tbuckley/cabot-search huggingface dataset:
Boosting Photothermal Theranostics via TICT and Molecular Motions for Photohyperthermia Therapy of Muscle‐Invasive Bladder Cancer
Authors: Sheng Zeng, Heqi Gao, Chuang Li, Shaoqiang Xing, Zhaoliang Xu, Qian Liu, Guangxue Feng, Dan Ding
Journal: Advanced Healthcare Materials (2021)

Abstract The development of photothermal agents with high photothermal conversion efficiency (PCE) can help to reduce drug and laser dosage, but still remains a big challenge. Herein, a novel approach is reported to design photothermal agents with high PCE values by promoting nonradiative heat generation processes through the cooperation of twisted intramolecular charge transfer (TICT) and molecular motions. Within the designed molecule 2DMTT‐BBTD, the tetraphenylethenes act as molecular rotors, the long alkyl chain grafted thiophene helps to twist the molecular geometry to facilitate TICT state formation and preserve molecular motions in aggregate, while the strong electron‐withdrawing BBTD unit enhances TICT effect. 2DMTT‐BBTD exhibits NIR‐absorption and a high PCE value of 74.8% under 808 nm laser irradiation. Gambogic acid (GA) which surmounts tumor cell thermotolerance by inhibiting heat shock protein 90 (HSP90) expression is coloaded into the nanoparticles, RGD peptide is further introduced to the nanoparticle surface to improve tumor accumulation. The resultant nanoparticles facilitate the effective low‐temperature hyperthermia therapy of muscle‐invasive bladder cancer (MIBC) with minimal damage to surrounding heathy tissues. This work delivers a new design concept for development of highly efficient photothermal agents, which also provides a safer approach for noninvasive treatment of MIBC and other malignant tumors.
Saphenous Vein Graft Failure: From Pathophysiology to Prevention and Treatment Strategies
Authors: Iosif Xenogiannis, Marco Zenati, Deepak L. Bhatt, Sunil V. Rao, Josep Rodés-Cabau, Steven Goldman, Kendrick A. Shunk, Kreton Mavromatis, Subhash Banerjee, Khaldoon Alaswad, Ilias Nikolakopoulos, Evangelia Vemmou, Judit Karacsonyi, Dimitrios Alexopoulos, M. Nicholas Burke, Vinayak N. Bapat, Emmanouil S. Brilakis
Journal: Circulation (2021)

Saphenous vein grafts (SVGs) remain the most frequently used conduits in coronary artery bypass graft surgery (CABG). Despite advances in surgical techniques and pharmacotherapy, SVG failure rates remain high, often leading to repeat coronary revascularization. The no-touch SVG harvesting technique (minimal graft manipulation with preservation of vasa vasorum and nerves) reduces the risk of SVG failure, whereas the effect of the off-pump technique on SVG patency remains unclear. Use of buffered storage solutions, intraoperative graft flow measurement, careful selection of the target vessels, and physiological assessment of the native coronary circulation before CABG may also reduce the incidence of SVG failure. Perioperative aspirin and high-intensity statin administration are the cornerstones of secondary prevention after CABG. Dual antiplatelet therapy is recommended for off-pump CABG and in patients with a recent acute coronary syndrome. Intermediate (30%–60%) SVG stenoses often progress rapidly. Stenting of intermediate SVG stenoses failed to improve outcomes; hence, treatment focuses on strict control of coronary artery disease risk factors. Redo CABG is associated with higher perioperative mortality compared with percutaneous coronary intervention (PCI); hence, the latter is preferred for most patients requiring repeat revascularization after CABG. SVG PCI is limited by high rates of no-reflow and a high incidence of restenosis during follow-up. Drug-eluting and bare metal stents provide similar long-term outcomes in SVG PCI. Embolic protection devices reduce no-reflow and should be used when feasible. PCI of the corresponding native coronary artery is associated with better short- and long-term outcomes and is preferred over SVG PCI, if technically feasible.
Targeted oral peptide delivery using multi-unit particulates: Drug and permeation enhancer layering approach
Authors: Puneet Tyagi, Ruchit Trivedi, Sergei Pechenov, Chandresh Patel, Jefferson Revell, Sarah Wills, Yue Huang, Anton I. Rosenbaum, J. Anand Subramony
Journal: Journal of Controlled Release (2021)
The essential role of dermatology publications in enhancing professional diversity, equity and inclusion
Authors: S. Burgin, N.C. Dlova, J.R. Ingram, L.C. Parish, L.A. Goldsmith
Journal: British Journal of Dermatology (2021)

Dermatology publications have substantial untapped potential to improve patient care for all patients and communities.The leadership role of both the editors and editorial boards of these journals, books and digital media provides an important opportunity to support professional diversity, equity and inclusion (DEI) plus democratization of knowledge. 1Multiple events in many countries in recent times have demonstrated the need to work harder at DEI to ensure a level playing field for all patients, clinicians and researchers.There follows a statement endorsed by a group of dermatology editors who wish to highlight DEI issues, set goals towards improvement, and suggest some specific actions that can be taken to support the necessary changes, with the understanding that different publications may pursue these goals using various approaches.
간학의 EM 영상 : 만성간질환의 미세구조 - 간섬유조직증식과 간유동의 성상세포 -
Authors: 정규원(Kyu Won Chung)
Journal: Clinical and Molecular Hepatology (2002)

성상세포는 근섬유아세포로의 형질전환을 통하여 여러원인의 간섬유조직증식에 중요한 역할을 한다. 간세포괴사 후 육아조직에서 활성화된 성상 세포는 크기가 커지고 별모양을 보이고 면역염색 조직(ASMA)에서 쉽게 판별이 되며, 전자현미경 소견에서 잘 발달된 조면내형질세망, 큰 Golgi복합체, 세포막하에 많은 수의 미세사상체다발과 치밀 소체 및 불규칙하게 퍼진 세포질돌기가 관찰된다. 이들 세포는 Kupffer세포, 대식세포, 임프구와 중 성구들과 밀접하게 어울려 있다. 시간이 지나면 성상세포는 세포외 기질을 활발하게 생성하고 분비 하여 젊은 섬유조직이 형성된다. 섬유조직증식이 진행되면 변형된 근섬유아세포는 방추상으로 바뀌고 치밀한 콜라겐섬유조직에 평행으로 배열되며, 조면내형질세망과 Golgi복합체가 소실되면서 원형질막하에 미세사상체의 뚜렷한 증가가 관찰된다. ASMA양성인 변형된 성상세포는 세포외 기질 생성과 오래된 섬유조직의 수축에 참여하는 것으로 생각된다. 반면에 문맥역 섬유 아세포는 섬유조직 증식과정에서 특별한 변화를 보이지 않는다. 간손상이 오면 성상세포는 활성화의 과정을 거친다. 활성화의 양상을 보면 성상 세포의 증식, 세포이동(화학주성), 간질성 기질의 생산증가, 수축성의 항진, 백혈구 화학주성물질과 싸이토카인의 분비, 기질성분의 분해증가 및 세포내 retinoid의 소실이 크다. 활성화된 성상세포는 섬유증식성 간에서 발견되는 거의 모든 세포외 기질을 대량 생산하며 여기에는 간질성 및 기저막성 콜라겐, proteoglycans과 당 단백등이 포함된다. 성상세포의 수축성은 결과적으로 혈관주위의 수축과 더불어 전체간의 수축을 유도하여 문맥압항진증을 초래하게된다. Endothelin-1이 현재까지 확인된 것 중 가장 강력한 성상세포수축제이고 nitric oxide(NO)는 그 반대의 작용을 하며 둘 다 성상세포에서 생산된다. 성상세포 활성화의 기전에 유전자 발현의 signaling 및 전사조절 등 분자생물학적 연구가 진행되고 있다. 이런 연구를 통하여 활성화의 주요 중개자를 밝힘으로서 섬유조직증식을 감소시켜 문맥압 항진증을 역전시킬 수 있는 새로운 치료방법이 개발될 수 있을 것으로 생각한다.
Noninvasive Continuous Blood Pressure Estimation From Pulse Transit Time: A Review of the Calibration Models
Authors: Daniel Barvik, Martin Cerny, Marek Penhaker, Norbert Noury
Journal: IEEE Reviews in Biomedical Engineering (2021)

Noninvasive continuous blood pressure estimation is a promising alternative to minimally invasive blood pressure measurement using cuff and invasive catheter measurement, because it opens the way to both long-term and continuous blood pressure monitoring in ecological situation. The most current estimation algorithm is based on pulse transit time measurement where at least two measured signals need to be acquired. From the pulse transit time values, it is possible to estimate the continuous blood pressure for each cardiac cycle. This measurement highly depends on arterial properties which are not easily accessible with common measurement techniques; but these properties are needed as input for the estimation algorithm. With every change of input arterial properties, the error in the blood pressure estimation rises, thus a periodic calibration procedure is needed for error minimization. Recent research is focused on simplified constant arterial properties which are not constant over time and uses only linear model based on initial measurement. The elaboration of continuous calibration procedures, independent of recalibration measurement, is the key to improving the accuracy and robustness of noninvasive continuous blood pressure estimation. However, most models in literature are based on linear approximation and we discuss here the need for more complete calibration models.
The Prognostic Implication of Inflammatory Factor-Based Scoring System in Diffuse Large B-Cell Lymphoma Patients in the Rituximab Era
Authors: Ji Hyun Lee, Sung Yong Oh, Jae-Cheol Jo, Yunsuk Choi, Ho-Jin Shin, Won-Sik Lee, Kwon Kyung A, Yoojin Lee, Ho Sup Lee
Journal: Blood (2017)
Distinct systemic and mucosal immune responses during acute SARS-CoV-2 infection
Authors: Nikaïa Smith, Pedro Goncalves, Bruno Charbit, Ludivine Grzelak, Maxime Beretta, Cyril Planchais, Timothée Bruel, Vincent Rouilly, Vincent Bondet, Jérôme Hadjadj, Nader Yatim, Helene Pere, Sarah H. Merkling, Amine Ghozlane, Solen Kernéis, Frederic Rieux-Laucat, Benjamin Terrier, Olivier Schwartz, Hugo Mouquet, Darragh Duffy, James P. Di Santo
Journal: Nature Immunology (2021)

Abstract Coordinated local mucosal and systemic immune responses following severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection either protect against coronavirus disease 2019 (COVID-19) pathologies or fail, leading to severe clinical outcomes. To understand this process, we performed an integrated analysis of SARS-CoV-2 spike-specific antibodies, cytokines, viral load and bacterial communities in paired nasopharyngeal swabs and plasma samples from a cohort of clinically distinct patients with COVID-19 during acute infection. Plasma viral load was associated with systemic inflammatory cytokines that were elevated in severe COVID-19, and also with spike-specific neutralizing antibodies. By contrast, nasopharyngeal viral load correlated with SARS-CoV-2 humoral responses but inversely with interferon responses, the latter associating with protective microbial communities. Potential pathogenic microorganisms, often implicated in secondary respiratory infections, were associated with mucosal inflammation and elevated in severe COVID-19. Our results demonstrate distinct tissue compartmentalization of SARS-CoV-2 immune responses and highlight a role for the nasopharyngeal microbiome in regulating local and systemic immunity that determines COVID-19 clinical outcomes.
Multiple Variants of SARS-CoV-2 in a University Outbreak After Spring Break — Chicago, Illinois, March–May 2021
Authors: Kate Doyle, Richard A. Teran, Jennita Reefhuis, Janna L. Kerins, Xueting Qiu, Stefan J. Green, Hyeree Choi, Sabrina A. Madni, Nazia Kamal, Emily Landon, Reynald Christopher Albert, Massimo Pacilli, Laura E. Furtado, Mary K. Hayden, Kevin J. Kunstman, Cindy Bethel, Lauren Megger, Marielle J. Fricchione, Isaac Ghinai
Journal: MMWR Morbidity and Mortality Weekly Report (2021)

To prevent transmission of SARS-CoV-2, the virus that causes COVID-19, colleges and universities have implemented multiple strategies including testing, isolation, quarantine, contact tracing, masking, and vaccination.In April 2021, the Chicago Department of Public Health (CDPH) was notified of a large cluster of students with COVID-19 at an urban university after spring break.A total of 158 cases of COVID-19 were diagnosed among undergraduate students during March 15-May 3, 2021; the majority (114; 72.2%) lived in on-campus dormitories.CDPH evaluated the role of travel and social connections, as well as the potential impact of SARS-CoV-2 variants, on transmission.Among 140 infected students who were interviewed, 89 (63.6%) reported recent travel outside Chicago during spring break, and 57 (40.7%) reported indoor social exposures.At the time of the outbreak, undergraduate-aged persons were largely ineligible for vaccination in Chicago; only three of the students with COVID-19 (1.9%) were fully vaccinated.Whole genome sequencing (WGS) of 104 specimens revealed multiple distinct SARS-CoV-2 lineages, suggesting several nearly simultaneous introductions.Most specimens (66; 63.5%) were B.1.1.222,a lineage not widely detected in Chicago before or after this outbreak.These results demonstrate the potential for COVID-19 outbreaks on university campuses after widespread student travel during breaks, at the beginning of new school terms, and when students participate in indoor social gatherings.To prevent SARS-CoV-2 transmission, colleges and universities should encourage COVID-19 vaccination; discourage unvaccinated students from travel, including during university breaks; implement serial COVID-19 screening among unvaccinated persons after university breaks; encourage masking; and implement universal serial testing for students based on community transmission levels.
Co-delivery of autophagy inhibitor and gemcitabine using a pH-activatable core-shell nanobomb inhibits pancreatic cancer progression and metastasis
Authors: Xiaoxiao Chen, Yuan Tao, Manmin He, Miao Deng, Rong Guo, Qinglin Sheng, Xuhui Wang, Kebai Ren, Ting Li, Xuan He, Shuya Zang, Zhirong Zhang, Man Li, Qin He
Journal: Theranostics (2021)

Metastasis is one of the main reasons for the high mortality associated with pancreatic ductal adenocarcinoma (PDAC), and autophagy regulates the metastatic migration of tumor cells, their invasion of tissues, and their formation of focal adhesions. Inhibiting autophagy may suppress tumor growth and metastasis, but the abundant extracellular matrix hinders the deep penetration of therapeutic agents.
Refining neoadjuvant therapy clinical trial design for muscle-invasive bladder cancer before cystectomy: a joint US Food and Drug Administration and Bladder Cancer Advocacy Network workshop
Authors: Elaine Chang, Andrea B. Apolo, Rick Bangs, Stephanie Chisolm, Vinay Duddalwar, Jason A. Efstathiou, Kirsten B. Goldberg, Donna E. Hansel, Ashish M. Kamat, Paul G. Kluetz, Seth P. Lerner, Elizabeth Plimack, Tatiana Prowell, Harpreet Singh, Daniel Suzman, Evan Y. Yu, Hui Zhang, Julia A. Beaver, Richard Pazdur, Chana Weinstock, Matthew D. Galsky
Journal: Nature Reviews Urology (2021)
Single-cell RNA-seq unravels alterations of the human spermatogonial stem cell compartment in patients with impaired spermatogenesis
Authors: Sara Di Persio, Tobias Tekath, Lara Marie Siebert-Kuss, Jann-Frederik Cremers, Joachim Wistuba, Xiaolin Li, Gerd Meyer zu Hörste, Hannes C.A. Drexler, Margot Julia Wyrwoll, Frank Tüttelmann, Martin Dugas, Sabine Kliesch, Stefan Schlatt, Sandra Laurentino, Nina Neuhaus
Journal: Cell Reports Medicine (2021)

Despite the high incidence of male infertility, only 30% of infertile men receive a causative diagnosis. To explore the regulatory mechanisms governing human germ cell function in normal and impaired spermatogenesis (crypto), we performed single-cell RNA sequencing (>30,000 cells). We find major alterations in the crypto spermatogonial compartment with increased numbers of the most undifferentiated spermatogonia (PIWIL4+). We also observe a transcriptional switch within the spermatogonial compartment driven by increased and prolonged expression of the transcription factor EGR4. Intriguingly, the EGR4-regulated chromatin-associated transcriptional repressor UTF1 is downregulated at transcriptional and protein levels. This is associated with changes in spermatogonial chromatin structure and fewer Adark spermatogonia, characterized by tightly compacted chromatin and serving as reserve stem cells. These findings suggest that crypto patients are disadvantaged, as fewer cells safeguard their germline's genetic integrity. These identified spermatogonial regulators will be highly interesting targets to uncover genetic causes of male infertility.
Abstract 16921: Noninvasive Quantification of Myocardial Elasticity in Patients With Hypertrophic Cardiomyopathy
Authors: Orawan Anupraiwan, Sorin V Pislaru, Patricia A Pellikka, Cristina Pislaru
Journal: Circulation (2018)

Introduction: Hypertrophic cardiomyopathy (HCM) is associated with excessive left ventricular (LV) hypertrophy (LVH), myocyte disarray and expansion of interstitial collagen. These factors alter mechanical properties of the myocardial tissue. Intrinsic velocity propagation (iVP) of myocardial stretch is a new validated measure of myocardial elasticity. Hypothesis: iVP in left ventricular (LV) myocardium of patients with HCM will be increased compared to normal subjects. Methods: We studied prospectively 100 subjects: 42 with HCM (age 57 ± 14 years; 79% with asymmetric septal LVH) and 58 normal controls without cardiovascular disease (age 48 ± 13 years). Patients had comprehensive transthoracic echocardiography and cardiac magnetic resonance imaging (MRI; n=29). iVP was measured throughout the LV myocardium during late diastole using ultra-high frame rate tissue Doppler imaging (350-460 fps) (6 LV walls, 3 standard apical views). Chamber stiffness (CS) was evaluated from end-diastolic pressure-volume relationship (EDPVR) estimated noninvasively by the single-beat method (EDP=αV β ). End-diastolic pressure (EDP) was estimated from E/e’. Results: LV ejection fraction was normal in both groups (HCM: 68 ± 7%; Controls: 65 ± 5%). Myocardial stiffness by iVP was markedly higher in HCM vs. controls (Fig.A, left panel). This was confirmed by EDPVRs, which were steeper and shifted leftward (Fig. B, left). The slope (β, load-independent) of EDPVR and CS (dP/dV) were higher and LV capacitance (V 30 , estimated volume at 30 mmHg EDP) was lower in HCM (Fig. B, right) and correlated significantly, though weakly, with iVP (β: r = 0.41; CS dP/dV: r = 0.48; EDP: r = 0.61; p&lt;0.002 for all). Patients with apical variant had lower levels of global iVP compared to patients with predominant septal LVH and diffuse concentric LVH (Fig. A, right). Conclusions: Myocardial stiffness measured noninvasively by the intrinsic wave method is highly abnormal in HCM. This novel approach allows mapping of myocardial elasticity of the entire left ventricle and shows promise to become a clinical tool for evaluation of patients with diastolic tissue abnormalities.
Serum Biomarkers are Associated With Atherosclerotic Cardiovascular Disease Among Patients With Nonalcoholic Fatty Liver Disease Undergoing Elective Angiography
Authors: Zobair M. Younossi, Sean Felix, Thomas Jeffers, Elena Younossi, Brian Lam, Fatema Nader, Henry A. Tran, Ingrid Schneider, Maria Stepanova
Journal: Clinical Gastroenterology and Hepatology (2021)
Dual targeting of JAK2 and ERK interferes with the myeloproliferative neoplasm clone and enhances therapeutic efficacy
Authors: Sime Brkic, Simona Stivala, Alice Santopolo, Jakub Szybinski, Sarah Jungius, Jakob R. Passweg, Dimitrios Tsakiris, Stefan Dirnhofer, Gregor Hutter, Katharina Leonards, Heidi E. L. Lischer, Matthias S. Dettmer, Benjamin G. Neel, Ross L. Levine, Sara C. Meyer
Journal: Leukemia (2021)

Abstract Myeloproliferative neoplasms (MPN) show dysregulated JAK2 signaling. JAK2 inhibitors provide clinical benefits, but compensatory activation of MAPK pathway signaling impedes efficacy. We hypothesized that dual targeting of JAK2 and ERK1/2 could enhance clone control and therapeutic efficacy. We employed genetic and pharmacologic targeting of ERK1/2 in Jak2 V617F MPN mice, cells and patient clinical isolates. Competitive transplantations of Jak2 V617F vs. wild-type bone marrow (BM) showed that ERK1/2 deficiency in hematopoiesis mitigated MPN features and reduced the Jak2 V617F clone in blood and hematopoietic progenitor compartments. ERK1/2 ablation combined with JAK2 inhibition suppressed MAPK transcriptional programs, normalized cytoses and promoted clone control suggesting dual JAK2/ERK1/2 targeting as enhanced corrective approach. Combined pharmacologic JAK2/ERK1/2 inhibition with ruxolitinib and ERK inhibitors reduced proliferation of Jak2 V617F cells and corrected erythrocytosis and splenomegaly of Jak2 V617F MPN mice. Longer-term treatment was able to induce clone reductions. BM fibrosis was significantly decreased in MPL W515L-driven MPN to an extent not seen with JAK2 inhibitor monotherapy. Colony formation from JAK2 V617F patients’ CD34 + blood and BM was dose-dependently inhibited by combined JAK2/ERK1/2 inhibition in PV, ET, and MF subsets. Overall, we observed that dual targeting of JAK2 and ERK1/2 was able to enhance therapeutic efficacy suggesting a novel treatment approach for MPN.
Frequency of homologous recombination-related (HRR) genes mutations in gastric cancer.
Authors: Wei Wang, Wang Huaiming, Yuhong Chen, Huanhuan Liu, Yanrui Zhang, Xiayuan Liang, Yun Zhang, Feng Lou, Shanbo Cao, Huina Wang
Journal: Journal of Clinical Oncology (2021)

4031 Background: Homologous recombination deficiency (HRD) might contribute to predict response of immunotherapy and Chemotherapy response and PARP inhibitor (PARPi) therapy. The HRD phenotype has been defined as the presence of a non-silent somatic mutation in homologous recombination-related (HRR) genes. We aimed to analyze the mutational pattern of HRR genes and the relationship between HRR-related genes and clinical outcomes in gastric cancer. Methods: We prospectively sequenced 386 Chinese patients with gastric cancer using next-generation sequencing techniques with 808 cancer-related genes. 440 patients with WES data from the TCGA project were included. The 15 HRR genes were selected on clinical evidence of sensitivity to PARP inhibitors and immunotherapy. Correlations between HRR genes and clinical outcomes were identified via bioinformatic analysis using TCGA datasets. Results: In the Chinese cohort, 10.4% (40/386) patients exhibited genomic alterations in HRR genes. The frequently mutated genes were BRCA2 (2.3%), ATM (1.8%), CDK12 (1.8%), BRCA1 (1.0%), CHEK2(1.0%), PALB2(0.8%), BARD1 (0.5%), RAD51B (0.5%), and RAD54L (0.3%). 8.3% patients had at least one somatic HRR genes mutation. Pathogenic germline variants were identified in 2.1% (8/386) patients. No participants carried both germline and somatic HRR gene mutations. In TCGA cohort, 19.1% (841/440) patients had at least one somatic mutation in an HRR gene. The frequently mutated genes were BRCA2 (6.4%), ATM (6.4%), CDK12 (3.2%), BRCA1 (3.2%), BARD1 (2.3%), PALB2 (2.3%), HEK2 (1.6%), CHEK1 (1.4%), BROP1 (1.1%), RAD54L (1.1%), FANCL (0.9%), RAD51D (0.9%), RAD51C (0.7%), PPP2R2A (0.5%), and RAD51B (0.5%). Chinese cohort had lower frequently somatic mutation of HRR genes compared to that in TCGA cohort (8.3% vs 19.1%, p &lt; 0.001). Interestingly, in the TCGA cohort, patients with HRR-mut had significantly elevated tumor mutational burden, microsatellite instability status and enhanced immune activity than patients with HRR-wt. In the MSK-IMPACT cohort comprising 49 patients treated with ICIs, patients with HRR-mut had significantly better overall survival compared to those in patients with HRR-wt (p = 0.027). Conclusions: Our data suggest that patients with altered HRR genes may be rational candidates for precision oncology treatment and provide new opportunities to predict the tumor response to multiple treatments, such as immunotherapeutic combine PARP inhibitor (PARPi) therapy. Exploring other biomarkers of HRD to predict the response to PARPi and immunotherapeutic in GC is necessary.