tbuckley/cabot-search huggingface dataset:
Early prognostication of COVID-19 to guide hospitalisation versus outpatient monitoring using a point-of-test risk prediction score
Authors: Felix Chua, Rama Vancheeswaran, Adrian Draper, Tejal Vaghela, Matthew Knight, Rahul Mogal, Jaswinder Singh, Lisa G Spencer, Erica Thwaite, Harry Mitchell, Sam Calmonson, Noor Mahdi, Shershah Assadullah, Matthew Leung, Aisling O'Neill, Chhaya Popat, Radhika Kumar, Thomas Humphries, Rebecca Talbutt, Sarika Raghunath, Philip L Molyneaux, Miriam Schechter, Jeremy Lowe, Andrew Barlow
Journal: Thorax (2021)

Risk factors of adverse outcomes in COVID-19 are defined but stratification of mortality using non-laboratory measured scores, particularly at the time of prehospital SARS-CoV-2 testing, is lacking.Multivariate regression with bootstrapping was used to identify independent mortality predictors in patients admitted to an acute hospital with a confirmed diagnosis of COVID-19. Predictions were externally validated in a large random sample of the ISARIC cohort (N=14 231) and a smaller cohort from Aintree (N=290).983 patients (median age 70, IQR 53-83; in-hospital mortality 29.9%) were recruited over an 11-week study period. Through sequential modelling, a five-predictor score termed SOARS (SpO2, Obesity, Age, Respiratory rate, Stroke history) was developed to correlate COVID-19 severity across low, moderate and high strata of mortality risk. The score discriminated well for in-hospital death, with area under the receiver operating characteristic values of 0.82, 0.80 and 0.74 in the derivation, Aintree and ISARIC validation cohorts, respectively. Its predictive accuracy (calibration) in both external cohorts was consistently higher in patients with milder disease (SOARS 0-1), the same individuals who could be identified for safe outpatient monitoring. Prediction of a non-fatal outcome in this group was accompanied by high score sensitivity (99.2%) and negative predictive value (95.9%).The SOARS score uses constitutive and readily assessed individual characteristics to predict the risk of COVID-19 death. Deployment of the score could potentially inform clinical triage in preadmission settings where expedient and reliable decision-making is key. The resurgence of SARS-CoV-2 transmission provides an opportunity to further validate and update its performance.
BMPR1A maintains skeletal stem cell properties in craniofacial development and craniosynostosis
Authors: Takamitsu Maruyama, Ronay Stevens, Alan Boka, Laura DiRienzo, Connie Chang, Hsiao-Man Ivy Yu, Katsuhiko Nishimori, Clinton Morrison, Wei Hsu
Journal: Science Translational Medicine (2021)

Stemness of skeletal stem cells in the calvarium is maintained by BMPR1A; disruption depletes stem cells and causes cranial bone fusion.
Assessing the impact of the COVID-19 pandemic on patients with genitourinary malignancies.
Authors: Hala Borno, Sylvia Zhang, Scarlett Lin Gomez, Celia Kaplan, Christine Miaskowski, Julian Hong, Dame Idossa, Adina Bailey, Eric Jay Small
Journal: Journal of Clinical Oncology (2021)

38 Background: The COVID-19 pandemic has vast implications on the health system. Patients with a cancer diagnosis may face greater challenges in the context of the current COVID-19 pandemic. Methods: We sought to assess the impact of the COVID-19 pandemic among patients with genitourinary malignancies. We performed a cross-sectional survey study at a Comprehensive Cancer Center during the current pandemic. Results: A total of 86 participants were recruited to the study to date, 72.1% had prostate, 19.8% had kidney, and 12.8% had bladder cancer. A subset (n = 5) had more than one primary tumor. The mean time from diagnosis was 6.47 years (std dev 6.01, range from 0 to 27 years). Overall, 73% reported having metastatic disease and prior treatment with surgery (62%), radiation (71%), or systemic therapy (68%), with 68.6% currently receiving cancer treatment. In the study, 78.9% of patients were &gt;65 years of age and 88.2% were White. The majority of participants had a bachelor’s degree or higher level of education (74.4%), were legally married (82.6%), were homeowners (91.9%), and reported an annual household income of &gt;$100,000 (56.0%). Among respondents, 7% reported loss/change of health insurance and 30% reported a decrease in household income. Among patients with reduced household income, 23% reported a reduction of more than 50%. In this study, 28% of patients reported that the pandemic impacted their cancer treatment. Overall 7% reported decrease in frequency of labs, 11% reported a delay in obtaining a scan, 5% reported treatment delays, and 96% reported use of telemedicine (video or telephone) visit. Overall, 59% reported fear of hospitalization, 23% reported delays in seeking medical care, and 16% reported missing required medications. Conclusions: The negative impact of the COVID-19 pandemic on patients with genitourinary malignancies is extensive. Ongoing research is evaluating the impact across socio-demographically groups and examine clinical outcomes associated with delays in care and medication non-adherence.
Deep-learning system to improve the quality and efficiency of volumetric heart segmentation for breast cancer
Authors: Roman Zeleznik, Jakob Weiss, Jana Taron, Christian Guthier, Danielle S. Bitterman, Cindy Hancox, Benjamin H. Kann, Daniel W. Kim, Rinaa S. Punglia, Jeremy Bredfeldt, Borek Foldyna, Parastou Eslami, Michael T. Lu, Udo Hoffmann, Raymond Mak, Hugo J. W. L. Aerts
Journal: npj Digital Medicine (2021)

Abstract Although artificial intelligence algorithms are often developed and applied for narrow tasks, their implementation in other medical settings could help to improve patient care. Here we assess whether a deep-learning system for volumetric heart segmentation on computed tomography (CT) scans developed in cardiovascular radiology can optimize treatment planning in radiation oncology. The system was trained using multi-center data ( n = 858) with manual heart segmentations provided by cardiovascular radiologists. Validation of the system was performed in an independent real-world dataset of 5677 breast cancer patients treated with radiation therapy at the Dana-Farber/Brigham and Women’s Cancer Center between 2008–2018. In a subset of 20 patients, the performance of the system was compared to eight radiation oncology experts by assessing segmentation time, agreement between experts, and accuracy with and without deep-learning assistance. To compare the performance to segmentations used in the clinic, concordance and failures (defined as Dice &lt; 0.85) of the system were evaluated in the entire dataset. The system was successfully applied without retraining. With deep-learning assistance, segmentation time significantly decreased (4.0 min [IQR 3.1–5.0] vs. 2.0 min [IQR 1.3–3.5]; p &lt; 0.001), and agreement increased (Dice 0.95 [IQR = 0.02]; vs. 0.97 [IQR = 0.02], p &lt; 0.001). Expert accuracy was similar with and without deep-learning assistance (Dice 0.92 [IQR = 0.02] vs. 0.92 [IQR = 0.02]; p = 0.48), and not significantly different from deep-learning-only segmentations (Dice 0.92 [IQR = 0.02]; p ≥ 0.1). In comparison to real-world data, the system showed high concordance (Dice 0.89 [IQR = 0.06]) across 5677 patients and a significantly lower failure rate ( p &lt; 0.001). These results suggest that deep-learning algorithms can successfully be applied across medical specialties and improve clinical care beyond the original field of interest.
Molecular biology of Hodgkin lymphoma
Authors: Marc A. Weniger, Ralf Küppers
Journal: Leukemia (2021)

Abstract Classical Hodgkin lymphoma (cHL) is unique among lymphoid malignancies in several key biological features. (i) The Hodgkin and Reed-Sternberg (HRS) tumor cells are rare among an extensive and complex microenvironment. (ii) They derive from B cells, but have largely lost the B-cell typical gene expression program. (iii) Their specific origin appears to be pre-apoptotic germinal center (GC) B cells. (iv) They consistently develop bi- or multinucleated Reed-Sternberg cells from mononuclear Hodgkin cells. (v) They show constitutive activation of numerous signaling pathways. Recent studies have begun to uncover the basis of these specific features of cHL: HRS cells actively orchestrate their complex microenvironment and attract many distinct subsets of immune cells into the affected tissues, to support their survival and proliferation, and to create an immunosuppressive environment. Reed-Sternberg cells are generated by incomplete cytokinesis and refusion of Hodgkin cells. Epstein-Barr virus (EBV) plays a major role in the rescue of crippled GC B cells from apoptosis and hence is a main player in early steps of lymphomagenesis of EBV + cHL cases. The analysis of the landscape of genetic lesions in HRS cells so far did not reveal any highly recurrent HRS cell-specific lesions, but major roles of genetic lesions in members of the NF-κB and JAK/STAT pathways and of factors of immune evasion. It is perhaps the combination of the genetic lesions and the peculiar cellular origin of HRS cells that are disease defining. A combination of such genetic lesions and multiple cellular interactions with cells in the microenvironment causes the constitutive activation of many signaling pathways, often interacting in complex fashions. In nodular lymphocyte predominant Hodgkin lymphoma, the GC B cell-derived tumor cells have largely retained their typical GC B-cell expression program and follicular microenvironment. For IgD-positive cases, bacterial antigen triggering has recently been implicated in early stages of its pathogenesis.
FDG PET/CT to Detect Incidental Findings in Patients With Hepatocellular Carcinoma—Additional Benefit for Patients Considered for Liver Transplantation?
Authors: Thomas Winkens, William Rudakoff, Falk Rauchfuss, Christina Malessa, Utz Settmacher, Martin Freesmeyer
Journal: Clinical Nuclear Medicine (2021)

Purpose FDG PET/CT has been described for noninvasive grading, detection of extrahepatic spread, and recurrence in hepatocellular carcinoma (HCC). As compared with localized imaging approaches (MRI, ultrasonography), FDG PET/CT not only focuses on the liver, but covers a long field of view from the base of the skull to the thighs, visualizing pathologic findings not related to HCC. The aims of this retrospective study were to (1) describe the frequency of relevant incidental findings on FDG PET/CT in HCC patients, (2) evaluate the impact on treatment strategy in HCC patients considered for liver transplantation, and (3) to discuss the role of FDG PET/CT in patients considered for transplantation in general. Methods Four hundred thirty-nine FDG PET/CT examinations of 345 HCC patients were screened for incidental findings. The clinical information system was searched for examinations performed after FDG PET/CT and aimed at verification of incidental findings. Of 345 HCC patients, 81 patients were considered for liver transplantation. The impact of incidental findings was recorded separately for this subgroup. Results One hundred one patients with incidental findings in 439 FDG PET/CT examinations were identified. The incidental findings comprised 22 neoplasms (9 malignant) and 52 inflammations. Liver transplantation was not performed because of an incidental finding on FDG PET/CT in 9 (11.1%) of 81 patients. Conclusions FDG PET/CT is capable of identifying relevant incidental findings (ie, secondary malignancy, benign tumors, and inflammation) in HCC patients and HCC patients considered for liver transplantation and thus influencing HCC patient management. FDG PET/CT might also be beneficial in patients considered for transplantation of different organs.
Peroral targeting of drug micro or nanocarriers to sites beyond the gastrointestinal tract
Authors: Zichen Zhang, Jianping Qi, Yi Lu, Wei Wu, Hailong Yuan
Journal: Medicinal Research Reviews (2021)

Abstract Targeted delivery of drug micro or nanocarriers has been attained via parenteral routes, especially the intravenous route. Conventionally, oral targeting refers to site‐specific delivery and triggered drug release at local sites within the gastrointestinal tract (GIT), or targeting to the enteric epithelia through ligand‐receptor or transporter interactions. Beyond that barrier, the concept of peroral targeting has not been clarified. Nevertheless, this is possible as long as drug carriers are able to be absorbed into the systemic circulation intact. Recent findings on in vivo translocation of drug micro or nanocarriers shed light on potential peroral targeting to remote sites beyond the GIT. Sequential processes of penetration across the enteric epithelia, transportation via the lymphatics and ultimate convergence with the systemic circulation are involved in the underlying mechanisms. The microfold cell (M cell) pathway plays a leading role in breaking through the enteric epithelial barrier. Accumulating evidence confirms primary targeting of a series of lipid and polymeric micro or nanocarriers to organs and tissues of the mononuclear phagocyte systems (MPS), such as the liver, spleen, lungs and kidneys. The total amount of lymph‐bound particles could reach 8%, as evidenced by quantification of glucan microparticles that specifically bind M cell. Migration or translocation of micro or nanocarrier‐bearing macrophages attains secondary targeting of the engulfed micro or nanocarriers to distant sites far beyond the MPS. The current findings foresee a probability of targeting to sites beyond the GIT. However, the content of exposure of micro or nanocarriers at target sites and potential therapeutic or diagnostic promises are yet to be unraveled.
Effect of exposure to fine particulate matter during pregnancy and infancy on paediatric allergic rhinitis
Authors: Yu-Ting Lin, Hao Shih, Chau-Ren Jung, Chi-Min Wang, Ya-Chu Chang, Chia-Yun Hsieh, Bing-Fang Hwang
Journal: Thorax (2021)

The effect of prenatal and postnatal exposure to fine particulate matter (PM2.5) on the development of allergic rhinitis (AR) is poorly understood. We further identified the vulnerable period for AR development to determine methods to decrease adverse effects.We used a large population-based birth cohort of 140 911 singleton live infants in Taichung, Taiwan with a highly temporal-resolution satellite-based hybrid model to evaluate the effects of prenatal and early postnatal exposure on the onset of AR.Among 140 911 children, 47 276 (33.55%) were cases of incident AR. The mean age of the children with AR at initial diagnosis was 2.97±1.78 years. We identified a significant association of AR with an interquartile range (IQR 17.98 µg/m3) increase in PM2.5 from 30 gestational weeks to 52 weeks after birth. The exposure-response relationship revealed that AR had a significant positive association between PM2.5 of 26-76 µg/m3 (adjusted hazard ratios ranged from 1.00 to 1.05).Our study provides evidence that both prenatal and postnatal exposures to PM2.5 are associated with later development of AR. The vulnerable time window may be within late gestation and the first year of life. Further study is required to confirm the vulnerable time period of PM2.5 on AR.
SUMOylation promotes extracellular vesicle–mediated transmission of lncRNA ELNAT1 and lymph node metastasis in bladder cancer
Authors: Changhao Chen, Hanhao Zheng, Yuming Luo, Yao Kong, Mingjie An, Yuting Li, Wang He, Bowen Gao, Yue Zhao, Hao Huang, Jian Huang, Tianxin Lin
Journal: Journal of Clinical Investigation (2021)

Small ubiquitin-like modifier (SUMO) binding (termed SUMOylation) emerged as the inducer for the sorting of bioactive molecules into extracellular vesicles (EVs), triggering lymphangiogenesis and further driving tumor lymph node (LN) metastasis, but the precise mechanisms remain largely unclear. Here, we show that bladder cancer (BCa) cell-secreted EVs mediated intercellular communication with human lymphatic endothelial cells (HLECs) through transmission of the long noncoding RNA ELNAT1 and promoted lymphangiogenesis and LN metastasis in a SUMOylation-dependent manner in both cultured BCa cell lines and mouse models. Mechanistically, ELNAT1 induced UBC9 overexpression to catalyze the SUMOylation of hnRNPA1 at the lysine 113 residue, which mediated recognition of ELNAT1 by the endosomal sorting complex required for transport (ESCRT) and facilitated its packaging into EVs. EV-mediated ELNAT1 was specifically transmitted into HLECs and epigenetically activated SOX18 transcription to induce lymphangiogenesis. Importantly, blocking the SUMOylation of tumor cells by downregulating UBC9 expression markedly reduced lymphatic metastasis in EV-mediated, ELNAT1-treated BCa in vivo. Clinically, EV-mediated ELNAT1 was correlated with LN metastasis and a poor prognosis for patients with BCa. These findings highlight a molecular mechanism whereby the EV-mediated ELNAT1/UBC9/SOX18 regulatory axis promotes lymphangiogenesis and LN metastasis in BCa in a SUMOylation-dependent manner and implicate ELNAT1 as an attractive therapeutic target for LN metastatic BCa.
2021 consensus statement for preventing and managing low back pain in elite and subelite adult rowers
Authors: Fiona Wilson, Jane S Thornton, Kellie Wilkie, Jan Hartvigsen, Anders Vinther, Kathryn E Ackerman, J P Caneiro, Larissa Trease, Frank Nugent, Conor Gissane, Sarah-Jane McDonnell, Alison McGregor, Craig Newlands, Clare L Ardern
Journal: British Journal of Sports Medicine (2021)

Purpose To synthesise evidence on low back pain (LBP) in adult rowers and to create a consensus statement to inform clinical practice. Methods There were four synthesis steps that informed the consensus statement. In step one, seven expert clinicians and researchers established the scope of the consensus statement and conducted a survey of experienced and expert clinicians to explore current practice. In step two, working groups examined current evidence relating to key scope questions and summarised key issues. In step three, we synthesised evidence for each group and used a modified Delphi process to aid in the creation of the overall consensus statements. Finally, in step four, we combined information from step three with the findings of the clinician survey (and with athlete and coach input) to produce recommendations for clinical practice. Results The scope of the consensus statement included epidemiology; biomechanics; management; the athlete’s voice and clinical expertise. Prevention and management of LBP in rowers should include education on risk factors, rowing biomechanics and training load. If treatment is needed, non-invasive management, including early unloading from aggravating activities, effective pain control and exercise therapy should be considered. Fitness should be maintained with load management and progression to full training and competition. The role of surgery is unclear. Management should be athlete focused and a culture of openness within the team encouraged. Conclusion Recommendations are based on current evidence and consensus and aligned with international LBP guidelines in non-athletic populations, but with advice aimed specifically at rowers. We recommend that research in relation to all aspects of prevention and management of LBP in rowers be intensified.
Gender representation in the authorship of dermatology publications
Authors: Melissa R. Laughter, Madeleine G. Yemc, Colby L. Presley, Kayd J. Pulsipher, Mindy D. Szeto, Tessa Zangara, Chandler W. Rundle, Mayra B.C. Maymone, Robert P. Dellavalle
Journal: Journal of the American Academy of Dermatology (2021)
Sports injuries and illnesses at the Lausanne 2020 Youth Olympic Winter Games: a prospective study of 1783 athletes from 79 countries
Authors: Debbie Palmer, Lars Engebretsen, Justin Carrard, Natalia Grek, Karsten Königstein, Debbie J Maurer, Thomas Roos, Lauren Stollenwerk, Stephane Tercier, Raphael Weinguni, Torbjørn Soligard
Journal: British Journal of Sports Medicine (2021)

To describe the injury and illness characteristics among participating athletes during the Lausanne 2020 Youth Olympic Winter Games (YOG 2020), 9-22 January 2020.The daily number of athlete injuries and illnesses were recorded (1) through the reporting of all National Olympic Committee (NOC) medical teams and (2) in the polyclinic and medical venues by the Lausanne 2020 medical staff.In total, 1783 athletes from 79 NOCs were observed. NOC and Lausanne 2020 medical staff reported 228 injuries and 167 illnesses, equating 11.7 injuries and 8.6 illnesses per 100 athletes over the 14-day period. Injury incidence was highest for snowboard slopestyle (39%), bobsleigh (36%), snowboard big air (29%), ski slopestyle (29%), snowboard cross (24%) and ski cross (21%), and lowest for speed skating, snowboard halfpipe and curling (2%-4%). The highest incidence of illness was recorded for curling (21%), ski mountaineering (15%), snowboard halfpipe (13%), bobsleigh (11%), cross-country skiing (10%) and figure skating (10%). Almost one-third of injuries were expected to result in time loss and 17% of illnesses. Most injuries occurred to the knee (12%) and head (11%), and 64% of illnesses affected the respiratory system. Overall, women suffered more injuries and illness than males.Overall, injury and illness rates were similar compared with recent YOG. While the rate and characteristics of injury and illness varied between sports, consistent patterns across YOG are emerging. If addressed, changes in highlighted areas of risk could have a positive impact on the health and well-being of these young athletes.
Determination of Effective Albumin in Patients With Decompensated Cirrhosis: Clinical and Prognostic Implications
Authors: Maurizio Baldassarre, Marina Naldi, Giacomo Zaccherini, Michele Bartoletti, Agnese Antognoli, Maristella Laggetta, Martina Gagliardi, Manuel Tufoni, Marco Domenicali, Katja Waterstradt, Paola Paterini, Anna Baldan, Simona Leoni, Manuela Bartolini, Pierluigi Viale, Franco Trevisani, Mauro Bernardi, Paolo Caraceni
Journal: Hepatology (2021)

Background and Aims Circulating albumin in cirrhosis can be dysfunctional because of accumulating structural damages, leading to the concept of effective albumin concentration (eAlb), referring to the albumin portion presenting structural and functional integrity. We aimed to estimate eAlb in patients with decompensated cirrhosis and analyze its relationships with albumin function and clinical outcomes as compared to total albumin concentration (tAlb). Approach and Results We evaluated 319 patients with cirrhosis hospitalized for acute decompensation (AD) with and without acute‐on‐chronic liver failure (ACLF) and 18 age‐ and sex‐comparable outpatients with compensated cirrhosis. tAlb was quantified by standard assay, whereas eAlb was estimated combining liquid chromatography/electrospray ionization/mass spectrometry and standard methods. Albumin binding and detoxification efficiency were evaluated by electron paramagnetic resonance analysis. Circulating albumin in patients with decompensated cirrhosis displayed multiple structural abnormalities, with reversible oxidation and glycation being the most frequent. As a result, eAlb progressively declined with the worsening of cirrhosis and was superior to tAlb in stratifying patients between compensated cirrhosis, AD, and ACLF, as well as patients with and without complications. Moreover, eAlb, but not tAlb, was closely associated with binding capacities in ACLF. Finally, eAlb at admission predicted the occurrence of ACLF within 30 days and mortality at 90 days better than tAlb. Conclusions This large, observational study provides the evidence in patients with decompensated cirrhosis that eAlb can be quantified and differentiated from tAlb routinely measured in clinical practice. As compared to tAlb, eAlb is more closely associated with disease severity and albumin dysfunction and carries a greater prognostic power. These results prompt future research assessing eAlb as a biomarker for predicting prognosis and treatment response.