Miracle-dz/UniFAR-FTUs huggingface dataset:
Definition of a quit attempt: a replication test.

INTRODUCTION The incidence of quit attempts is often used to measure the effects of tobacco control interventions. Many surveys of quit attempts require that the attempt last ≥24 hr, presumably to provide a more objective definition and to eliminate less serious attempts; however, this criterion may bias outcomes by excluding the more dependent quitters who cannot stop for 1 day despite a serious quit attempt. METHODS We examined the 2003 and the 2006-2007 Tobacco Use Supplements to the Current Population Survey to determine the prevalence of quit attempts that did and did not last 24 hr, both in the last 12 months and in one's lifetime among current daily smokers. We also tested the hypothesis that those unable to quit for 24 hr were the more dependent smokers. RESULTS Requiring quit attempts to last 24 hr excluded 6%-17% of smokers who stated they made a quit attempt. Whether smokers who could not quit for more than 24 hr were more dependent varied across survey, recall duration, and measure. CONCLUSIONS We conclude restricting quit attempts to those who have quit for 24 hr underestimates the prevalence of attempts. Whether those unable to quit for 24 hr are the more dependent smokers is unclear. Empirical tests of whether the addition of a 24-hr criterion increases reliability or validity are needed.
Seasonality in sales of nicotine replacement therapies: patterns and implications for tobacco control.

INTRODUCTION Over the counter, nicotine replacement therapies (NRTs) are the most widely used smoking cessation treatment. This study sheds light on the seasonality of sales of NRT. METHODS A seasonal adjustment algorithm was applied to data on the sales of NRT products for 50 metro markets in the United States to test for and characterize seasonality in NRT sales. Granger's test was applied to the data to test whether changes in NRT sales systematically predicted changes in cigarette sales 1 month later. RESULTS The results show (a) that sales of NRT products are seasonal, (b) that the seasonality pattern is the opposite of the seasonality pattern for cigarette sales, (c) that seasonally higher NRT sales in a given month tend to be followed by seasonally lower cigarette sales in the following month, and (d) that seasonally high months for NRT sales (January to March) correspond to seasonally low months for cigarette sales. CONCLUSIONS NRT sales show a strong seasonality pattern that is the opposite of the seasonality pattern for cigarette sales. These patterns are indicative of seasonal variations in quitting behavior.
Functional Outcome after Free Flap Reconstructions in Oral and Pharyngeal Cancer

Oral cancer ranks significantly among the ten most common cancers worldwide. Since oral cancer is commonly diagnosed at locally advanced stage, curing the cancer demands extensive tissue resection. The emergent defect is reconstructed generally with a free flap transfer. Modern reconstruction techniques aim at attaining optimal function. The oral functions of breathing, speaking, chewing, and swallowing are vital and essential for an individual. Repair of the upper aerodigestive track with maintenance of its multiform activities is challenging. Comprehensive studies on function advance the improvement of the treatment outcomes. Fifty consecutive patients having undergone free flap reconstruction for oral, oropharyngeal, or hypopharyngeal cancer between 1989 and 1995 were analyzed retrospectively for postoperative survival and complications. Forty-four similar consecutive patients were prospectively followed-up between 1996 and 1999 and analyzed for postoperative survival and complications. Their functional outcome was also determined in terms of quality of life, speech, swallowing, and intraoral sensation. The parameters were measured preoperatively, and at four time points during a follow-up period of 12 months. The instrument used in quality of life assessment was the University of Washington Head and Neck Questionnaire. Speech was analyzed instrumentally for aerodynamic parameters as well as for nasal acoustic energy. Speech was also assessed perceptually for articulatory proficiency, voice quality, and intelligibility. Videofluorography was performed to determine the swallowing ability with various bolus consistencies. Intraoral sensation was measured by moving 2-point discrimination. The 3-year overall survival after microvascular free flap reconstruction was 42% (Study I) and 45% (Study II). In the follow-up study (II), the 1-year diseasefree survival was 43%. Postoperative complications arose in 58% (Study I) and 66% (Study II) of the patients. Flap success rate was 96% (Study I) and 98% (Study II). Perioperative mortality varied between 2% (Study I) and 11% (Study II). Unemployment and heavy drinking were the strongest predictors of survival. Unemployment and heavy drinking increased the risk of dying 4.4-fold and 2.4fold, respectively. The global quality of life score deteriorated after the operation and did not return to the preoperative level during the follow-up. Significant reduction was detectable in the domains measuring chewing and speech, and in appearance and shoulder function. The result highlights the importance of the functional outcome of the treatment. The basic elements necessary for normal speech were maintained. Perceived articulatory and vocal dysfunction, however, particularly when co-occurring, carry a risk for speech intelligibility. Oral nutrition was almost always re-established although swallowing often proved impaired and unsafe. Sensation weakened but was unrelated to oral functions.
Subunit composition of a DEG/ENaC mechanosensory channel of Caenorhabditis elegans

Significance The molecular organization of eukaryotic mechanosensory channels is largely uncharacterized. This characterization, having the correct parts list, is a necessary beginning step toward understanding how the channel transduces mechanical signals. Here we investigate the organization of the degenerin/epithelial sodium channel (DEG/ENaC) mechanosensory transduction channel in the six touch receptor neurons of Caenorhabditis elegans. Previous work has suggested that four membrane proteins formed a channel complex: the DEG/ENaC proteins MEC-4 and MEC-10 form the channel pore and the stomatin-like protein MEC-2 and paraoxonase-like protein MEC-6 act as auxiliary proteins. Using single molecule imaging, we find that the transduction complex is simpler, being a MEC-4:MEC-4:MEC-10 trimer. In contrast to the previous suggestion, this trimer does not appear to associate substantially with MEC-2 or MEC-6. Caenorhabditis elegans senses gentle touch in the six touch receptor neurons (TRNs) using a mechanotransduction complex that contains the pore-forming degenerin/epithelial sodium channel (DEG/ENaC) proteins MEC-4 and MEC-10. Past work has suggested these proteins interact with the paraoxonase-like MEC-6 and the cholesterol-binding stomatin-like MEC-2 proteins. Using single molecule optical imaging in Xenopus oocytes, we found that MEC-4 forms homotrimers and MEC-4 and MEC-10 form 4:4:10 heterotrimers. MEC-6 and MEC-2 do not associate tightly with these trimers and do not influence trimer stoichiometry, indicating that they are not part of the core channel transduction complex. Consistent with the in vitro data, MEC-10, but not MEC-6, formed puncta in TRN neurites that colocalize with MEC-4 when MEC-4 is overexpressed in the TRNs.
Understanding the evidence for and against the role of breastfeeding in allergy prevention

The relationship between breastfeeding and allergic disease risk has been controversial. This article reviews the current evidence for the role of breastfeeding in the prevention of allergic disease. We found considerable methodological limitations inherent in most studies evaluating the effect of breastfeeding in allergic disease. Nevertheless, since randomized control trials in breast feeding research would be considered unethical, the evidence remains limited to poorer quality observational studies where participation and recall bias can severely affect the objectivity of the data collected. Furthermore, reporting of type of breastfeeding (exclusive, full or partial) may be biased by a participant's inherent belief system of what they think they should be doing. Current evidence is inconclusive regarding the effect of breastfeeding on the development of eczema, with the most recent systemic review reporting no protective effect. There is insufficient data regarding the effects of breastfeeding on objective measures of food allergy at any age. Studies show a paradoxical effect of breastfeeding on the prevention of asthma, with an apparent protective effect against early wheezing illness in the first years of life yet an increased risk of asthma in later life; however, these findings must be interpreted with caution. Existing studies fail to adequately adjust for confounders, including the critical issues of protection against early life respiratory illnesses and reverse causation. Therefore, it is possible that the effect of breastfeeding on early wheezing illness reflects protection against respiratory infection, the predominant trigger of wheezing in early childhood, rather than a true reduction in risk of asthma. In summary, future research that takes into account the potential contribution of confounding factors and effect modifiers is needed to clarify the role of breastfeeding in development of allergic disease and to inform current clinical guidelines on the prevention of allergic disease.
Mitochondrial Hsp90 is a ligand-activated molecular chaperone coupling ATP binding to dimer closure through a coiled-coil intermediate

Significance Mitochondrial heat-shock protein of 90 kDa (Hsp90) (TRAP1) promotes cell survival and is essential for neoplastic growth. Exploiting human TRAP1 for drug development requires detailed structural and mechanistic understanding. Whereas TRAP1 adopts different conformations associated with distinct nucleotide states, how the TRAP1 dimer senses the bound nucleotide and signals this information to the neighboring subunit remains unknown. We show that unliganded TRAP1 forms a previously unobserved coiled-coil dimer and is found in an autoinhibited state. ATP binding in cis displaces the ATP lid that signals the nucleotide status to the trans subunit. Our findings suggest that human TRAP1 is a ligand-activated molecular chaperone, which couples ATP binding to local changes in structure facilitating dimer closure needed for protein folding. Heat-shock protein of 90 kDa (Hsp90) is an essential molecular chaperone that adopts different 3D structures associated with distinct nucleotide states: a wide-open, V-shaped dimer in the apo state and a twisted, N-terminally closed dimer with ATP. Although the N domain is known to mediate ATP binding, how Hsp90 senses the bound nucleotide and facilitates dimer closure remains unclear. Here we present atomic structures of human mitochondrial Hsp90N (TRAP1N) and a composite model of intact TRAP1 revealing a previously unobserved coiled-coil dimer conformation that may precede dimer closure and is conserved in intact TRAP1 in solution. Our structure suggests that TRAP1 normally exists in an autoinhibited state with the ATP lid bound to the nucleotide-binding pocket. ATP binding displaces the ATP lid that signals the cis-bound ATP status to the neighboring subunit in a highly cooperative manner compatible with the coiled-coil intermediate state. We propose that TRAP1 is a ligand-activated molecular chaperone, which couples ATP binding to dramatic changes in local structure required for protein folding.
Neonatal IL‐10 production and risk of allergy development

We read with interest the recent report of Belderbos and coworkers in this journal showing that low neonatal TLR-4-mediated IL-10 production is associated with subsequent development of atopic dermatitis [1]. The authors stimulated whole blood of 1-month-old neonates with ultrapure lipopolysaccharide (LPS) and Interferon (IFN)-γ, and measured IL-10 in the culture supernatants. Neonates who developed physician-diagnosed atopic dermatitis at age 1 year had 1.8-fold lower TLR-4-mediated IL-10 production at the age of 1 month [1]. In a birth cohort ‘Follow-up of Newborn's Immune development in relation to Allergic outcome’ (FONIA) study, we obtained data on the association between allergen-induced IL-10 production by cord blood cells and prospective risk of allergy development. The diagnosis of ‘clinical allergy’ was based on the presence of symptoms (skin, gastrointestinal or respiratory) in association with relevant IgE sensitization [2]. Cord blood mononuclear cells (CBMC) (n = 67) isolated immediately after uncomplicated vaginal delivery were stimulated by either ovalbumine (OVA) or by recombinant(r) Der p 2 (a kind gift from JM-Saint Rémy, KULeuven, Belgium). r IL-4 was added because we have previously found that rIL-4 increases in vitro allergen-induced IL-10 production by T cells from non-allergic subjects, but not by those from allergic subjects [3]. As shown in Fig. 1, IL-10 was significantly lower in OVA/IL-4 stimulated CBMC cultures from children who had developed clinical allergy at age 6 (n = 19) compared with the others (n = 45). IL-10 above 0.5 pg/mL was present in OVA/IL-4 stimulated cultures from 19 of 45 non-allergics and predicted a non-allergic outcome at age 6 (Relative Risk (RR) (in fact ‘relative benefit’) 1.49 (95% CI 1.1–2.0), Chi-square df 6.1; P = 0.007). Nine children were egg-allergic at 12 months and in only one of these nine children, OVA/IL-4-induced
Determinants of tobacco use and renaming the FTND to the Fagerstrom Test for Cigarette Dependence.

When the first version (the Tolerance Questionnaire, Fagerstrom, 1978) of the Fagerstrom Test for Nicotine Dependence (FTND; Heatherton, Kozlowski, Frecker, & Fagerstrom, 1991) was developed, tobacco smoking was not regarded as an addiction. Nevertheless, evidence that this might be the case was beginning to appear, and some researchers became increasingly interested in investigating the importance of nicotine in the smoking habit and educating the public about it. The research led to a profound change in the understanding of cigarette smoking, and in 1988, the U.S. Surgeon General, in the remarkable book Nicotine Addiction, established once and “forever” the importance of nicotine in tobacco smoking (U.S. Department of Health and Human Services [U.S. DHHS], 1988). However, as the role of nicotine was established, researchers lost sight of the possibility that other determinants might also be important. More recently, it has been found that, although nicotine is the most important addictive component of tobacco smoke, it is probably not the only substance involved in the development of tobacco dependence. In light of what is now known about what determines cigarette smoking, it seems timely to propose a renaming of the FTND to the Fagerstrom Test for Cigarette Dependence (FTCD). The background for this is discussed in this commentary.
Widespread collapse of the Ross Ice Shelf during the late Holocene

Significance The Ross Sea is a major drainage basin for the Antarctic Ice Sheet and contains the world’s largest ice shelf. Newly acquired swath bathymetry data and sediment cores provide evidence for two episodes of ice-shelf collapse. Two novel geochemical proxies, compound specific radiocarbon dating and radiogenic beryllium (10Be), constrain the timing of the most recent and widespread (∼280,000 km2) breakup as having occurred in the late Holocene. Three-dimensional ice-shelf/ocean modeling results and comparison with ice-core records indicate that oceanic and atmospheric warming caused ice-shelf collapse. The stability of modern ice shelves is threatened by atmospheric and oceanic warming. The geologic record of formerly glaciated continental shelves provides a window into the past of how ice shelves responded to a warming climate. Fields of deep (−560 m), linear iceberg furrows on the outer, western Ross Sea continental shelf record an early post-Last Glacial Maximum episode of ice-shelf collapse that was followed by continuous retreat of the grounding line for ∼200 km. Runaway grounding line conditions culminated once the ice became pinned on shallow banks in the western Ross Sea. This early episode of ice-shelf collapse is not observed in the eastern Ross Sea, where more episodic grounding line retreat took place. More widespread (∼280,000 km2) retreat of the ancestral Ross Ice Shelf occurred during the late Holocene. This event is recorded in sediment cores by a shift from terrigenous glacimarine mud to diatomaceous open-marine sediment as well as an increase in radiogenic beryllium (10Be) concentrations. The timing of ice-shelf breakup is constrained by compound specific radiocarbon ages, the first application of this technique systematically applied to Antarctic marine sediments. Breakup initiated around 5 ka, with the ice shelf reaching its current configuration ∼1.5 ka. In the eastern Ross Sea, the ice shelf retreated up to 100 km in about a thousand years. Three-dimensional thermodynamic ice-shelf/ocean modeling results and comparison with ice-core records indicate that ice-shelf breakup resulted from combined atmospheric warming and warm ocean currents impinging onto the continental shelf.
Systematic study of constitutive cyclooxygenase-2 expression: Role of NF-κB and NFAT transcriptional pathways

Significance Nonsteroidal antiinflammatory drugs (NSAIDs) work by inhibiting cyclooxygenase-2 (COX-2) induced at sites of inflammation. They are among the most widely used drugs worldwide, but their cardiovascular side effects are a major concern for patients, regulators, and industry. NSAID side effects are mediated by inhibition of constitutively expressed COX-2 present in discrete regions, including the kidney. However, the pathways driving constitutive COX-2 remain poorly understood. The work presented here defines these pathways and importantly shows constitutive COX-2 expression in the kidney occurs through pathways distinct to those driving COX-2 in inflammation. These data therefore highlight the potential that targeting COX-2 at the transcriptional level may provide a way to dissociate antiinflammatory benefits of NSAIDs from their treatment-limiting cardiovascular side effects. Cyclooxygenase-2 (COX-2) is an inducible enzyme that drives inflammation and is the therapeutic target for widely used nonsteroidal antiinflammatory drugs (NSAIDs). However, COX-2 is also constitutively expressed, in the absence of overt inflammation, with a specific tissue distribution that includes the kidney, gastrointestinal tract, brain, and thymus. Constitutive COX-2 expression is therapeutically important because NSAIDs cause cardiovascular and renal side effects in otherwise healthy individuals. These side effects are now of major concern globally. However, the pathways driving constitutive COX-2 expression remain poorly understood. Here we show that in the kidney and other sites, constitutive COX-2 expression is a sterile response, independent of commensal microorganisms and not associated with activity of the inflammatory transcription factor NF-κB. Instead, COX-2 expression in the kidney but not other regions colocalized with nuclear factor of activated T cells (NFAT) transcription factor activity and was sensitive to inhibition of calcineurin-dependent NFAT activation. However, calcineurin/NFAT regulation did not contribute to constitutive expression elsewhere or to inflammatory COX-2 induction at any site. These data address the mechanisms driving constitutive COX-2 and suggest that by targeting transcription it may be possible to develop antiinflammatory therapies that spare the constitutive expression necessary for normal homeostatic functions, including those important to the cardiovascular-renal system.
Localized granulomatous reaction to a semi‐permanent hyaluronic acid and acrylic hydrogel cosmetic filler

Dermalive, an injectable skin filler composed of a combination of synthetic hyaluronic acid and acrylic hydrogel particles was recently developed for soft tissue augmentation. Dermalive produces longer term results than temporary injectable fillers and is associated with a reportedly low incidence of adverse reactions. We describe a marked local reaction to the injection of Dermalive in the nasolabial fold developing within 4 months with histological confirmation of a granulomatous response. To our knowledge there has been only one previous report of a local granulomatous reaction to Dermalive.
Monitoramento do processo de assistência pré-natal entre as usuárias do Sistema Único de Saúde em município do Sudeste brasileiro

PURPOSE: to evaluate the evolution of adequacy of the care process among pregnant users of the Brazilian Single Health System (SUS, acronym in Portuguese) and to consolidate a methodology for monitoring the prenatal care. METHODS: this is a multiple time series study with auditing of prenatal cards of pregnant women who were attended for prenatal care in a city of the Brazilian Southeast (Juiz de Fora, Minas Gerais) in the initial semesters of 2002 and 2004 (370 and 1,200 cards, respectively) and gave birth using SUS services in term pregnancies (p < 0.05). A three complementary level sequence was respected: utilization of prenatal care (beginning and number of visits) at level 1; utilization of prenatal care and obligatory clinical-obstetric procedures during prenatal visits (assessment of blood pressure (BP), weight, uterine fundal height (FH), gestational age (GA), fetal heart rate (FHR) and fetal presentation) at level 2; and utilization of prenatal care, obligatory clinical-obstetric procedures and basic laboratory tests, according to the Humanization Program of Prenatal Care and Birth (PHPN, acronym in Portuguese) (ABO/Rh, hemoglobin/hematocrit (Hb/Htc), VDRL, glycemia and urinalisys) at level 3. RESULTS: it was confirmed the high prenatal care coverage (99%), the increased mean number of visits per pregnant woman (6.4 versus 7.2%) and the decreased gestational age at the time of the first visit (17.4 versus 15.7 weeks). The proper registration of procedures and exams (exceptions: fetal presentation and blood typing) has significantly increased: BP (77.8 versus 83.9%); weight (75.4 versus 83.5%); FH (72.7 versus 81.3%); GA (58.1 versus 71.5%); FHR (79.5 versus 86.7%); Hb/Htc (14.9 versus 29%), VDRL (11.1 versus 20.7%), glycemia (16.5 versus 29%) and urinalisys (13.8 versus 29.8%). As a result, there was significant (p < 0.001) improvement of the adequacy between 2002 and 2004: 27.6 versus 44.8% (level 1); 7.8 versus 15.4% (level 2); 1.1 versus 4.5% (level 3). This trend was also noted in care provided by the majority of the municipal services/teams. CONCLUSIONS: the persistence of low adequacy, despite good coverage and PHPN implementation, confirmed the need to increase health managers, professionals and users' compliance with the rules and routines of care, including the institutionalization of a monitoring program of prenatal care.