tbuckley/cabot-search huggingface dataset:
Safety of Combined Division vs Separate Division of the Splenic Vein in Patients Undergoing Distal Pancreatectomy
Authors: Suguru Yamada, Tsutomu Fujii, Fuminori Sonohara, Manabu Kawai, Kazuto Shibuya, Ippei Matsumoto, Kengo Fukuzawa, Hideo Baba, Takeshi Aoki, Michiaki Unno, Sohei Satoi, Yoji Kishi, Etsuro Hatano, Kenichiro Uemura, Akihiko Horiguchi, Masayuki Sho, Yutaka Takeda, Toshio Shimokawa, Yasuhiro Kodera, Hiroki Yamaue
Journal: JAMA Surgery (2021)

In distal pancreatectomy (DP), the splenic vein is isolated from the pancreatic parenchyma prior to being ligated and divided to prevent intra-abdominal hemorrhage from the splenic vein stump with pancreatic fistula (PF). Conversely, dissecting the splenic vein with the pancreatic parenchyma is easy and time-saving.To establish the safety of combined division of the splenic vein compared with separate division of the splenic vein.This study was designed as a multicenter prospective randomized phase 3 trial. All results were analyzed using the modified intent-to-treat set. Patients undergoing DP for pancreatic body and tail tumors were eligible for inclusion. Patients were randomly assigned between August 10, 2016, and July 30, 2019.Patients were centrally randomized (1:1) to either separate division of the splenic vein or combined division of the splenic vein.The primary end point was the incidence of grade B/C PF, and the incidence of intra-abdominal hemorrhage was included as one of the secondary end points.A total of 318 patients were randomly assigned, and 2 patients were excluded as ineligible. Of the 316 remaining patients, 150 (50.3%) were male. The modified intent-to-treat population constituted 159 patients (50.3%) in the separate division group and 157 patients (49.7%) in the combined division group. In the modified intent-to-treat set, the proportion of grade B/C PF in the separate division group was 27.1% (42 of 155) vs 28.6% (44 of 154) in the combined division group (adjusted odds ratio, 1.108; 95% CI, 0.847-1.225; P = .047), demonstrating noninferiority of the combined division of the splenic vein against separate division. The incidence of postoperative intra-abdominal hemorrhage in the 2 groups was identical at 1.3%.This study demonstrated noninferiority of the combined division of the splenic vein compared with separate division of the splenic vein regarding safety. Thus, isolating the splenic vein from the pancreatic parenchyma is deemed unnecessary.ClinicalTrials.gov Identifier: NCT02871804.
2P Molecular imaging evaluation of a novel Claudin18.2 specific monoclonal antibody labeled with radionuclide
Authors: H. Zhu, J. Ding, X. Chong, C. Ji, C. Zhang, F. Teng, Y. Gu, X. Qian, Z. Yang, L. Shen, J. Gao
Journal: Annals of Oncology (2021)
Suppression of Myocardial Hypoxia-Inducible Factor-1α Compromises Metabolic Adaptation and Impairs Cardiac Function in Patients With Cyanotic Congenital Heart Disease During Puberty
Authors: Yiwei Liu, Qipeng Luo, Zhanhao Su, Junyue Xing, Jinlin Wu, Li Xiang, Yuan Huang, Haizhou Pan, Xie Wu, Xiaoling Zhang, Jun Li, Fuxia Yan, Hao Zhang
Journal: Circulation (2021)

Background: Cyanotic congenital heart disease (CCHD) is a complex pathophysiological condition involving systemic chronic hypoxia (CH). Some patients with CCHD are unoperated for various reasons and remain chronically hypoxic throughout their lives, which heightens the risk of heart failure as they age. Hypoxia activates cellular metabolic adaptation to balance energy demands by accumulating hypoxia-inducible factor 1-α (HIF-1α). This study aims to determine the effect of CH on cardiac metabolism and function in patients with CCHD and its association with age. The role of HIF-1α in this process was investigated, and potential therapeutic targets were explored. Methods: Patients with CCHD (n=25) were evaluated for cardiac metabolism and function with positron emission tomography/computed tomography and magnetic resonance imaging. Heart tissue samples were subjected to metabolomic and protein analyses. CH rodent models were generated to enable continuous observation of changes in cardiac metabolism and function. The role of HIF-1α in cardiac metabolic adaptation to CH was investigated with genetically modified animals and isotope-labeled metabolomic pathway tracing studies. Results: Prepubertal patients with CCHD had glucose-dominant cardiac metabolism and normal cardiac function. In comparison, among patients who had entered puberty, the levels of myocardial glucose uptake and glycolytic intermediates were significantly decreased, but fatty acids were significantly increased, along with decreased left ventricular ejection fraction. These clinical phenotypes were replicated in CH rodent models. In patients with CCHD and animals exposed to CH, myocardial HIF-1α was upregulated before puberty but was significantly downregulated during puberty. In cardiomyocyte-specific Hif-1α –knockout mice, CH failed to initiate the switch of myocardial substrates from fatty acids to glucose, thereby inhibiting ATP production and impairing cardiac function. Increased insulin resistance during puberty suppressed myocardial HIF-1α and was responsible for cardiac metabolic maladaptation in animals exposed to CH. Pioglitazone significantly reduced myocardial insulin resistance, restored glucose metabolism, and improved cardiac function in pubertal CH animals. Conclusions: In patients with CCHD, maladaptation of cardiac metabolism occurred during puberty, along with impaired cardiac function. HIF-1α was identified as the key regulator of cardiac metabolic adaptation in animals exposed to CH, and pubertal insulin resistance could suppress its expression. Pioglitazone administration during puberty might help improve cardiac function in patients with CCHD.
Abstract PO-083: Artificial intelligence based detection of breast cancer from transilluminated optical data
Authors: P. Ponram
Journal: Clinical Cancer Research (2021)

Abstract Breast Cancer is a second deadly cancer disease and more than 2 million new cases are being reported annually in recent years. Early diagnosis and mass screening is validated as an effective tool for better disease management. The development of non-invasive affordable first-level screening techniques is required for efficient mass screening. The proposed system consists of a near infra-red optical transmitter connected with a signal modulator and receiver coupled with a demodulator mechanism. A modulated optical waveform provides deep tissue details by high tissue penetration. The constant signal waveform generator and signal oscilloscope were connected for wave generation and measurement. The optical waveform is digitally modulated by light modulation techniques at the transmitter side and demodulated at the receiver side. The normal spot and cancerous spot of the breast phantom model are placed in the path of the optical transmitter and the reflected signal is received by the receiver prior to demodulation. Phase Jitter, Time Jitter, and 3dB noise level were measured from the received signal for the normal as well as a cancerous spot of the breast phantom. The obtained data is given as input to a backpropagation based Artificial Intelligence system for training, validation, and classification. The results indicate that AI based classification of breast tumor from optically transilluminated data will provide substantial improvement of efficiency of the AI system. Also the proposed system can be utilized along with ultrasonography as a hybrid imaging modality. Citation Format: P. Ponram. Artificial intelligence based detection of breast cancer from transilluminated optical data [abstract]. In: Proceedings of the AACR Virtual Special Conference on Artificial Intelligence, Diagnosis, and Imaging; 2021 Jan 13-14. Philadelphia (PA): AACR; Clin Cancer Res 2021;27(5_Suppl):Abstract nr PO-083.
Abstract 12111: 17β-estradiol Suppresses Foam Cell Formation in a Suppressor of Cytokine Signaling 3 Dependent Manner
Authors: Xiao Liang, Ming He, Tao Chen, Yuliang Wu, Yuling Tian, Zuyi Yuan
Journal: Circulation (2012)

Background Evidence from clinical trials and animal experiments has shown that estrogen has anti-atherosclerotic effects when administered to young women or experimental animals. The mechanisms inv...
Maternal 17q21 genotype influences prenatal vitamin D effects on offspring asthma/recurrent wheeze
Authors: Hanna M. Knihtilä, Rachel S. Kelly, Nicklas Brustad, Mengna Huang, Priyadarshini Kachroo, Bo L. Chawes, Jakob Stokholm, Klaus Bønnelykke, Casper-Emil T. Pedersen, Hans Bisgaard, Augusto A. Litonjua, Jessica A. Lasky-Su, Scott T. Weiss
Journal: European Respiratory Journal (2021)

Prenatal vitamin D3 supplementation has been linked to reduced risk of early-life asthma/recurrent wheeze. This protective effect appears to be influenced by variations in the 17q21 functional single nucleotide polymorphism rs12936231 of the child, which regulates the expression of ORMDL3 (ORM1-like 3) and for which the high-risk CC genotype is associated with early-onset asthma. However, this does not fully explain the differential effects of supplementation. We investigated the influence of maternal rs12936231 genotype variation on the protective effect of prenatal vitamin D3 supplementation against offspring asthma/recurrent wheeze.We determined the rs12936231 genotype of mother-child pairs from two randomised controlled trials: the Vitamin D Antenatal Asthma Reduction Trial (VDAART, n=613) and the Copenhagen Prospective Studies on Asthma in Childhood 2010 (COPSAC2010, n=563), to examine the effect of maternal genotype variation on offspring asthma/recurrent wheeze at age 0-3 years between groups who received high-dose prenatal vitamin D3 supplementation versus placebo.Offspring of mothers with the low-risk GG or GC genotype who received high-dose vitamin D3 supplementation had a significantly reduced risk of asthma/recurrent wheeze when compared with the placebo group (hazard ratio (HR) 0.54, 95% CI 0.37-0.77; p<0.001 for VDAART and HR 0.56, 95% CI 0.35-0.92; p=0.021 for COPSAC2010), whereas no difference was observed among the offspring of mothers with the high-risk CC genotype (HR 1.05, 95% CI 0.61-1.84; p=0.853 for VDAART and HR 1.11, 95% CI 0.54-2.28; p=0.785 for COPSAC2010).Maternal 17q21 genotype has an important influence on the protective effects of prenatal vitamin D3 supplementation against offspring asthma/recurrent wheeze.
Representation of Female Faculty at US Medical Schools and Success in Obtaining National Institutes of Health Funding, 2008-2018
Authors: Elizabeth Burney Malinzak, Daniel Weikel, Madhav Swaminathan
Journal: JAMA Network Open (2021)

This cross-sectional study assesses the representation and success of female faculty at US medical schools and their success in obtaining funding from the National Institutes of Health (NIH) between 2008 and 2018.
Abstract 2411: Usefulness of Deblurring (High-Contrast Enhancement) for Detecting Coronary Stents in Multislice Helical CT
Authors: Takahisa Sato, Hirofumi Anno, Sadako Motoyama, Masayoshi Sarai, Kaori Inoue, Hiroto Harigaya, Masanori Okumura, Yukio Ozaki, Hitoshi Hishida, Kazuhiro Katada, Jagat Narula
Journal: Circulation (2006)

Purpose High-speed MSCT with a larger number of detector rows has made coronary CTA clinically useful. However, blooming artifact around high-contrast objects such as stents in the coronary arterie...
Combining behavioral harm-reduction treatment and extended-release naltrexone for people experiencing homelessness and alcohol use disorder in the USA: a randomised clinical trial
Authors: Susan E Collins, Mark H Duncan, Andrew J Saxon, Emily M Taylor, Nigel Mayberry, Joseph O Merrill, Gail E Hoffmann, Seema L Clifasefi, Richard K Ries
Journal: The Lancet Psychiatry (2021)
Not only in silico drug discovery: Molecular modeling towards in silico drug delivery formulations
Authors: Tommaso Casalini
Journal: Journal of Controlled Release (2021)

The use of methods at molecular scale for the discovery of new potential active ligands, as well as previously unknown binding sites for target proteins, is now an established reality. Literature offers many successful stories of active compounds developed starting from insights obtained in silico and approved by Food and Drug Administration (FDA). One of the most famous examples is raltegravir, a HIV integrase inhibitor, which was developed after the discovery of a previously unknown transient binding area thanks to molecular dynamics simulations. Molecular simulations have the potential to also improve the design and engineering of drug delivery devices, which are still largely based on fundamental conservation equations. Although they can highlight the dominant release mechanism and quantitatively link the release rate to design parameters (size, drug loading, et cetera), their spatial resolution does not allow to fully capture how phenomena at molecular scale influence system behavior. In this scenario, the "computational microscope" offered by simulations at atomic scale can shed light on the impact of molecular interactions on crucial parameters such as release rate and the response of the drug delivery device to external stimuli, providing insights that are difficult or impossible to obtain experimentally. Moreover, the new paradigm brought by nanomedicine further underlined the importance of such computational microscope to study the interactions between nanoparticles and biological components with an unprecedented level of detail. Such knowledge is a fundamental pillar to perform device engineering and to achieve efficient and safe formulations. After a brief theoretical background, this review aims at discussing the potential of molecular simulations for the rational design of drug delivery systems.
Validation of the American Joint Committee on Cancer Eighth Edition Staging of Patients With Metastatic Cutaneous Melanoma Treated With Immune Checkpoint Inhibitors
Authors: Jessica J. Waninger, Vincent T. Ma, Sara Journey, Jeremy Skvarce, Zoey Chopra, Alangoya Tezel, Alex K. Bryant, Charles Mayo, Yilun Sun, Kamya Sankar, Nithya Ramnath, Christopher Lao, Jeremy B. Sussman, Leslie Fecher, Ajjai Alva, Michael D. Green
Journal: JAMA Network Open (2021)

Immune checkpoint inhibitors (ICIs) have transformed the survival of patients with metastatic melanoma. Patient prognosis is reflected by the American Joint Committee on Cancer (AJCC) staging system; however, it is unknown whether the metastatic (M) stage categories for cutaneous melanoma remain informative of prognosis in patients who have received ICIs.To evaluate the outcomes of patients with metastatic cutaneous melanoma based on the M stage category from the AJCC eighth edition and to determine whether these designations continue to inform the prognosis of patients who have received ICIs.This cohort study included patients with metastatic cutaneous melanoma who were treated between August 2006 and August 2019 at the University of Michigan. The estimated median follow-up time was 35.5 months. Patient data were collected via the electronic medical record system. Critical findings were externally validated in a multicenter nationwide cohort of patients treated within the Veterans Affairs health care system. Data analysis was conducted from February 2020 to January 2021.All patients were treated with dual-agent concurrent ipilimumab and nivolumab followed by maintenance nivolumab or single-agent ipilimumab, nivolumab, or pembrolizumab therapy. Patients were staged using the AJCC eighth edition.Univariable and multivariable analyses were used to assess the prognostic value of predefined clinicopathologic baseline factors on survival.In a discovery cohort of 357 patients (mean [SD] age, 62.6 [14.2] years; 254 [71.1%] men) with metastatic cutaneous melanoma treated with ICIs, the M category in the AJCC eighth edition showed limited prognostic stratification by both univariable and multivariable analyses. The presence of liver metastases and elevated levels of serum lactate dehydrogenase (LDH) offered superior prognostic separation compared with the M category (liver metastases: hazard ratio, 2.22; 95% CI, 1.48-3.33; P < .001; elevated serum LDH: hazard ratio, 1.73; 95% CI, 1.16-2.58; P = .007). An updated staging system based on these factors was externally validated in a cohort of 652 patients (mean [SD] age, 67.9 [11.6] years; 630 [96.6%] men), with patients without liver metastases or elevated LDH levels having the longest survival (median overall survival, 30.7 months).This study found that the AJCC eighth edition M category was poorly reflective of prognosis in patients receiving ICIs. Future staging systems could consider emphasizing the presence of liver metastases and elevated LDH levels. Additional studies are needed to confirm the importance of these and other prognostic biomarkers.
CARM1 Inhibition Enables Immunotherapy of Resistant Tumors by Dual Action on Tumor Cells and T Cells
Authors: Sushil Kumar, Zexian Zeng, Archis Bagati, Rong En Tay, Lionel A. Sanz, Stella R. Hartono, Yoshinaga Ito, Fieda Abderazzaq, Elodie Hatchi, Peng Jiang, Adam N.R. Cartwright, Olamide Olawoyin, Nathan D. Mathewson, Jason W. Pyrdol, Mamie Z. Li, John G. Doench, Matthew A. Booker, Michael Y. Tolstorukov, Stephen J. Elledge, Frédéric Chédin, X. Shirley Liu, Kai W. Wucherpfennig
Journal: Cancer Discovery (2021)

A number of cancer drugs activate innate immune pathways in tumor cells but unfortunately also compromise antitumor immune function. We discovered that inhibition of CARM1, an epigenetic enzyme and cotranscriptional activator, elicited beneficial antitumor activity in both cytotoxic T cells and tumor cells. In T cells, Carm1 inactivation substantially enhanced their antitumor function and preserved memory-like populations required for sustained antitumor immunity. In tumor cells, Carm1 inactivation induced a potent type 1 interferon response that sensitized resistant tumors to cytotoxic T cells. Substantially increased numbers of dendritic cells, CD8 T cells, and natural killer cells were present in Carm1-deficient tumors, and infiltrating CD8 T cells expressed low levels of exhaustion markers. Targeting of CARM1 with a small molecule elicited potent antitumor immunity and sensitized resistant tumors to checkpoint blockade. Targeting of this cotranscriptional regulator thus offers an opportunity to enhance immune function while simultaneously sensitizing resistant tumor cells to immune attack. SIGNIFICANCE: Resistance to cancer immunotherapy remains a major challenge. Targeting of CARM1 enables immunotherapy of resistant tumors by enhancing T-cell functionality and preserving memory-like T-cell populations within tumors. CARM1 inhibition also sensitizes resistant tumor cells to immune attack by inducing a tumor cell-intrinsic type 1 interferon response.This article is highlighted in the In This Issue feature, p. 1861.
Estimating Chinese foreign health aid: an analysis of AidData's Global Chinese Official Finance dataset
Authors: Paige Kleidermacher, Wenhui Mao, Gavin Yamey, Kaci Kennedy McDade
Journal: The Lancet Global Health (2021)

BackgroundChinese global health aid has expanded tremendously since the 2000s. Unlike many donors, China has no official aid reporting obligations, nor does it voluntarily disclose detailed aid information. Therefore, several third parties have attempted to estimate China's health aid footprint. However, current estimates use varied definitions of health aid, geographic regions, and time spans. These distinct methodological approaches make comparisons of Chinese aid to other aid donors difficult. Our study builds on previous tracking efforts and improves on them by creating a standardised estimate using commonly accepted definitions of aid and frameworks for categorising health projects.MethodsWe categorised AidData's Chinese Official Finance Dataset health-related projects according to health aid frameworks from the Organization for Economic Co-operation and Development (OECD) and the Institute for Health Metrics and Evaluation (IHME). Only projects that fitted the definition of official development assistance were included. We analysed data by both total project count and financial value to assess priority health-aid focus areas for China. We also provide an updated estimate for projects with missing financial values in AidData's database by applying the median cost of similar projects to projects with missing financial values, allowing for comparison with other donors.FindingsBetween 2000 and 2014, China funded 620 health-related aid projects, which made up more than 20% of its total aid project portfolio. Most of these projects were located in Africa. According to the OECD framework, the priority focus areas of these 620 projects were: basic health care, such as medical teams, drugs, and medicine (n=244, 36%); malaria control (118, 19%); medical services, such as specialty equipment, infrastructure and services (108, 17%); and basic health infrastructure (78, 13%). According to the IHME framework, health-systems strengthening accounted for 70% (n=434) of total projects, primarily due to China's contributions to human resources for health, infrastructure, and equipment. The only other significant allocation under the IHME framework was malaria (n=118, 19%). When we estimate missing financial values, we noted that China was the fourth largest health aid donor to African countries from 2008–2014, after the USA, UK, and Canada.InterpretationThese findings enable a better understanding of Chinese health aid in the absence of transparent aid reporting. Such understanding could lead to better coordination, collaboration, and resource allocation for both fellow donors and recipient countries.FundingHuang Fellows Program, Duke University Science & Society (PK).
Methacholine reactivity in lymphangioleiomyomatosis is inversely related to FEV<sub>1</sub> and VEGF-D
Authors: Roberto Cassandro, Davide Elia, Antonella Caminati, Gustavo Pacheco-Rodriguez, Mario Stylianou, Joel Moss, Sergio Harari
Journal: European Respiratory Journal (2021)

<b>Methacholine bronchoprovocation in LAM patients was used to assess airway reactivity. A negative methacholine challenge was associated with a lack of a response to β-adrenergic agonist, higher levels of FEV<sub>1</sub>, and higher levels of VEGF-D</b>https://bit.ly/3aVTFl2
Covid-19: UK officials try to trace unidentified case of Brazil variant
Authors: Gareth Iacobucci
Journal: BMJ (2021)

Public health officials are trying to trace an unidentified person in England who has been infected with the variant of SARS-CoV-2 first identified in Manaus in Brazil.Lawrence Young, professor of molecular oncology at Warwick Medical School, warned that the Brazilian variant could pose a real danger, including to people who had been infected with other variants of the virus."Recent reports from Manaus in Brazil, where the P1 variant is fuelling a surge in infections, suggest that this variant is responsible for reinfecting people who were previously infected with a different variant of the virus," he said."That's why it's even more important to do everything to stop the spread of this virus and all other variants including strict border controls and an efficient test, trace, and isolate system."Three cases of the P.1 variant of concern had been identified in England as of 28 February.This includes two people in one household in south Gloucestershire who flew back from Brazil to London on 10 February.