tbuckley/cabot-search huggingface dataset:
Prognostic Implications of the Distribution of Lymph Node Metastases in Rectal Cancer After Neoadjuvant Chemoradiotherapy
Authors: Tobias Leibold, Jinru Shia, Leyo Ruo, Bruce D. Minsky, Timothy Akhurst, Marc J. Gollub, Michelle S. Ginsberg, Steven Larson, Elyn Riedel, W. Douglas Wong, José G. Guillem
Journal: Journal of Clinical Oncology (2008)

Purpose After preoperative chemoradiotherapy of rectal cancer, the number of retrievable and metastatic lymph nodes is decreased. The current TNM classification is based on number and not location of lymph node metastases and may understage disease after chemoradiotherapy. The aim of this study was to examine the prognostic significance of location of involved lymph nodes in rectal cancer patients after preoperative chemoradiotherapy. Patients and Methods We prospectively examined whole-mount specimens from 121 patients with uT3-4 and/or N+ rectal cancer who received preoperative chemoradiotherapy followed by resection. Location of involved lymph nodes was compared with median number of lymph nodes involved as well as presence of distant metastasis at presentation. Results Lymph node metastases were detected in 37 patients (31%). Thirteen patients with lymph node involvement along major supplying vessels (proximal lymph node metastases) had a significantly higher rate of distant metastatic disease at time of surgery than patients without proximal lymph node involvement (P &lt; .001); median number of lymph nodes involved was two for patients with proximal lymph node metastases and 1.5 for patients with mesorectal lymph node involvement alone. Conclusion Our data suggest that, after preoperative chemoradiotherapy, proximal lymph node involvement is associated with a high incidence of metastatic disease at time of surgery. Because the median number of involved lymph nodes is low after preoperative chemoradiotherapy, the TNM staging system may not provide an accurate assessment of metastatic disease. Therefore, the ypTNM staging system should incorporate distribution as well as number of lymph node metastases after preoperative chemoradiotherapy for rectal cancer.
Intracellular Na+ regulation in cardiac myocytes
Authors: D Bers
Journal: Cardiovascular Research (2003)

Intracellular [Na+] ([Na+]i) is regulated in cardiac myocytes by a balance of Na+ influx and efflux mechanisms. In the normal cell there is a large steady state electrochemical gradient favoring Na+ influx. This potential energy is used by numerous transport mechanisms, including Na+ channels and transporters which couple Na+ influx to either co- or counter-transport of other ions and solutes. Six sarcolemmal Na+ influx pathways are discussed in relatively quantitative terms: Na+ channels, Na+/Ca2+ exchange, Na+/H+ exchange, Na+/Mg2+ exchange, Na+/HCO3− cotransport and Na+/K+/2Cl− cotransport. Under normal conditions Na+/Ca2+ exchange and Na+ channels are the dominant Na+ influx pathways, but other transporters may become increasingly important during altered conditions (e.g. acidosis or cell volume stress). Mitochondria also exhibit Na+/Ca2+ antiporter and Na+/H+ exchange activity that are important in mitochondrial function. These coupled fluxes of Na+ with Ca2+, H+ and HCO3− make the detailed understanding of [Na+]i regulation pivotal to the understanding of both cardiac excitation–contraction coupling and pH regulation. The Na+/K+-ATPase is the main route for Na+ extrusion from cells and [Na+]i is a primary regulator under physiological conditions. [Na+]i is higher in rat than rabbit ventricular myocytes and the reason appears to be higher Na+ influx in rat with a consequent rise in Na+/K+-ATPase activity (rather than lower Na+/K+-ATPase function in rat). This has direct functional consequences. There may also be subcellular [Na+]i gradients locally in ventricular myocytes and this may also have important functional implications. Thus, the balance of Na+ fluxes in heart cells may be complex, but myocyte Na+ regulation is functionally important and merits focused attention as in this issue.
Aetiological classification of injuries in sportsmen
Authors: J. G. P. Williams
Journal: British Journal of Sports Medicine (1971)

Both in the management and prevention of injuries in sportsmen a clear understanding of the aetiology as well as the pathology is required.Even when the exact mechanism of injury remains in doubt it should always be possible to determine the aetiological type.Logical treatment, to say nothing of prevention, is imnpossible unless the type of injury as well as its pathology is determined.Previous attempts at aetiological classification (Williams, 1965 Corrigan, 1968) have failed on the basis of over-simplification.A more extended classification is therefore proposed which appears to take into account all possible types of injury and which provides a useful framework against which to set the aetiology of any sports injury.In the first instance all injuries occurring in sportsmen are divided into two basic categories :-
Regulation of deoxynucleotide metabolism in cancer: novel mechanisms and therapeutic implications
Authors: Rebecca Kohnken, Karthik M. Kodigepalli, Li Wu
Journal: Molecular Cancer (2015)

Regulation of intracellular deoxynucleoside triphosphate (dNTP) pool is critical to genomic stability and cancer development. Imbalanced dNTP pools can lead to enhanced mutagenesis and cell proliferation resulting in cancer development. Therapeutic agents that target dNTP synthesis and metabolism are commonly used in treatment of several types of cancer. Despite several studies, the molecular mechanisms that regulate the intracellular dNTP levels and maintain their homeostasis are not completely understood. The discovery of SAMHD1 as the first mammalian dNTP triphosphohydrolase provided new insight into the mechanisms of dNTP regulation. SAMHD1 maintains the homeostatic dNTP levels that regulate DNA replication and damage repair. Recent progress indicates that gene mutations and epigenetic mechanisms lead to downregulation of SAMHD1 activity or expression in multiple cancers. Impaired SAMHD1 function can cause increased dNTP pool resulting in genomic instability and cell-cycle progression, thereby facilitating cancer cell proliferation. This review summarizes the latest advances in understanding the importance of dNTP metabolism in cancer development and the novel function of SAMHD1 in regulating this process.
PASTORAL-PSYCHIATRIC WORKSHOPS: THE ST. JOHN'S MENTAL HEALTH INSTITUTE
Authors: HYMAN LIPPMAN, FRANCIS GERTY, DAVID A. BOYD
Journal: American Journal of Psychiatry (1958)

It is conceived that the pastor has important duties of counseling to perform for his parishioners in addition to his service as spiritual leader and advisor. Undoubtedly, this part of his work could be performed better if he could have some of the benefit that the psychiatrist has gained through his experience in treating patients. Particular advantage would come from the judicious use of the technics of interviewing and from the feeling and understanding that result from seeing more clearly the roots of human behavior. If he were so prepared for counseling troubled people, the pastor could give advice on the basis of more adequate information, thus avoiding pitfalls and obtaining positive advantages for the person he advises. The implication of these premises was that a means of communication with an approach to optimal control but without denominational restrictions had to be found. A workshop in a location remote from distracting influences with residency there as a group for nearly a full week was decided upon as the best means of meeting the required conditions. No similar workshop approach had been attempted. Other considerations were the inclusion of a sufficient number of participants for each workshop, and a sufficient number of repetitions of the workshops for purposes of comparison and gradual adjustment of details of operation as experience increased. The history of 9 workshops, each including about 40 pastors and about 10 faculty members, three each summer during 3 consecutive weeks and in 4 consecutive years at St. John's University at Collegeville, Minnesota, has been given. Evaluation of results is going on as the fifth series of workshops is being planned. It is believed that the participants have derived a number of important benefits. Some of these are of an intellectual and informational kind. Some concern an increased skill in the use of technics, particularly in interviewing. Probably most important of all is an inner modification of feeling and understanding, a sincerely experienced change in ideas and conviction about the great importance of unconscious motivation and the evidences and means by which it is revealed. There is also a realization of an increased power to help through the possession of such understanding. It cannot be claimed that these changes occur uniformly in all participants, or, indeed, that many of them occur at all in some participants. The faculty is convinced that no participant can go through the workshop experience entirely unaffected ideationally and emotionally. Most of the pastors admit readily that they have gained considerable benefit from their attendance in one or more of the respects that have been mentioned and most importantly in the last respect–a useful and yet disturbing knowledge that the hidden springs of motivation in the natural man must be correctly gauged before he can be given intelligent help.
Human Papillomavirus Type 16 and 18 Variants: Race-Related Distribution and Persistence
Authors: Long Fu Xi, Nancy B. Kiviat, Allan Hildesheim, Denise A. Galloway, Cosette M. Wheeler, Jesse Ho, Laura A. Koutsky
Journal: JNCI Journal of the National Cancer Institute (2006)

Background: Analogous to the geographic distribution of variants of human papillomavirus (HPV) types, the distribution and persistence of these variants among infected individuals may be related to the racial composition of a population living in one geographic region. Methods: We studied 1114 women in the United States participating in the Atypical Squamous Cells of Undetermined Significance/Low-Grade Squamous Intraepithelial Lesion Triage Study who were positive for HPV16 and/or HPV18 at enrollment. Race was self-reported. HPV samples were characterized by sequencing the E6 gene and part of the long control region and classified as variants according to established lineages. Subjects were examined for HPV every 6 months for 2 years. All statistical tests were two-sided. Results: HPV18 African variants were predominant in the 97 HPV18-infected African American women (i.e., 62 women or 63.9%, 95% confidence interval [CI] = 53.5% to 73.4%), and European variants were common in the 168 HPV18-infected white women (i.e., 91 women or 54.2%, 95% CI = 46.3% to 61.9%). HPV16 African variants accounted for 43 (26.5%, 95% CI = 19.9% to 34.0%) of the infections in the 162 HPV16-infected African American women but for only 25 (4.3%, 95% CI = 2.8% to 6.3%) in the 584 HPV16-infected white women. The likelihood of remaining HPV18 positive was statistically significantly higher in white women infected with European than in white women infected with African variants ( P = .04); the reverse was observed in African American women ( P = .03). A similar pattern was observed for persistence of HPV16 variants, with the likelihood of remaining positive being higher for white women, but lower for African American women, infected with an European variant than with an African variant ( P = .03 and P = .16, respectively). Conclusions: Variants of HPV16 and HPV18 appear to persist longer in a host whose race indicates an ancestral geographic distribution that was once shared with that of the variant—i.e., European variants persist longer in white women, and African variants persist longer in African American women.
Preoperative weekly cisplatin–epirubicin–paclitaxel with G-CSF support in triple-negative large operable breast cancer
Authors: G. Frasci, P. Comella, M. Rinaldo, G. Iodice, M. Di Bonito, M. D'Aiuto, A. Petrillo, S. Lastoria, C. Siani, G. Comella, G. D'Aiuto
Journal: Annals of Oncology (2009)
Small airways involvement is associated with bronchial hyperresponsiveness in asthma
Authors: Eef Telenga, Dirkje Postma, Roland Riemersma, Thys van der Molen, Maarten van den Berge, Nick ten Hacken
Journal: European Respiratory Journal (2012)

Background: Bronchial hyperresponsiveness (BHR) is a hallmark of asthma. Although, the role of small airways involvement in asthma has been well established, little is known about the association between BHR and small airways obstruction. We hypothesize that small airways disease contributes to BHR.  Methods: A total of 119 patients with a doctor9s diagnosis of asthma were included. All subjects underwent spirometry and a BHR testing (PD 20  histamine). Small airways involvement was defined as an MEF 50  ≤ the lower limit of normal (LLN). We compared the severity of BHR between asthmatics with and without small airways involvement.  Results: We found 36 patients with and 83 patients without small airways involvement (MEF 50  ≤LLN and MEF 50  >LLN respectively). Patients with small airways involvement showed a more severe BHR than patients without (PD 20  histamine 0.2 vs. 1.1 mg). In addition, FEV 1 , FEV 1 /FVC and reversibility were lower in patients with small airways involvement. Both a lower MEF 50  and FEV 1  were independent predictors of more severe BHR in multivariate linear regression models.  Conclusion: Small airways involvement is associated with more severe BHR in asthma. Since FEV 1  is used as a read-out in current BHR tests, we hypothesize that further research with small airways measurements during BHR tests will provide more insight into the relation between BHR and small airways involvement.
Exercise associated hyponatraemia: quantitative analysis to understand the aetiology
Authors: S J Montain, S N Cheuvront, M N Sawka
Journal: British Journal of Sports Medicine (2006)

Background: The development of symptomatic hyponatraemia consequent on participation in marathon and ultraendurance races has led to questions about its aetiology and prevention. Objectives: To evaluate: ( a ) the assertion that sweat sodium losses cannot contribute to the development of hyponatraemia during endurance exercise; ( b ) the adequacy of fluid replacement recommendations issued by the International Marathon Medical Directors Association (IMMDA) for races of 42 km or longer; ( c ) the effectiveness of commercial sports drinks, compared with water, for attenuating plasma sodium reductions. Methods: A mathematical model was used to predict the effects of different drinking behaviours on hydration status and plasma sodium concentration when body mass, body composition, running speed, weather conditions, and sweat sodium concentration were systematically varied. Results: Fluid intake at rates that exceed sweating rate is predicted to be the primary cause of hyponatraemia. However, the model predicts that runners secreting relatively salty sweat can finish ultraendurance exercise both dehydrated and hyponatraemic. Electrolyte-containing beverages are predicted to delay the development of hyponatraemia. The predictions suggest that the IMMDA fluid intake recommendations adequately sustain hydration over the 42 km distance if qualifiers—for example, running pace, body size—are followed. Conclusions: Actions to prevent hyponatraemia should focus on minimising overdrinking relative to sweating rate and attenuating salt depletion in those who excrete salty sweat. This simulation demonstrates the complexity of defining fluid and electrolyte consumption rates during athletic competition.
AKAP150 Contributes to Enhanced Vascular Tone by Facilitating Large-Conductance Ca <sup>2+</sup> -Activated K <sup>+</sup> Channel Remodeling in Hyperglycemia and Diabetes Mellitus
Authors: Matthew A. Nystoriak, Madeline Nieves-Cintrón, Patrick J. Nygren, Simon A. Hinke, C. Blake Nichols, Chao-Yin Chen, Jose L. Puglisi, Leighton T. Izu, Donald M. Bers, Mark L. Dell’Acqua, John D. Scott, Luis F. Santana, Manuel F. Navedo
Journal: Circulation Research (2013)

Increased contractility of arterial myocytes and enhanced vascular tone during hyperglycemia and diabetes mellitus may arise from impaired large-conductance Ca(2+)-activated K(+) (BKCa) channel function. The scaffolding protein A-kinase anchoring protein 150 (AKAP150) is a key regulator of calcineurin (CaN), a phosphatase known to modulate the expression of the regulatory BKCa β1 subunit. Whether AKAP150 mediates BKCa channel suppression during hyperglycemia and diabetes mellitus is unknown.To test the hypothesis that AKAP150-dependent CaN signaling mediates BKCa β1 downregulation and impaired vascular BKCa channel function during hyperglycemia and diabetes mellitus.We found that AKAP150 is an important determinant of BKCa channel remodeling, CaN/nuclear factor of activated T-cells c3 (NFATc3) activation, and resistance artery constriction in hyperglycemic animals on high-fat diet. Genetic ablation of AKAP150 protected against these alterations, including augmented vasoconstriction. d-glucose-dependent suppression of BKCa channel β1 subunits required Ca(2+) influx via voltage-gated L-type Ca(2+) channels and mobilization of a CaN/NFATc3 signaling pathway. Remarkably, high-fat diet mice expressing a mutant AKAP150 unable to anchor CaN resisted activation of NFATc3 and downregulation of BKCa β1 subunits and attenuated high-fat diet-induced elevation in arterial blood pressure.Our results support a model whereby subcellular anchoring of CaN by AKAP150 is a key molecular determinant of vascular BKCa channel remodeling, which contributes to vasoconstriction during diabetes mellitus.
Plasma circulating tumor DNA as an alternative to metastatic biopsies for mutational analysis in breast cancer
Authors: F. Rothé, J.-F. Laes, D. Lambrechts, D. Smeets, D. Vincent, M. Maetens, D. Fumagalli, S. Michiels, S. Drisis, C. Moerman, J.-P. Detiffe, D. Larsimont, A. Awada, M. Piccart, C. Sotiriou, M. Ignatiadis
Journal: Annals of Oncology (2014)
Serum immunoglobulin values in patients with scabies
Authors: EDVARD S. FALK
Journal: British Journal of Dermatology (1980)

Serum total IgE levels were found to be increased in thirty-nine of ninety-four patients with scabies investigated at the time of clinical presentation. One hundred and fifty-four patients were found to have a slightly lower serum concentration of IgA during infection than when measured 6 weeks and 9 months following successful treatment (P less than 0.05). The serum concentration of IgA at 6 weeks and 9 months after treatment did not differ significantly. The serum concentration of IgG during infection was significantly higher than 6 weeks later (P less than 0.05), and than 9 months later (P less than 0.01). The 6 weeks levels were significantly higher than the results at 9 month (P less than 0.01). The serum concentration of IgM during infection was higher than 6 weeks later (P less than 0.1). The 6 weeks levels were lower than those at 9 months (P less than 0.1), whereas there was no difference between the pretreatment and 9 months levels. No differences were noted in the concentration of C3 and C4. Antinuclear antibodies (ANA) and rheumatoid factor (RF) were not found in any of the patients. In thirty-two patients with lichen planus no changes in immunoglobulins or complement were observed. This suggests that scabies infection may be associated with a humoral immumological response against the scabies infection.
Foldable Artiflex Phakic Intraocular Lens for the Correction of Myopia
Authors: H. Burkhard Dick, Camille Budo, Francois Malecaze, Josep L. Güell, Antonio A.P. Marinho, Rudy M.M.A. Nuijts, Gregorius P.M. Luyten, Jose L. Menezo, Thomas Kohnen
Journal: Ophthalmology (2009)
PRESERVE-β
Authors: John Gerich, Philip Raskin, Lisa Jean-Louis, Das Purkayastha, Michelle A. Baron
Journal: Diabetes Care (2005)

OBJECTIVE—To compare long-term efficacy and safety of initial combination therapy with nateglinide/metformin versus glyburide/metformin. RESEARCH DESIGN AND METHODS—We conducted a randomized, multicenter, double-masked, 2-year study of 428 drug-naïve patients with type 2 diabetes. Patients received 120 mg a.c. nateglinide or 1.25 mg q.d. glyburide plus 500 mg q.d. open-label metformin for the initial 4 weeks. During a subsequent 12-week titration period, glyburide and metformin were increased by 1.25- and 500-mg increments to maximum daily doses of 10 and 2,000 mg, respectively, if biweekly fasting plasma glucose (FPG) ≥6.7 mmol/l. Nateglinide was not titrated. Blinding was maintained by use of matching placebo for nateglinide and glyburide. An 88-week monitoring period followed, during which HbA1c (A1C), FPG, and postprandial glucose excursions (PPGEs) during an oral glucose tolerance test were measured. RESULTS—In nateglinide/metformin-treated patients, mean A1C was 8.4% at baseline and 6.9% at week 104. In glyburide/metformin-treated patients, mean A1C was 8.3% at baseline and 6.8% at week 104 (P &amp;lt; 0.0001 vs. baseline for both treatments, NS between treatments). The ΔPPGE averaged −96 ± 19 (P &amp;lt; 0.0001) and −57 ± 22 mmol · l−1 · min−1 (P &amp;lt; 0.05) in patients receiving nateglinide/metformin and glyburide/metformin, respectively, whereas ΔFPG was –1.6 ± 0.2 (P &amp;lt; 0.0001) and −2.4 ± 0.2 mmol/l (P &amp;lt; 0.0001) in patients receiving nateglinide/metformin and glyburide/metformin, respectively (P &amp;lt; 0.01 between groups). Thus, the two treatments achieved similar efficacy with differential effects on FPG versus PPGE. Hypoglycemia occurred in 8.2 and 17.7% of patients receiving nateglinide/metformin and glyburide/metformin, respectively. CONCLUSIONS—Similar good glycemic control can be maintained for 2 years with either treatment regimen, but nateglinide/metformin may represent a safer approach to initial combination therapy.
Perceived barriers and facilitators to physical activity for children with disability: a systematic review
Authors: Nora Shields, Anneliese Jane Synnot, Megan Barr
Journal: British Journal of Sports Medicine (2011)

The aim of this systematic review was to investigate the perceived barriers and facilitators to physical activity among children with disability.10 electronic databases were searched from the earliest time available to September 2010 to identify relevant articles. Articles were included if they examined the barriers or facilitators to physical activity for children with disability and were written in English. Articles were excluded if they included children with an acute, transient or chronic medical condition, examined sedentary leisure activities, or societal participation in general. Two reviewers independently assessed the search yields, extracted the data and assessed trial quality. Data were analysed descriptively.14 articles met the inclusion criteria. Barriers included lack of knowledge and skills, the child's preferences, fear, parental behaviour, negative attitudes to disability, inadequate facilities, lack of transport, programmes and staff capacity, and cost. Facilitators included the child's desire to be active, practising skills, involvement of peers, family support, accessible facilities, proximity of location, better opportunities, skilled staff and information.Personal, social, environmental, and policy and programme-related barriers and facilitators influence the amount of activity children with disability undertake. The barriers to physical activity have been studied more comprehensively than the facilitators.