tbuckley/cabot-search huggingface dataset:
Tumor-associated macrophages induced spheroid formation by CCL18-ZEB1-M-CSF feedback loop to promote transcoelomic metastasis of ovarian cancer
Authors: Lingli Long, Yue Hu, Tengfei Long, Xiaofang Lu, Ying Tuo, Yubing Li, Min Wang, Zunfu Ke
Journal: Journal for ImmunoTherapy of Cancer (2021)

Ovarian cancer (OvCa)-tumor-associated macrophages (TAMs) spheroids are abundantly present within ascites of high malignant patients. This study investigated the mutual interaction of OvCa cells and TAMs in the spheroids.
Self-assembling, supramolecular chemistry and pharmacology of amphotericin B: Poly-aggregates, oligomers and monomers
Authors: Raquel Fernández-García, Juan C. Muñoz-García, Matthew Wallace, Laszlo Fabian, Elena González-Burgos, M. Pilar Gómez-Serranillos, Rafaela Raposo, Francisco Bolás-Fernández, M. Paloma Ballesteros, Anne Marie Healy, Yaroslav Z. Khimyak, Dolores R. Serrano
Journal: Journal of Controlled Release (2021)
Late-Breaking Basic Science Abstracts From the American Heart Association’s Scientific Sessions 2021
Authors: Olivia T Ly, Grace Brown, Hanna Chen, Liang HONG, Xinge Wang, Yong Duk Han, Mahmud Arif Pavel, Arvind Sridhar, Mark Maienschein-Cline, Sang Ging Ong, khaled Abdelhady, Malek G Massad, Lona Ernst Rizkallah, Jalees Rehman, SALMAN KHETANI, Dawood Darbar, Univ of Illinois COM, Chicago, Chicago, Univ of Illinois at Chicago, Orland Park, Chicago, Univ of Illinois at Chicago, Chicago, Univ of Illinois, Chicago, Chicago, Univ of Illinois Chicago, Chicago, IL,
Journal: Circulation Research (2021)

Introduction: Induced pluripotent stem cell (iPSC)-derived cardiomyocytes (CMs) are ideally suited for modeling heritable atrial fibrillation (AF) and testing personalized pharmacological therapy, but there is limited data on the maturation of iPSCatrial (a) CMs.While we reported the only non-ion channel gene (NPPA), encoding atrial natriuretic peptide (ANP), as a cause of familial AF, the underlying cellular mechanisms remain unclear.Immaturity of iPSC-aCMs is one potential explanation.Hypothesis: We hypothesized that a combinatorial engineering approach to maturation with biochemical cues (T3 [T], IGF-1[I], dexamethasone [D]; [TID]), bioenergetic supplement (fatty acids [FA]), and electrical stimulation (ES), synergistically promotes the electrophysiological (EP), structural, and metabolic maturity of iPSC-aCMs to a level comparable to human atrial tissue (HAT) and will unmask the underlying cellular mechanisms of an NPPA mutation.Methods: We differentiated iPSC-aCMs with retinoic acid, applied TID+FA+ES, and compared the EP (patch clamping, optical voltage mapping), structural (immunofluorescence, western blots [WB]), metabolic (Seahorse Analyzer, WB, RT-PCR), and transcriptomic (RNA-seq) maturity with immature iPSC-aCMs and adult human aCMs from the same patient.We generated iPSC-aCMs from a family carrying the NPPA-S64R mutation, an isogenic control using CRISPR-Cas9, and used our matured iPSC-aCMs to elucidate the EP signature of AF.Results: TID+FA+ES treated iPSC-aCMs displayed improved sarcomeric organization and oxidative capacity (Figure 1a,b), more hyperpolarized RMP and increased APA (Figure 1c,d).Only mature NPPA-S64R iPSC-aCMs prolonged APD, and increased I Ks density when compared to immature aCMs (Figure 1e,f,g,h).Conclusion: We established a combinatorial engineering approach that promoted the comprehensive maturation of iPSC-aCMs and unmasked the underlying mechanism of an AF-causing NPPA mutation.
Slow-wave sleep affects synucleinopathy and regulates proteostatic processes in mouse models of Parkinson’s disease
Authors: Marta M. Morawska, Carlos G. Moreira, Varun R. Ginde, Philipp O. Valko, Tobias Weiss, Fabian Büchele, Lukas L. Imbach, Sophie Masneuf, Sedef Kollarik, Natalia Prymaczok, Juan A. Gerez, Roland Riek, Christian R. Baumann, Daniela Noain
Journal: Science Translational Medicine (2021)

Slow-wave modulation alters synuclein accumulation and regulates proteostatic pathways in Parkinson’s disease mice.
The 12- and 24-Month Effects of Intravitreal Ranibizumab, Aflibercept, and Bevacizumab on Intraocular Pressure
Authors: Keean Nanji, Gurkaran S. Sarohia, Kevin Kennedy, Tiandra Ceyhan, Tyler McKechnie, Mark Phillips, Tahira Devji, Lehana Thabane, Peter Kaiser, David Sarraf, Sunir J. Garg, Sobha Sivaprasad, Charles C. Wykoff, Sophie J. Bakri, Tom Sheidow, Mohit Bhandari, Varun Chaudhary
Journal: Ophthalmology (2021)
Maternal and Neonatal SARS-CoV-2 Immunoglobulin G Antibody Levels at Delivery After Receipt of the BNT162b2 Messenger RNA COVID-19 Vaccine During the Second Trimester of Pregnancy
Authors: Nir Kugelman, Chen Nahshon, Pninit Shaked-Mishan, Nadav Cohen, Maayan Lahav Sher, Maya Gruber, Inbal Marom, Avi Zolotarevsky, Ofer Lavie, Amit Damti, Ariel Zilberlicht, Mordehai Bardicef, Reuven Kedar
Journal: JAMA Pediatrics (2021)

<h3>Importance</h3> BNT162b2 messenger RNA (mRNA) COVID-19 vaccination in the third trimester was found to be associated with a strong maternal humoral IgG response that crossed the placenta and approached maternal titers in the newborn. <h3>Objective</h3> To evaluate maternal and neonatal SARS-CoV-2 immunoglobulin G (IgG) antibody levels at birth after mRNA COVID-19 vaccination during the second trimester of pregnancy. <h3>Design, Setting, and Participants</h3> This prospective cohort study, conducted at a single medical center in Haifa, Israel, from May to July 2021, included women with a singleton pregnancy over 24 weeks of gestation at least 7 days after receipt of their second COVID-19 vaccine dose who were not known to be previously infected with COVID-19. <h3>Exposures</h3> BNT162b2 (Pfizer/BioNTech) vaccination. <h3>Main Outcomes and Measures</h3> The primary outcomes were SARS-CoV-2 IgG antibody titers measured in the parturient at admission and in the umbilical cord blood within 30 minutes after delivery. Secondary outcomes were the correlation between antibody titers, feto-maternal characteristics, maternal adverse effects after vaccination, and time interval from vaccination to delivery. <h3>Results</h3> Antibody levels were measured for 129 women (mean [SD] age, 31.9 [4.9] years) and 114 neonates, with 100% of the tests having positive results. The mean (SD) gestational age at administration of the second vaccine dose was 24.9 (3.3) weeks. Neonatal IgG titers were 2.6 times higher than maternal titers (median [range], 3315.7 [350.1-17 643.5] AU/mL vs 1185.2 [146.6-32 415.1] AU/mL). A positive correlation was demonstrated between maternal and neonatal antibodies (<i>r</i> = 0.92; 95% CI, 0.89-0.94). Multivariable analysis revealed that for each week that passed since receipt of the second vaccine dose, maternal and neonatal antibody levels changed by −10.9% (95% CI, −17.2% to −4.2%;<i>P</i> = .002) and −11.7% (95% CI, −19.0 to −3.8%;<i>P</i> = .005), respectively. For each 1-year increase in the mother's age, maternal and neonatal antibody levels changed by −3.1% (95% CI, −5.3% to −0.9%;<i>P</i> = .007) and −2.7% (95% CI, −5.2% to −0.1%;<i>P</i> = .04), respectively. <h3>Conclusions and Relevance</h3> In this cohort study, receipt of the BNT162b2 mRNA COVID-19 vaccine during the second trimester of pregnancy was associated with maternal and neonatal humoral responses, as reflected in maternal and neonatal SARS-CoV-2 IgG antibody levels measured after delivery. These findings support COVID-19 vaccination of pregnant individuals during the second trimester to achieve maternal protection and newborn safety during the pandemic.
Tumor Mutational Burden in Histiocytic Neoplasms
Authors: Aldo A. Acosta-Medina, Jithma P. Abeykoon, Surendra Dasari, Antonious Z. Hazim, N. Nora Bennani, Terra Lasho, Aishwarya Ravindran, Karen Rech, Mithun V. Shah, Gaurav Goyal, Ronald Go
Journal: Blood (2021)
Molecular features encoded in the ctDNA reveal heterogeneity and predict outcome in high-risk aggressive B-cell lymphoma
Authors: Leo Meriranta, Amjad Alkodsi, Annika Pasanen, Maija Lepistö, Parisa Mapar, Yngvild Nuvin Blaker, Judit Jørgensen, Marja-Liisa Karjalainen-Lindsberg, Idun Fiskvik, Lars Tore G. Mikalsen, Matias Autio, Magnus Björkholm, Mats Jerkeman, Øystein Fluge, Peter Brown, Sirkku Jyrkkiö, Harald Holte, Esa Pitkänen, Pekka Ellonen, Sirpa Leppä
Journal: Blood (2021)
SARS-CoV-2 Vaccine Antibody Response and Breakthrough Infection in Patients Receiving Dialysis
Authors: Shuchi Anand, Maria E. Montez-Rath, Jialin Han, Pablo Garcia, LinaCel Cadden, Patti Hunsader, Curt Morgan, Russell Kerschmann, Paul Beyer, Mary Dittrich, Geoffrey A. Block, Glenn M. Chertow, Julie Parsonnet
Journal: Annals of Internal Medicine (2021)

Background: Whether breakthrough SARS-CoV-2 infections after vaccination are related to the level of postvaccine circulating antibody is unclear. Objective: To determine longitudinal antibody-based response and risk for breakthrough infection after SARS-CoV-2 vaccination. Design: Prospective study. Setting: Nationwide sample from dialysis facilities. Patients: 4791 patients receiving dialysis. Measurements: Remainder plasma from a laboratory processing routine monthly tests was used to measure qualitative and semiquantitative antibodies to the receptor-binding domain (RBD) of SARS-CoV-2. To evaluate whether peak or prebreakthrough RBD values were associated with breakthrough infection, a nested case–control analysis matched each breakthrough case patient to 5 control patients by age, sex, and vaccination month and adjusted for diabetes status and region of residence. Results: Of the 4791 patients followed with monthly RBD assays, 2563 were vaccinated as of 14 September 2021. Among the vaccinated patients, the estimated proportion with an undetectable RBD response increased from 6.6% (95% CI, 5.5% to 7.8%) 14 to 30 days after vaccination to 20.2% (CI, 17.0% to 23.3%) 5 to 6 months after vaccination. Estimated median index values decreased from 91.9 (CI, 78.6 to 105.2) 14 to 30 days after vaccination to 8.4 (CI, 7.6 to 9.3) 5 to 6 months after vaccination. Breakthrough infections occurred in 56 patients, with samples collected a median of 21 days before breakthrough infection. Compared with prebreakthrough index RBD values of 23 or higher (equivalent to ≥506 binding antibody units per milliliter), prebreakthrough RBD values less than 10 and values from 10 to less than 23 were associated with higher odds for breakthrough infection (rate ratios, 11.6 [CI, 3.4 to 39.5] and 6.0 [CI, 1.5 to 23.6], respectively). Limitations: Single measure of vaccine response; ascertainment of COVID-19 diagnosis from electronic health records. Conclusion: The antibody response to SARS-CoV-2 vaccination wanes rapidly in persons receiving dialysis. In this population, the circulating antibody response is associated with risk for breakthrough infection. Primary Funding Source: Ascend Clinical Laboratory.
IL-17–dependent fibroblastic reticular cell training boosts tissue protective mucosal immunity through IL-10–producing B cells
Authors: Dongwen Wu, Catherine H. Poholek, Saikat Majumder, Qixing Liu, Shankar K. Revu, Kanishka Mohib, David M. Rothstein, Mandy J. McGeachy
Journal: Science Immunology (2021)

Prior experience of pathogen-associated stimuli reduces morbidity and mortality to newly encountered infections through innate immune training, which can be enhanced by childhood vaccination. Fibroblastic reticular cells (FRCs) are stromal cells in lymphoid organs that support lymphocyte localization and survival and modulate adaptive immune responses. IL-17 signaling is important for FRC metabolism and proliferation during inflammatory responses. Here, we show that FRC-intrinsic IL-17 signaling was required for protective antibody-mediated immunity to the gut bacterial pathogen
Snare-tip spray spark coagulation technique for bleeding secondary to gastric antral vascular ectasia
Authors: Koudai Hamaguchi, Tatsuma Nomura, Keiichi Ito, Makoto Kobayashi
Journal: Endoscopy (2021)

Gastric antral vascular ectasia is a condition characterized by dilatation of blood vessels in the gastric mucosa. Argon plasma coagulation (APC) was reportedly effective in treating the condition with progressive anemia [1] [2] [3] [4] [5]. However, APC requires special equipment and probe preparation. We developed a new method called the "snare-tip spray spark coagulation technique" to treat bleeding secondary to gastric antral vascular ectasia without using APC.
Bispecific Antibody Takes Down FL
Journal: Cancer Discovery (2021)

In a pivotal phase I/II trial, the investigational bispecific T-cell engaging antibody mosunetuzumab demonstrated high response rates, significantly bettering those historically seen with standard care in patients with relapsed/refractory follicular lymphoma. Drug maker Genentech announced it will file for FDA approval of mosunetuzumab to treat this form of non-Hodgkin lymphoma.
Abstract 11964: Citizen Responders Provide Emotional Support for Relatives to Out-of-Hospital Cardiac Arrest Patients
Authors: Astrid Rolin Kragh, Linn Andelius, Mads Christian Tofte Gregers, Julie Kjoelbye, Line Zinckernagel, Christian Torp-Pedersen, Fredrik Folke, Carolina M Hansen
Journal: Circulation (2021)

Introduction: A citizen responder (CR) system to activate volunteer citizens by a smartphone application (HeartRunner) to nearby cardiac arrests was implemented in 2017 in the Capital Region of Denmark. Participating in resuscitation may not only involve provision of cardio-pulmonary resuscitation (CPR) but also include provision of emotional support for relatives to the cardiac arrest patient. We examined the proportion of CR who reported provision of support to relatives to out-of-hospital cardiac arrest (OHCA) patients during resuscitation attempt. Hypothesis: We hypothesized that CR not only deliver CPR but also provide emotional support to relatives of OHCA patients. Methods: All CR activated by the HeartRunner app received a follow-up questionnaire 90 minutes after the alarm including questions about how CRs participated in resuscitation and whether they provided emotional support to relatives present during the resuscitation attempt. All surveys from March 12, 2020 to June 1, 2021, from CR who accepted an alarm and arrived at the cardiac arrest location were included. Results: A total of 1,868 CR responded to the survey (median age 37 years (IQR 28-37). Half (54.4%) were male and 23.9% health care professionals. CRs arrived before the emergency medical services (EMS) in almost 1/3 (28.9%) of OHCA cases with CR activation, with 227 CRs (41.9%) performing CPR and 139 (25.7%) attaching an automated external defibrillator. In total, more than 433 CRs (23.2%) reported provision of support for relatives at the OHCA location. Even though a higher proportion of support was observed among CR who arrived before the EMS, almost 12% reported provision of support to relatives even when arriving after EMS (Figure). Conclusions: Citizen responders provide not only resuscitative efforts but offer emotional support to relatives to OHCA patients. Citizen responders may be an important resource for both EMS personnel and relatives who are present at the cardiac arrest scene.
Systemic Light Chain Amyloidosis across Europe: Key Outcomes from a Retrospective Study of 4500 Patients
Authors: Giovanni Palladini, Stefan Schönland, Giampaolo Merlini, Paolo Milani, Arnaud Jaccard, Frank Bridoux, Meletios A. Dimopoulos, Sriram Ravichandran, Ute Hegenbart, Wilfried Roeloffzen, M. Teresa Cibeira, Hermine Agis, Monique C. Minnema, Rui Bergantim, Roman Hajek, Cristina João, Alexandros Leonidakis, Giorgos Cheliotis, Pieter Sonneveld, Efstathios Kastritis, Ashutosh D. Wechalekar
Journal: Blood (2021)
An overview of substrate stiffness guided cellular response and its applications in tissue regeneration
Authors: Bingcheng Yi, Qi Xu, Wei Liu
Journal: Bioactive Materials (2021)

Cell-matrix interactions play a critical role in tissue repair and regeneration. With gradual uncovering of substrate mechanical characteristics that can affect cell-matrix interactions, much progress has been made to unravel substrate stiffness-mediated cellular response as well as its underlying mechanisms. Yet, as a part of cell-matrix interaction biology, this field remains in its infancy, and the detailed molecular mechanisms are still elusive regarding scaffold-modulated tissue regeneration. This review provides an overview of recent progress in the area of the substrate stiffness-mediated cellular responses, including 1) the physical determination of substrate stiffness on cell fate and tissue development; 2) the current exploited approaches to manipulate the stiffness of scaffolds; 3) the progress of recent researches to reveal the role of substrate stiffness in cellular responses in some representative tissue-engineered regeneration varying from stiff tissue to soft tissue. This article aims to provide an up-to-date overview of cell mechanobiology research in substrate stiffness mediated cellular response and tissue regeneration with insightful information to facilitate interdisciplinary knowledge transfer and enable the establishment of prognostic markers for the design of suitable biomaterials.
Exploration of Cognitive Outcomes and Risk Factors for Cognitive Decline Shared by Couples
Authors: Hee Won Yang, Jong Bin Bae, Dae Jong Oh, Dong Gyu Moon, Eunji Lim, Jin Shin, Bong Jo Kim, Dong Woo Lee, Jeong Lan Kim, Jin Hyeong Jhoo, Joon Hyuk Park, Jung Jae Lee, Kyung Phil Kwak, Seok Bum Lee, Seok Woo Moon, Seung-Ho Ryu, Shin Gyeom Kim, Ji Won Han, Ki Woong Kim
Journal: JAMA Network Open (2021)

<h3>Importance</h3> Although couples could share many risk factors of cognitive disorders in their lifetime, whether shared risk factors mediate the shared risk of cognitive disorders has rarely been investigated. <h3>Objective</h3> To identify the risk factors of cognitive decline shared within couples and investigate their mediating roles in the shared risk of cognitive disorders and cognitive functions within couples. <h3>Design, Setting, and Participants</h3> A prospective cohort study was launched in November 1, 2010, and 784 participants were followed up every 2 years until December 31, 2020. This nationwide, multicenter, community-based study included older couples from the Korean Longitudinal Study on Cognitive Aging and Dementia (KLOSCAD) and a cohort of their spouses (KLOSCAD-S). <h3>Exposures</h3> The cognitive disorder of a spouse was defined as mild cognitive impairment or dementia. <h3>Main Outcomes and Measures</h3> The mediating roles of factors shared within couples on the association between one spouse's cognitive disorder and the other's risk of cognitive disorders was examined with structural equation modeling. <h3>Results</h3> Included were 784 KLOSCAD participants (307 women [39.2%] and 477 men [60.8%]; mean [SD] age, 74.8 [4.8] years) and their spouses (477 women [60.8%] and 307 men [39.2%]; mean [SD] age, 73.6 [6.2] years). The cognitive disorder of the KLOSCAD participants was associated with almost double the risk of cognitive disorder of their spouses in the KLOSCAD-S cohort (odds ratio, 1.74; 95% CI, 1.12-2.69;<i>P</i> = .01). History of head injury (β = 0.50; 95% CI, 0.09-0.90;<i>P</i> = .02) and age (β = 2.57; 95% CI, 1.37-3.76;<i>P</i> &lt; .001) mediated the association between cognitive disorder in the KLOSCAD participants and their spouses' risk of cognitive disorder. Physical inactivity mediated the association through major depressive disorder (β = 0.33, 95% CI, 0.09-0.57,<i>P</i> = .006 for physical inactivity; β = 0.28, 95% CI, 0.13-0.44,<i>P</i> &lt; .001 for major depressive disorder). These factors similarly mediated the association between spousal cognitive disorder and cognitive functions such as memory and executive function. <h3>Conclusions and Relevance</h3> These findings suggest that the risk factors shared within couples may mediate approximately three-quarters of the spousal risk of cognitive disorders. Identification of and intervention in the shared risk factors of dementia within couples may reduce the risk of cognitive disorders in the spouses of people with dementia.
Pharmacodynamic effects of direct AMP kinase activation in humans with insulin resistance and non-alcoholic fatty liver disease: A phase 1b study
Authors: Pascale Fouqueray, Sebastien Bolze, Julie Dubourg, Sophie Hallakou-Bozec, Pierre Theurey, Jean-Marie Grouin, Clémence Chevalier, Pascale Gluais-Dagorn, David E. Moller, Kenneth Cusi
Journal: Cell Reports Medicine (2021)
Transition from <i>cMyc</i> to <i>L-Myc</i> during dendritic cell development coordinated by rising levels of IRF8
Authors: David A. Anderson, Feiya Ou, Sunkyung Kim, Theresa L. Murphy, Kenneth M. Murphy
Journal: The Journal of Experimental Medicine (2021)

During dendritic cell (DC) development, Myc expression in progenitors is replaced by Mycl in mature DCs, but when and how this transition occurs is unknown. We evaluated DC development using reporters for MYC, MYCL, and cell cycle proteins Geminin and CDT1 in wild-type and various mutant mice. For classical type 1 dendritic cells (cDC1s) and plasmacytoid DCs (pDCs), the transition occurred upon their initial specification from common dendritic cell progenitors (CDPs) or common lymphoid progenitors (CLPs), respectively. This transition required high levels of IRF8 and interaction with PU.1, suggesting the use of EICEs within Mycl enhancers. In pDCs, maximal MYCL induction also required the +41kb Irf8 enhancer that controls pDC IRF8 expression. IRF8 also contributed to repression of MYC. While MYC is expressed only in rapidly dividing DC progenitors, MYCL is most highly expressed in DCs that have exited the cell cycle. Thus, IRF8 levels coordinate the Myc-Mycl transition during DC development.