tbuckley/cabot-search huggingface dataset:
FRI0207 Assessment of trio as the candidate gene for familial chondrocalcinosis ccal2
Authors: A Pendleton, GD Wright, MD Doherty, R Shiang, AE Hughes
Journal: Annals of the Rheumatic Diseases (2001)

<h3>Background</h3> Chondrocalcinosis is usually caused by the deposition of calcium pyrophosphate crystals on articular cartilage. There is a clear relationship between this crystal deposition and excess extracellular triphosphate and pyrophosphate. TRIO, a novel multidomain transmembrane protein which promotes the exchange of guanine diphosphate for guanine triphosphate in the extracellular space is an excellent positional candidate gene for CCAL2. <h3>Objectives</h3> <h3>Methods</h3> A positional candidate gene strategy was employed as a valid approach to identify the putative disease locus for CCAL2. The Online Mendelian Inheritance in Man OMIM cytogenetic map was used to identify TRIO as a possible candidate gene within the critical region on chromosome 5p. Mutation analysis required the design of PCR primers to amplify the coding DNA from human genomic DNA in affected individuals. The coding DNA sequence for TRIO was known<sup>1</sup> but information on the intron-exon splicing sequences was unavailable. Sotgun sequence obtained from a P1-derived artificial chromosome (PAC) 514p4 from a PAC contig of the critical region had shown homology with TRIO using the homology search algorithms BLASTN. The intron-exon junctions were identified from this PAC and other adjacent PACs on the contig, using a combination of vectorette PCR and the Genome Priming System (New England Biolabs inc) followed by Big Dye Terminator sequencing on an 377 ABI genetic analyser. <h3>Results</h3> From the TRIO coding DNA sequence of 9 kilobases over 55 exons were identified. Both of the functional guanine exchange factor (GEF) domains (18 exons) have been fully sequenced but no mutations have yet been identified in affected members from two large families. <h3>Conclusion</h3> TRIO is a novel multidomain transmembrane protein which is localised within the CCAL2 region on chromosome 5p. It is likely to influence the availability of extracellular triphophate and thus pyrophosphate through the function of the active GEF domains. This gene however has no mutations within the coding regions for both the GEF domains in two large kindreds with familial chondrocalcinosis. <h3>Reference</h3> Debant A, Serra-Pages C, Seipel K, O'Brien S, Tang M, Park S-H, <i>et al</i>. The multidomain protein Trio binds the LAR transmembrane tyrosine phosphatase, contains a protein kinase domain, and has a separate rac-specific and rho-specific guanine nucleotide exchange factor domains. Proc Natl Acad Sci USA 1996;93:5466–71
"Who me? I thought you would never ask!” Applying qualitative methods in sports injury prevention research (PhD Academy Award)
Authors: Caroline Bolling
Journal: British Journal of Sports Medicine (2020)

In my thesis I aimed to explore how injury prevention happens in sports practice, and to describe the perspectives of various stakeholders with regard to injury and its prevention. I studied 3 high-performance contexts, namely elite sports, professional dance and circus arts.

There is ample evidence that shows it is possible to prevent sports injuries.1 Unfortunately, prevention approaches are not translated into lasting real-world effects that truly benefit athletes. As a physiotherapist who has worked for over 10 years with elite athletes, professional dancers and Cirque du Soleil artists, I was always challenged to apply the best available evidence for my patients. However, that evidence was typically not developed considering a practical context.2 I recognised many times that the evidence-based interventions did …
The prognostic significance of bone metastases and skeletal-related events (SREs) in prostate cancer survival: A population-based historical cohort study in Denmark (1999–2007)
Authors: J. P. Fryzek, K. Cetin, M. Nørgaard, A. Ø. Jensen, J. Jacobsen, H. T. Sørensen
Journal: Journal of Clinical Oncology (2009)

5160 Background: Common among advanced prostate cancer patients, bone metastases indicate cancer progression and poor prognosis but few studies have quantified their influence on patient survival, particularly in the presence of subsequent skeletal-related complications. We therefore sought to examine this in a large population-based cohort of prostate cancer patients. Methods: Using data from the Danish National Patient Registry (covering all Danish hospitals), we studied 23,087 patients diagnosed with prostate cancer between 1999 and 2007, with follow-up through April 2008 (median follow-up: 2.2 years). We estimated the incidence of bone metastases following cancer diagnosis and the subsequent occurrence of SREs (radiation and surgery to the bone, fracture, spinal cord compression). We then computed and compared survival for three prostate cancer subgroups - no bone metastases, bone metastases, and bone metastases with SREs - using Kaplan-Meier and multivariate Cox proportional hazards models. Results: Across the study period, 14% (n = 3,261) of the prostate cancer patients developed bone metastases: 6.8% (n = 1,570) had bone metastases and no SRE and 7.3% (n = 1,691) had both bone metastases and at least one SRE (radiation to the bone was most frequent). One-year survival was lowest for prostate cancer patients with bone metastases and SREs (40%) compared to the groups with no bone metastases (87%) and with bone metastases but no SREs (47%). Similarly, after adjusting for age and the presence of comorbidities, short-term prognosis was poorest in patients with both bone metastases and SREs: compared to prostate cancer patients with no bone metastases, the 1-year mortality rate was 6.7 times greater for those with bone metastases and SREs (95% confidence interval (CI): 6.0–7.6) versus just 4.7 times higher in those with only bone metastases (95% CI: 4.3–5.2). Less than 1% of prostate cancer patients who developed bone metastases and suffered any SRE survived beyond five years. Conclusions: Although the presence of bone metastases confers a short-term prognosis in prostate cancer patients, survival is even poorer for patients who also experience skeletal-related complications. [Table: see text]
A phase II study of bevacizumab (B) and erlotinib (E) in combination for Asian patients (pts) with advanced/metastatic hepatocellular carcinoma (HCC): An interim safety report
Authors: C. Hsu, Y. Kang, T. Yang, W. Su, J. Sandoval-Tan, T. Chiou, K. Jin, P. Button, C. Hsu, A. Cheng
Journal: Journal of Clinical Oncology (2009)

4585 Background: Asian pts with advanced HCC have a poor prognosis, and a median survival of 2–4 months with best supportive care (ph III). As HCCs are highly vascular tumors, dual inhibition of VEGF and EGFR with B plus E is an attractive combination strategy. B has demonstrated promising phase II results in 34 HCC patients, with 75% non-progression at 16 weeks (wks) (65% in Caucasians) (Thomas et al., 2007). However, 6–11% of pts had variceal bleeding, some cases of which were fatal. This study was initiated to investigate the safety and efficacy of B+E in Asian HCC pts. Methods: Screening esophagogastroduodenoscopy (EGD) was used to exclude pts with high risk of variceal bleeding. Asian pts with advanced/metastatic, measurable HCC who were unsuitable for surgery or other loco-regional therapies received B 5mg/kg q2w i.v. and E 150mg/day orally. The primary endpoint was PFS at 16 wks. Responses were evaluated using RECIST. Tumor tissue samples were collected for biomarker analysis. Results: Baseline characteristics of the 51 pts enrolled between March and October 2008 were median age: 58 years (range 26–84); male/female: 44/7; ECOG PS 0/1/2: 30/20/1; Child-Pugh A/B: 50/1; BCLC stage C n=44 (88%); hepatitis B/C/B+C/nonB+nonC: 42/4/3/2; grade I/II varices n=16 (none with red sign). Pts received a median 8 wks of study treatment. No variceal bleeding was observed; 3 pts had upper GI bleeding (grade 1/2; 2 peptic ulcer, 1 gastritis). See table for most common toxicities. 7/10 deaths were due to disease progression, none were due to study treatment. At the time of analysis, 2 pts had a confirmed partial response (PR; duration 24+ and 8+ wks). 1 pt with an unconfirmed PR continued on treatment. Data for the primary analysis were immature. Conclusions: Bevacizumab plus erlotinib was well tolerated. Screening EGD was feasible and reduced the risk of variceal bleeding. Follow-up is ongoing. [Table: see text] [Table: see text]
Autonomic innervation of the carotid body as a determinant of its sensitivity: implications for cardiovascular physiology and pathology
Authors: Fernanda Brognara, Igor S A Felippe, Helio C Salgado, Julian F R Paton
Journal: Cardiovascular Research (2020)

The motivation for this review comes from the emerging complexity of the autonomic innervation of the carotid body (CB) and its putative role in regulating chemoreceptor sensitivity. With the carotid bodies as a potential therapeutic target for numerous cardiorespiratory and metabolic diseases, an understanding of the neural control of its circulation is most relevant. Since nerve fibres track blood vessels and receive autonomic innervation, we initiate our review by describing the origins of arterial feed to the CB and its unique vascular architecture and blood flow. Arterial feed(s) vary amongst species and, unequivocally, the arterial blood supply is relatively high to this organ. The vasculature appears to form separate circuits inside the CB with one having arterial venous anastomoses. Both sympathetic and parasympathetic nerves are present with postganglionic neurons located within the CB or close to it in the form of paraganglia. Their role in arterial vascular resistance control is described as is how CB blood flow relates to carotid sinus afferent activity. We discuss non-vascular targets of autonomic nerves, their possible role in controlling glomus cell activity, and how certain transmitters may relate to function. We propose that the autonomic nerves sub-serving the CB provide a rapid mechanism to tune the gain of peripheral chemoreflex sensitivity based on alterations in blood flow and oxygen delivery, and might provide future therapeutic targets. However, there remain a number of unknowns regarding these mechanisms that require further research that is discussed.
Surface Engineering of Cardiovascular Devices for Improved Hemocompatibility and Rapid Endothelialization
Authors: Jing Zhao, Yakai Feng
Journal: Advanced Healthcare Materials (2020)

Abstract Cardiovascular devices have been widely applied in the clinical treatment of cardiovascular diseases. However, poor hemocompatibility and slow endothelialization on their surface still exist. Numerous surface engineering strategies have mainly sought to modify the device surface through physical, chemical, and biological approaches to improve surface hemocompatibility and endothelialization. The alteration of physical characteristics and pattern topographies brings some hopeful outcomes and plays a notable role in this respect. The chemical and biological approaches can provide potential signs of success in the endothelialization of vascular device surfaces. They usually involve therapeutic drugs, specific peptides, adhesive proteins, antibodies, growth factors and nitric oxide (NO) donors. The gene engineering can enhance the proliferation, growth, and migration of vascular cells, thus boosting the endothelialization. In this review, the surface engineering strategies are highlighted and summarized to improve hemocompatibility and rapid endothelialization on the cardiovascular devices. The potential outlook is also briefly discussed to help guide endothelialization strategies and inspire further innovations. It is hoped that this review can assist with the surface engineering of cardiovascular devices and promote future advancements in this emerging research field.
Outcomes of Patients with Newly Diagnosed Aggressive B Cell Lymphoma Presenting with Hepatic and/ or Renal Dysfunction
Authors: Nilanjan Ghosh, Jigar Trivedi, Srinivasa Reddy Sanikommu, Myra M Robinson, Ryan Jacobs, Steven I Park, Danyu Sun, James T Symanowski, Taylor Brown, Belinda Rene Avalos, Edward A Copelan
Journal: Blood (2017)
Immunization With Recombinant Human Granulocyte-Macrophage Colony-Stimulating Factor as a Vaccine Adjuvant Elicits Both a Cellular and Humoral Response to Recombinant Human Granulocyte-Macrophage Colony-Stimulating Factor
Authors: Douglas G. McNeel, Kathy Schiffman, Mary L. Disis
Journal: Blood (1999)
ECM‐derived Scaffolds: Scaffolds Functionalized with Matrix from Induced Pluripotent Stem Cell Fibroblasts for Diabetic Wound Healing (Adv. Healthcare Mater. 16/2020)
Authors: Francesco Santarella, Rukmani Sridharan, Milica Marinkovic, Ronaldo Jose Farias Correa Do Amaral, Brenton Cavanagh, Avi Smith, Olga Kashpur, Behzad Gerami‐Naini, Jonathan A. Garlick, Fergal J. O'Brien, Cathal J. Kearney
Journal: Advanced Healthcare Materials (2020)

Extracellular matrix (ECM)-derived scaffolds show promise in a variety of tissue engineering applications. In article number 2000307, Cathal J. Kearney and co-workers exploit ECM grown by cells differentiated from induced pluripotent stem cells for scaffold fabrication and examine their potential for diabetic wound healing. This ECM has previously been shown to be enriched in foetal-like components, which can augment healing.
A novel technique for adjusting traction direction during colorectal endoscopic submucosal dissection using S-O clip
Authors: Yutaka Okagawa, Seiichiro Abe, Hiroyuki Takamaru, Masau Sekiguchi, Masayoshi Yamada, Taku Sakamoto, Yutaka Saito
Journal: Endoscopy (2020)

A 67-year-old man had an elevated lesion with central shallow depression, approximately 20 mm in size across a colonic fold in the splenic flexure ([Fig. 1]). Magnified chromoendoscopy revealed a noninvasive pit pattern (type VI mild in Kudo’s classification). The patient opted for endoscopic submucosal dissection (ESD) ([Video 1]).
So-called bifocal tumors with diabetes insipidus and negative tumor markers: are they all germinoma?
Authors: Masayuki Kanamori, Hirokazu Takami, Shigeru Yamaguchi, Takashi Sasayama, Koji Yoshimoto, Teiji Tominaga, Akihiro Inoue, Naokado Ikeda, Atsushi Kambe, Toshihiro Kumabe, Masahide Matsuda, Shota Tanaka, Manabu Natsumeda, Ken-Ichiro Matsuda, Masahiro Nonaka, Jun Kurihara, Masayoshi Yamaoka, Naoki Kagawa, Naoki Shinojima, Tetsuya Negoto, Yukiko Nakahara, Yoshiki Arakawa, Seiji Hatazaki, Hiroaki Shimizu, Atsuo Yoshino, Hiroshi Abe, Jiro Akimoto, Yu Kawanishi, Tomonari Suzuki, Atsushi Natsume, Motoo Nagane, Yukinori Akiyama, Dai Keino, Tadateru Fukami, Takahiro Tomita, Kohei Kanaya, Tsutomu Tokuyama, Shuichi Izumoto, Mitsutoshi Nakada, Daisuke Kuga, Shohei Yamamoto, Ryogo Anei, Takeo Uzuka, Junya Fukai, Noriyuki Kijima, Keita Terashima, Koichi Ichimura, Ryo Nishikawa
Journal: Neuro-Oncology (2020)

The Delphi consensus statements on the management of germ cell tumors (GCTs) failed to reach agreements on the statement that the cases with (i) pineal and neurohypophyseal bifocal lesion, (ii) with diabetes insipidus, and (iii) with negative tumor markers can be diagnosed as germinoma without histological verification. To answer this, multicenter retrospective analysis was performed.
3D Myocardial Mechanical Wave Measurements
Authors: Sebastien Salles, Torvald Espeland, Alfonso Molares, Svein Arne Aase, Tommy Arild Hammer, Asbjørn Støylen, Svend Aakhus, Lasse Lovstakken, Hans Torp
Journal: JACC. Cardiovascular imaging (2020)

This study aimed to investigate the potential of a novel 3-dimensional (3D) mechanical wave velocity mapping technique, based on the natural mechanical waves produced by the heart itself, to approach a noninvasive 3D stiffness mapping of the left ventricle. Myocardial fibrosis is recognized as a pathophysiological substrate of major cardiovascular disorders such as cardiomyopathies and valvular heart disease. As fibrosis leads to increased myocardial stiffness, ultrasound elastography measurements could provide important clinical information. A 3D high frame rate imaging sequence was implemented on a high-end clinical ultrasound scanner to achieve 820 volumes/s when gating over 4 consecutive cardiac cycles. Five healthy volunteers and 10 patients with various degrees of aortic stenosis were included to evaluate feasibility and reproducibility. Mechanical waves were detected using the novel Clutter Filter Wave Imaging approach, shown to be highly sensitive to the weak tissue displacements caused by natural mechanical waves. 3D spatiotemporal maps of mechanical wave velocities were produced for all subjects. Only the specific mechanical wave at atrial contraction provided a full 3D coverage of the left ventricle (LV). The average atrial kick propagation velocity was 1.6 ± 0.2 m/s in healthy volunteers and 2.8 ± 0.8 m/s in patients (p = 0.0016). A high correlation was found between mechanical wave velocity and age (R2 = 0.88, healthy group), septal wall thickness (R2 = 0.73, entire group), and peak jet velocity across the aortic valve (R2 = 0.70). For 3 of the patients, the higher mechanical wave velocity coexisted with the presence of late gadolinium enhancement on cardiac magnetic resonance. In this study, 3D LV mechanical wave velocities were visualized and measured in healthy volunteers and patients with aortic stenosis. The proposed imaging sequence and measurement technique allowed, for the first time, the measurement of full spatiotemporal 3D elasticity maps of the LV using ultrasound. (Ultrasonic markers for myocardial fibrosis and prognosis in aortic stenosis; NCT03422770)
Tumor microenvironment-responsive and oxygen self-sufficient oil droplet nanoparticles for enhanced photothermal/photodynamic combination therapy against hypoxic tumors
Authors: Reesha Kv, Te-I Liu, I.-Lin Lu, Chia-Chen Liu, Hsin-Hung Chen, Ting-Yu Lu, Wen-Hsuan Chiang, Hsin-Cheng Chiu
Journal: Journal of Controlled Release (2020)
The prevention of periodontal disease—An overview
Authors: Frank A. Scannapieco, Eva Gershovich
Journal: Periodontology 2000 (2020)

Abstract It is widely accepted that common diseases of the oral cavity, such as gingivitis and periodontitis, are preventable. Based on a large body of scientific evidence, a number of preventive strategies are known to prevent these diseases, but only if routinely implemented. Unfortunately, while most preventive strategies are theoretically simple to understand, they are often difficult to employ in practice at individual and public health levels. This volume of Periodontology 2000 provides the most current information on the state of the science and the evidence base supporting a preventive perspective for the management of periodontal disease, including evidence for proven interventions as well as cutting‐edge ideas for potential future interventions. In addition to well‐established and scientifically proven approaches (tooth and implant cleansing, topical chemotherapeutics, reduction in risk factors such as tobacco smoking), a number of new ideas are now under investigation, including antioxidant agents, probiotics, vaccines, and slow‐release alternative chemotherapeutics. Furthermore, there are new ideas to alter patient behaviors with the aim to improve adherence to preventive strategies. Finally, examples from implementation science and public health are provided that suggest novel approaches to bring new ideas into clinical practice.
Ductal carcinoma in situ of the breast and gene expression markers for prediction of invasive recurrence
Authors: H. A. McKean, C. Reynolds, T. L. Hoskin, V. J. Suman, C. S. Grant, M. G. Erlander, X. Ma, J. Ingle, M. P. Goetz
Journal: Journal of Clinical Oncology (2009)

550 Background: Ductal carcinoma in situ (DCIS) is a heterogeneous group of non-invasive cancers with varying propensity for recurrence. There are no validated markers that identify patients at risk for invasive recurrence following lumpectomy. HOXB13/IL17BR (H/I) is expressed in both DCIS and invasive cancer (Ma Cancer Cell. 2004) and associated with recurrence in stage I cancer. A 5-gene molecular grade index (MGI) distinguishes outcome in grade II disease (Ma Clin Cancer Res. 2008). We sought to determine whether H/I or MGI was associated with invasive recurrence in resected DCIS. Methods: We identified patients at Mayo Rochester who underwent lumpectomy ± radiation for DCIS between 1988 and 2001 and performed a nested case/control study. Cases were patients with ipsilateral invasive recurrence, matched to controls based on age, surgery date, length of follow-up, and adjuvant radiation. DCIS was macrodissected from paraffin sections and RNA extracted to obtain H/I and MGI RT-PCR profiles. The association of H/I and MGI with case-control status was assessed with conditional logistic regression; results reported are odds ratios (OR) with 95% confidence intervals (CI). The association of H/I and MGI as continuous variables with nuclear grade (low, intermediate, high) was estimated with Spearman's rank correlation. Results: 427 patients underwent lumpectomy for DCIS, and 33 were identified as possible cases. Histologic review excluded 8 (non-sufficient tissue or DCIS recurrence without invasion). 25 cases were matched to 48 controls (2 controls for 23 cases, 1 control for 2 cases). Both H/I (r = 0.43, p = 0.0001) and MGI (r = 0.41, p = 0.0004) were significantly correlated with nuclear grade. Positive H/I was associated with trend towards higher recurrence (OR 1.9; p = 0.22) that was most pronounced in cases/controls (15/28) treated with lumpectomy alone (OR 3.3; CI: 0.8–13.2, p = 0.09). Similarly, positive MGI was associated with a trend towards higher recurrence risk in patients treated with surgery alone (OR 2.0; CI: 0.6–6.4, p = 0.27). Conclusions: These data suggest that both HOXB13/IL17BR and MGI can identify a subset of patients with surgically resected DCIS who are at risk for invasive recurrence. Further studies in larger cohorts are needed to confirm these findings. [Table: see text]
Piezo1-Mediated Ca2+ Activities Regulate Brain Vascular Pathfinding during Development
Authors: Ting-ting Liu, Xu-fei Du, Bai-bing Zhang, Hua-xing Zi, Yong Yan, Jiang-an Yin, Han Hou, Shan-ye Gu, Qi Chen, Jiu-lin Du
Journal: Neuron (2020)