tbuckley/cabot-search huggingface dataset:
The emerging role of SPOP protein in tumorigenesis and cancer therapy
Authors: Yizuo Song, Yichi Xu, Chunyu Pan, Linzhi Yan, Zhi-wei Wang, Xueqiong Zhu
Journal: Molecular Cancer (2020)

Abstract The nuclear speckle-type pox virus and zinc finger (POZ) protein (SPOP), a representative substrate-recognition subunit of the cullin-RING E3 ligase, has been characterized to play a dual role in tumorigenesis and cancer progression. Numerous studies have determined that SPOP suppresses tumorigenesis in a variety of human malignancies such as prostate, lung, colon, gastric, and liver cancers. However, several studies revealed that SPOP exhibited oncogenic function in kidney cancer, suggesting that SPOP could exert its biological function in a cancer type-specific manner. The role of SPOP in thyroid, cervical, ovarian, bone and neurologic cancers has yet to be determined. In this review article, we describe the structure and regulation of SPOP in human cancer. Moreover, we highlight the critical role of SPOP in tumorigenesis based on three major categories: physiological evidence (animal models), pathological evidence (human cancer specimens) and biochemical evidence (downstream ubiquitin substrates). Furthermore, we note that SPOP could be a promising therapeutic target for cancer treatment.
Magnesium oxide-crosslinked low-swelling citrate-based mussel-inspired tissue adhesives
Authors: Xili Lu, Sanjun Shi, Hanmei Li, Ethan Gerhard, Zhihui Lu, Xinyu Tan, Wenliang Li, Kevin M. Rahn, Denghui Xie, Guodong Xu, Fang Zou, Xiaochun Bai, Jinshan Guo, Jian Yang
Journal: Biomaterials (2019)
Identification of HCMV-derived T cell epitopes in seropositive individuals through viral deletion models
Authors: Maren Lübke, Stefanie Spalt, Daniel J. Kowalewski, Cosima Zimmermann, Liane Bauersfeld, Annika Nelde, Leon Bichmann, Ana Marcu, Janet Kerstin Peper, Oliver Kohlbacher, Juliane S. Walz, Vu Thuy Khanh Le-Trilling, Hartmut Hengel, Hans-Georg Rammensee, Stefan Stevanović, Anne Halenius
Journal: The Journal of Experimental Medicine (2019)

In healthy individuals, immune control of persistent human cytomegalovirus (HCMV) infection is effectively mediated by virus-specific CD4+ and CD8+ T cells. However, identifying the repertoire of T cell specificities for HCMV is hampered by the immense protein coding capacity of this betaherpesvirus. Here, we present a novel approach that employs HCMV deletion mutant viruses lacking HLA class I immunoevasins and allows direct identification of naturally presented HCMV-derived HLA ligands by mass spectrometry. We identified 368 unique HCMV-derived HLA class I ligands representing an unexpectedly broad panel of 123 HCMV antigens. Functional characterization revealed memory T cell responses in seropositive individuals for a substantial proportion (28%) of these novel peptides. Multiple HCMV-directed specificities in the memory T cell pool of single individuals indicate that physiologic anti-HCMV T cell responses are directed against a broad range of antigens. Thus, the unbiased identification of naturally presented viral epitopes enabled a comprehensive and systematic assessment of the physiological repertoire of anti-HCMV T cell specificities in seropositive individuals.
Use of Machine Learning for Predicting Escitalopram Treatment Outcome From Electroencephalography Recordings in Adult Patients With Depression
Authors: Andrey Zhdanov, Sravya Atluri, Willy Wong, Yasaman Vaghei, Zafiris J. Daskalakis, Daniel M. Blumberger, Benicio N. Frey, Peter Giacobbe, Raymond W. Lam, Roumen Milev, Daniel J. Mueller, Gustavo Turecki, Sagar V. Parikh, Susan Rotzinger, Claudio N. Soares, Colleen A. Brenner, Fidel Vila-Rodriguez, Mary Pat McAndrews, Killian Kleffner, Esther Alonso-Prieto, Stephen R. Arnott, Jane A. Foster, Stephen C. Strother, Rudolf Uher, Sidney H. Kennedy, Faranak Farzan
Journal: JAMA Network Open (2020)

<h3>Importance</h3> Social and economic costs of depression are exacerbated by prolonged periods spent identifying treatments that would be effective for a particular patient. Thus, a tool that reliably predicts an individual patient's response to treatment could significantly reduce the burden of depression. <h3>Objective</h3> To estimate how accurately an outcome of escitalopram treatment can be predicted from electroencephalographic (EEG) data on patients with depression. <h3>Design, Setting, and Participants</h3> This prognostic study used a support vector machine classifier to predict treatment outcome using data from the first Canadian Biomarker Integration Network in Depression (CAN-BIND-1) study. The CAN-BIND-1 study comprised 180 patients (aged 18-60 years) diagnosed with major depressive disorder who had completed 8 weeks of treatment. Of this group, 122 patients had EEG data recorded before the treatment; 115 also had EEG data recorded after the first 2 weeks of treatment. <h3>Interventions</h3> All participants completed 8 weeks of open-label escitalopram (10-20 mg) treatment. <h3>Main Outcomes and Measures</h3> The ability of EEG data to predict treatment outcome, measured as accuracy, specificity, and sensitivity of the classifier at baseline and after the first 2 weeks of treatment. The treatment outcome was defined in terms of change in symptom severity, measured by the Montgomery-Åsberg Depression Rating Scale, before and after 8 weeks of treatment. A patient was designated as a responder if the Montgomery-Åsberg Depression Rating Scale score decreased by at least 50% during the 8 weeks and as a nonresponder if the score decrease was less than 50%. <h3>Results</h3> Of the 122 participants who completed a baseline EEG recording (mean [SD] age, 36.3 [12.7] years; 76 [62.3%] female), the classifier was able to identify responders with an estimated accuracy of 79.2% (sensitivity, 67.3%; specificity, 91.0%) when using only the baseline EEG data. For a subset of 115 participants who had additional EEG data recorded after the first 2 weeks of treatment, use of these data increased the accuracy to 82.4% (sensitivity, 79.2%; specificity, 85.5%). <h3>Conclusions and Relevance</h3> These findings demonstrate the potential utility of EEG as a treatment planning tool for escitalopram therapy. Further development of the classification tools presented in this study holds the promise of expediting the search for optimal treatment for each patient.
Diffuse granulomatous disease: looking inside and outside the lungs
Authors: Alan Williams, W Peter Kelleher, Andrew G Nicholson, Anand Devaraj, Carlos Pavesio, Felix Chua
Journal: Thorax (2020)

A 39-year-old woman presented with a 6-month history of breathlessness, productive cough and painful lumps on her lower legs. She had suffered with recurrent rhinosinusitis and frequent infections of the ears, throat and chest since childhood, as well as cutaneous herpes zoster in her 20s. There was no documented history of pneumonia, invasive or deep-seated infections. She had smoked lightly, was allergic to penicillin and worked as a commercial tea buyer.

Examination showed a slim female with a normal breathing pattern. Chest expansion was reduced and fine inspiratory crackles were detected over the lower lung zones. Pulmonary function tests showed ventilatory restriction with decreased gas transfer. Forced expiratory volume in one second (FEV1) 2.10 L, 71% predicted; forced vital capacity (FVC) 2.22 L, 65% predicted; spirometric ratio 0.93; total lung capacity 3.04 L, 62% predicted; haemoglobin (Hb)-adjusted carbon monoxide transfer factor/TLco 45% predicted and its coefficient/Kco 81% predicted. Indices related to small airway function were normal, maximal expiratory flow (MEF)75/50/25 all above 80% predicted and air-trapping was absent.

Bloods tests showed normal full blood count, C-reactive protein as well as kidney, bone and liver biochemistry. Serum ACE was elevated at 93 ACEU (ref: 12–68). Elispot assay and HIV serology were negative.

A prereferral chest radiograph revealed widening of the superior mediastinum and ill-defined nodular opacities in the middle and lower zones. Despite the history of possible erythema nodosum and raised serum ACE, the account of recurrent infections suggested a differential diagnosis broader than typical sarcoidosis. Demonstration of ventilatory restriction and impaired gas transfer factor hinted towards an interstitial or diffuse lung pathology. The Kco, at nearly twice the TLco in %-predicted terms, indicated a low likelihood of major pulmonary vasculopathy and the absence of airflow limitation or small airway dysfunction steered the diagnosis away from primary bronchiolar disorders. CT with contiguous …
Letter to the Editor: The Association Between Diabetes and Hepatocellular Carcinoma in Patients With Cirrhosis Caused by Nonalcoholic Fatty Liver Disease
Authors: Xinxing Tantai, Na Liu, Jinhai Wang
Journal: Hepatology (2020)

Potential conflict of interest: Nothing to report. To The Editor: We read with great interest the original article written by Yang et al.,1 who found that diabetes was an independent risk factor for hepatocellular carcinoma (HCC) in patients with cirrhosis and nonalcoholic fatty liver disease (NAFLD). We commend the authors for completing such a rigorous work. However, we would like to raise several concerns. First, some important impact factors were not adjusted in multivariate analysis, such as the use of statins and aspirin.2 As indicated from Table 1,1 more than 70% of patients had hyperlipidemia. In addition, cardiovascular disease and NAFLD are associated with each other. The proportions of the patients using statins and aspirin may be high. These medication histories appear to be obtainable, judging from the diagnosis of hyperlipidemia in the article. These protective factors should be considered. Second, the vast majority of patients with NAFLD coexisted with metabolic syndrome, and these patients were clearly at high risk of diabetes.3 Some nondiabetic patients are more likely to be diagnosed with incident diabetes during several years of follow‐up. These regrouped patients are important and need to be analyzed additionally. Third, the effect sizes of diabetes for HCC were very different in the Mayo Clinic and United Network for Organ Sharing (UNOS) data sets (hazard ratio = 4.18 vs. 1.30). The authors believed that the difference should be attributed to selection bias or severity of liver disease. In fact, the definitions and diagnostic criteria of patients are quite different in the two databases. Adjusted variables are obviously insufficient in the UNOS data set. The definitions and diagnoses are more accurate and rigorous for patients from the Mayo Clinic data set. For instance, diabetes was diagnosed using only self‐reported disease history in the UNOS data set. Some patients without a diabetes diagnosis may have had diabetes but not been recognized, and these undetected patients with diabetes may be misclassified as nondiabetes. This may underestimate the risk of diabetes‐induced HCC. In the UNOS data set, nonalcoholic steatohepatitis (NASH) cirrhosis was diagnosed with cryptogenic cirrhosis and a body mass index of 30 or higher, which missed a part of lean patients with NAFLD.4 For the UNOS patients, the study used the date of registration for liver transplantation (LT) as the index date rather than the date of NASH cirrhosis diagnosis, which reduced the actual follow‐up time. Between the date of cirrhosis diagnosis and LT registration, some patients may develop HCC but not be registered on the wait list because of advanced HCC or death.
Roles of microbiota in response to cancer immunotherapy
Authors: Kentaro Inamura
Journal: Seminars in Cancer Biology (2020)

Immunotherapy, which shows great promise for treating patients with metastatic malignancies, has dramatically changed the therapeutic landscape of cancer, particularly subsequent to the discovery of immune checkpoint inhibitors. However, the responses to immunotherapy are heterogeneous and often transient. More problematic is that a high proportion of patients with cancer are resistant to such therapy. Much effort has been expended to identify reliable biomarkers that accurately predict clinical responses to immunotherapy. Unfortunately, such tools are lacking, and our knowledge of the mechanisms underlying its efficacy and safety is insufficient. The microbiota is increasingly recognized for its influence on human health and disease. Microbes create a pro- or an anti-inflammatory environment through complex interactions with host cells and cytokines. Emerging evidence indicates that microbes alter the efficacy and toxicity of immunotherapy by modulating the host's local and systemic immune responses. It is therefore critically important to exploit the microbiota to develop biomarkers as well as to identify therapeutic targets that can be applied to cancer immunotherapy. This review provides insights into the challenges that must be addressed to achieve these goals.
A New Role of Glutathion Peroxydase 4 in Human Erythroblast Enucleation
Authors: Hakim Ouled-Haddou, Kahia Messaoudi, Roggiero Lopes Dos Santos, Candice Carola, Yohann Demont, Alexis Caulier, Pascal Vong, Nicolas Jankovsky, Delphine Lebon, Jessica Platon, Julien Demagny, Nicolas Guillaume, Jean-Pierre Marolleau, Jacques Rochette, Loïc Garçon
Journal: Blood (2019)
“Eye-Black” Sign Secondary to Nivolumab Immunotherapy
Authors: Sarv Priya, Michael Graham
Journal: Clinical Nuclear Medicine (2019)

A 54-year-old woman with known chest wall melanoma (post-wide local excision) presented for imaging after a yearlong therapy with nivolumab. F-FDG PET/CT was performed 1 day after she completed the immunotherapy. Maximum intensity projection images showed bilateral relatively symmetrical uptake in the facial region. On fused PET/CT images, the uptake was seen corresponding to subcutaneous malar prominence underneath the orbits (like eye-black stripe used in sports) with subcutaneous malar calcification. Repeat PET/CT performed after 3 months revealed significant decrease in the malar uptake. Interval resolution of the uptake likely suggested this being inflammatory and secondary to immunotherapy.
Occupational Reproductive Hazards for Female Surgeons in the Operating Room
Authors: Matilda Anderson, Rose H. Goldman
Journal: JAMA Surgery (2020)

Higher rates of infertility and pregnancy complications have been found for female surgeons compared with the general population. Several reproductive hazards are present in the operating room and may be associated with these findings. Hazards should be identified and controlled to minimize risks.Studies comparing surgeons with the general population show increased rates of infertility and pregnancy complications, including conditions affecting both mother and fetus, such as spontaneous abortion, preterm delivery, growth restriction, and congenital abnormalities. Attention has focused on older age and demanding working conditions of pregnant surgeons; however, there are reproductive hazards present in the operating room that might also be contributing. Relevant hazards include radiation, surgical smoke, working conditions, sharps injury, anesthetic gases, and intraoperative use of toxic agents. Published evidence is limited to retrospective studies. Robust data are often unavailable to guide specific dose-response relationships, making it difficult to quantify risk and create occupational safety guidelines. Nevertheless, regulatory agencies have set exposure limits for some agents, relying on limited evidence. Various workplace interventions have shown success in reducing exposure levels for many reproductive hazards and should be adopted by surgical workplaces.Reproductive hazards exist in the operating room that may contribute to pregnancy complications and infertility in surgeons. Information and guidance should be given to female surgeons and trainees of reproductive age, and efforts should be made in the workplace to control exposures but not restrict female surgeons' activities unnecessarily.
Separating the myths from facts: time to take another look at Osgood-Schlatter ‘disease’
Authors: Sinead Holden, Michael Skovdal Rathleff
Journal: British Journal of Sports Medicine (2019)

Osgood Schlatter ‘disease’ (OSD) is a condition that most have heard of, and that parents of elite adolescent athletes fear. Despite being so common, what do we actually know about OSD and what can we tell adolescents and their parents based on current available evidence?

Osgood Schlatter is considered an apophysitis of the tibial tuberosity, and affects up to 1 in 10 adolescents aged 9–15- particularly athletes. The apophysis is the point of attachment of the patellar tendon onto the bone and may be vulnerable to high stress before maturation. Osgood Schlatter is characterised by localised pain and swelling at the tibial tuberosity. This injury has a negative effect on adolescent’s ability to participate in sports and is associated with decreased lower limb strength and power, poor function and low quality of life and pain.1 2 

Osgood Schlatter was originally thought to be a result of repetitive loading causing traction of the patellar tendon at its’ insertion on the tibial tuberosity. Since being first described over 100 years ago, there have …
Material category of visual objects computed from specular image structure
Authors: Alexandra C. Schmid, Pascal Barla, Katja Doerschner
Journal: Nature Human Behaviour (2023)

Abstract Recognizing materials and their properties visually is vital for successful interactions with our environment, from avoiding slippery floors to handling fragile objects. Yet there is no simple mapping of retinal image intensities to physical properties. Here, we investigated what image information drives material perception by collecting human psychophysical judgements about complex glossy objects. Variations in specular image structure—produced either by manipulating reflectance properties or visual features directly—caused categorical shifts in material appearance, suggesting that specular reflections provide diagnostic information about a wide range of material classes. Perceived material category appeared to mediate cues for surface gloss, providing evidence against a purely feedforward view of neural processing. Our results suggest that the image structure that triggers our perception of surface gloss plays a direct role in visual categorization, and that the perception and neural processing of stimulus properties should be studied in the context of recognition, not in isolation.
Silica Perturbs Primary Cilia and Causes Myofibroblast Differentiation during Silicosis by Reduction of the KIF3A-Repressor GLI3 Complex
Authors: Shifeng Li, Zhongqiu Wei, Gengxu Li, Qiaodan Zhang, Siyu Niu, Dingjie Xu, Na Mao, Si Chen, Xuemin Gao, Wenchen Cai, Ying Zhu, Guizhen Zhang, Dan Li, Xue Yi, Fang Yang, Hong Xu
Journal: Theranostics (2020)

The purpose of this study was to determine the effects of Kinesin family member 3A (KIF3A) on primary cilia and myofibroblast differentiation during silicosis by regulating Sonic hedgehog (SHH) signalling.Methods: Changes in primary cilia during silicosis and myofibroblast differentiation were detected in silicotic patients, experimental silicotic rats, and a myofibroblast differentiation model induced by SiO2.We also explored the mechanisms underlying KIF3A regulation of Glioma-associated oncogene homologs (GLIs) involved in myofibroblast differentiation.Results: Primary cilia (marked by ARL13B and Ac-α-Tub) and ciliary-related proteins (IFT 88 and KIF3A) were increased initially and then decreased as silicosis progressed.Loss and shedding of primary cilia were also found during silicosis.Treatment of MRC-5 fibroblasts with silica and then transfection of KIF3A-siRNA blocked activation of SHH signalling, but increased GLI2 FL as a transcriptional activator of SRF, and reduced the inhibitory effect of GLI3 R on ACTA2.Conclusion: Our findings indicate that primary cilia are markedly altered during silicosis and the loss of KIF3A may promote myofibroblast differentiation induced by SiO2.
Prognostic markers in stage II/III rectal cancer after neoadjuvant 5-fluorouracil-based chemoradiotherapy
Authors: C. Pinto, F. Di Fabio, C. Longobardi, C. Ceccarelli, D. Cuicchi, B. Iacopino, G. Ugolini, F. Minni, B. Cola, A. A. Martoni
Journal: Journal of Clinical Oncology (2007)

14514 Background: The aim of this study was to evaluate the prognostic value of histologic tumor regression grade (TRG) and pathological biomarkers after neoadjuvant chemoradiotherapy (CT/RT) in rectal cancer pts. Methods: Pts entering the study had rectal adenocarcinoma and stage uT3-T4 N-/+ with location &lt;12 cm from the anal margin. CT consisted of 5-fluorouracil (5FU) 225 mg/m 2 /die continuous infusion IV d1–38 with/without oxaliplatin (OXA) 60 mg/m 2 weekly infusion IV for 6 times. RT was delivered up to a dose of 50.4 Gy in daily fractions of 1.8 Gy. Rectal surgery with TME was performed 6–8 weeks after neoadjuvant therapy. Eight courses of adjuvant CT (LV5FU2) were given after surgery. Immunohistochemical determination of Ki67, p53, bcl2, TS, EGFR, MLH1, MSH2 was performed in pre-treatment biopsy and operative specimen; TRG (Dworak) response (0=none, 1=low, 2–3= intermediate, 4=complete) and circumferential resection margin (CRM) were evaluated on surgical specimens. Results: Between March 2002 and December 2006, 56 pts had completed the integrated treatment. Pt characteristics were: 39M/17F; stage uT3N- 32(57.1%), uT3N+ 15(26.8%), uT3Nx 4(7.1%), uT4N+ 4(7.1%), uT4Nx 1(1.8%). CT was 5FU in 15(26.8%) pts, 5FU/OXA in 41(73.2%) pts. Pathological downstaging was achieved in 31(55.4%) pts, including 9(16.1%) pCR. After a median follow-up of 28.5(6–58) months, 7(12.5%) pts had disease recurrence. TRG evaluation was: no TRG0, 9(16.1%) TRG1, 21(37.5%) TRG2, 17(30.4%) TRG3, 9(16.1%) TRG4. CRM was negative in 91% of pts. By means of univariate analysis, TRG was found to be significantly correlated with DFS (estimated median DFS was 23 months in TRG1 pts, not achieved in TRG2–4 pts; p&lt;0.0001). Other factors correlating significantly with a better DFS by univariate analysis included ypT0–2 (p=0.013) and pN- (p=0.002) categories, CRM- (p=0.024) and lower Ki67 expression post-CT/RT (p=0.012). Using multivariate analysis, we found that TRG2–4 was the strongest DFS prognostic factor (HR=0.0312; 95% CI: 0.003–0.40, p=0.008). Conclusions: In this analysis complete (TRG4) and intermediate (TRG2+3) pathological response produced improved DFS. Significant favorable prognostic factors were the ypT0–2/pN- categories, CRM- status and lower Ki67 expression after CT/RT. No significant financial relationships to disclose.