tbuckley/cabot-search huggingface dataset:
The tomato pan-genome uncovers new genes and a rare allele regulating fruit flavor
Authors: Lei Gao, Itay Gonda, Honghe Sun, Qiyue Ma, Kan Bao, Denise M. Tieman, Elizabeth A. Burzynski-Chang, Tara L. Fish, Kaitlin A. Stromberg, Gavin L. Sacks, Theodore W. Thannhauser, Majid R. Foolad, Maria Jose Diez, Jose Blanca, Joaquin Canizares, Yimin Xu, Esther van der Knaap, Sanwen Huang, Harry J. Klee, James J. Giovannoni, Zhangjun Fei
Journal: Nature Genetics (2019)
The metastatic potential of grade I breast carcinoma of no special type: A deep insight into putative molecular mechanisms
Authors: F. Lessi, C. Scopelliti, P. Aretini, M. Menicagli, S. Franceschi, C.M. Mazzanti, A.G. Naccarato, C. Scatena
Journal: Annals of Oncology (2019)

Background: Metastasis continues to be a crucial problem for the clinical management and treatment of breast cancer (BC). Among breast carcinoma of no special type (BC-NST), grade 1 tumors do have the best prognosis in terms of recurrence and overall survival. However, rarely they metastasize to the axilla, suggesting a more aggressive behaviour. Our study aimed to uncover the mechanism responsible for the dissemination of tumor cells of grade 1 BC-NST into axillary lymph nodes in order to better understand lymph node metastasis phenomenon in BC. Methods: Whole-exome sequencing technique was used to analyze a total of 7 BC with lymph node metastases and 8 without, all Luminal A BCs. Analysis compared the molecular profiles of the selected cases by Enlis Genome Research software, Cravat application and QueryOr software. Results: Analyzing the data, we can explain the presence of metastasis for 3 different samples because of the presence of mutation in AKT1 and PI3K. However, surprisingly, the group of patients with positive lymph node shared the same polymorphism (rs406113) in GPX6 gene. The rs406113 polymorphism is a missense variation, which in combination with other mutations, had previously been associated with the risk of breast cancer. To further investigate the role of the GP6X polymorphism on the onset of metastases, we collected 32 blood samples from breast cancer female patient. We performed a Kaplan-Meier analysis on metastatic free survival, without highlighting an increased risk due to the presence of the mutation (HR 1.01; 95% CI 0.41-2.45; P = 0.976). By using Cox Regression Analysis, after adjusting the model, to confound for Triple Negative status, MIB-1 levels, neoadjuvant and adjuvant therapy, the presence of GPX6 polymorphism confers an increased risk of metastasis onset (HR 2.1; 95% CI 0.76-5.8; P = 0.15). We have genotyped further 80 triple negative breast cancer blood samples and are in the process of collecting all clinical-pathological information to strengthen the statistical analysis. Conclusions: Further analysis will be performed to confirm data obtained, to make in vitro study to investigate it possible role in metastatic process of breast cancer. Legal entity responsible for the study: Fabio Beltram. Funding: Has not received any funding. Disclosure: All authors have declared no conflicts of interest.
Oral autoimmune vesicobullous diseases: Classification, clinical presentations, molecular mechanisms, diagnostic algorithms, and management
Authors: Stefania Leuci, Elvira Ruoppo, Daniela Adamo, Elena Calabria, Michele Davide Mignogna
Journal: Periodontology 2000 (2019)

Abstract Mucocutaneous blistering autoimmune diseases are a group of systemic, rare, chronic disorders characterized by humoral‐mediated immunologic mechanisms against epithelial, basement membrane, and subepithelial tissues. Morbidity and mortality can be completely different among these diseases, with outcome being dependent on an early and accurate diagnosis, systemic comorbidities, and the patient's response to treatment. Definitive diagnosis is based on clinical and histopathologic findings. Because clinical presentations among these diseases are often similar, different immunofluorescence tests and ELISAs are used to confirm the specific diagnosis. Oral mucosa may often be the first site of clinical manifestation from which the disease spreads to other mucosal surfaces and skin. Thus, often dentists and oral medicine specialists may be the first to encounter patients with such diseases. In this review we discuss the most frequent autoimmune vesicobullous disorders, namely pemphigus vulgaris, mucous membrane pemphigoid, bullous pemphigoid, and linear IgA disease.
GEL IMMERSION ENDOSCOPY: INNOVATION IN SECURING THE VISUAL FIELD. CLINICAL EXPERIENCE OF 265 CONSECUTIVE CASES
Authors: T Yano, T Takezawa, K Hashimoto, A Ohmori, H Sakamoto, K Sunada, A Kawarai Lefor, H Yamamoto
Journal: Endoscopy (2019)

During endoscopy, especially in patients with gastrointestinal bleeding, it is often difficult to secure the visual field using water, because the injected water is rapidly mixed with fresh blood or stool. Clear gel with an appropriate viscosity to prevent rapid mixing is injected through the accessory channel, instead of water. In the space occupied by the clear gel, it is easy to secure the visual field. We reported this method as “gel immersion endoscopy”. The safety and efficacy of this method were evaluated.
Perioperative factors and complications after delayed reconstruction in breast cancer patients in relation to outcome
Authors: H.E. Dillekås, C.M. Kristoffersen, S.A. Jensen, O. Straume
Journal: Annals of Oncology (2019)

Background: Complications to surgery have been implicated in recurrence in many cancer forms. Methods for breast reconstruction after mastectomy vary substantially in magnitude of surgical trauma. We have previously reported an impact of delayed reconstructive surgery on the relapse dynamics in breast cancer patients. In the current study, our aim was to determine the rate of complications after delayed breast reconstruction, and explore a potential link to oncologic outcome between these events as well as perioperative factors such as use of LMWH. Methods: The study population consists of all patients who had delayed breast reconstruction at Haukeland University Hospital after mastectomy for breast cancer between 1977 and 2007, n = 312. Complications, relapses and deaths were registered from patients' records. Survival was evaluated by the Kaplan-Meier method. Results: 41% received implant surgery alone, the remaining had autologous reconstructions (28%), or combinations of implant and contralateral reduction (31%). In total 28% experienced complications > = grade 2 (Common Terminology Criteria for Adverse Events, CTCAE version 4.0). In the group receiving autologous flap reconstructions 56% had complications grade > =2. Patients with complications grade > =2 demonstrated a bimodal relapse patterns with a near doubling of the first peak at 18 months, compared to patients with none or minor (grade 1) complications. Overweight or obesity at the time of reconstruction was associated with an increase in relapses the first 18 months after reconstruction, but not with increased complications. Surprisingly, perioperative anticoagulation with LMWH was associated with reduced relapse-free survival. Conclusions: In our material, complications were significantly more prevalent in patients undergoing extensive reconstructive procedures. This did not result in significantly reduced breast cancer specific or overall survival. The relapse dynamics, however, were affected. This suggests an accelerating effect on the escape of micrometastases from tumor dormancy as a result from an additional inflammatory response induced by the complication. Legal entity responsible for the study: University of Bergen. Funding: Has not received any funding. Disclosure: S.A. Jensen: Consult cosmetic surgery: Sørlandet Privatsykehus AS. All other authors have declared no conflicts of interest.
Endoscopic ultrasound-guided transmural approach versus ERCP-guided transpapillary approach for primary decompression of malignant biliary obstruction: a meta-analysis
Authors: Kirles Bishay, Devon Boyne, Mohammad Yaghoobi, Mouen A. Khashab, Risa Shorr, Yervant Ichkhanian, Nauzer Forbes
Journal: Endoscopy (2019)

Abstract Background Primary decompression in patients with malignant biliary obstruction can be achieved via endoscopic retrograde cholangiopancreatography (ERCP) with transpapillary stenting, or, more recently, via transmural endoscopic ultrasound-guided biliary drainage (EUS-BD). It is unclear whether either approach is superior in terms of clinical success or adverse events in the primary setting. Methods A comprehensive systematic electronic search was performed for studies comparing EUS-BD and ERCP as the primary approach with respect to clinical success and any other outcome(s). Pooled relative risks (RRs) and weighted mean differences were obtained as appropriate using DerSimonian and Laird random effects models. Sensitivity analyses were also performed. Results 5 out of 776 studies with a total of 396 patients were included. Overall clinical success was not significantly different between EUS-BD and ERCP (RR 0.98, 95 % confidence interval [CI] 0.93 to 1.03). There was no significant difference in overall adverse events (RR 0.84, 95 %CI 0.35 to 2.01), though results suggested that EUS-BD may be associated with a reduced risk of pancreatitis (RR 0.22, 95 %CI 0.05 to 1.02). There were no significant differences between EUS-BD and ERCP in terms of procedure time or the risk of stent occlusion. Conclusions EUS-BD had similar clinical success rates and occlusion rates to ERCP in the primary decompression of malignant biliary obstruction from meta-analysis including a modest number of patients. EUS-BD may be a practical alternative to the ERCP-guided approach in such patients, but further well-designed prospective studies with larger numbers of patients are required to more clearly delineate potential differences in adverse events and cost.
Efficacité de la Dissection sous-muqueuse pour les tumeurs superficielles du rectum atteignant la ligne pectinée
Authors: D Roland, G Rahmi, G Perrod, S Leblanc, J Jacques, J Albouys, S Chaussade, C Cellier
Journal: Endoscopy (2019)

La résection endoscopique est un traitement mini-invasif, conservateur d'organe, recommandé pour les tumeurs superficielles colorectales. En France, la dissection sous-muqueuse (DSM) est réservée aux polypes colorectaux de plus de 40 mm ou en cas de suspicion d'envahissement superficiel de la sous-muqueuse. L'atteinte de la ligne pectinée est une indication de DSM mais cette zone est techniquement difficile à réséquer. L'objectif de l'étude était d'évaluer pour la première fois en France, l'efficacité de la DSM pour les tumeurs superficielles du rectum atteignant la ligne pectinée.
Diagnosis and Management of the Antiphospholipid Syndrome
Authors: Karl J Lackner, Nadine Müller‑Calleja
Journal: New England Journal of Medicine (2018)

the timing of intussusception relative to vaccination, a comparison of intussusception rates is not required.Also, the underidentification of intussusception cases would not bias our results unless we selectively missed cases of intussusception immediately after vaccination; we do not believe that this occurred.
ENDOSCOPIC TREATMENT OF PERSISTENT GASTROCUTANEOUS FISTULA COMBINED WITH TRICHLORACETIC ACID. DESCRIPTION OF A NEW TERAPEUTIC METHOD
Authors: F Souza de Macedo, J Andrade Franco Neto, S Diniz Carvalho, PF Souto Bittencourt, V Nunes Arantes, A Rodrigues Ferreira
Journal: Endoscopy (2019)

Persistent gastrocutaneous fistula is a complication after the removal of the gastrostomy tube. It is reported in 1/3 of patients. Persistent gastrocutaneous fistula is defined by the non-closure of gastrostomy opening after one month. This situation results on abdominal skin burning by the gastric secretion and decreasing quality of life for those patients. This study describes a new method of endoscopic closure of persistent gastrocutaneous fistula using combined endoscopic techniques with trichloracetic acid.
Oral corticosteroid use, morbidity and mortality in asthma: A nationwide prospective cohort study in Sweden
Authors: Magnus Ekström, Bright I. Nwaru, Pål Hasvold, Fredrik Wiklund, Gunilla Telg, Christer Janson
Journal: Allergy (2019)

Patterns and determinants of long-term oral corticosteroid (OCS) use in asthma and related morbidity and mortality are not well-described. In a nationwide asthma cohort in Sweden, we evaluated the patterns and determinants of OCS use and risks of OCS-related morbidities and mortality.Data for 217 993 asthma patients (aged ≥ 6 years) in secondary care were identified between 2007 and 2014 using Swedish national health registries. OCS use at baseline was categorized: regular users (≥5 mg/d/y; n = 3299; 1.5%); periodic users (>0 but <5 mg/d/y; n = 49 930; 22.9%); and nonusers (0 mg/d/y; n = 164 765; 75.6%). Relative risks of becoming a regular OCS user and for morbidity and mortality were analysed using multivariable Cox regression.At baseline, 24% of asthma patients had used OCS during the last year and 1.5% were regular users. Of those not using OCS at baseline, 26% collected at least one OCS prescription and 1.3% became regular OCS users for at least 1 year during the median follow-up of 5.3 years. Age at asthma diagnosis, increasing GINA severity and Charlson Comorbidity Index were associated with regular OCS use. Compared to periodic and non-OCS use, regular use was associated with increased incidence of OCS-related morbidities and greater all-cause mortality, adjusted HR 1.34 (95% CI 1.24-1.45).Oral corticosteroids use is frequent for asthma patients, and many are regular users. Regular OCS use is associated with increased risk of morbidity and mortality. These findings indicate that there is a need of other treatment options for patients with severe asthma who are using regular OCS.
England’s “messy” detention system is unable to locate 200 children
Authors: Zosia Kmietowicz
Journal: BMJ (2019)

The Children’s Commissioner for England has described as “messy” the system that detains children for their safety. Often it has no information about who the children are, where they are living, and why they are there.

Anne Longfield said it was shocking that her team had found “over 200 children who would have remained completely invisible in the national data had we not asked about them.”

A review by the commission1 found that 1465 children were securely detained for their own safety in England in 2018: 873 in youth justice settings, 505 in mental health wards, and 87 in secure children’s homes.

An additional 211 children are authorised …
SINGLE-OPERATOR PANCREATOSCOPY (SOP) WITH SPYGLASS SYSTEM IN PATIENTS WITH CHRONIC PANCREATITIS
Authors: R Mansilla-Vivar, L Argüello-Viudez, C Sanchez-Montes, N Alonso-Lazaro, M Ponce-Romero, M Bustamante-Balén, V Pons-Beltrán
Journal: Endoscopy (2019)

Interventional procedures for pain treatment in chronic pancreatitis include extracorporeal shock wave lithotripsy, endoscopic stone extraction and bridging of pancreatic strictures. Standard treatment is effective in 90% of cases. Direct pancreatoscopy using smaller-caliber endoscopic equipments have been developed to explore and treat in biliary and pancreatic duct with promissory results.
Phase III study of [fam-] trastuzumab deruxtecan vs investigator’s choice in T-DM1-pretreated HER2+ breast cancer
Authors: F. André, J. Shahidi, C. Lee, K. Wang, I. Krop
Journal: Annals of Oncology (2019)

Background: There is no uniform standard of care for HER2+ breast cancer (BC) after disease progression on T-DM1. [Fam-] trastuzumab deruxtecan (DS-8201a) is a novel HER2-targeted antibody-drug conjugate with a humanized HER2 antibody, topoisomerase I inhibitor payload, and cleavable peptide-based linker. In an ongoing phase 1 trial, [fam-] trastuzumab deruxtecan showed promising antitumor activity in T-DM1-pretreated HER2+ BC (confirmed objective response rate [ORR] of 54.5%; April 2018 data cutoff). The pivotal, phase 2 DESTINY-Breast01 trial in this population is ongoing. Trial design: This multicenter, open-label, phase 3 trial will assess efficacy and safety of [fam-] trastuzumab deruxtecan in subjects with HER2 + (IHC 3+ or IHC 2+/ISH+; confirmed by centralized testing) unresectable and/or metastatic BC whose disease progressed on or after T-DM1 (NCT03523585, DESTINY-Breast02). Approximately 600 subjects will be randomized (2:1) to [fam-] trastuzumab deruxtecan (5.4 mg/kg IV q3wk) or investigator's choice (trastuzumab/capecitabine or lapatinib/capecitabine). Randomization is stratified by hormone receptor status, prior pertuzumab treatment, and history of visceral disease. The primary efficacy endpoint is progression free survival (PFS) based on blinded, independent central review using RECIST v1.1; overall survival (OS) is the key secondary endpoint. Other secondary efficacy endpoints are ORR, duration of response, clinical benefit rate, and PFS based on investigator assessment. Primary analysis for PFS will occur when approximately 372 PFS events are observed; providing 90% power to detect a hazard ratio of 0.70 in PFS (a 43% improvement in median PFS from 3.3 months with investigator's choice to 4.7 months with [fam-] trastuzumab deruxtecan) with a 1-sided alpha of 0.025. An interim OS analysis is planned at the time of PFS analysis. Final OS analysis will occur when approximately 428 OS events have been observed. Long-term follow-up will continue after the primary analysis every 3 months until death, withdrawal of consent, loss to follow-up, or study closure. Efficacy analyses will include all randomized subjects, and safety analyses will include all subjects receiving ≥1 dose of study treatment. Editorial acknowledgement: Marie-Louise Ricketts, PhD; and Stefan Kolata, PhD, of AlphaBioCom, LLC. Clinical trial identification: NCT03523585; release date May 14, 2018. Legal entity responsible for the study: Daiichi Sankyo, Inc., Basking Ridge, NJ, USA. Funding: Daiichi Sankyo, Inc, Basking Ridge, NJ, USA. Disclosure: F. André: Fees: Pfizer, Lilly, AstraZeneca. J. Shahidi, C. Lee, K. Wang: Salaried employee: Daiichi Sankyo, Inc. I. Krop: Consulting fees: Daiichi Sankyo, Inc.
COMBINATION ENDOSCOPIC THERAPY USING ENDOSPONGE AND OVER-THE-SCOPE-CLIP FOR THE THERAPY OF COMPLEX GASTROINTESTINAL LEAKS AND DEHISCENCES
Authors: A Martinez-Alcala, JP Gutierrez, MA D'Assuncao, PT Kroener, K Mönkemüller
Journal: Endoscopy (2019)

To evaluate the success, safety and complications rates of an endoscopic approach using sponge and over-the-scope clips to close large endoluminal GI defects.
NAB-Paclitaxel Improves Disease-Free Survival in Early Breast Cancer: GBG 69–GeparSepto
Authors: Michael Untch, Christian Jackisch, Andreas Schneeweiss, Sabine Schmatloch, Bahriye Aktas, Carsten Denkert, Christian Schem, Hermann Wiebringhaus, Sherko Kümmel, Mathias Warm, Peter A. Fasching, Marianne Just, Claus Hanusch, John Hackmann, Jens-Uwe Blohmer, Kerstin Rhiem, Wolfgang D. Schmitt, Jenny Furlanetto, Bernd Gerber, Jens Huober, Valentina Nekljudova, Gunter von Minckwitz, Sibylle Loibl
Journal: Journal of Clinical Oncology (2019)

The GeparSepto trial demonstrated that weekly nanoparticle albumin-bound (NAB)-paclitaxel significantly improves the pathologic complete remission rate compared with weekly solvent-based (sb) paclitaxel followed by epirubicin plus cyclophosphamide as neoadjuvant treatment in patients with primary breast cancer (BC). Here, we report data on long-term outcomes.Patients with histologically confirmed primary BC were randomly assigned in a 1:1 ratio to 12 times weekly NAB-paclitaxel 150 mg/m2 (after study amendment, 125 mg/m2) or weekly sb-paclitaxel 80 mg/m2 followed in both arms by four times epirubicin 90 mg/m2 plus cyclophosphamide 600 mg/m2 every 3 weeks. Patients with human epidermal growth factor receptor 2 (HER2)-positive BC received dual antibody treatment with trastuzumab (8 mg/kg loading dose followed by 6 mg/kg every 3 weeks) and pertuzumab (840 mg loading dose followed by 420 mg every 3 weeks) concurrently to chemotherapy and continued for 1 year.A total of 1,206 patients started treatment, 606 with NAB-paclitaxel and 600 with sb-paclitaxel. After a median follow-up of 49.6 months (range, 0.5 to 64.0 months), 243 invasive disease-free survival (iDFS) events were reported (143 in the sb-paclitaxel and 100 in the NAB-paclitaxel arm). At 4 years, overall patients treated with NAB-paclitaxel had a significantly better iDFS compared with sb-paclitaxel (84.0% v 76.3%; hazard ratio, 0.66; 95% CI, 0.51 to 0.86; P = .002), whereas overall survival did not significantly differ between the two treatment arms (89.7% v 87.2%, respectively; hazard ratio, 0.82; 95% CI, 0.59 to 1.16; P = .260). Long-term follow-up of the treatment-related peripheral sensory neuropathy (PSN) showed a significant decrease of the median time to resolve PSN after NAB-paclitaxel 125 mg/m2 compared with NAB-paclitaxel 150 mg/m2.The significantly higher pathologic complete response rate with NAB-paclitaxel translated into a significantly improved iDFS in patients with early BC as compared with sb-paclitaxel. PSN improved much faster under NAB-paclitaxel 125 mg/m2 compared with NAB-paclitaxel 150 mg/m2.
Cyclooxygenase 2-dependent autocrine action of amphiregulin in oral cancer cells
Authors: Li-Wha Wu, Kai-Ying Yang, Sen-Tien Tsai
Journal: Cancer Research (2005)

961  Cancer of the oral cavity is newly diagnosed in approximately 50,000 Americans and 500,000 others worldwide including Taiwan each year. The death toll from oral cancer is now ranking the third among Taiwanese cancer males. Although the risk factors for this type of cancer are well known, little is known about the molecular mechanisms responsible for this malignancy. Epidermal growth factor receptor (EGFR) is expressed or highly expressed in a range of solid tumors and overexpression of this receptor has been associated with poor prognosis of these patients including oral cancer. Amphiregulin (AR) is one of six mammalian ligands that bind to epidermal growth factor receptors. AR not only can stimulate the growth of epithelial cells and fibroblasts but is also involved in upregulation of matrix metalloproteases, invasion of tumor cells, as well as hyperproliferation and inflammation observed in psoriasis. However, the role of AR in oral carcinogenesis remains elusive. We first used semi-quantitative RT-PCR to analyze the mRNA expression level of AR in 39 oral cancer specimens with their normal counterparts. Consistent with the hypothesis of AR being oncogenic, we found the expression of AR mRNA increase with the progression of clinical stages although they did not achieve statistical significance. Individual and pooled stable clones expressing different levels of AR were established. Overexpression of AR increased the ability of oral cancer cells to proliferate, migrate and invade through Matrigel. Although AR was reported to up-regulate the expression of metalloprotease 9 (MMP-9), there was no correlation of increased MMP-9 expression with the presence of AR in AR-expressing stable clones. Instead, the expression of MMP-2 was increased in the AR-expressing clones. Moreover, all the stable clones expressing AR displayed an increased expression of cyclooxygenase 2 (Cox-2), a master regulator of proliferation, invasion and transformation. Although more works are warranted to address the underlying mechanism whereby AR overexpression increase the oncogenic properties of oral cancer cells, this study implicates that AR may behave as a tumor promoting factor via increased expression of Cox-2 for oral cancer cells.