tbuckley/cabot-search huggingface dataset:
Molecular imaging in oncology: Current impact and future directions
Authors: Steven P. Rowe, Martin G. Pomper
Journal: CA A Cancer Journal for Clinicians (2021)

The authors define molecular imaging, according to the Society of Nuclear Medicine and Molecular Imaging, as the visualization, characterization, and measurement of biological processes at the molecular and cellular levels in humans and other living systems. Although practiced for many years clinically in nuclear medicine, expansion to other imaging modalities began roughly 25 years ago and has accelerated since. That acceleration derives from the continual appearance of new and highly relevant animal models of human disease, increasingly sensitive imaging devices, high-throughput methods to discover and optimize affinity agents to key cellular targets, new ways to manipulate genetic material, and expanded use of cloud computing. Greater interest by scientists in allied fields, such as chemistry, biomedical engineering, and immunology, as well as increased attention by the pharmaceutical industry, have likewise contributed to the boom in activity in recent years. Whereas researchers and clinicians have applied molecular imaging to a variety of physiologic processes and disease states, here, the authors focus on oncology, arguably where it has made its greatest impact. The main purpose of imaging in oncology is early detection to enable interception if not prevention of full-blown disease, such as the appearance of metastases. Because biochemical changes occur before changes in anatomy, molecular imaging-particularly when combined with liquid biopsy for screening purposes-promises especially early localization of disease for optimum management. Here, the authors introduce the ways and indications in which molecular imaging can be undertaken, the tools used and under development, and near-term challenges and opportunities in oncology.
Data Errors and a Wording Error
Journal: JAMA Network Open (2021)

Hong-Qiu Gu, PhD; Xin Yang, MD; Chun-Juan Wang, MD; Xing-Quan Zhao, MD; Yi-Long Wang, MD; Li-Ping Liu, MD; Xia Meng, MD; Yong Jiang, PhD; Hao Li, MD, PhD; Chelsea Liu, MHS; Runqi Wangqin, MD; Gregg C. Fonarow, MD; Lee H. Schwamm, MD; Ying Xian, MD, PhD; Zi-Xiao Li, MD; Yong-Jun Wang, MD, PhD
Large-sized bone defect repair by combining a decalcified bone matrix framework and bone regeneration units based on photo-crosslinkable osteogenic microgels
Authors: Junxiang Hao, Baoshuai Bai, Zheng Ci, Jincheng Tang, Guanhuai Hu, Chengxiang Dai, Mengyuan Yu, Meng Li, Wei Zhang, Yixin Zhang, Wenjie Ren, Yujie Hua, Guangdong Zhou
Journal: Bioactive Materials (2021)

Physiological repair of large-sized bone defects is great challenging in clinic due to a lack of ideal grafts suitable for bone regeneration. Decalcified bone matrix (DBM) is considered as an ideal bone regeneration scaffold, but low cell seeding efficiency and a poor osteoinductive microenvironment greatly restrict its application in large-sized bone regeneration. To address these problems, we proposed a novel strategy of bone regeneration units (BRUs) based on microgels produced by photo-crosslinkable and microfluidic techniques, containing both the osteogenic ingredient DBM and vascular endothelial growth factor (VEGF) for accurate biomimic of an osteoinductive microenvironment. The physicochemical properties of microgels could be precisely controlled and the microgels effectively promoted adhesion, proliferation, and osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) in vitro. BRUs were successfully constructed by seeding BMSCs onto microgels, which achieved reliable bone regeneration in vivo. Finally, by integrating the advantages of BRUs in bone regeneration and the advantages of DBM scaffolds in 3D morphology and mechanical strength, a BRU-loaded DBM framework successfully regenerated bone tissue with the desired 3D morphology and effectively repaired a large-sized bone defect of rabbit tibia. The current study developed an ideal bone biomimetic microcarrier and provided a novel strategy for bone regeneration and large-sized bone defect repair.
Abstract 10559: Association of Intra-Arrest Transport versus Continued On-scene Resuscitation with Survival to Hospital Discharge Among Pediatric Patients with Out-of-Hospital Cardiac Arrest
Authors: Masashi Okubo, Sho Komukai, Junichi Izawa, Ian Drennan, Brian Grunau, Thomas Rea, Clifton W CALLAWAY
Journal: Circulation (2021)

Introduction: For pediatric patients with out-of-hospital cardiac arrest (OHCA) who do not achieve return of spontaneous circulation (ROSC), it remains unclear whether patients should be transported to a hospital with ongoing resuscitation or remain on-scene for further resuscitation. We therefore evaluated: (1) the association between intra-arrest transport, with reference to continued on-scene resuscitation, and survival to hospital discharge; and, (2) whether the association differs across the timing of intra-arrest transport. Methods: We conducted a secondary analysis of the Resuscitation Outcomes Consortium Epidemiologic Registry. We included pediatrics (&lt;18 years) with emergency medical services (EMS)-treated OHCA between 2005 and 2015. Our exposure of interest was intra-arrest transport, defined as transport to a hospital prior to ROSC. Patients who had intra-arrest transport at any minute after EMS arrival underwent risk-set matching with patients who had continued on-scene resuscitation within the same minute using time-dependent propensity score calculated from patient demographics, arrest characteristics, and EMS interventions. We repeated the main analysis with 5-minute strata by the time of matching. Results: Of 2,854 included patients, the median age was 1 year (IQR, 0-9), 59.3% were male, 9.8% were public location, 22.1% were bystander witnessed, 6.0% had initial shockable rhythms, and 66.3% underwent intra-arrest transport at a median of 15 minutes (IQR 9-22) after EMS arrival. In the propensity-matched cohort including 2,080 patients, 5.5 % (57/1040) in intra-arrest transport group and 5.9% (61/1040) in continued on-scene resuscitation group had survival to hospital discharge (risk ratio [RR]=0.94, 95% CI 0.65-1.37). We did not detect an association within the time-based strata: 0-5 minutes (RR=0.74, 95% CI 0.19-2.85), 5-10 minutes (RR=0.52, 95% CI 0.23-1.16), 10-15 minutes (RR=1.13, 95% CI 0.58-2.22), 15-20 minutes, (RR=1.70, 95% CI 0.78-3.71), or &gt;20 minutes (RR=0.73, 95% CI 0.32-1.63) after EMS arrival. Conclusions: Among pediatric patients with OHCA, intra-arrest transport was not associated with survival to hospital discharge. The findings persisted across the timing of intra-arrest transport.
HIC2 Controls Developmental Hemoglobin Switching By Repressing BCL11A Transcription
Authors: Peng Huang, Scott A. Peslak, Eugene Khandros, Xianjiang Lan, Kunhua Qin, Malini Sharma, Cheryl A. Keller, Belinda Giardine, Osheiza Abdulmalik, Stella T. Chou, Junwei Shi, Ross C. Hardison, Gerd A. Blobel
Journal: Blood (2021)
Extracellular ATP is increased by release of ATP-loaded microparticles triggered by nutrient deprivation
Authors: Valentina Vultaggio-Poma, Simonetta Falzoni, Paola Chiozzi, Alba Clara Sarti, Elena Adinolfi, Anna Lisa Giuliani, Alejandro Sánchez-Melgar, Paola Boldrini, Michele Zanoni, Anna Tesei, Paolo Pinton, Francesco Di Virgilio
Journal: Theranostics (2021)

Rationale: Caloric restriction improves the efficacy of anti-cancer therapy.This effect is largely dependent on the increase of the extracellular ATP concentration in the tumor microenvironment (TME).Pathways for ATP release triggered by nutrient deprivation are largely unknown.Methods: The extracellular ATP (eATP) concentration was in vivo measured in the tumor microenvironment of B16F10-inoculated C57Bl/6 mice with the pmeLuc probe.Alternatively, the pmeLuc-TG-mouse was used.Caloric restriction was in vivo induced with hydroxycitrate (HC).B16F10 melanoma cells or CT26 colon carcinoma cells were in vitro exposed to serum starvation to mimic nutrient deprivation.Energy metabolism was monitored by Seahorse.Microparticle release was measured by ultracentrifugation and by Nanosight.Results: Nutrient deprivation increases eATP release despite the dramatic inhibition of intracellular energy synthesis.Under these conditions oxidative phosphorylation was dramatically impaired, mitochondria fragmented and glycolysis and lactic acid release were enhanced.Nutrient deprivation stimulated a P2X7-dependent release of ATP-loaded, mitochondria-containing, microparticles as well as of naked mitochondria.Conclusions: Nutrient deprivation promotes a striking accumulation of eATP paralleled by a large release of ATP-laden microparticles and of naked mitochondria.This is likely to be a main mechanism driving the accumulation of eATP into the TME.
2O IMpower010: Biomarkers of disease-free survival (DFS) in a phase III study of atezolizumab (atezo) vs best supportive care (BSC) after adjuvant chemotherapy in stage IB-IIIA NSCLC
Authors: C. Zhou, M. Das Thakur, M.K. Srivastava, W. Zou, H. Xu, M. Ballinger, E. Felip, H. Wakelee, N.K. Altorki, M. Reck, R. Liersch, A. Kryzhanivska, M. Harada, H. Tanaka, J. Hamm, S. McCune, V. McNally, E. Bennett, B. Gitlitz, S. Novello
Journal: Annals of Oncology (2021)
Macrophage-Targeting by CSF1/1R Blockade in Pancreatic Cancers
Authors: Won Jin Ho, Elizabeth M. Jaffee
Journal: Cancer Research (2021)

Abstract Published in Cancer Research in 2014, Zhu and colleagues achieved a mechanistic leap in our understanding of cancer-associated macrophage biology with their proof-of-concept study showing that macrophage-specific targeting, via blocking colony-stimulating factor–1 (CSF1) signaling through its cognate receptor CSF1R, synergized with checkpoint immunotherapy to enhance antitumor immunity in mouse models of pancreatic cancer. Here, we reflect on the critical set of observations presented in this study and how the study's findings fueled the subsequent efforts to translate CSF1/1R-specific and other tumor-associated macrophage modulating therapies into the clinic. See related article by Zhu and colleagues, Cancer Res 2014;74:5057–5069.
Effect of antiresorptive therapy on aromatase inhibitor induced bone loss in postmenopausal women with early-stage breast cancer: A systematic review and meta-analysis of randomized controlled trials
Authors: Aya Bassatne, Abir Bou Khalil, Marlene Chakhtoura, Asma Arabi, Catherine Van Poznak, Ghada El-Hajj Fuleihan
Journal: Metabolism (2021)
Covid-19: Long covid symptoms among hospital inpatients show little improvement after a year, data suggest
Authors: Ingrid Torjesen
Journal: BMJ (2021)

Covid-19: Long covid symptoms among hospital inpatients show little improvement after a year, data suggest Ingrid TorjesenPeople admitted to hospital with covid-19 who reported "long covid" symptoms five months after discharge had made only limited improvement after a full year, preliminary data from the PHOSP-COVID study show. 2
COVID-19 Breakthrough Infection Among Immunocompromised Persons
Authors: Alfred H. J. Kim, Mary C. Nakamura
Journal: JAMA Internal Medicine (2021)

Jing Sun, MD, MPH, PhD; Qulu Zheng, MS; Vithal Madhira, MS; Amy L. Olex, MS; Alfred J. Anzalone, MS; Amanda Vinson, MD; Jasvinder A. Singh, MD; Evan French, BS; Alison G. Abraham, PhD; Jomol Mathew, PhD; Nasia Safdar, MD, PhD; Gaurav Agarwal, MD, MSPH; Kathryn C. Fitzgerald, ScD; Namrata Singh, MD; Umit Topaloglu, PhD; Christopher G. Chute, MD, DrPH, MPH; Roslyn B. Mannon, MD; Gregory D. Kirk, MD, MPH, PhD; Rena C. Patel, MD, MPH; National COVID Cohort Collaborative (N3C) Consortium; Sandra Safo; David A. Patch; Melissa A. Haendel; Jessica Y. Islam; Hana Akselrod; Nora Franceschini; Teresa P. Chiang; Sharmodeep Bhattacharyya; Carolyn Bramante; Tim Duong; Elizabeth A. Chirischilles
Does Body Mass Index (BMI) during Maintenance Influence Relapse Risk in Children with Acute Lymphoblastic Leukemia (ALL)? Results from COG-AALL03N1
Authors: Aman Wadhwa, Yanjun Chen, Lindsey Hageman, Anna Hoppmann, Anne L Angiolillo, David Dickens, Glen Lew, Joseph P. Neglia, Yaddanapudi Ravindranath, Arthur K. Ritchey, Amanda Muench Termuhlen, Lennie Wong, Wendy Landier, Smita Bhatia
Journal: Blood (2021)
Association of Logic’s hip hop song “1-800-273-8255” with Lifeline calls and suicides in the United States: interrupted time series analysis
Authors: Thomas Niederkrotenthaler, Ulrich S Tran, Madelyn Gould, Mark Sinyor, Steven Sumner, Markus J Strauss, Martin Voracek, Benedikt Till, Sean Murphy, Frances Gonzalez, Matthew J Spittal, John Draper
Journal: BMJ (2021)

Abstract Objective To assess changes in daily call volumes to the US National Suicide Prevention Lifeline and in suicides during periods of wide scale public attention to the song “1-800-273-8255” by American hip hop artist Logic. Design Time series analysis. Setting United States, 1 January 2010 to 31 December 2018. Participants Total US population. Lifeline calls and suicide data were obtained from Lifeline and the Centers for Disease Control and Prevention. Main outcome measures Daily Lifeline calls and suicide data before and after the release of the song. Twitter posts were used to estimate the amount and duration of attention the song received. Seasonal autoregressive integrated moving average time series models were fitted to the pre-release period to estimate Lifeline calls and suicides. Models were fitted to the full time series with dummy variables for periods of strong attention to the song. Results In the 34 day period after the three events with the strongest public attention (the song’s release, the MTV Video Music Awards 2017, and Grammy Awards 2018), Lifeline received an excess of 9915 calls (95% confidence interval 6594 to 13 236), an increase of 6.9% (95% confidence interval 4.6% to 9.2%, P&lt;0.001) over the expected number. A corresponding model for suicides indicated a reduction over the same period of 245 suicides (95% confidence interval 36 to 453) or 5.5% (95% confidence interval 0.8% to 10.1%, P=0.02) below the expected number of suicides. Conclusions Logic’s song “1-800-273-8255” was associated with a large increase in calls to Lifeline. A reduction in suicides was observed in the periods with the most social media discourse about the song.
Infant T cells are developmentally adapted for robust lung immune responses through enhanced T cell receptor signaling
Authors: Puspa Thapa, Rebecca S. Guyer, Alexander Y. Yang, Christopher A. Parks, Todd M. Brusko, Maigan Brusko, Thomas J. Connors, Donna L. Farber
Journal: Science Immunology (2021)

Infants require coordinated immune responses to prevent succumbing to multiple infectious challenges during early life, particularly in the respiratory tract. The mechanisms by which infant T cells are functionally adapted for these responses are not well understood. Here, we demonstrated using an in vivo mouse cotransfer model that infant T cells generated greater numbers of lung-homing effector cells in response to influenza infection compared with adult T cells in the same host, due to augmented T cell receptor (TCR)–mediated signaling. Mouse infant T cells showed increased sensitivity to low antigen doses, originating at the interface between T cells and antigen-bearing accessory cells—through actin-mediated mobilization of signaling molecules to the immune synapse. This enhanced signaling was also observed in human infant versus adult T cells. Our findings provide a mechanism for how infants control pathogen load and dissemination, which is important for designing developmentally targeted strategies for promoting immune responses at this vulnerable life stage.
Efficacy of Long-Acting Bedaquiline Regimens in a Mouse Model of Tuberculosis Preventive Therapy
Authors: Amit Kaushik, Nicole C. Ammerman, Rokeya Tasneen, Sophie Lachau-Durand, Koen Andries, Eric Nuermberger
Journal: American Journal of Respiratory and Critical Care Medicine (2021)

Rationale: Completion of preventive therapy is a major bottleneck in global tuberculosis control. Long-acting injectable drug formulations would shorten therapy administration and may thereby improve completion rates. Recently, a long-acting formulation of bedaquiline demonstrated antituberculosis activity for up to 12 weeks after injection in a validated mouse model of preventive therapy. Objectives: The objectives of this study were to 1) determine the total duration of activity after an injection of long-acting bedaquiline and 2) evaluate the activity of regimens comprised of long-acting bedaquiline plus short (2–4 wk) oral companion courses of bedaquiline, with or without rifapentine, using the validated mouse model of tuberculosis preventive therapy. Methods: After the establishment of a stable Mycobacterium tuberculosis lung infection in bacillus Calmette-Guérin (BCG)-immunized BALB/c mice, treatment was initiated with 1 of 12 randomly assigned regimens. In addition to positive and negative controls, six regimens included one or two injections of long-acting bedaquiline (alone or with oral bedaquiline with or without rifapentine), and four comparator regimens consisted of oral agents only. Lung bacterial burden was measured monthly for up to 28 weeks. Measurements and Main Results: One injection of long-acting bedaquiline at 160 mg/kg exerted antituberculosis activity for 12 weeks. Compared with the positive control (daily isoniazid-rifapentine for 4 wk), six regimens had equivalent bactericidal activity (including two all-oral comparator regimens), and two regimens had superior sterilizing activity: one injection with 2 weeks of oral bedaquiline and high-dose rifapentine; and two injections with 4 weeks of oral bedaquiline. Conclusions: Long-acting injectable bedaquiline has significant potential for shortening tuberculosis preventive therapy.
Abstract 11156: Thoracic Bioimpedance Ventilation Waveforms: Increased Amplitude with Larger Tidal Volume and Female Sex
Authors: Sarah Shaver, Amanda Gonzalez, Mary Chang, james manley, ELISABETE ARAMENDI, Ahamed Idris
Journal: Circulation (2021)

Introduction: Effective ventilation during 30:2 CPR has been linked to improved outcomes, but definitive evidence is lacking. We developed a method to identify thoracic bioimpedance ventilation waveforms from defibrillator recordings. Hypothesis: Bioimpedance ventilation waveform amplitude is proportional to tidal volume. It is possible to identify a minimum amplitude for a valid ventilation waveform. Methods: To determine the relationship between tidal volume and bioimpedance waveform amplitude, we studied 26 healthy volunteers (12 males and 14 females). Volunteers breathed fixed positive pressure tidal volumes (250mL, 300 mL, 400 mL, 600 mL, and 800 mL) given by a Maquet SERVO-I ventilator (Getinge US Sales, Wayne, NJ, USA) through a mouthpiece while a Lifepak12 (Physio-Control, Redmond, WA) defibrillator recorded thoracic bioimpedance through electrode pads placed on the chest. We measured the impedance amplitudes of six breaths at each tidal volume and the weight and height of each volunteer. We set the minimum effective tidal volume at 250 mL. Results: For males and females, respectively, mean (±SD) was 180.1±8 cm vs. 164±3.5 cm, and mean weight was 85.6±9.6 kg vs. 58.3±8.6 kg. Median (IQR) bioimpedance amplitude for each tidal volume split by sex is shown in the Figure (Y-axis, 1 mm = 0.25 Ohm). Conclusion: Bioimpedance amplitude is proportional to tidal volume and also varies by height, weight, and sex. Sex may be a possible surrogate for height and weight. The minimum amplitude is 0.375 Ohm for a valid bioimpedance ventilation waveform.
Tenofovir Alafenamide for Pregnant Chinese Women With Active Chronic Hepatitis B: A Multicenter Prospective Study
Authors: Qing-Lei Zeng, Hong-Xu Zhang, Ji-Yuan Zhang, Shuo Huang, Wei-Zhe Li, Guang-Ming Li, Ya-Jie Pan, Ying-Hua Feng, Zhi-Qin Li, Guo-Fan Zhang, Jiang-Hai Xu, Wan-Bao Lin, Guang-Hua Xu, Na Liu, Guo-Qiang Zhang, Guo-Tao Li, Wei Li, Yan-Li Zeng, Ning Song, Meng Wang, Da-Wei Zhang, Zhi-Min Chen, Guang-Lin Cui, Juan Li, Jun Lv, Yan-Min Liu, Hong-Xia Liang, Chang-Yu Sun, Yi-Hua Zhou, Zu-Jiang Yu, Fu-Sheng Wang
Journal: Clinical Gastroenterology and Hepatology (2021)
Covid-19: High Court overturns decision to ban GP from posting views on pandemic on social media
Authors: Clare Dyer
Journal: BMJ (2021)

A tribunal made an "error of law" when it restrained a GP accused of spreading misinformation about the covid-19 pandemic from discussing the matter on social media, a High Court judge has ruled. 1 Samuel White, who was a partner in a practice in Hampshire, cast doubt on the safety of vaccines and the need to have them and claimed "masks do nothing" in a video posted on social media in June.He said he could no longer work as a GP because of the "lies" surrounding the NHS and the government approach to the pandemic and was leaving conventional medicine to pursue a career in functional medicine.
Dynamic Nanocomposite Microgel Assembly with Microporosity, Injectability, Tissue‐Adhesion, and Sustained Drug Release Promotes Articular Cartilage Repair and Regeneration
Authors: Qi Feng, Dingguo Li, Qingtao Li, Shuxian Li, Hanhao Huang, Haofei Li, Hua Dong, Xiaodong Cao
Journal: Advanced Healthcare Materials (2021)

Abstract Owing to the lack of blood vessels, nerves, and lymph, articular cartilage defect is difficult to self‐repair. Although several cartilage tissue engineering products have been authorized for clinical use, there are still some problems such as large surgical wounds, weak adhesion with the host tissue, and the limited source of autologous chondrocytes. In this paper, a novel dynamic nanocomposite microgel assembly with excellent microporosity, injectability, tissue‐adhesion, and sustained kartogenin (KGN) release is reported. Specifically, KGN‐loaded cyclodextrin nanoparticles are synthesized through nanoemulsification and incorporated into bone marrow mesenchymal stem cell (BMSCs)‐laden microgels via droplet‐based microfluidics and photo‐crosslinking, which are then bottom‐up assembled via dynamic crosslinking between dopamine‐modified hyaluronic acid and phenylboronic acid groups on microgel surface. Results reveal that the microgel assembly can avoid the cell endocytosis of nanoparticles, ensure the high BMSC viability during the regular cell culture, cryopreservation and injection process, promote the chondrogenic differentiation of BMSCs. In addition, animal expriment proves the newborn cartilages present the typical characteristics of articular cartilage. In brief, this microgel assembly not only offers convenience for clinical use (injectability, tissue adhesion) but also provides good microenvironments for chondrogenesis (controlled drug release, interconnected micropores), indicative of its promising application for cartilage repair and regeneration.
Surgical Outcomes Should Know No Identity—The Case for Equity Between Patients and Surgeons
Authors: Andrea N. Riner, Amalia Cochran
Journal: JAMA Surgery (2021)

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