsAn observational cohort study of 392 older adults (ages 50 to 88) with chronic back pain participating in APA for 12 months. APA was a community-based group exercise program given for 1-hour, twice weekly, in local gyms. Primary outcome measures were improved pain based on a global rating of change evaluation and adherence to the APA program (defined as participation in >75% of exercise sessions). Potential predictor variables were entered into multivariate logistic regression models to determine the most accurate set of variables for predicting improved pain and adherence. ResultsPresence of depressive symptoms, poor self-rated health and adherence to APA were the best predictors of improved pain status, with adherence being the strongest predictor [odds ratio: 13.88 (95% confidence interval: 8.17, 23.59)]. Better physical function, longer pain duration, and positive rating of the trainer were all positively associated with adherence to APA; whereas poor self-rated health and further distance from the gym were inversely associated. ConclusionsGiven that adherence to APA is the key predictor of improved back pain, future efforts should focus on strategies to improve adherence. Our data suggest that enhanced training of exercise trainers, development of separate classes for people with different functional levels, and use of psychosocial interventions to reduce health pessimism and depression may be potential targets for improving adherence.
Radiation therapy (with or without neck surgery) for phenotypic human papillomavirus–associated oropharyngeal cancer

Favorable outcomes for human papillomavirus–associated oropharyngeal cancer have led to interest in identifying a subgroup of patients with the lowest risk of disease recurrence after therapy. De‐intensification of therapy for this group may result in survival outcomes that are similar to those associated with current therapy but with less toxicity. To advance this effort, this study analyzed the outcomes of oropharyngeal cancer patients treated with or without systemic therapy.