tbuckley/cabot-search huggingface dataset:
Far-red light-activated human islet-like designer cells enable sustained fine-tuned secretion of insulin for glucose control
Authors: Guiling Yu, Mingliang Zhang, Ling Gao, Yang Zhou, Longliang Qiao, Jianli Yin, Yiwen Wang, Jian Zhou, Haifeng Ye
Journal: Molecular Therapy (2021)

Diabetes affects almost half a billion people, and all individuals with type 1 diabetes (T1D) and a large portion of individuals with type 2 diabetes rely on self-administration of the peptide hormone insulin to achieve glucose control. However, this treatment modality has cumbersome storage and equipment requirements and is susceptible to fatal user error. Here, reasoning that a cell-based therapy could be coupled to an external induction circuit for blood glucose control, as a proof of concept we developed far-red light (FRL)-activated human islet-like designer (FAID) cells and demonstrated how FAID cell implants achieved safe and sustained glucose control in diabetic model mice. Specifically, by introducing a FRL-triggered optogenetic device into human mesenchymal stem cells (hMSCs), which we encapsulated in poly-(l-lysine)-alginate and implanted subcutaneously under the dorsum of T1D model mice, we achieved FRL illumination-inducible secretion of insulin that yielded improvements in glucose tolerance and sustained blood glucose control over traditional insulin glargine treatment. Moreover, the FAID cell implants attenuated both oxidative stress and development of multiple diabetes-related complications in kidneys. This optogenetics-controlled "living cell factory" platform could be harnessed to develop multiple synthetic designer therapeutic cells to achieve long-term yet precisely controllable drug delivery. Diabetes affects almost half a billion people, and all individuals with type 1 diabetes (T1D) and a large portion of individuals with type 2 diabetes rely on self-administration of the peptide hormone insulin to achieve glucose control. However, this treatment modality has cumbersome storage and equipment requirements and is susceptible to fatal user error. Here, reasoning that a cell-based therapy could be coupled to an external induction circuit for blood glucose control, as a proof of concept we developed far-red light (FRL)-activated human islet-like designer (FAID) cells and demonstrated how FAID cell implants achieved safe and sustained glucose control in diabetic model mice. Specifically, by introducing a FRL-triggered optogenetic device into human mesenchymal stem cells (hMSCs), which we encapsulated in poly-(l-lysine)-alginate and implanted subcutaneously under the dorsum of T1D model mice, we achieved FRL illumination-inducible secretion of insulin that yielded improvements in glucose tolerance and sustained blood glucose control over traditional insulin glargine treatment. Moreover, the FAID cell implants attenuated both oxidative stress and development of multiple diabetes-related complications in kidneys. This optogenetics-controlled "living cell factory" platform could be harnessed to develop multiple synthetic designer therapeutic cells to achieve long-term yet precisely controllable drug delivery.
Safety and pharmacokinetics of first-line amg 479 (mab to igf1r) or amg 102 (mab to hgf/sf) with platinum-based chemotherapy in extensive-stage small cell lung cancer (sclc)
Authors: P. Lorigan, J. Soria, J. Stephenson, A. Maru, R. Gervais, M. Zhu, I. McCaffery, Y. Jiang, J. McGreivy, B. Glisson
Journal: Annals of Oncology (2010)
Is Colorectal Cancer Screening Absolutely Beneficial for Older Adults?
Authors: Wenjie Ma, Mingyang Song, Andrew T. Chan
Journal: JAMA Oncology (2021)

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Using community health advisors to increase lung cancer screening awareness in the Black Belt: A pilot study.
Authors: Soumya J. Niranjan, William Opoku-Agyeman, Tara Bowman, Claudia M. Hardy, Monica L. Baskin, Mark T. Dransfield
Journal: Journal of Clinical Oncology (2021)

117 Background: Disease stage at the time of diagnosis is the most important determinant of prognosis for lung cancer. Despite demonstrated effectiveness of lung cancer screening (LCS) in reducing lung cancer mortality, early detection continues to elude populations with the highest risk for lung cancer death. Consistent with the national rate, current screening rate in Alabama is dismal at 4.2%. While public awareness of LCS may be a likely cause there are no studies that have thoroughly evaluated current knowledge of LCS within the Deep South. Therefore, we measured (LCS) knowledge before and after receiving education delivered by Community Health Advisors (CHAs) among high-risk individuals living in medically-underserved communities of Alabama and to determine impact of psychological, demographic, health status and cognitive factors on rate of lung cancer screening participation. Methods: Participants were recruited from one urban county and six rural Black Belt counties (characterized by poverty, rurality, unemployment, low educational attainment and disproportionate lack of access to health services).100 individuals (i) aged between 55 to 80 years (ii) Currently smoke or have quit within the past 15 years. (iii) Have at least a total of 30-pack-year smoking history were recruited. Knowledge scores to assess lung cancer knowledge were calculated. Paired t-test was used to assess pre and post knowledge score improvement. Screening for lung cancer was modeled as a function of predisposed factors (age, gender, insurance, education, fatalism, smoking status, and history of family lung cancer). Results: Average age was 62.94(SD = 6.28), mostly female (54%); mostly current smokers (53% ). Most participants (80.85%) reported no family history of cancer. Fatalism was low, with a majority of the participants disagreeing that a cancer diagnosis is pre-destined (67.7%) and that there are no treatments for lung cancer (88.66%). Overall, lung cancer knowledge increased significantly from baseline of 4.64(SD = 2.37) to 7.61(SD = 2.26). Of the 100 participants, only 23 underwent screening due to lack of access to primary care providers and reluctance of PCPs to provide referral to LCS. 65% of those who were screened reported family history of lung cancer. Regression analysis revealed no significant association between risk factors and the decision to get screened by participants. Conclusions: Our study demonstrates that while CHA delivered education initiatives increases lung cancer screening knowledge, there are significant structural barriers that prohibit effective utilization of LCS which needs to be addressed.
Overall survival following implementation of clinical pathways for cancer care.
Authors: Rohit P. Ojha, Yan Lu, Kalyani Narra, Rachel J. Meadows, Aaron Gehr, Emmanuel Mantilla, Bassam Ghabach
Journal: Journal of Clinical Oncology (2021)

328 Background: Clinical pathways are decision support tools designed to enhance accessibility and ease of use of treatment recommendations. Prior studies that evaluated cancer clinical pathways largely focused on process measures such as concordance with treatment guidelines, but little evidence is available about the effect of clinical pathways on survival. We thus aimed to evaluate the effect of cancer clinical pathways on overall survival. Methods: We used institutional registry data from the JPS Oncology and Infusion Center, which is a Comprehensive Community Cancer Program. Eligible patients were aged ≥18 years, diagnosed with first primary breast, colorectal, or lung cancer between December 2013 and December 2017 with follow-up through June 2020. We used a natural experiment framework, where intervention was implementation of clinical pathways (December 2015). The pre-intervention period was December 2013 – November 2015 and post-intervention period was January 2016 – December 2017. We used marginal structural models with stabilized inverse probability weights for each cancer type to estimate restricted mean survival time (RMST) differences and 95% confidence limits (CL) comparing overall survival between pre- and post-clinical pathways within a 36-month horizon, where weights were based on a minimal sufficient set of covariates (sociodemographics, tumor characteristics, and comorbidities) to reduce confounding bias. Results: Our study population comprised 327 breast, 254 colorectal, and 431 lung cancer patients. Median age ranged between 55 years (breast) and 60 years (lung). The frequency of racial/ethnic minorities ranged between 45% (lung) and 68% (colorectal). The frequency of uninsured patients ranged between 47% (lung) and 58% (colorectal). Adherence to pathways was consistently over 80%. RMST was largely similar between pre- and post-clinical pathways for breast (RMST difference = -0.10 months, 95% CL: -1.9, 1.7), colorectal (RMST difference = -0.48 months, 95% CL: -3.4, 2.5) and lung cancer (RMST difference = 1.1 month, 95% CL: -1.5, 3.7). Conclusions: Our results suggest that implementation of clinical pathways has minimal effect on overall survival within 36 months despite high adherence in a safety-net population, but the estimates are compatible with up to 3.4 month decrease or 3.7 month increase depending on cancer type. Longer follow-up, particularly for breast and colorectal cancer, may provide further insight. Our findings may be useful for informing deliberations about implementing clinical pathways and setting expectations about the effect of clinical pathways on overall survival.
EFFICACY OF ALIROCUMAB IN 1,191 PATIENTS WITH A WIDE SPECTRUM OF MUTATIONS IN GENES CAUSATIVE FOR FAMILIAL HYPERCHOLESTEROLEMIA
Authors: John J.P. Kastelein, Gisle Langslet, Paul Hopkins, Joep Defesche, Werner Seiz, Marie Baccara-Dinet, Sara Hamon, Poulabi Banerjee, Claudia Stefanutti
Journal: Journal of the American College of Cardiology (2016)
Single‐centre experience of using pegylated liposomal doxorubicin as maintenance treatment in mycosis fungoides
Authors: D. Falkenhain‐López, J. Fulgencio‐Barbarin, M. Puerta‐Peña, J. Montero‐Menárguez, A. Sánchez‐Velázquez, P.L. Ortiz‐Romero
Journal: British Journal of Dermatology (2021)
TG-1701 A selective bruton tyrosine kinase (btk) inhibitor, as monotherapy and in combination with ublituximab and umbralisib (u2) in chronic lymphocytic leukemia (cll) and lymphoma
Authors: C. Cheah, W. Jurczak, M. Lasica, N. Wickham, T. Wrobel, J. Walewski, C. Yannakou, S. Cheung, K. Lewi, M. Długosz-Danecka, K. Giannopoulos, H. Miskin, J. P. Tang, E. Normant, O. O'Connor, A. Ricart, C. Tam
Journal: HemaSphere (2021)
Infections, hospitalisations, and deaths averted via a nationwide vaccination campaign using the Pfizer–BioNTech BNT162b2 mRNA COVID-19 vaccine in Israel: a retrospective surveillance study
Authors: Eric J Haas, John M McLaughlin, Farid Khan, Frederick J Angulo, Emilia Anis, Marc Lipsitch, Shepherd R Singer, Gabriel Mircus, Nati Brooks, Meir Smaja, Kaijie Pan, Jo Southern, David L Swerdlow, Luis Jodar, Yeheskel Levy, Sharon Alroy-Preis
Journal: The Lancet Infectious Diseases (2021)

BackgroundOn Dec 20, 2020, Israel initiated a nationwide COVID-19 vaccination campaign for people aged 16 years and older and exclusively used the Pfizer–BioNTech BNT162b2 mRNA COVID-19 vaccine (tozinameran). We provide estimates of the number of SARS-CoV-2 infections and COVID-19-related admissions to hospital (ie, hospitalisations) and deaths averted by the nationwide vaccination campaign.MethodsIn this retrospective surveillance study, we used national surveillance data routinely collected by the Israeli Ministry of Health from the first 112 days (Dec 20, 2020, up to our data cutoff of April 10, 2021) of Israel's vaccination campaign to estimate the averted burden of four outcomes: SARS-CoV-2 infections and COVID-19-related hospitalisations, severe or critical hospitalisations, and deaths. As part of the campaign, all individuals aged 16 years and older were eligible for inoculation with the BNT162b2 vaccine in a two-dose schedule 21 days apart. We estimated the direct effects of the immunisation programme for all susceptible individuals (ie, with no previous evidence of laboratory-confirmed SARS-CoV-2 infection) who were at least partly vaccinated (at least one dose and at least 14 days of follow-up after the first dose). We estimated the number of SARS-CoV-2 infection-related outcomes averted on the basis of cumulative daily, age-specific rate differences, comparing rates among unvaccinated individuals with those of at least partly vaccinated individuals for each of the four outcomes and the (age-specific) size of the susceptible population and proportion that was at least partly vaccinated.FindingsWe estimated that Israel's vaccination campaign averted 158 665 (95% CI 144 640–172 690) SARS-CoV-2 infections, 24 597 (18 942–30 252) hospitalisations, 17 432 (12 770–22 094) severe or critical hospitalisations, and 5532 (3085–7982) deaths. 16 213 (65·9%) of 24 597 hospitalisations and 5035 (91·0%) of 5532 of deaths averted were estimated to be among those aged 65 years and older. We estimated 116 000 (73·1%) SARS-CoV-2 infections, 19 467 (79·1%) COVID-19-related hospitalisations, and 4351 (79%) deaths averted were accounted for by the fully vaccinated population.InterpretationWithout the national vaccination campaign, Israel probably would have had triple the number of hospitalisations and deaths compared with what actually occurred during its largest wave of the pandemic to date, and the health-care system might have become overwhelmed. Indirect effects and long-term benefits of the programme, which could be substantial, were not included in these estimates and warrant future research.FundingIsrael Ministry of Health and Pfizer.
Revisiting genetic artifacts on DNA methylation microarrays exposes novel biological implications
Authors: Benjamin Planterose Jiménez, Manfred Kayser, Athina Vidaki
Journal: Genome biology (2021)

Illumina DNA methylation microarrays enable epigenome-wide analysis vastly used for the discovery of novel DNA methylation variation in health and disease. However, the microarrays' probe design cannot fully consider the vast human genetic diversity, leading to genetic artifacts. Distinguishing genuine from artifactual genetic influence is of particular relevance in the study of DNA methylation heritability and methylation quantitative trait loci. But despite its importance, current strategies to account for genetic artifacts are lagging due to a limited mechanistic understanding on how such artifacts operate.To address this, we develop and benchmark UMtools, an R-package containing novel methods for the quantification and qualification of genetic artifacts based on fluorescence intensity signals. With our approach, we model and validate known SNPs/indels on a genetically controlled dataset of monozygotic twins, and we estimate minor allele frequency from DNA methylation data and empirically detect variants not included in dbSNP. Moreover, we identify examples where genetic artifacts interact with each other or with imprinting, X-inactivation, or tissue-specific regulation. Finally, we propose a novel strategy based on co-methylation that can discern between genetic artifacts and genuine genomic influence.We provide an atlas to navigate through the huge diversity of genetic artifacts encountered on DNA methylation microarrays. Overall, our study sets the ground for a paradigm shift in the study of the genetic component of epigenetic variation in DNA methylation microarrays.
Segregational Drift Constrains the Evolutionary Rate of Prokaryotic Plasmids
Authors: Ana Garoña, Nils F Hülter, Devani Romero Picazo, Tal Dagan
Journal: Molecular Biology and Evolution (2021)

Plasmids are extrachromosomal genetic elements in prokaryotes that have been recognized as important drivers of microbial ecology and evolution. Plasmids are found in multiple copies inside their host cell where independent emergence of mutations may lead to intracellular genetic heterogeneity. The intracellular plasmid diversity is thus subject to changes upon cell division. However, the effect of plasmid segregation on plasmid evolution remains understudied. Here, we show that genetic drift during cell division-segregational drift-leads to the rapid extinction of novel plasmid alleles. We established a novel experimental approach to control plasmid allele frequency at the levels of a single cell and the whole population. Following the dynamics of plasmid alleles in an evolution experiment, we find that the mode of plasmid inheritance-random or clustered-is an important determinant of plasmid allele dynamics. Phylogenetic reconstruction of our model plasmid in clinical isolates furthermore reveals a slow evolutionary rate of plasmid-encoded genes in comparison to chromosomal genes. Our study provides empirical evidence that genetic drift in plasmid evolution occurs at multiple levels: the host cell and the population of hosts. Segregational drift has implications for the evolutionary rate heterogeneity of extrachromosomal genetic elements.
Chitosan coatings with distinct innate immune bioactivities differentially stimulate angiogenesis, osteogenesis and chondrogenesis in poly-caprolactone scaffolds with controlled interconnecting pore size
Authors: Caroline D. Hoemann, Javier Rodríguez González, Jessica Guzmán-Morales, Gaoping Chen, Ebrahim Jalali Dil, Basil D. Favis
Journal: Bioactive Materials (2021)

This study tested whether osseous integration into poly (ε-caprolactone) (PCL) bioplastic scaffolds with fully-interconnecting 155 ± 8 μm pores is enhanced by an adhesive, non-inflammatory 99% degree of deacetylation (DDA) chitosan coating (99-PCL), or further incorporation of pro-inflammatory 83% DDA chitosan microparticles (83-99-PCL) to accelerate angiogenesis. New Zealand White rabbit osteochondral knee defects were press-fit with PCL, 99-PCL, 83-99-PCL, or allowed to bleed (drill-only). Between day 1 and 6 weeks of repair, drill-only defects repaired by endochondral ossification, with an 8-fold higher bone volume fraction (BVF) versus initial defects, compared to a 2-fold (99-PCL), 1.1-fold (PCL), or 0.4-fold (83-99-PCL) change in BVF. Hematoma innate immune cells swarmed to 83-99-PCL, elicited angiogenesis throughout the pores and induced slight bone resorption. PCL and 99-PCL pores were variably filled with cartilage or avascular mesenchyme near the bone plate, or angiogenic mesenchyme into which repairing trabecular bone infiltrated up to 1 mm deep. More repair cartilage covered the 99-PCL scaffold (65%) than PCL (18%) or 83-99-PCL (0%) (p < 0.005). We report the novel finding that non-inflammatory chitosan coatings promoted cartilage infiltration into and over a bioplastic scaffold, and were compatible with trabecular bone integration. This study also revealed that in vitro osteogenesis assays have limited ability to predict osseous integration into porous scaffolds, because (1) in vivo, woven bone integrates from the leading edge of regenerating trabecular bone and not from mesenchymal cells adhering to scaffold surfaces, and (2) bioactive coatings that attract inflammatory cells induce bone resorption.
SARS-CoV-2 and the rheumatology patient: the last 12 months and a boost in the future
Authors: Kevin L Winthrop, Richard J Whitley, Daniel Aletaha
Journal: Annals of the Rheumatic Diseases (2021)

<h3>ABSTRACT</h3> Vitamin D and its biomarker 25(OH)D are known to vary by race/ethnicity with African Americans (AAs) having significantly lower levels than non-Hispanic whites (white Americans). However, AAs have better bone mineral density (BMD) and less arterial calcification, one marker of cardiovascular risk, than white Americans, with some studies showing higher vit. D levels harmful to AAs. This study analyzes NHANES data from 2011 to 2014, NHANES being a biennially published national survey of nearly 10,000 people, with interview, examination, and lab data components. The analyses, using count regression and linear regression models to avoid thresholding of variables, find that abdominal aortic calcification scores rise with 24(OH)D in white Americans, with no statistically significant effect in AAs; femoral BMD falls with 25(OH)D in both groups; osteoporotic fracture risks fall with 25(OH)D in white Americans; and periodontal attachment loss falls with rising 25(OH)D in both groups. Overall, higher 25(OH)D seems protective for oral and skeletal health in white Americans, protective for periodontal health in AAs, negative for their skeletal health, and negative for arterial calcification in white Americans, after controlling for the demographic factors of age and sex, the physiological elements of blood pressure and BMI, the biochemical variables of LDL and cholesterol levels, the socioeconomic indicators of income-to-poverty-level ratio and education levels, and the environmental influence of the season. As periodontitis is low on the disease hazard scale compared to arterial calcification and skeletal health, the results point to a lack of significant protection with rising OH(D) levels in AAs, even after their low base levels, and some harmful impact from those higher levels. That combination should trigger a closer look at the single population-wide vitamin D threshold of 30 to 50 ng/mL currently recommended in the US.
Progress toward implementation of human papillomavirus vaccination - the Americas, 2006-2010.
Authors: A. S. Vicari, L. G. Dilsa, S. Deeks, S. P. Cerón Mireles, M. L. L. San Román, R. Espinosa Romero, M. del C. Domínguez Mulato, V. R. López-Collada, Y. de Moltó, I. S. de Hewitt, M. Saraiya, T. Hyde, L. E. Markowitz, E. F. Dunne, E. Meites, D. Surie
Journal: MMWR Morbidity and Mortality Weekly Report (2011)