tbuckley/cabot-search huggingface dataset:
Developmental Trajectories of Symptom Severity and Adaptive Functioning in an Inception Cohort of Preschool Children With Autism Spectrum Disorder
Authors: Peter Szatmari, Stelios Georgiades, Eric Duku, Teresa A. Bennett, Susan Bryson, Eric Fombonne, Pat Mirenda, Wendy Roberts, Isabel M. Smith, Tracy Vaillancourt, Joanne Volden, Charlotte Waddell, Lonnie Zwaigenbaum, Mayada Elsabbagh, Ann Thompson
Journal: JAMA Psychiatry (2015)

IMPORTANCE Symptom severity and adaptive functioning are fundamental domains of the autism spectrum disorder (ASD) phenotype.To date, the longitudinal association between these 2 domains has not been examined.OBJECTIVE To describe the developmental trajectories of autistic symptom severity and adaptive functioning in a large inception cohort of preschool children with ASD. DESIGN, SETTING, AND PARTICIPANTSThe sample consisted of 421 newly diagnosed preschool children with ASD 2 to 4 years old (355 boys; mean age at study enrollment, 39.87 months) participating in a large Canadian multisite longitudinal study (Pathways in ASD Study).Prospective data collected at 4 points from time of diagnosis to age 6 years were used to track the developmental trajectories of children.MAIN OUTCOMES AND MEASURES Autistic symptom severity was indexed using the Autism Diagnostic Observation Schedule.Adaptive functioning was indexed using the Vineland Adaptive Behavior Scales, Second Edition. RESULTSTwo distinct trajectory groups provided the best fit to the autistic symptom severity data.Group 1 (11.4% of the sample) had less severe symptoms and an improving trajectory (P < .05),whereas group 2 (88.6% of the sample) had more severe symptoms and a stable trajectory.Three distinct trajectory groups provided the best fit to the adaptive functioning data.Group 1 (29.2% of the sample) showed lower functioning and a worsening trajectory, group 2 (49.9% of the sample) had moderate functioning and a stable trajectory, and group 3 (20.9% of the sample) had higher functioning and an improving trajectory (P < .05).Cross-trajectory overlap between the autistic symptom severity and adaptive functioning groups was low (φ = 0.13, P < .05).Sex was a significant predictor of autistic symptom severity group membership and age at diagnosis, and language and cognitive scores at baseline predicted membership in adaptive functioning trajectories.Trajectories of both symptom severity and adaptive functioning predicted several different outcomes at age 6 years. CONCLUSIONS AND RELEVANCEFindings confirm the heterogeneous nature of developmental trajectories in ASD.Change in adaptive functioning suggests that improvement is possible in roughly 20% of the sample.Autistic symptom severity appears to be more stable, with roughly 11% of the sample showing a marked decrease in symptom severity.During the preschool years, there appears to be only a small amount of "yoking" of developmental trajectories in autistic symptom severity and adaptive functioning.It is imperative that a flexible suite of interventions that target both autistic symptom severity and adaptive functioning should be implemented and tailored to each child's strengths and difficulties.
Efficacy and Safety of Recombinant Human Nerve Growth Factor in Patients With Diabetic Polyneuropathy
Authors: Stuart C. Apfel, Sherwin Schwartz, Bruce T. Adornato, Roy Freeman, Victor Biton, Marc Rendell, Aaron Vinik, Michael Giuliani, J. Clarke Stevens, Richard Barbano, Peter J. Dyck, None for the rhNGF Clinical Investigator Group
Journal: JAMA (2000)

ERVE GROWTH FACTOR (NGF) is a protein that plays a major role in the development and maintenance of the peripheral nervous system.Nerve growth factor selectively promotes the survival of small fiber sensory neurons that mediate pain, temperature sensation, and sympathetic neurons. 1 Nerve growth factor is expressed in target tissues innervated by responsive neurons, where it binds to specific high-affinity receptors and is retrogradely transported back to the neuronal cell body. 2 Recent data suggest that reduced availability of NGF may play a significant role in the pathogenesis of diabetic polyneuropathy.In animals with diabetes mellitus, retrograde axonal transport of NGF is impaired, [3][4][5] and lev-els of NGF messenger RNA are reduced in neuronal target tissues. 6In patients with diabetes mellitus, levels of NGF are reduced in skin biopsy specimens.Furthermore, the diminished lev-
The proteins of the surfactant system
Authors: J Johansson, T Curstedt, B Robertson
Journal: European Respiratory Journal (1994)

The structural and functional integrity of pulmonary surfactant depends on several specific proteins. Two of these, SP-A and SP-D, are large and water-soluble, while SP-B and SP-C are small and very hydrophobic. SP-A is an 18-mer of 26 kDa polypeptide chains and contains N-linked oligosaccharides. Structurally, it can be characterized as a collagen/lectin hybrid. Together with SP-B, SP-A is required for conversion of secreted endogenous surfactant to tubular myelin in the alveolar lining. It also regulates surfactant secretion and reuptake of surfactant lipids by type II cells; these functions are probably receptor mediated. SP-D, a 12-mer of 39 kDa polypeptide chains, is a collagenous glycoprotein with structural similarities to C-type lectins. Both SP-A and SP-D stimulate alveolar macrophages. SP-B is a 79-residue polypeptide that contains three intrachain disulphide bridges. It exists mainly as a homodimer, which is strongly positively charged and may selectively remove anionic and unsaturated lipid species from the alveolar surface film, thereby increasing surface pressure. SP-C is a mainly alpha-helical, extraordinarily hydrophobic polypeptide containing 35 amino acid residues and covalently linked palmitoyl groups. Its alpha-helical portion is inserted into surfactant lipid bilayers. SP-C accelerates the adsorption of lipid bilayers to an interfacial monolayer. In babies with respiratory distress syndrome, the clinical response to treatment with surfactant containing SP-B and SP-C is much faster than in babies treated with protein-free synthetic surfactant. We speculate that, in the near future, surfactant preparations based on recombinant hydrophobic proteins will be available for clinical use.
Ureter Myogenesis
Authors: Claire M. Lye, Laurent Fasano, Adrian S. Woolf
Journal: Journal of the American Society of Nephrology (2009)

After the basic shape of the mammalian ureter is established, its epithelia mature and a coat of smooth muscle cells differentiate around nascent urothelia. The ureter actively propels tubular fluid from the renal pelvis to the bladder, and this peristalsis, which starts in the fetal period, requires coordinated smooth muscle contraction. Teashirt-3 (Tshz3) is expressed in smooth muscle cell precursors that form the wall of the forming mammalian ureter. The Teashirt gene family was first identified in Drosophila where Teashirt (Tsh) protein acts as a transcription factor directing embryonic anterior-posterior patterning and leg and eye development. In fly embryonic renal tubules, Tsh is expressed in mesodermally derived stellate cells intercalating between principal cells, and a paralogue, tiptop, is expressed in forming tubules. Teashirt is a component of several gene networks in flies and it is notable that similar networks control mammalian renal tract development. Null mutation of Tshz3 in mice leads to failure of functional muscularization in the top of the ureter and this is followed by congenital hydronephrosis. A signaling pathway can be envisaged, starting with sonic hedgehog secreted by the nascent ureteric urothelium and ending with ureteric smooth muscle cell differentiation, with Tshz3 downstream of bone morphogenetic protein 4 and upstream of myocardin and smooth muscle cell contractile protein synthesis. The phenotype of Tshz3 mutant mice resembles that of human congenital pelviureteric junction obstruction, and we suggest these individuals may have mutations of genes encoding molecules in the differentiation pathway mediated by Tshz3.
Medical management of primary pulmonary hypertension
Authors: MP Kneussl, IM Lang, FP Brenot
Journal: European Respiratory Journal (1996)

Primary pulmonary hypertension (PPH) is a poorly understood, progressive disease that is characterized by elevation of pulmonary artery pressure and vascular resistance, leading to right ventricular failure and death within 2-3 yrs after diagnosis. Based upon the concept that vasoconstriction and thrombotic occlusion of resistance vessels precipitate this process, vasodilator therapy and anticoagulation have become the main strategies for improving survival in these patients. Whereas, a few years ago, medical therapy of primary pulmonary hypertension was perceived as a bridging therapy to lung or heart lung transplantation, modes of therapy are being clinically tested at this time to offer an alternative to the surgical treatment of this disease. However, no selective pulmonary vasodilator is yet available. Therefore, and because of the potential hazards of vasodilator treatment, standardized haemodynamic testing is performed prior to initiation of vasodilator treatment. In this update, the currently available compounds both for haemodynamic testing and chronic therapy, their mode of action, method of administration and efficacy are reviewed.
Paraplegia and Paraparesis From Intrathecal Methotrexate and Cytarabine Contaminated With Trace Amounts of Vincristine in China During 2007
Authors: Guang Zeng, Huilai Ma, Xiangbo Wang, Huifang Yan, Xinhua Wan, Bin Jiang, Robert E. Fontaine, Zhenglai Wu, Shaobin Lin, Feng Ruan, Huihui Liu
Journal: Journal of Clinical Oncology (2011)

Purpose The production and administration of drugs used intrathecally requires special care to prevent contamination with neurotoxic agents. In 2007, we investigated a widespread outbreak of paraplegia and paraparesis among Chinese patients who received intrathecal drugs to identify the presumed contaminant and its source to prevent further cases. Patients and Methods We defined a case as onset from January 1 to October 31, 2007, of bilateral flaccid paraparesis or paraplegia or retention and incontinence of stool or urine, in a patient receiving intrathecal drugs. Using a retrospective cohort approach, we selected 12 hospitals from all hospitals that had reported cases. In these hospitals, we identified all 448 patients (including 107 cases) who received intrathecal chemotherapy or chemoprophylaxis in 2007. We calculated attack rates and Mantel-Haenszel adjusted risk ratios for intrathecal drug type and lot. Results All 12 hospitals used intrathecal methotrexate or cytarabine produced by one pharmaceutical plant. Only two lots of each drug were associated with cases. Lot-specific attack rates ranged from 42% to 100% (risk ratio, ∞; lower confidence bounds, 1.8 to 7.3). Vincristine production had immediately preceded production of the implicated lots on the same equipment. By using ultra performance liquid chromatography, we detected vincristine (0.28 to 18 μg) in unused vials from implicated lots of methotrexate and cytarabine. Conclusion Trace amounts of vincristine that contaminated intrathecal drugs caused a large outbreak of severe neurologic damage. Vincristine and other neurotoxic drugs should not be produced on any equipment that is also used for producing drugs that are to be administered intrathecally.
Prevalence and Clinical Significance of Aortic Root Dilation in Highly Trained Competitive Athletes
Authors: Antonio Pelliccia, Fernando M. Di Paolo, Elvira De Blasiis, Filippo M. Quattrini, Cataldo Pisicchio, Emanuele Guerra, Franco Culasso, Barry J. Maron
Journal: Circulation (2010)

Background— Few data are available that address the impact of athletic training on aortic root size. We investigated the distribution, determinants, and clinical significance of aortic root dimension in a large population of highly trained athletes. Methods and Results— Transverse aortic dimensions were assessed in 2317 athletes (56% male), free of cardiovascular disease, aged 24.8±6.1 (range, 9 to 59) years, engaged in 28 sports disciplines (28% participated in Olympic Games). In males, aortic root was 32.2±2.7 mm (range, 23 to 44; 99th percentile=40 mm); in females, aortic root was 27.5±2.6 mm (range, 20 to 36; 99th percentile=34 mm). Aortic root was enlarged ≥40 mm in 17 male (1.3%) and ≥34 mm in 10 female (0.9%) subjects. Over an 8-year follow-up period, aortic dimension increased in these male athletes (40.9±1.3 to 42.9±3.6 mm; P &lt;0.01) and dilated substantially (to 50, 50, and 48 mm) in 3, after 15 to 17 years of follow-up, in the absence of systemic disease. Aortic root did not increase significantly (34.9±0.9 to 35.4±2.1 mm; P =0.11) in female athletes. Multiple regression and covariance analysis showed that aortic dimension was largely explained by weight, height, left ventricular mass, and age ( R 2 =0.63; P &lt;0.001), with type of sports training having a significant but lower impact ( P &lt;0.003). Conclusions— An aortic root dimension &gt;40 mm in highly conditioned male athletes (and &gt;34 mm in female athletes) is uncommon, is unlikely to represent the physiological consequence of exercise training, and is most likely an expression of a pathological condition, mandating close clinical surveillance.
CD40 signaling pathway: anti-CD40 monoclonal antibody induces rapid dephosphorylation and phosphorylation of tyrosine-phosphorylated proteins including protein tyrosine kinase Lyn, Fyn, and Syk and the appearance of a 28-kD tyrosine phosphorylated protein.
Authors: M Faris, F Gaskin, J T Parsons, S M Fu
Journal: The Journal of Experimental Medicine (1994)

CD40 plays an important role in B cell activation, proliferation, and Ig class switching. The signal transduction pathway mediated by CD40 was studied using monoclonal antibody (mAb) 626.1 to CD40. Burkitt's lymphoma and Epstein-Barr virus-transformed B cell lines and tonsilar B lymphocytes were treated with the anti-CD40 mAb for various lengths of time. The early events triggered by CD40 were examined by monitoring the changes in tyrosine phosphorylation of cellular proteins with anti-phosphotyrosine mAb. Dephosphorylation of specific proteins ranging between 50-110 kD and the appearance of a 28-kD tyrosine phosphorylated protein were seen within 30 s in human B cell lines. The dephosphorylation was reversed and the 28-kD protein was dephosphorylated in cells stimulated for 1 min. In resting B cells, the appearance of the 28-kD phosphoprotein was observed in 30 s after the addition of the anti-CD40 mAb. The tyrosine phosphorylation of this protein persisted. The patterns of protein tyrosine phosphorylation differed from those induced by an anti-immunoglobulin M mAb. The changes in the state of tyrosine phosphorylation induced by the anti-CD40 mAb were obviated by mAb to CD45, a protein tyrosine phosphatase (PTP) or by the addition of sodium orthovanadate, a broad PTP inhibitor. They were also blocked by protein tyrosine kinase (PTK) inhibitors, herbimycin A and genistein, and PKC and protein serine/threonine kinase inhibitors, H7 and HA1004. In addition, the alteration in the tyrosine phosphorylation of PTKs Lyn, Fyn, and Syk was directly demonstrated. Engagement of CD40 for 30 s induced a transient decrease in tyrosine phosphorylation of these PTKs. These results indicate that the early events in CD40 signaling involve the complex interaction between PTP and protein kinases.
Quality of life and preferences for treatment following systemic adjuvant therapy for early-stage breast cancer.
Authors: C Lindley, S Vasa, W T Sawyer, E P Winer
Journal: Journal of Clinical Oncology (1998)

To evaluate the quality of life (QOL) of breast cancer patients who survived 2 to 5 years following initiation of adjuvant cytotoxic and/or hormonal therapy and to characterize relationships between QOL and patient physical symptoms, sexual function, and preferences regarding adjuvant treatment.Eighty-six patients who had completed systemic adjuvant therapy for early-stage breast cancer between 1988 and 1991 were surveyed by written questionnaire and telephone interview. Sociodemographic information was obtained for each patient, and patients were asked to complete the Functional Living Index-Cancer (FLIC), the Symptom Distress Scale (SDS), the Medical Outcomes Study (MOS) Short Form 36 (SF-36), a series of questions regarding sexual function, and a survey about preferences for adjuvant therapy in relation to possible benefit.The mean FLIC score among all patients was 138.3 (+/- 12.2), which suggests a high level of QOL. The reported frequency of moderate to severe symptoms was generally low (ie, < 15%), with fatigue (31.4%), insomnia (23.3%), and local numbness at the site of surgery (22.1%) occurring with greatest frequency. Patients reported a wide range of sexual difficulties. Preference assessment showed that more than 65% of patients were willing to undergo 6 months of chemotherapy for a 5% increase in likelihood of cancer cure.Self-rated QOL in breast cancer patients 2 to 5 years following adjuvant therapy was generally favorable. Less than one third of patients reported moderate to severe symptoms. Selected aspects of sexual function appeared to be compromised. The majority of patients indicated a willingness to accept 6 months of chemotherapy for small to modest potential benefit.
The Football Association Medical Research Programme: an audit of injuries in professional football: an analysis of ankle sprains
Authors: C Woods, R Hawkins, M Hulse, A Hodson
Journal: British Journal of Sports Medicine (2003)

Aim: To conduct a detailed analysis of ankle sprains sustained in English professional football over two competitive seasons. Methods: Club medical staff at 91 professional football clubs annotated player injuries. A specific injury audit questionnaire was used together with a weekly form that documented each club’s current injury status. Results: Completed injury records for the two competitive seasons were obtained from 87% and 76% of the participating clubs. Ankle ligament sprains accounted for 11% of the total injuries over the two seasons, with over three quarters (77%) of sprains involving the lateral ligament complex. A total of 12 138 days and 2033 matches were missed because of ankle sprains. More sprains were caused by contact mechanisms than non-contact mechanisms (59% v 39%) except in goalkeepers who sustained more non-contact sprains (21% v 79%, p&lt;0.01). Ankle sprains were most often observed during tackles (54%). More ankle sprains were sustained in matches than in training (66% v 33%), with nearly half (48%) observed during the last third of each half of matches. A total of 44% of sprains occurred during the first three months of the season. A high number of players (32%) who sustained ankle sprains were wearing some form of external support. The recurrence rate for ankle sprains was 9% (see methodology for definition of reinjury). Conclusion: Ankle ligament sprains are common in football usually involving the lateral ligament complex. The high rate of occurrence and recurrence indicates that prevention is of paramount importance.
Quantification of Free Circulating DNA As a Diagnostic Marker in Lung Cancer
Authors: Gabriella Sozzi, Davide Conte, MariaElena Leon, Rosalia Cirincione, Luca Roz, Cathy Ratcliffe, Elena Roz, Nicola Cirenei, Massimo Bellomi, Giuseppe Pelosi, Marco A. Pierotti, Ugo Pastorino
Journal: Journal of Clinical Oncology (2003)

Analysis of circulating DNA in plasma can provide a useful marker for earlier lung cancer detection. This study was designed to assess the sensitivity and specificity of a quantitative molecular assay of circulating DNA to identify patients with lung cancer and monitor their disease.The amount of plasma DNA was determined through the use of real-time quantitative polymerase chain reaction (PCR) amplification of the human telomerase reverse transcriptase gene (hTERT) in 100 non-small-cell lung cancer patients and 100 age-, sex-, and smoking-matched controls. Screening performance of the assay was calculated through the receiver operating characteristic (ROC) curve. Odds ratios were calculated using conditional logistic regression analysis.Median concentration of circulating plasma DNA in patients was almost eight times the value detected in controls (24.3 v 3.1 ng/mL). The area under the ROC curve was 0.94 (95% CI, 0.907 to 0.973). Plasma DNA was a strong risk factor for lung cancer; concentrations in the upper tertile were associated with an 85-fold higher risk than were those in the lowest tertile.This study shows that higher levels of free circulating DNA can be detected in patients with lung cancer compared with disease-free heavy smokers by a PCR assay, and suggests a new, noninvasive approach for early detection of lung cancer. Levels of plasma DNA could also identify higher-risk individuals for lung cancer screening and chemoprevention trials.
PM-04 * IN SILICO ANALYSIS OF AVAglio AND RTOG 0825 PHASE III CLINICAL TRIALS SUGGESTS SIGNATURES OF PATIENTS TO RECEIVE BENEFIT FROM COMBINED BEVACIZUMAB AND RADIATION THERAPIES
Authors: A. Hawkins-Daarud, R. Rockne, D. Corwin, A. Anderson, P. Kinahan, K. Swanson
Journal: Neuro-Oncology (2014)

Despite the growing interest in anti-angiogenic therapies for glioblastoma (GBM), no statistically significant evidence has been found to indicate that bevacizumab in combination with other therapies increases the overall survival of glioblastoma patients. Most recently two phase III trials, AVAglio and RTOG 0825, were concluded considering bevacizumab in the upfront setting in combination with radiation and chemotherapy. Although the aggregate results of these Phase III studies were disappointing, there remains an open question of the potential benefits of this combination therapy for predictable subpopulations of patients. We utilize a mathematical model of GBM growth which incorporates vascular density, hypoxia and necrosis to investigate differential benefits of combination therapy consisting of surgical resection, radiation and bevacizumab. Proliferation and migration rates of the simulated tumors were varied across known growth dynamics observed in human GBMs. The model assumes that the anti-angiogenic therapy normalizes vasculature and thus decreases hypoxia. We assess the differential hypoxic burden left after a gross total resection along with the change in radiation cell kill from re-normalization of the tissue due to treatment with bevacizumab. We found that hypoxic burden and the resulting change in radiation induced cell kill varied dramatically across a range of tumor growth kinetics. Under the assumption of vasculature renormalization leading to decreased hypoxia, we determined that patients undergoing a gross total resection, which is the case for about 50% of the patients enrolled in the AVAglio and RTOG 0825 Phase III trials, would not likely benefit from combination therapy because the majority of the hypoxic burden would have been surgically removed. For patients not undergoing a gross total resection, our results indicate that there is a sub-population of patients, those with large tumors and high proliferation rates, who would have a dramatic change in the total radiation cell kill when combined with anti-angiogenic therapy.