tbuckley/cabot-search huggingface dataset:
Elastin-Like Polypeptides for Biomedical Applications
Authors: Anastasia K. Varanko, Jonathan C. Su, Ashutosh Chilkoti
Journal: Annual Review of Biomedical Engineering (2020)

Elastin-like polypeptides (ELPs) are stimulus-responsive biopolymers derived from human elastin. Their unique properties-including lower critical solution temperature phase behavior and minimal immunogenicity-make them attractive materials for a variety of biomedical applications. ELPs also benefit from recombinant synthesis and genetically encoded design; these enable control over the molecular weight and precise incorporation of peptides and pharmacological agents into the sequence. Because their size and sequence are defined, ELPs benefit from exquisite control over their structure and function, qualities that cannot be matched by synthetic polymers. As such, ELPs have been engineered to assemble into unique architectures and display bioactive agents for a variety of applications. This review discusses the design and representative biomedical applications of ELPs, focusing primarily on their use in tissue engineering and drug delivery.
Electric Conductivity on Aligned Nanofibers Facilitates the Transdifferentiation of Mesenchymal Stem Cells into Schwann Cells and Regeneration of Injured Peripheral Nerve
Authors: Xiaofang Hu, Xianghai Wang, Yizhou Xu, Lixia Li, Jingmin Liu, Yutong He, Ying Zou, Lei Yu, Xiaozhong Qiu, Jiasong Guo
Journal: Advanced Healthcare Materials (2020)

Schwann cells (SCs) are the most promising seed cells for peripheral nerve tissue engineering, but clinical applications are limited by the lack of cell sources. Existing data demonstrate that bone marrow mesenchymal stem cells (BMSCs) can be induced to differentiate into Schwann-like cells and aligned nanofibers can enhance the differentiation. Considering that SCs are living along with the electrical conductive axons, it is hypothesized that conductivity properties may play roles in SCs differentiation and then facilitate nerve regeneration. To verify this hypothesis, amine functionalized multi-walled carbon nanotubes (MWCNTs) are incorporated with polycaprolactone and gelatin to fabricate aligned or random conductive nanofibers by electrospinning. Current data demonstrate that MWCNTs can dramatically increase the electrical conductive properties but do not alter the biocompatibility of the nanofibers. It is found that endowing conductive properties into the aligned nanofibers can significantly enhance their capability to promote the SCs differentiation. Furthermore, the aligned and conductive nanofibers with induced BMSCs can dramatically promote peripheral axonal regeneration. Collectively, the present study demonstrates that the conductive properties in the aligned nanofiber plays significant roles in SCs differentiation and the aligned and conductive nanofibers can be used as a promising scaffold for SCs differentiation and peripheral nerve tissue engineering.
Central Nervous System as Possible Site of Relapse in <i>ERBB2</i>-Positive Metastatic Colorectal Cancer
Authors: Andrea Sartore-Bianchi, Sara Lonardi, Massimo Aglietta, Cosimo Martino, Fortunato Ciardiello, Silvia Marsoni, Salvatore Siena
Journal: JAMA Oncology (2020)

should be hypothesis generating. 3,4In some cases, however, such as the STAMPEDE trial testing prostate radiotherapy in patients with advanced prostate cancer, 5 methodological strengths and weaknesses of the subgroup analysis were correctly discussed by the study presenter.Positive analyses of secondary end points in trials with a negative primary analysis carry the same risk of falsepositive results inherent in multiple testing.Furthermore, the primary end point is the measure used for the study hypothesis and should condition study interpretation.When a trial is designed to test the superiority of an experimental treatment, post hoc interpretation of noninferiority is methodologically debatable.The noninferiority hypothesis should be prospectively planned, with a clear definition of the margin acceptable to define noninferiority.In conclusion, we believe that more attention should be paid to the statements included in the conclusions of oral presentations at meetings, and the discussants' role is crucial.When the primary end point is not met, the word negative should be explicitly used.
Stable suppression of membrane type 1 matrix metalloproteinase impairs MMP-2 activation, cell invasion, and tumorigenesis.
Authors: Jaclyn A. Freudenberg, Donghai Chen, Wen-Tien Chen
Journal: Cancer Research (2004)

2295  Cell invasiveness toward extracellular matrix components plays an essential role in tumor angiogenesis and metastasis. Membrane type 1 matrix metalloproteinase (MT1-MMP) has been proposed to be a key cell surface protease involved in extracellular matrix degradation and the activation of other proteolytic enzymes that are necessary for the cell invasive phenotype. Specifically, MT1-MMP has been shown to degrade such extracellular matrix components as collagen I, II, and III; laminin-1 and -5; fibronectin; vitronectin; fibrin. Likewise, MT1-MMP can activate proteolytic enzymes such as proMMP-2 and proMMP-13. We have used RNA interference to suppress gene expression that enables us to further analyze the function of MT1-MMP. An invasive fibrosarcoma cell line, HT1080, which has a high endogenous level of MT1-MMP and proMMP-2, was used to generate stable cells with suppressed cell surface proteolytic activity by utilizing shRNAs to stably suppress MT1-MMP. Parental cells were transfected with a vector containing a U6 promoter, a short MT1-MMP specific DNA encoding shRNA to target MT1-MMP mRNA, GFP expression cassette, and a G418 selection cassette. Clones were selected based on drug resistance and green color detection. Suppression of MT1-MMP mRNA and protein were confirmed using quantitative Real-Time PCR and Western immunoblotting, respectively. In addition, genomic DNA was isolated from each clone and insertion of the vector into the genomic DNA was confirmed using PCR. When cells were cultured in serum free media containing DQ gelatin, MT1-MMP suppressed cells showed significantly less degradation of the gelatin when compared to parental cells. Gelatin zymography of conditioned media by cells with contrasting levels of MT1-MMP expression showed that MT1-MMP suppression eliminated proMMP-2 activation and did not have any effect on MMP-9 activation. When cells were cultured on fluorescently labeled fibronectin-coated gelatin films, cells with MT1-MMP expression generated black holes in the fibronectin-gelatin film. In contrast, MT1-MMP suppressed cells reduced their abilities to remove the fibronectin-gelatin film. When parental HT1080 cells were injected subcutaneously into female nude mice, tumors grew rapidly within 20 days. However, when MT1-MMP suppressed cells were injected, the tumors that formed were 5-10 fold smaller than tumors formed by parental cells, thus suggesting MT1-MMP plays a role in tumorigenesis. In conclusion, we confirmed that MT1-MMP is responsible for gelatin degradation and proMMP-2 activation. In addition, we found that MT1-MMP is required for the degradation of fibronectin-gelatin films in vitro and the growth of tumors in nude mice, suggesting that MT1-MMP may be required for cellular invasion and tumorigenesis of HT1080 cells.
A combination of LightOn gene expression system and tumor microenvironment-responsive nanoparticle delivery system for targeted breast cancer therapy
Authors: Xinyu Hou, Chenting Shou, Muye He, Jiajun Xu, Yi Cheng, Zeting Yuan, Minbo Lan, Yuzheng Zhao, Yi Yang, Xianjun Chen, Feng Gao
Journal: Acta Pharmaceutica Sinica B (2020)

A light-switchable transgene system called LightOn gene expression system could regulate gene expression with a high on/off ratio under blue light, and have great potential for spatiotemporally controllable gene expression. We developed a nanoparticle drug delivery system (NDDS) to achieve tumor microenvironment-responsive and targeted delivery of diphtheria toxin A (DTA) fragment-encoded plasmids to tumor sites. The expression of DTA was induced by exposure to blue light. Nanoparticles composed of polyethylenimine and vitamin E succinate linked by a disulfide bond, and PEGylated hyaluronic acid modified with RGD peptide, accumulated in tumor tissues and were actively internalized into 4T1 cells via dual targeting to CD44 and αvβ3 receptors. The LightOn gene expression system was able to control target protein expression through regulation of the intensity or duration of blue light exposure. In vitro studies showed that light-induced DTA expression reduced 4T1 cell viability and induced apoptosis. Furthermore, the LightOn gene expression system enabled spatiotemporal control of the expression of DTA in a mouse 4T1 tumor xenograft model, which resulted in excellent antitumor effects, reduced tumor angiogenesis, and no systemic toxicity. The combination of the LightOn gene expression system and NDDS may be an effective strategy for treatment of breast cancer.
Metal mining and birth defects: a case-control study in Lubumbashi, Democratic Republic of the Congo
Authors: Daan Van Brusselen, Tony Kayembe-Kitenge, Sébastien Mbuyi-Musanzayi, Toni Lubala Kasole, Leon Kabamba Ngombe, Paul Musa Obadia, Daniel Kyanika wa Mukoma, Koen Van Herck, Dirk Avonts, Koen Devriendt, Erik Smolders, Célestin Banza Lubaba Nkulu, Benoit Nemery
Journal: The Lancet Planetary Health (2020)

BackgroundWidespread environmental contamination caused by mining of copper and cobalt has led to concerns about the possible association between birth defects and exposure to several toxic metals in southern Katanga, Democratic Republic of the Congo (DRC). We therefore aimed to assess the possible contribution of parental and antenatal exposure to trace metals to the occurrence of visible birth defects among neonates.MethodsWe did a case-control study between March 1, 2013, and Feb 28, 2015, in Lubumbashi, DRC. We included newborns with visible birth defects (cases) and healthy neonates born in the same maternity ward (controls). Mothers were interviewed about potentially relevant exposures, including their partners' jobs. Various trace metals were measured by inductively coupled plasma mass spectrometry in maternal urine, maternal blood, umbilical cord blood, placental tissue, and surface dust at home. Multivariable logistic regression analyses were done to calculate adjusted odds ratios and their 95% CIs (CI).FindingsOur study included 138 neonates with visible birth defects (about 0·1% of the 133 662 births in Lubumbashi during the study period) and 108 control neonates. Potential confounders were similarly distributed between cases and controls. Vitamin consumption during pregnancy was associated with a lower risk of birth defects (adjusted odds ratio 0·2, 95% CI 0·1–0·5). Mothers having paid jobs outside the home (2·8, 1·2–6·9) and fathers having mining-related jobs (5·5, 1·2–25·0) were associated with a higher risk of birth defects. We found no associations for trace metal concentrations in biological samples, except for a doubling of manganese (Mn; 1·7, 1·1–2·7) and zinc (Zn; 1·6, 0·9–2·8) in cord blood. In a separate model including placentas, a doubling of Mn at the fetal side of the placenta was associated with an increased risk of birth defects (3·3, 1·2–8·0), as was a doubling of cord blood Zn (5·3, 1·6–16·6).InterpretationTo our knowledge, this is the first study of the effects of mining-related pollution on newborns in sub-Saharan Africa. Paternal occupational mining exposure was the factor most strongly associated with birth defects. Because neither Mn nor Zn are mined in Lubumbashi, the mechanism of the association between their increased prenatal concentrations and birth defects is unclear.FundingFlemish Interuniversity Council—University Development Cooperation, The Coalition of the North-South movement in Flanders 11.11.11.
18F-PSMA 1007 Uptake in a Man With Metastatic Breast Cancer
Authors: Fahad Marafi, Arun Sasikumar, Mahamoud Alfeeli, Sanjay Thuruthel
Journal: Clinical Nuclear Medicine (2020)

Abstract A 72-year-old man, who is known with a case of metastatic carcinoma of the breast, was referred for 18 F-PMSA 1007 PET/CT with clinical suspicion of synchronous prostate cancer. 18 F-PSMA 1007 PET/CT scan detected no abnormal tracer concentrating lesion in the prostate gland; however, abnormal tracer concentration was noted in soft tissue lesions in left breast, metastatic lymph nodes, and skeletal lesions. Compared with 18 F-FDG PET/CT, more bone lesions were detected on 18 F-PSMA 1007 imaging. The findings of our case open the possibility of imaging metastatic breast cancer with 18 F-PSMA 1007 in men.
Universal Do-Not-Resuscitate Orders, Social Worth, and Life-Years: Opposing Discriminatory Approaches to the Allocation of Resources During the COVID-19 Pandemic and Other Health System Catastrophes
Authors: Thomas A. Bledsoe, Janet A. Jokela, Noel N. Deep, Lois Snyder Sulmasy
Journal: Annals of Internal Medicine (2020)

T oday's coronavirus pandemic is novel, but the ethi- cal dilemmas it presents are not.In the modern era, physicians have helped patients face the influenza pandemics of 1918, the 1950s, the 1960s, and 2009; HIV/ AIDS (1980s and beyond); severe acute respiratory syndrome (2002); and Middle East respiratory syndrome (2015).Physicians cannot do it alone: Institutions must support their efforts (and have a responsibility to provide protection from occupational exposures).Longstanding principles of medical ethics should guide the profession, individual clinicians, health systems, and our society.They must be reaffirmed in the circumstances of health system catastrophes, during which their application-but not the principles themselvesmay change.These principles include justice; equity; and, fundamentally, the physician's duty to care for all and not discriminate against a class or category of patients (for example, on the basis of age, race, ethnicity, disability, sex, gender identity, social status, or other personal characteristics) (1).During a public health catastrophe, although the physician's responsibility remains with the health and welfare of individual patients under his or her care, the well-being of the community must also be considered, including in institutional and other guidelines.Prioritization of resources becomes critical, but prioritization does not mean discrimination against groups.Fairness does not require that everyone be treated identically, but it does require giving each person his or her due.When crisis triage is necessary, the fairest approach will use clinical criteria applied to individualized patient assessments of likely recovery-not assumptions that disfavor or favor groups.Fairness will not tolerate judgments about worthiness or ask physicians to make quality-of-life assessments.Some current proposals, including universal donot-resuscitate orders, social worth, and life-years, contravene fairness and conflict with ethical principles.They risk clinician moral distress and public distrust, further dividing our society.
Relationship between Coxiella burnetii (Q fever) antibody serology and time spent outdoors
Authors: Gijs Klous, Lidwien AM Smit, Wim van der Hoek, Mirjam EE Kretzschmar, Piet Vellema, Roel A Coutinho, Dick JJ Heederik, Anke Huss
Journal: Journal of Infection (2020)

From 2007 through 2010, the Netherlands experienced the largest recorded Q fever outbreak to date. People living closer to Coxiella burnetii infected goat farms were at increased risk for acute Q fever. Time spent outdoors near infected farms may have contributed to exposure to C. burnetii. The aim of this study was to retrospectively evaluate whether hours/week spent outdoors, in the vicinity of previously C. burnetii infected goat farms, was associated with presence of antibodies against C. burnetii in residents of a rural area in the Netherlands.Between 2014-2015, we collected C. burnetii antibody serology and self-reported data about habitual hours/week spent outdoors near the home from 2494 adults. From a subgroup we collected 941 GPS tracks, enabling analyses of active mobility in the outbreak region. Participants were categorised as exposed if they spent time within specified distances (500m, 1000m, 2000m, or 4000m) of C. burnetii infected goat farms. We evaluated whether time spent near these farms was associated with positive C. burnetii serology using spline analyses and logistic regression.People that spent more hours/week outdoors near infected farms had a significantly increased risk for positive C. burnetii serology (time spent within 2000m of a C. burnetii abortion-wave positive farm, OR 3.6 (1.2-10.6)), compared to people spending less hours/week outdoors.Outdoor exposure contributed to the risk of becoming C. burnetii serology positive. These associations were stronger if people spent more time near C. burnetii infected farms. Outdoor exposure should, if feasible, be included in outbreak investigations.
Brief Cognitive Tests for Distinguishing Clinical Alzheimer-Type Dementia From Mild Cognitive Impairment or Normal Cognition in Older Adults With Suspected Cognitive Impairment
Authors: Laura S. Hemmy, Eric J. Linskens, Pombie C. Silverman, Margaret A. Miller, Kristine M.C. Talley, Brent C. Taylor, Jeannine M. Ouellette, Nancy L. Greer, Timothy J. Wilt, Mary Butler, Howard A. Fink
Journal: Annals of Internal Medicine (2020)

The accuracy and harms of brief cognitive tests for identifying clinical Alzheimer-type dementia (CATD) are uncertain.To summarize evidence on accuracy and harms of brief cognitive tests for CATD in older adults with suspected cognitive impairment.Electronic bibliographic databases (from inception to November 2019) and systematic review bibliographies.English-language, controlled observational studies in older adults that evaluated the accuracy of brief cognitive tests (standalone tests; memory, executive function, and language tests; and brief multidomain batteries) for distinguishing CATD from mild cognitive impairment (MCI) or normal cognition as defined by established diagnostic criteria. Studies with low or medium risk of bias (ROB) were analyzed.Two reviewers rated ROB. One reviewer extracted data; the other verified extraction accuracy.Fifty-seven studies met analysis criteria. Many brief, single cognitive tests were highly sensitive and specific for distinguishing CATD from normal cognition. These included standalone tests (clock-drawing test, median sensitivity 0.79 and specificity 0.88 [8 studies]; Mini-Mental State Examination, 0.88 and 0.94 [7 studies]; Montreal Cognitive Assessment, 0.94 and 0.94 [2 studies]; and Brief Alzheimer Screen, 0.92 and 0.97 [1 study]), memory tests (list delayed recall, 0.89 and 0.94 [5 studies]), and language tests (category fluency, 0.92 and 0.89 [9 studies]). Accuracy was lower in distinguishing mild CATD from normal cognition and distinguishing CATD from MCI. No studies reported on testing harms.Studies were small. Few test metrics were evaluated by multiple studies. Few studies directly compared different tests, scores, cut points, or test combinations.Many brief, single cognitive tests accurately distinguish CATD from normal cognition in older adults but are less accurate in distinguishing mild CATD from normal cognition or CATD from MCI. No studies reported on testing harms.Agency for Healthcare Research and Quality. (PROSPERO: CRD42018117897).
사례보고 : 만성 B형간염 환자에서 adefovir dipivoxil 투여에 의해 발생한 심한 저인산염혈증 1예
Authors: 이헌주 ( Heon Ju Lee ), 김태년 ( Tae Nyeun Kim ), 은종렬 ( Jong Ryul Eun ), 최재원 ( Jae Won Choi )
Journal: Clinical and Molecular Hepatology (2008)
Tnfaip3 expression in pulmonary conventional type 1 Langerin‐expressing dendritic cells regulates T helper 2‐mediated airway inflammation in mice
Authors: Heleen Vroman, Denise van Uden, Ingrid M. Bergen, Jennifer A. C. van Hulst, Melanie Lukkes, Geert van Loo, Björn E. Clausen, Louis Boon, Bart N. Lambrecht, Hamida Hammad, Rudi W. Hendriks, Mirjam Kool
Journal: Allergy (2020)

Conventional type 1 dendritic cells (cDC1s) control anti-viral and anti-tumor immunity by inducing antigen-specific cytotoxic CD8+ T-cell responses. Controversy exists whether cDC1s also control CD4+ T helper 2 (Th2) cell responses, since suppressive and activating roles have been reported. DC activation status, controlled by the transcription factor NF-κB, might determine the precise outcome of Th-cell differentiation upon encounter with cDC1s. To investigate the role of activated cDC1s in Th2-driven immune responses, pulmonary cDC1s were activated by targeted deletion of A20/Tnfaip3, a negative regulator of NF-κB signaling.To target pulmonary cDC1s, Cd207 (Langerin)-mediated excision of A20/Tnfaip3 was used, generating Tnfaip3fl/fl xCd207+/cre (Tnfaip3Lg-KO ) mice. Mice were exposed to house dust mite (HDM) to provoke Th2-mediated immune responses.Mice harboring Tnfaip3-deficient cDC1s did not develop Th2-driven eosinophilic airway inflammation upon HDM exposure, but rather showed elevated numbers of IFNγ-expressing CD8+ T cells. In addition, Tnfaip3Lg-KO mice harbored increased numbers of IL-12-expressing cDC1s and elevated PD-L1 expression in all pulmonary DC subsets. Blocking either IL-12 or IFNγ in Tnfaip3Lg-KO mice restored Th2 responses, whereas administration of recombinant IFNγ during HDM sensitization in C57Bl/6 mice blocked Th2 development.These findings indicate that the activation status of cDC1s, shown by their specific expression of co-inhibitory molecules and cytokines, critically contributes to the development of Th2 cell-mediated disorders, most likely by influencing IFNγ production in CD8+ T cells.
Multi-parameter flow cytometry immunophenotyping distinguishes different stages of tuberculosis infection
Authors: Olivia Estévez, Luis Anibarro, Elina Garet, Amparo Martínez, Alberto Pena, Laura Barcia, Mercedes Peleteiro, África González-Fernández
Journal: Journal of Infection (2020)

ObjectivesTo identify new potential host biomarkers in blood to discriminate between active TB patients, uninfected (NoTBI) and latently infected contacts (LTBI).MethodsA blood cell count was performed to study parent leukocyte populations. Peripheral blood mononuclear cells (PBMCs) were isolated and a multi-parameter flow cytometry assay was conducted to study the distribution of basal and Mycobacterium tuberculosis (Mtb)-stimulated lymphocytes. Differences between groups and the area under the ROC curve (AUC) were investigated to assess the diagnostic accuracy.ResultsActive TB patients presented higher Monocyte-to-lymphocyte and Neutrophil-to-lymphocyte ratios than LTBI and NoTBI contacts (p<0.0001; AUC>0.8). Lymphocyte subsets with differences (p >0.05; AUC >0.7) between active TB and both contact groups include the basal distribution of Th1/Th2 ratio, Th1-Th17, CD4+ Central Memory (TCM) or MAIT cells. Expression of CD154 is increased in Mtb-activated CD4+ TCM and Effector Memory T cells in active TB and LTBI compared to NoTBI. In CD4+ T cells, expression of CD154 showed a higher accuracy than IFNγ to discriminate Mtb-specific activation.ConclusionsWe identified different cell subsets with potential use in tuberculosis diagnosis. Among them, distribution of CD4 TCM cells and their expression of CD154 after Mtb-activation are the most promising candidates.
Transcription factor MafB in podocytes protects against the development of focal segmental glomerulosclerosis
Authors: Toshiaki Usui, Naoki Morito, Hossam H. Shawki, Yoshinori Sato, Hiroyasu Tsukaguchi, Michito Hamada, Hyojung Jeon, Manoj Kumar Yadav, Akihiro Kuno, Yuki Tsunakawa, Risa Okada, Takaaki Ojima, Maho Kanai, Keigo Asano, Yuki Imamura, Ryusuke Koshida, Keigyou Yoh, Joichi Usui, Hideki Yokoi, Masato Kasahara, Ashio Yoshimura, Masafumi Muratani, Takashi Kudo, Hisashi Oishi, Kunihiro Yamagata, Satoru Takahashi
Journal: Kidney International (2020)