tbuckley/cabot-search huggingface dataset:
Protein Melting Temperature Cannot Fully Assess Whether Protein Folding Free Energy Underlies the Universal Abundance–Evolutionary Rate Correlation Seen in Proteins
Authors: Rostam M Razban
Journal: Molecular Biology and Evolution (2019)

The protein misfolding avoidance hypothesis explains the universal negative correlation between protein abundance and sequence evolutionary rate across the proteome by identifying protein folding free energy (ΔG) as the confounding variable. Abundant proteins resist toxic misfolding events by being more stable, and more stable proteins evolve slower because their mutations are more destabilizing. Direct supporting evidence consists only of computer simulations. A study taking advantage of a recent experimental breakthrough in measuring protein stability proteome-wide through melting temperature (Tm) (Leuenberger et al. 2017), found weak misfolding avoidance hypothesis support for the Escherichia coli proteome, and no support for the Saccharomyces cerevisiae, Homo sapiens, and Thermus thermophilus proteomes (Plata and Vitkup 2018). I find that the nontrivial relationship between Tm and ΔG and inaccuracy in Tm measurements by Leuenberger et al. 2017 can be responsible for not observing strong positive abundance-Tm and strong negative Tm-evolutionary rate correlations.
Stereotactic Body Radiation Therapy Versus Nonradiotherapeutic Ablative Procedures (Laser/Cryoablation and Electrocautery) for Early-Stage Non–Small Cell Lung Cancer
Authors: Michael J. Baine, Richard Sleightholm, Beth K. Neilsen, David Oupický, Lynette M. Smith, Vivek Verma, Chi Lin
Journal: Journal of the National Comprehensive Cancer Network (2019)

Background: Despite the fact that stereotactic body radiation therapy (SBRT) is the only recommended first-line therapy for inoperable early-stage non–small cell lung cancer (NSCLC), several thermal ablative procedures (TAPs; defined herein as laser/cryoablation and electrocautery) are available. Studies showing outcomes of these procedures and how they compare with SBRT are scarce. We sought to evaluate the comparative efficacy of SBRT versus TAPs using the National Cancer Database (NCDB). Methods: The NCDB was queried for patients with early-stage NSCLC who did not undergo surgical resection. Treatment-specific inclusion criteria were applied to select for patients receiving either TAPs or SBRT. Univariate logistic regression and Cox proportional hazards modeling were performed, and Kaplan-Meier curves were generated. Serial propensity matches were performed using a modified greedy 8→n matching 1:1 algorithm. Results: A total of 27,734 patients were analyzed; 26,725 underwent SBRT and 1,009 underwent TAPs. Patients who received SBRT were older and more likely to have clinical stage IB (vs IA) disease. Despite this, SBRT was associated with longer median overall survival (mOS; 37.7 vs 33.5 months; P =.001) and 1-, 2-, and 5-year OS rates compared with the TAPs cohort (86.7% vs 83.1%, 67.5% vs 62.7%, and 30.6% vs 26.9%, respectively; P =.001). Upon propensity matching, improved OS with SBRT remained, with a mOS of 40.4 versus 33.4 months and 1-, 2-, and 5-year OS rates of 89.0% versus 82.9%, 69.7% versus 62.7%, and 34.4% versus 26.4%, respectively ( P =.003). Conclusions: Despite being associated with more higher-risk factors, SBRT was associated with higher OS compared with TAPs for treatment of nonoperative patients diagnosed with early-stage NSCLC. However, causation cannot be implied owing to the inherent limitations of large heterogeneous datasets such as the NCDB.
Center-Related Variation in Cardiac Stress Testing in the 18 Months Prior to Renal Transplantation
Authors: Adam A. Shpigel, Mohammed J. Saeed, Eric Novak, Tarek Alhamad, Michael W. Rich, David L. Brown
Journal: JAMA Internal Medicine (2019)

This analysis of data from US Renal Data System examined patient- and center-level variables for patients who did and did not undergo cardiac stress testing to determine which were associated with stress testing 18 months prior to renal transplantation.
UTILITY OF NEWLY DEVELOPED SHORT TYPE DOUBLE BALLOON ENDOSCOPY FOR ERCP IN POSTOPERATIVE PATIENTS WITH SURGICAL ANATOMIC VARIATIONS: A LARGE CASE SERIES
Authors: M Shimatani, T Mitsuyama, M Tokuhara, M Masuda, T Ito, H Miyoshi, T Ikeura, M Takaoka, K Okazaki
Journal: Endoscopy (2019)

The aim of this study was to evaluate the usefulness of new short DBE for ERCP in postoperative patients.
ENDOSCOPIC TREATMENT OF RECTAL NEUROENDOCRINE TUMORS IN A 12 YEAR RETROSPECTIVE SINGLE CENTER STUDY
Authors: K Dąbkowski, A Białek, N Rusiniak-Rossińska, K Michalska, B Kos-Kudła, T Starzyńska
Journal: Endoscopy (2019)

Our aim was to analyse the clinical, endoscopic and pathological characteristics of rectal neuroendocrine tumors and check whether the neuroendocrine origin of lesions was suspected during endoscopy and subsequently were these lesions removed with appropriate method.
The analysis of statistics of breast cancer in Cherkassy region before and after Chernobyl disaster
Authors: L. Zrielykh
Journal: Annals of Oncology (2019)

Background: Ionizing radiation can influence on cells of organisms through the chain of electric, physico-chemical, chemical and biological effects leading to different damages, genetic abnomalities and death. On 26 April 1986 the explosion of atomic reactor of the fourth power unit of Chernobyl Nuclear Power Station happened, having thrown into the atmosphere nearly 50 tons of nuclear fuel with the activity of 15-20 thousands of rentgen per hour. This disaster had detrimental outcome for people living in Ukraine and other countries, resulted to increase of morbidity and mortality from different diseases, especially oncological. Methods: Analysis of data of National and regional cancer registries, statistical reports on the work done by the regional center and district hospitals of Cherkassy region on oncological patients in 1985, 2015 yy. Results: Number of new breast cancer (BC) cases in 1985 in Cherkassy region was 335 (man – 1, women – 334), in 2015 – 520 ( men – 4, women – 516). The number of BC cases increased by 35,6% ( by 25% in men, by 35,3% in women) in 2015 in comparison to 1985. Crude incidence rate per 100000 of population in 1985 was 21,87 ( men – 0,06, women – 21,8), in 2015- 43,8 ( men – 0,7, women – 80,2). So this rate increased by 49,9%. The number of cases of BC in women under 29 years old in 1985 was 2, in 2015 – 9 ( increased in 4,5 times), showing tendency to rise of incidence of this disease at a young age. Number of deaths from BC in 1985 was 164, in 2015 – 210, so this index increased by 22%. In 1985 stage distribution of new BC cases (according to TNM) was: I, II – 56,2%; III – 31,6%, IV – 12,2%. In 2015 this ratio was: I, II – 74,5%, III – 13,6%, IV – 11,3%. The number of BC cases detected during the preventive examination in 1985 was 25%, in 2015 – 42,8%. The percentage of morphologically verified BC in 1985 was 84,2%, in 2015 – 90,4%. Conclusions: Chernobyl disaster and subsequent spread and influence of radiation led to increase of oncological diseases in Ukraine, including breast cancer. Despite the new advances in medicine the morbidity of BC in Cherkassy region continues to grow and Chornobyl disaster had a strong impact on this fact. Legal entity responsible for the study: Cherkassy Regional Oncology Center. Funding: Has not received any funding. Disclosure: The author has declared no conflicts of interest.
Association between exposure to the natural environment, rurality, and attention-deficit hyperactivity disorder in children in New Zealand: a linkage study
Authors: Geoffrey H Donovan, Yvonne L Michael, Demetrios Gatziolis, Andrea 't Mannetje, Jeroen Douwes
Journal: The Lancet Planetary Health (2019)

BackgroundSeveral small experimental studies and cross-sectional observational studies have shown that exposure to the natural environment might protect against attention-deficit hyperactivity disorder (ADHD) or moderate the symptoms of ADHD in children. We aimed to assess whether exposure to the natural environment protects against ADHD and whether this hypothesised protective effect varies across a child's life course.MethodsWe did a longitudinal study with data collected from all children born in New Zealand in 1998, excluding those without an address history, those who were not singleton births, and those who died or emigrated before 18 years of age. We used Statistics New Zealand's Integrated Data Infrastructure to identify children with ADHD and to define covariates. ADHD was defined according to hospital diagnosis or pharmacy records (two or more prescriptions for ADHD drugs). Exposure to green space for each year of a child's life (from gestation to 18 years of age) was estimated at the meshblock level (the smallest geographical unit for which the New Zealand Census reports data) using normalised difference vegetation index (NDVI), and land-use data from Landcare Research New Zealand. We used logit models to assess the associations between ADHD prevalence and minimum, maximum, and mean lifetime NDVI, as well as rural living, controlling for sex, ethnicity, mother's educational level, mother's smoking status, mother's age at parturition, birth order, antibiotic use, and low birthweight.FindingsOf the 57 450 children born in New Zealand in 1998, 49 923 were eligible and had available data, and were included in the analysis. Children who had always lived in a rural area after 2 years of age were less likely to develop ADHD (odds ratio [OR] 0·670 [95% CI 0·461–0·974), as were those with increased minimum NDVI exposure after age 2 years (standardised OR for exposure vs first quartile: second quartile 0·841 [0·707–0·999]; third quartile 0·809 [0·680–0·963]; fourth quartile 0·664 [0·548–0·805]). In early life (prenatal to age 2 years), neither rural living nor NDVI were protective against ADHD. Neither mean nor maximum greenness was significantly protective against ADHD.InterpretationRurality and increased minimum greenness were strongly and independently associated with a reduced risk of ADHD. Increasing a child's minimum lifetime greenness exposure, as opposed to maximum or mean exposure, might provide the greatest increment of protection against the disorder.FundingNone.
ENDOSCOPIC MANAGEMENT OF OCCLUDED SELF-EXPANDABLE METAL STENTS USED FOR MALIGNANT STRICTURES OF THE BILE DUCT: RESULTS OF A SINGLE-CENTER RETROSPECTIVE STUDY
Authors: T Voiosu, H Zacheu, D Bobeica, M Barbu, A Bengus, A Voiosu, RB Mateescu
Journal: Endoscopy (2019)

Self-expandable metal stents (SEMS) have become a mainstay of palliation for cholestasis in patients with malignant strictures of the bile duct, providing longer patency than plastic stents. There is, however, limited data regarding management of stent dysfunction in these patients, with current guidelines supporting use of both plastic and metal stents. We report our experience with management of SEMS dysfunction.
METHYLENE BLUE-MMX FOR SCREENING COLONOSCOPY
Authors: A Repici, C Hassan, R Bisschops, P Bhandari, E Dekker, M Rutter, J East, R Kiesslich, P Siersema, M Spaander, F Radaelli
Journal: Endoscopy (2019)

Topically applied methylene blue dye chromoendoscopy is effective in improving detection of colorectal neoplasia. When combined with a pH- and time-dependent multimatrix structure, a per-oral formulation methylene blue formulation (MB-MMX) is directly delivered to colorectal mucosa.
Intermittent versus continuous chemotherapy beyond first-line for patients with HER2-negative advanced breast cancer (BOOG 2010-02)
Authors: F.L.G. Erdkamp, A.K.M. Claessens, M. Lopez-Yurda, J.M. Bouma, H. van Tinteren, J.M. Rademaker-Lakhai, A.H. Honkoop, H. de Graaf, V.C.G. Tjan-Heijnen, M.M.E.M. Bos
Journal: Annals of Oncology (2019)

Background: This study investigates efficacy and safety of intermittent versus continuous scheduling of chemotherapy over two treatment lines for patients within the Stop & Go trial. Methods: Participants were randomized to two sets of four cycles (intermittent) or eight consecutive cycles (continuous) of chemotherapy in two treatment lines. First-line consisted of paclitaxel plus bevacizumab, second-line of capecitabine or non-pegylated liposomal doxorubicin. The primary endpoint of the present study was progression-free survival (PFS) of second-line treatment. Results: Characteristics at randomization were well-balanced. Patients with a good baseline performance status, only non-visceral metastasis, longer disease-free-interval, and HR-positive disease more often started second-line study treatment. For patients who started second line study treatment (n = 270; 131 vs. 139 in intermittent vs. continuous arm) median PFS in second-line was respectively 3.5 vs. 5.0 months with a Hazard Ratio (HR) of 1.04 (95%CI 0.69-1.57), and median OS in second-line was 10.6 vs.12.0 months, with a HR of 1.64 (95%CI 1.08 – 2.48). The median combined first- and second-line PFS for this population was 14.6 vs. 16.6 months with a HR of 1.59 (95%CI 1.04 – 2.45), and median OS measured from randomization was 20.3 vs. 23.0 months with a HR of 1.93 (95%CI 1.26 – 2.95). For all randomized patients (n = 420) median combined first- and second-line PFS was 12.7 vs. 13.9 months, with a HR of 1.21 (95%CI 0.9 – 1.63), and OS measured from randomization was 17.1 vs. 20.9 months with a HR of 1.37 (95%CI 1.03 - 1.54) for intermittent vs. continuous scheduling respectively. Selected baseline characteristics and first-line PFS duration were not significantly associated with second-line PFS in exploratory analyses. However, patients with longer first-line PFS more often started second-line study treatment (odds ratio 2.13; 95%CI 1.20 – 3.78) compared to patients with shorter first-line PFS. Details on safety will be presented at the meeting. Conclusions: In conclusion, considering the overall survival benefits of continuous scheduling in both first- and second-line chemotherapy, we recommend this strategy for treatment of advanced breast cancer. Clinical trial identification: EudraCT 2010-021519-18; BOOG 2010-02. Legal entity responsible for the study: Dutch Breast Cancer Research Group (BOOG). Funding: F. Hoffmann-La Roche Ltd, The Netherlands TEVA Nederland, B.V. Disclosure: F.L.G. Erdkamp: Honoraria, consulting/advisory role: Roche, Novartis. V.C.G. Tjan-Heijnen: Honoraria: E. Lilly, Pfizer; Funding for her institution: E. Lilly, Roche, Eisai, Pfizer, Novartis; Travel expenses: E. Lilly, Pfizer, Novartis, Roche; Consulting or advisory role: E. Lilly, Pfizer, Roche. All other authors have declared no conflicts of interest.
THE GREAT MISTAKE: A COMPLETELY COLONICAL CLOSURE WITH AN OTSC CLIP PLACED FOR A COLO-RECTAL ANASTOMOTIC FISTULA
Authors: B Mangiavillano, F Auriemma, M Bianchetti, A Repici
Journal: Endoscopy (2019)

Colorectal postsurgical leaks and fistulas are severe complications that increase morbidity and mortality. The recent develop of the over-the-scope clip (OTSC) has dramatically decreased the number of surgical reinterventions.
A Febrile, Hypotensive Patient With Bilateral Lung Crackles
Authors: Nicholas Oh, Peter Downey, Abbas Ardehali
Journal: JAMA (2019)

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SALVAGING EUS GUIDED GASTROJEJUNOSTOMY PERFORMED TO TREAT SMA SYNDROME BY "CONTROLLING THE TWO ENDS OF THE WIRE" TECHNIQUE
Authors: M Lajin
Journal: Endoscopy (2019)

The endoscope was removed, CRE balloon catheter was advanced over the wire inside the overtube. The CRE balloon was positioned past the narrowing opposing the gastric silhouette.
Ocular Carotenoid Status in Health and Disease
Authors: Lydia Sauer, Binxing Li, Paul S. Bernstein
Journal: Annual Review of Nutrition (2019)

Retinal carotenoids are dietary nutrients that uniquely protect the eye from light damage and various retinal pathologies. Their antioxidative properties protect the eye from many retinal diseases, such as age-related macular degeneration. As many retinal diseases are accompanied by low carotenoid levels, accurate noninvasive assessment of carotenoid status can help ophthalmologists identify the patients most likely to benefit from carotenoid supplementation. This review focuses on the different methods available to assess carotenoid status and highlights disease-related changes and potential nutritional interventions.
Association of serum IGF1 and adiponectin in prognosis of breast cancer metastasis
Authors: S. Akter, M. Faruque, K. Nahar
Journal: Annals of Oncology (2019)

Background: The WHO report revealed that breast cancer (BC) topped the list among various types of cancers in women in Bangladesh. The prognosis of metastatic breast cancer depends on certain factors, like surgery, radiotherapy, chemotherapy, hormonal receptor content of the tumor or associated illness such as diabetes mellitus and obesity. Among the associated illness, diabetes mellitus is one of the most common metabolic disease worldwide, which is linked to an increased risk of developing breast cancer and an even higher risk of recurrence and dying from this disease. In this context, we studied diabetic and metabolic disease related growth and metabolic factors in breast cancer patients for the better prognosis of BC. Methods: A total of 180 mastectomy patients were purposively taken in the present study. Data were collected from retrospective information. Anthropometric and biochemical parameters were taken by standard methods. Growth and metabolic factors were determined by enzyme-linked immunosorbent assay (ELISA) method. Results: Serum level of insulin-like growth factor 1 (IGF1) was found to be significantly higher (p = 0.001) in ER and PR negative breast cancer than their positive counterparts. Patients who had lymph node positive and Her2 borderline showed a significant reduction in serum adiponectin level (p < 0.05) and this association was retained after adjusting the confounding variables. Furthermore, delayed treatment, IGF-1, ALP, sleeping hours were significant predictors for metastasis of breast cancer patients in Bangladesh. The Diabetic-BC patients treated with both insulin and oral drug was found to be negatively associated with metastasis breast cancer while comparing with Diabetic-BC patients treated with only oral drugs (p < 0.05). However, BC metastasis did not any have an association with serum fasting insulin or insulin resistance. Obesity also did not show any relation with BC prognosis. Conclusions: Serum IGF-1 and adiponectin may have an association with invasiveness and metastasis of breast cancer. Diabetes treatment management may also be related to breast cancer prognosis; however, this study result is unable to reveal its mechanism. Legal entity responsible for the study: Salima Akter, Department of Medical Biotechnology, Bangladesh University of Health Sciences (BUHS), Dhaka, Bangladesh. Funding: The World Academy of Sciences (TWAS). Disclosure: All authors have declared no conflicts of interest.
Repermeabilisation duodénale sous echoendoscopie
Authors: H Elbacha, C Jung, B Brieau, B Bordacahar, S Leblanc, M Barret, B Dousset, F Prat
Journal: Endoscopy (2019)

l'exclusion duodénale par suture du pylore est souvent necessaire dans la prise en charge des lésions duodénales graves. La repérméabilisation duodénale s'effectue normalement de façon spontanée. En cas de persistance de l'occlusion pylorique la chirurgie est souvent nécessaire. Nous présentons ici une serie de 3 cas de repérméabilisation duodénale sous echoendoscopie.
Glucose Homeostasis following Diesel Exhaust Particulate Matter Exposure in a Lung Epithelial Cell-Specific IKK2-Deficient Mouse Model
Authors: Sufang Chen, Minjie Chen, Wei Wei, Lianglin Qiu, Li Zhang, Qi Cao, Zhekang Ying
Journal: Environmental Health Perspectives (2019)

Background: Pulmonary inflammation is believed to be central to the pathogenesis due to exposure to fine particulate matter with aerodynamic diameter ≤2.5 μm (PM2.5). This central role, however, has not yet been systemically examined. Objective: In the present study, we exploited a lung epithelial cell-specific inhibitor κB kinase 2 (IKK2) knockout mouse model to determine the role of pulmonary inflammation in the pathophysiology due to exposure to diesel exhaust particulate matter (DEP). Methods: SFTPC-rtTA+/−tetO-cre+/−IKK2flox/flox (lung epithelial cell-specific IKK2 knockout, KO) and SFTPC-rtTA+/−tetO-cre+/−IKK2flox/flox (wild-type, tgWT) mice were intratracheally instilled with either vehicle or DEP for 4 months, and their inflammatory response and glucose homeostasis were then assessed. Results: In comparison with tgWT mice, lung epithelial cell-specific IKK2-deficient mice had fewer DEP exposure-induced bronchoalveolar lavage fluid immune cells and proinflammatory cytokines as well as fewer DEP exposure-induced circulating proinflammatory cytokines. Glucose and insulin tolerance tests revealed that lung epithelial cell-specific IKK2 deficiency resulted in markedly less DEP exposure–induced insulin resistance and greater glucose tolerance. Akt phosphorylation analyses of insulin-responsive tissues showed that DEP exposure primarily targeted hepatic insulin sensitivity. Lung epithelial cell–specific IKK2-deficient mice had significantly lower hepatic insulin resistance than tgWT mice had. Furthermore, this difference in insulin resistance was accompanied by consistent differences in hepatic insulin receptor substrate 1 serine phosphorylation and inflammatory marker expression. Discussion: Our findings suggest that in a tissue-specific knockout mouse model, an IKK2-dependent pulmonary inflammatory response was essential for the development of abnormal glucose homeostasis due to exposure to DEP. https://doi.org/10.1289/EHP4591
Zona incerta GABAergic neurons integrate prey-related sensory signals and induce an appetitive drive to promote hunting
Authors: Zheng-dong Zhao, Zongming Chen, Xinkuan Xiang, Mengna Hu, Hengchang Xie, Xiaoning Jia, Fang Cai, Yuting Cui, Zijun Chen, Lechen Qian, Jiashu Liu, Congping Shang, Yiqing Yang, Xinyan Ni, Wenzhi Sun, Ji Hu, Peng Cao, Haohong Li, Wei L. Shen
Journal: Nature Neuroscience (2019)