tbuckley/cabot-search huggingface dataset:
Mutation in the key enzyme of sialic acid biosynthesis causes severe glomerular proteinuria and is rescued by N-acetylmannosamine
Authors: Belinda Galeano, Riko Klootwijk, Irini Manoli, MaoSen Sun, Carla Ciccone, Daniel Darvish, Matthew F. Starost, Patricia M. Zerfas, Victoria J. Hoffmann, Shelley Hoogstraten-Miller, Donna M. Krasnewich, William A. Gahl, Marjan Huizing
Journal: Journal of Clinical Investigation (2007)

Mutations in the key enzyme of sialic acid biosynthesis, uridine diphospho–N-acetylglucosamine 2-epimerase/N-acetylmannosamine (ManNAc) kinase (GNE/MNK), result in hereditary inclusion body myopathy (HIBM), an adult-onset, progressive neuromuscular disorder. We created knockin mice harboring the M712T Gne/Mnk mutation. Homozygous mutant (GneM712T/M712T) mice did not survive beyond P3. At P2, significantly decreased Gne-epimerase activity was observed in GneM712T/M712T muscle, but no myopathic features were apparent. Rather, homozygous mutant mice had glomerular hematuria, proteinuria, and podocytopathy. Renal findings included segmental splitting of the glomerular basement membrane, effacement of podocyte foot processes, and reduced sialylation of the major podocyte sialoprotein, podocalyxin. ManNAc administration yielded survival beyond P3 in 43% of the GneM712T/M712T pups. Survivors exhibited improved renal histology, increased sialylation of podocalyxin, and increased Gne/Mnk protein expression and Gne-epimerase activities. These findings establish this GneM712T/M712T knockin mouse as what we believe to be the first genetic model of podocyte injury and segmental glomerular basement membrane splitting due to hyposialylation. The results also support evaluation of ManNAc as a treatment not only for HIBM but also for renal disorders involving proteinuria and hematuria due to podocytopathy and/or segmental splitting of the glomerular basement membrane.
Physical testing prior to returning to normal sports activity for elite athletes following ACL injury
Authors: Georgios G Ziogas
Journal: British Journal of Sports Medicine (2011)

Anterior cruciate ligament (ACL) injury is among the most frequent sports-related injuries especially in contact sports such as football, basketball, soccer and skiing. In professional sports, ACL injury has a significant financial impact on both athlete and team, since several months are required before full return to professional sport activity. At the end of the rehab program an overall assessment is taking place which traditionally includes isokinetic testing, functional tests and stability clinical assessment prior to the final approval for returning to normal professional sports activity. However, these tests do not examine whether running economy has been altered following ACL injury and rehabilitation. Deterioration in running economy will increase the physical load on the injured knee and may increase the risk for injury in the future. In addition, the traditional tests do not assess whether muscle fatigue at given submaximal and maximal loads has returned to preinjury levels although most researchers agree that fatigue appears to have a central role in non-contact ACL injuries, since it affects most of the modifiable risk factors which are related to ACL tear such as hamstring recruitment, proprioception, lateral trunk motion, tibial rotation, knee abduction, dynamic foot pronation, ground reaction, hip abduction, balance and flexibility. In addition, fatigue can cause alterations in landing and cutting mechanics similar to the ones proposed to increase the risk of ACL tear. Based on preliminary data from our lab, these tests may be very useful for a safe return of the injured athlete to normal sports activity and for the evaluation of the rehabilitation process. These tests may include running economy assessment at low, medium and high intensities, lactate curve analysis at all intensities, lactate removal rate and cardiovascular endurance assessment.
Paediatric sports injuries in Hong Kong: a seven year survey.
Authors: N Maffulli, R C Bundoc, K M Chan, J C Cheng
Journal: British Journal of Sports Medicine (1996)

To ascertain the epidemiological characteristics of sports injuries in children in Hong Kong.Retrospective review of all cases seen in the Sports Injury Clinic of the Prince of Wales Hospital, Shatin, Hong Kong, in the period May 1984 to December 1990. The variables studied were age at presentation, gender, side of the body injured, anatomical location of the injury, type and severity of injury, sport played, level (school, recreational, amateur and professional) and frequency of sports participation, length in years of sports practice, and initial management of the injury.Of the 2293 patients seen, 238 were youngsters (54% boys) 16 years old or younger. Ball games accounted for the greatest number of injuries, with 37 children taking part in basketball, 28 in soccer, 12 in volleyball, and 31 children taking part in a variety of other ball games. Of the remaining children, the single largest group was practising track and field, with sprinting and middle distance running accounting for 42 injuries, and 28 children were injured while cycling. Most of the injuries (85%) were classified as non-serious, but 15% of children presented with a total of 21 fractures, two joint dislocations, five concussions, and seven torn knee ligaments.Children sports participation in Hong Kong, although not at high level and not as widespread as in the West, accounts for significant morbidity. These injuries should be carefully monitored to ascertain whether they result in any detrimental long term effects.
What is the true role of surfactant in the lung?
Authors: B A Hills
Journal: Thorax (1981)

What is the true role of surfactant in the lung?The surfactant identified' in the lung has been accorded two major roles.Firstly, it is believed that surfactant "reduces the work of expanding the lung with each breath" by reducing surface tension at the air-alveolar interface and secondly, in so doing, it also tends to "keep alveoli dry" by on July 25,
Growth in infancy and bone mass in later life
Authors: C. Cooper, C. Fall, P. Egger, R. Hobbs, R. Eastell, D. Barker
Journal: Annals of the Rheumatic Diseases (1997)

To examine the association between weight in infancy and bone mass during the seventh decade of life in a population based cohort for which detailed birth and childhood records were preserved.189 women and 224 men who were aged 63-73 years and were born in East Hertfordshire underwent bone densitometry by dual energy x ray absorptiometry. Measurements were also made of serum osteocalcin and urinary excretion of type 1 collagen cross linked N-telopeptide.There were statistically significant associations between weight at 1 year and bone mineral content (but not bone mineral density) at the spine (P < 0.02) and femoral neck (P < 0.01) among women, and spine (P < 0.03) among men. Although serum osteocalcin was negatively correlated with bone mineral density at both sites among men and women, infant weight was not significantly associated with either biochemical marker of bone turnover.These data confirm our previous observations that growth in infancy is associated with skeletal size in adulthood, and suggest that skeletal growth may be programmed during intrauterine or early postnatal life.
Down-Regulation of the Homeodomain Factor Cdx2 in Colorectal Cancer by Collagen Type I
Authors: Thomas Brabletz, Simone Spaderna, Jochen Kolb, Falk Hlubek, Gerhard Faller, Christiane J. Bruns, Andreas Jung, Jens Nentwich, Isabelle Duluc, Claire Domon-Dell, Thomas Kirchner, Jean-Noel Freund
Journal: Cancer Research (2004)

Abstract The homeobox transcription factor Cdx2 specifies intestinal development and homeostasis and is considered a tumor suppressor in colorectal carcinogenesis. However, Cdx2 mutations are rarely found. Invasion of colorectal cancer is characterized by a transient loss of differentiation and nuclear accumulation of the oncoprotein β-catenin in budding tumor cells. Strikingly, this is reversed in growing metastases, indicating that tumor progression is a dynamic process that is not only driven by genetic alterations but also regulated by the tumor environment. Here we describe a transient loss of Cdx2 in budding tumor cells at the tumor host interface, and reexpression of Cdx2 in metastases. Cell culture experiments show that collagen type I, through β1 integrin signaling, triggers a transient transcriptional down-regulation of Cdx2 and its intestine-specific target gene sucrase isomaltase, associated with a loss of differentiation. These data indicate an active role for the tumor environment in malignant tumor progression.
Risk of Breast Cancer in Women With a <i>CHEK2</i> Mutation With and Without a Family History of Breast Cancer
Authors: Cezary Cybulski, Dominika Wokołorczyk, Anna Jakubowska, Tomasz Huzarski, Tomasz Byrski, Jacek Gronwald, Bartłomiej Masojć, Tadeusz Dębniak, Bohdan Górski, Paweł Blecharz, Steven A. Narod, Jan Lubiński
Journal: Journal of Clinical Oncology (2011)

To estimate the risk of breast cancer in a woman who has a CHEK2 mutation depending on her family history of breast cancer.Seven thousand four hundred ninety-four BRCA1 mutation-negative patients with breast cancer and 4,346 control women were genotyped for four founder mutations in CHEK2 (del5395, IVS2+1G>A, 1100delC, and I157T).A truncating mutation (IVS2+1G>A, 1100delC, or del5395) was present in 227 patients (3.0%) and in 37 female controls (0.8%; odds ratio [OR], 3.6; 95% CI, 2.6 to 5.1). The OR was higher for women with a first- or second-degree relative with breast cancer (OR, 5.0; 95% CI, 3.3 to 7.6) than for women with no family history (OR, 3.3; 95% CI, 2.3 to 4.7). If both a first- and second-degree relative were affected with breast cancer, the OR was 7.3 (95% CI, 3.2 to 16.8). Assuming a baseline risk of 6%, we estimate the lifetime risks for carriers of CHEK2 truncating mutations to be 20% for a woman with no affected relative, 28% for a woman with one second-degree relative affected, 34% for a woman with one first-degree relative affected, and 44% for a woman with both a first- and second-degree relative affected.CHEK2 mutation screening detects a clinically meaningful risk of breast cancer and should be considered in all women with a family history of breast cancer. Women with a truncating mutation in CHEK2 and a positive family history of breast cancer have a lifetime risk of breast cancer of greater than 25% and are candidates for magnetic resonance imaging screening and for tamoxifen chemoprevention.
Treatment of In-Stent Restenosis With Excimer Laser Coronary Angioplasty
Authors: Roxana Mehran, Gary S. Mintz, Lowell F. Satler, Augusto D. Pichard, Kenneth M. Kent, Theresa A. Bucher, Jeffery J. Popma, Martin B. Leon
Journal: Circulation (1997)

Background This study determined the clinical safety, mechanisms, and 6-month results of excimer laser angioplasty (ELCA)+adjunct PTCA for the treatment of in-stent restenosis and (via lesion matching) compared the results of ELCA+PTCA to PTCA alone. Methods and Results Using quantitative angiography (QCA) and intravascular ultrasound (IVUS), we studied 107 restenotic previously stented lesions in 98 patients before and after intervention. QCA measurements included minimum lumen diameter (MLD) and diameter stenosis (DS). IVUS measurements included stent, lumen, and intimal hyperplasia (IH=stent−lumen) cross-sectional areas (CSA) and volumes. In the 54 lesions treated with ELCA+PTCA, the MLD increased from 0.73±0.38 mm before ELCA to 2.10±0.47 mm after ELCA+PTCA ( P &lt;.0001); the DS decreased from 70±14% to 25±12% ( P &lt;.0001). By IVUS, the minimum lumen CSA increased from 1.58±0.78 mm 2 before ELCA to 6.34±1.75 mm 2 after ELCA+PTCA ( P &lt;.0001) as a result of an increase in minimum stent CSA from 7.70±2.41 to 9.10±2.60 mm 2 ( P &lt;.0001) and a decrease in IH CSA from 5.25±2.84 to 2.63±1.41 mm 2 ( P &lt;.0001). Volumetric analysis showed that tissue ablation (during ELCA) contributed 29±15%, tissue extrusion (during adjunct PTCA) contributed 31±14%, and additional stent expansion (during adjunct PTCA) contributed 40±16% to the overall lumen gain. There were no ELCA-related complications. Matched to lesions treated with PTCA alone, ELCA+PTCA resulted in greater lumen gain, more IH ablation/extrusion, larger final lumen CSA (IVUS), and a tendency for less frequent need for subsequent target vessel revascularization (TVR, 21% versus 38%, P =.0823). Conclusions ELCA safely and effectively ablates in-stent neointimal tissue. Adjunct PTCA extrudes neointimal tissue out of the stent and also further expands the stent. Compared with PTCA alone, ELCA+PTCA achieves better short-term and, potentially, better long-term results.
Preoperative A1C and Clinical Outcomes in Patients With Diabetes Undergoing Major Noncardiac Surgical Procedures
Authors: Patricia Underwood, Reza Askari, Shelley Hurwitz, Bindu Chamarthi, Rajesh Garg
Journal: Diabetes Care (2013)

OBJECTIVE To evaluate the relationship between preoperative A1C and clinical outcomes in individuals with diabetes mellitus undergoing noncardiac surgery. RESEARCH DESIGN AND METHODS Data were obtained from the National Surgical Quality Improvement Program database and the Research Patient Data Registry of the Brigham and Women’s Hospital. Patients admitted to the hospital for ≥1 day after undergoing noncardiac surgery from 2005 to 2010 were included in the study. RESULTS Of 1,775 patients with diabetes, 622 patients (35%) had an A1C value available within 3 months before surgery. After excluding same-day surgeries, patients with diabetes were divided into four groups (A1C ≤6.5% [N = 109]; &amp;gt;6.5–8% [N = 202]; &amp;gt;8–10% [N = 91]; &amp;gt;10% [N = 47]) and compared with age-, sex-, and BMI-matched nondiabetic control subjects (N = 888). Individuals with A1C values between 6.5 and 8% had a hospital length of stay (LOS) similar to the matched control group (P = 0.5). However, in individuals with A1C values ≤6.5 or &amp;gt;8%, the hospital LOS was significantly longer compared with the control group (P &amp;lt; 0.05). Multivariate regression analysis demonstrated that a higher A1C value was associated with increased hospital LOS after adjustments for age, sex, BMI, race, type of surgery, Charlson Comordity Index, smoking status, and glucose level on the day of surgery (P = 0.02). There were too few events to meaningfully evaluate for death, infections, or readmission rate. CONCLUSIONS Our study suggests that chronic hyperglycemia (A1C &amp;gt;8%) is associated with poor surgical outcomes (longer hospital LOS). Providing a preoperative intervention to improve glycemic control in individuals with A1C values &amp;gt;8% may improve surgical outcomes, but prospective studies are needed.
Seasonality and determinants of moderate and severe COPD exacerbations in the TORCH study
Authors: C.R. Jenkins, B. Celli, J.A. Anderson, G.T. Ferguson, P.W. Jones, J. Vestbo, J.C. Yates, P.M.A. Calverley
Journal: European Respiratory Journal (2011)

We investigated the impact of season relative to other determinants of chronic obstructive pulmonary disease (COPD) exacerbation frequency in a long-term international study of patients with forced expiratory volume in 1 s (FEV 1 ) &lt;60% predicted. COPD exacerbations were defined by worsening symptoms requiring systemic corticosteroids and/or antibiotics (moderate) or hospital admission (severe). Seasonality effect was calculated as the proportion of patients experiencing an exacerbation each month. Exacerbations in the northern and southern regions showed an almost two-fold increase in the winter months. No seasonal pattern occurred in the tropics. Overall, 38% of exacerbations were treated with antibiotics only, 19% with systemic corticosteroids only and 43% with both, while 20% required hospital admission irrespective of the season. Exacerbation frequency was associated with older age, lower body mass index, lower FEV 1 % pred and history of prior exacerbations. Females and patients with worse baseline breathlessness, assessed using the Medical Research Council (MRC) dyspnoea scale, exacerbated more often (rate ratio (RR) for male versus female 0.7, 95% CI 0.7–0.8 (p&lt;0.001); RR for MRC dyspnoea score 3 versus 1 and 2 combined 1.1, 95% CI 1.1–1.2 (p&lt;0.001)). The effect of season was independent of these risk factors. COPD exacerbations and hospitalisations were more frequent in winter.
A High-Throughput Functional Complementation Assay for Classification of<i>BRCA1</i>Missense Variants
Authors: Peter Bouwman, Hanneke van der Gulden, Ingrid van der Heijden, Rinske Drost, Christiaan N. Klijn, Pramudita Prasetyanti, Mark Pieterse, Ellen Wientjens, Jost Seibler, Frans B.L. Hogervorst, Jos Jonkers
Journal: Cancer Discovery (2013)

Abstract Mutations in BRCA1 and BRCA2 account for the majority of hereditary breast and ovarian cancers, and therefore sequence analysis of both genes is routinely conducted in patients with early-onset breast cancer. Besides mutations that clearly abolish protein function or are known to increase cancer risk, a large number of sequence variants of uncertain significance (VUS) have been identified. Although several functional assays for BRCA1 VUSs have been described, thus far it has not been possible to conduct a high-throughput analysis in the context of the full-length protein. We have developed a relatively fast and easy cDNA-based functional assay to classify BRCA1 VUSs based on their ability to functionally complement BRCA1-deficient mouse embryonic stem cells. Using this assay, we have analyzed 74 unclassified BRCA1 missense mutants for which all predicted pathogenic variants are confined to the BRCA1 RING and BRCT domains. Significance: BRCA1 VUSs are frequently found in patients with hereditary breast or ovarian cancer and present a serious problem for clinical geneticists. This article describes the generation, validation, and application of a reliable high-throughput assay for the functional classification of BRCA1 sequence variants of uncertain significance. Cancer Discov; 3(10); 1142–55. ©2013 AACR. This article is highlighted in the In This Issue feature, p. 1083
Prognostic value of expression of ERCC1, thymidylate synthase, and glutathione S-transferase P1 for 5-fluorouracil/oxaliplatin chemotherapy in advanced gastric cancer
Authors: H.-C. Kwon, M.S. Roh, S.Y. Oh, S.-H. Kim, M.C. Kim, J.-S. Kim, H.-J. Kim
Journal: Annals of Oncology (2007)
Anti-Friend virus antibody is associated with recovery from viremia and loss of viral leukemia cell-surface antigens in leukemic mice. Identification of Rfv-3 as a gene locus influencing antibody production.
Authors: D Doig, B Chesebro
Journal: The Journal of Experimental Medicine (1979)

A single genetic locus, Rfv-3, influenced Friend virus (FV) viremia, loss of FV-induced cell-surface antigens from leukemia cells, and generation of anti-FV antibodies. 30--90 d after FV infection leukemic spleen cells from (B10.A X A)F1 and (B10.A X A.BY)F1 mice (Rfv-3r/s) were found to have low FV-induced cell-surface antigen expression compared to leukemic spleen cells from A and A.BY mice (Rfv-3s/s). In addition, these F1 mice recovered from viremia and generated cytotoxic anti-FV antibodies. A and A.BY mice did not recover from viremia and failed to generate anti-FV antibodies. Anti-FV leukemia cell antibody appeared to mediate FV-antigen loss because decrease of FV cell-surface antigens occurred at the same time as anti-FV antibody appeared in the plasma of F1 mice, and passive transfer of anti-FV antisera induced modulation of FV cell-surface antigens. Rfv-3 did not influence an intrinsic ability of FV antigens to be modulated from Rfv-3s/s leukemia cells because FV antigen loss from Rfv-3s/s spleen cells occurred after transfer of cells to an immune environment.
The neglected universals: Learnability constraints and discourse cues
Authors: Heidi Waterfall, Shimon Edelman
Journal: Behavioral and Brain Sciences (2009)

Abstract Converging findings from English, Mandarin, and other languages suggest that observed “universals” may be algorithmic. First, computational principles behind recently developed algorithms that acquire productive constructions from raw texts or transcribed child-directed speech impose family resemblance on learnable languages. Second, child-directed speech is particularly rich in statistical (and social) cues that facilitate learning of certain types of structures.
Mediterranean diet in pregnancy is protective for wheeze and atopy in childhood
Authors: L Chatzi, M Torrent, I Romieu, R Garcia-Esteban, C Ferrer, J Vioque, M Kogevinas, J Sunyer
Journal: Thorax (2008)

Introduction: Dietary intake of specific nutrients or food groups during pregnancy could play a role in the risk of asthma and atopy in offspring, but specific dietary patterns have not been implicated. The authors evaluated the impact of maternal (during pregnancy) and child adherence to a Mediterranean diet on asthma and atopy in childhood. Methods: Women presenting for antenatal care at all general practices in Menorca, a Mediterranean island in Spain, over a 12 month period starting in mid-1997 were recruited. 460 children were included in the analysis after 6.5 years of follow-up. Maternal dietary intake during pregnancy and children’s dietary intake at age 6.5 years were assessed by food frequency questionnaires, and adherence to a Mediterranean diet was evaluated by a priori defined scores. During follow-up, parents completed questionnaires on the child’s respiratory and allergic symptoms. Children underwent skin prick tests with six common aeroallergens. Results: The prevalence rates of persistent wheeze, atopic wheeze and atopy at age 6.5 years were 13.2%, 5.8% and 17.0%, respectively. One-third (36.1%) of mothers had a low quality Mediterranean diet during pregnancy according to the Mediterranean Diet Score, while the rest had a high score. A high Mediterranean Diet Score during pregnancy (at two levels, using “low” score as the reference) was found to be protective for persistent wheeze (OR 0.22; 95% CI 0.08 to 0.58), atopic wheeze (OR 0.30; 95% CI 0.10 to 0.90) and atopy (OR 0.55; 95% CI 0.31 to 0.97) at age 6.5 years after adjusting for potential confounders. Childhood adherence to a Mediterranean diet was negatively associated with persistent wheeze and atopy although the associations did not reach statistical significance. Conclusion: These results support a protective effect of a high level of adherence to a Mediterranean diet during pregnancy against asthma-like symptoms and atopy in childhood.
Frederick Baar John ("Jack") Alfred Campbell Burridge Finlay Graham Campbell Adele Patricia Chatterjee (nee Powell) George Archibald Craig Ronald Dent James Montgomery Leishman Howat Maurice Kenig John Douglas Wilkinson Alastair Milner Macdonald Wilson Robert Baird Wilson Thomas Henry Wilson
Authors: M. Baar, B. Ross, W R Morris, G. Moore, B. Y Craig, J. T Leeming, R F Gillie, M D J Kenig, M F Lewis, G. Collee, A R Lorimer, I. Brown, J. Surtees
Journal: BMJ (1999)

Jack joined the Royal Army Medical Corps soon after Dunkirk