Search

A new Cu,P-doped, sodium fluorosilicate-based optically stimulated luminescence (OSL) phosphor is developed. This phosphor shows good OSL properties, and the sensitivity is comparable with that of the commercial Al2O3:C (Landauer, Inc.) phosphor. For the luminescence averaged over initial 1 s, blue-stimulated luminescence and green-stimulated luminescence sensitivities were found to be 0.76 and 3.8 times, respectively, of Al2O3:C (Landauer, Inc.) with 28 % of post-irradiation fading in 3 days and nil thereafter. The simple preparation procedure, fast decay, very good sensitivity and moderate fading will make this phosphor suitable for radiation dosimetry, using OSL. [ABSTRACT FROM PUBLISHER]

Tb3+-doped SrSiO3 phosphor synthesised by co-precipitation technique exhibits intense green emission due to cross-relaxation phenomena between Tb3+ ions. Dosimetric properties of this phosphor have been investigated using thermoluminescence (TL) technique. A dosimetrically useful glow peak observed was at 581 K along with a linear dose response over the wide dose range (100 mGy–4 Gy). TL parameters such as trap depth (E), frequency factor (s) and the order of kinetics (b) are determined by different methods such as Chen's peak shape, initial rise, isothermal decay and variable heating rate methods. Results of these methods are compared and reported in this study. [ABSTRACT FROM PUBLISHER]

Background: Early diagnosis of pulmonary hypertension (PH) is critical for effective treatment and management. We aimed to develop and externally validate an artificial intelligence algorithm that could serve as a PH screening tool, based on analysis of a standard 12-lead ECG., Methods: The PH Early Detection Algorithm (PH-EDA) is a convolutional neural network developed using retrospective ECG voltage-time data, with patients classified as "PH-likely" or "PH-unlikely" (controls) based on right heart catheterisation or echocardiography. In total, 39 823 PH-likely patients and 219 404 control patients from Mayo Clinic were randomly split into training (48%), validation (12%) and test (40%) sets. ECGs taken within 1 month of PH diagnosis (diagnostic dataset) were used to train the PH-EDA at Mayo Clinic. Performance was tested on diagnostic ECGs within the test sets from Mayo Clinic (n=16 175/87 998 PH-likely/controls) and Vanderbilt University Medical Center (VUMC; n=6045/24 256 PH-likely/controls). In addition, performance was tested on ECGs taken 6-18 months (pre-emptive dataset), and up to 5 years prior to a PH diagnosis at both sites., Results: Performance testing yielded an area under the receiver operating characteristic curve (AUC) of 0.92 and 0.88 in the diagnostic test sets at Mayo Clinic and VUMC, respectively, and 0.86 and 0.81, respectively, in the pre-emptive test sets. The AUC remained a minimum of 0.79 at Mayo Clinic and 0.73 at VUMC up to 5 years before diagnosis., Conclusion: The PH-EDA can detect PH at diagnosis and 6-18 months prior, demonstrating the potential to accelerate diagnosis and management of this debilitating disease., Competing Interests: Conflict of interest: H.M. DuBrock and R.P. Frantz report personal fees from Janssen Research and Development, LLC, a Johnson and Johnson company, outside the submitted work; and that additionally, Mayo Clinic may benefit financially from the algorithm described. T.E. Wagner, K. Carlson, C.L. Carpenter, S. Awasthi, M. Babu, A. Prasad, U. Yoo, R. Barve and V. Soundararajan are employees of nference, which received financial support from Janssen Research and Development, LLC, a Johnson and Johnson company, for work on this study. T.E. Wagner, S. Awasthi and V. Soundararajan also have patent application numbers 63/091,715 (non-invasive methods for detection of pulmonary hypertension) and 63/126,331 (systems and methods for diagnosing a health condition based on patient time series data) pending. K. Carlson, C.L. Carpenter, M. Babu, A. Prasad and R. Barve also have a patent application number 63/126,331 (systems and methods for diagnosing a health condition based on patient time series data) pending. Z.I. Attia, P.A. Friedman and S. Kapa have nothing to disclose apart from the fact that Mayo Clinic may financially benefit from the algorithm described in future. A.R. Hemnes, J. Annis and E.L. Brittain have no competing interests to report. S.J. Asirvatham reports personal fees from Abiomed, Atricure, Biotronik, Blackwell Futura, Boston Scientific, Medtronic, Medtelligence, Spectranetics, St. Jude, Zoll, Aegis, ATP, Nevro, Sanovas, Sorin Medical and FocusStart, outside the submitted work; and additionally, Mayo Clinic may financially benefit from the algorithm described in future. S.J. Asirvatham also receives royalties for work licensed through Mayo Clinic to a privately held company for contributions related to the use of nerve signal modulation to treat central, autonomic and peripheral nervous system disorders, including pain. Mayo Clinic receives royalties and owns equity in this company. The company does not currently license or manufacture any drug or device in the medical field. S.J. Asirvatham is a co-patent holder for technique to minimise coagulum formation during radiofrequency ablation. Products/techniques related to the above disclosures are not being discussed in this publication. M. Selej, P. Agron, E. Kogan, D. Quinn, P. Dunnmon and N. Khan are employees of Janssen Research and Development, LLC, a Johnson and Johnson company and own shares in the company., (Copyright ©The authors 2024.)

Purpose: The number of older adults with head and neck squamous cell carcinoma (HNSCC) is increasing, and treatment of these patients is challenging. Although cisplatin-based chemotherapy concomitantly with radiation therapy is considered the standard regimen for patients with locoregionally advanced HNSCC, there is substantial real-world heterogeneity regarding concomitant chemotherapy in older patients with HNSCC., Methods and Materials: The SENIOR study is an international multicenter cohort study including older patients (≥65 years) with HNSCC treated with definitive radiation therapy at 13 academic centers in the United States and Europe. Patients with concomitant chemoradiation were analyzed regarding overall survival (OS) and progression-free survival (PFS) via Kaplan-Meier analyses. Fine-Gray competing risk regressions were performed regarding the incidence of locoregional failures and distant metastases., Results: Six hundred ninety-seven patients with a median age of 71 years were included in this analysis. Single-agent cisplatin was the most common chemotherapy regimen (n = 310; 44%), followed by cisplatin plus 5-fluorouracil (n = 137; 20%), carboplatin (n = 73; 10%), and mitomycin C plus 5-fluorouracil (n = 64; 9%). Carboplatin-based regimens were associated with diminished PFS (hazard ratio [HR], 1.39 [1.03-1.89]; P < .05) and a higher incidence of locoregional failures (subdistribution HR, 1.54 [1.00-2.38]; P = .05) compared with single-agent cisplatin, whereas OS (HR, 1.15 [0.80-1.65]; P = .46) was comparable. There were no oncological differences between single-agent and multiagent cisplatin regimens (all P > .05). The median cumulative dose of cisplatin was 180 mg/m 2 (IQR, 120-200 mg/m 2 ). Cumulative cisplatin doses ≥200 mg/m 2 were associated with increased OS (HR, 0.71 [0.53-0.95]; P = .02), increased PFS (HR, 0.66 [0.51-0.87]; P = .003), and lower incidence of locoregional failures (subdistribution HR, 0.50 [0.31-0.80]; P = .004). Higher cumulative cisplatin doses remained an independent prognostic variable in the multivariate regression analysis for OS (HR, 0.996 [0.993-0.999]; P = .009)., Conclusions: Single-agent cisplatin can be considered in the standard chemotherapy regimen for older patients with HNSCC who can tolerate cisplatin. Cumulative cisplatin doses are prognostically relevant in older patients with HNSCC., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: Pericoronary adipose tissue (PCAT) may influence plaque development through inflammatory mechanisms. We assessed PCAT density, as a measure of pericoronary inflammation, in relationship to coronary plaque among people with human immunodeficiency virus (HIV [PWH]) and to a matched control population., Methods: In this baseline analysis of 727 participants of the Randomized Trial to Prevent Vascular Events in HIV (REPRIEVE) Mechanistic Substudy, we related computed tomography-derived PCAT density to presence and extent (Leaman score) of coronary artery disease (CAD), noncalcified plaque, coronary artery calcium (CAC), and vulnerable plaque features using multivariable logistic regression analyses. We further compared the PCAT density between PWH and age, sex, body mass index, CAC score, and statin use-matched controls from the community-based Framingham Heart Study (N = 464), adjusting for relevant clinical covariates., Results: Among 727 REPRIEVE participants (age 50.8 ± 5.8 years; 83.6% [608/727] male), PCAT density was higher in those with (vs without) coronary plaque, noncalcified plaque, CAC >0, vulnerable plaque, and high CAD burden (Leaman score >5) (P < .001 for each comparison). PCAT density related to prevalent coronary plaque (adjusted odds ratio [per 10 HU]: 1.44; 95% confidence interval, 1.22-1.70; P < .001), adjusted for clinical cardiovascular risk factors, body mass index, and systemic immune/inflammatory biomarkers. Similarly, PCAT density related to CAC >0, noncalcified plaque, vulnerable plaque, and Leaman score >5 (all P ≤ .002). PCAT density was greater among REPRIEVE participants versus Framingham Heart Study (-88.2 ± 0.5 HU versus -90.6 ± 0.4 HU; P < .001)., Conclusions: Among PWH in REPRIEVE, a large primary cardiovascular disease prevention cohort, increased PCAT density independently associated with prevalence and severity of coronary plaque, linking increased coronary inflammation to CAD in PWH., Competing Interests: Potential conflicts of interest. B. F. reports institutional research support from AstraZeneca, MedImmune, and MedTrace, all outside of the submitted work. M. V. Z. reports grant support through her institution from NIH/NIAID and Gilead Sciences, Inc., relevant to the conduct of the study, as well as grants from NIH/NIAID and NIH/NHLBI (RO1AI123001 PI, R01 HL137562 PI, R01HL146267 PI, K24AI157882 PI, U01HL123336 Co-I, U01HL123336-06S2 Co-I, R01HL151283 Co-I) outside the submitted work; travel support from conference organizing committees for CROI and International Workshop for HIV and Women; and unpaid participation in DSMB for NIH-funded studies. A. L. reports institutional research support from NIH/NIA, outside of the submitted work. T. H. B. reports equity in Excision Bio Therapeutics and serves on its Scientific Advisory Board, outside the submitted work. G. S. B. reports research grants (R01HL157531, U01HL146382, R56HL152803, R01MD013493) and royalties from UpToDate.com. C. D. M. reports institutional research support by Lilly and personal fees from ViiV Healthcare, Pfizer, and Gilead Sciences for participation in advisory board meetings outside the submitted work. C. J. F. reports grant support through his institution from Gilead Sciences, ViiV Healthcare, GSK, Janssen, Abbvie, Merck, Amgen, and Cytodyn, outside the submitted work; and personal fees from Theratechnologies and ViiV for consulting and participation on Advisory Board unrelated to REPRIEVE with Theratechnologies and ViiV, and role as Chair on DSMB for Intrepid Study, outside the submitted work. J. A. A. reports institutional research support for clinical trials from Atea, Emergent Biosolutions, Frontier Technologies, Gilead Sciences, Glaxo Smith Kline, Janssen, Merck, Pfizer, Regeneron, and ViiV Healthcare and personal fees for data safety monitoring or advisory boards from Kintor Pharmaceuticals, Glaxo Smith Kline, and Merck; all outside the submitted work. J. S. C. reports consulting fees from Merck and Company. H. J. R. reports grants from NIH/NHLBI and Kowa Pharmaceuticals during the conduct of the study as well as grants from NIH/NIAID, and NIH/NHLBI, NIH/NIDDK, and NIH/NIA outside the submitted work. U. H. reports institutional research support from Kowa, AstraZeneca, MedImmune, and HeartFlow; consulting fees from Recor Medical, Stanford University, Clinical Cardiovascular Sciences, MedTrace Inc., and Rapid AI; stock or stock options in Cleerly Inc. as Chief Scientific Officer; and personal fees from Duke University, all outside of the submitted work. M. T. L. reports grant support through his institution from NIH/NHLIBI and Kowa Pharmaceuticals America, Inc., for the conduct of the study; institutional grant support from MedImmune, CRICO, Ionis, Johnson & Johnson Innovation, National Academy of Medicine, and Astrazeneca; and personal fees from PQBypass, outside of the current work. P. S. D. reports consulting fees from Foresite Labs; receipt of equipment or drugs from Kowa and Caption Health; and an institutional grant for HeartFlow (outside of the current work). S. K. G. reports grants from NIH, KOWA Pharmaceuticals, Gilead Sciences, and ViiV Healthcare during the conduct of the study as well as personal consulting fees from TheraTechnologies, Navidea, and ViiV Healthcare, and Marathon Asset Management outside the submitted work. All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2023. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

The incidence of human papillomavirus (HPV) associated oropharyngeal squamous cell carcinoma (OPSCC) is increasing among elderly (≥70 years) patients and the optimal treatment approach is not known. In this study, we aimed to determine disease and toxicity outcomes in an elderly HPV-OPSCC population primarily treated with a chemoradiation (CRT) approach. We identified 70 elderly HPV-OPSCC patients who were treated with either surgery, radiotherapy, or CRT between 2011 and 2021. Time-to-event analysis for overall survival (OS), progression-free survival (PFS), and local control (LC) were conducted using the Kaplan-Meier method. Univariate and multivariable cox regression models were used to estimate the hazard ratio associated with covariates. The median follow-up for our cohort was 43.9 months. Of the 70 elderly patients, 55 (78.6%) receive CRT and 15 (22.4%) received RT alone. Two patients underwent TORS resection. Of the 55 patients treated with CRT, the most common systemic agents were weekly carboplatin/taxol (n = 18), cetuximab (n = 17), and weekly cisplatin (n = 11). The 5-year OS, PFS, and LC were 57%, 52%, and 91%, respectively. On univariate analysis, Eastern Cooperative Oncology Group performance status and Charlson Comorbidity Index (CCI) were significant predictors of OS, while on multivariate analysis only CCI was a significant predictor of OS (p = 0.006). The rate of late peg tube dependency, osteoradionecrosis, and aspiration was 10%, 4%, and 4%, respectively. Definitive local therapy in elderly HPV-OPSCC patients is associated with excellent LC and a low rate of late toxicities. Prospective studies are needed to further stratify subgroups of elderly patients who may benefit from aggressive definitive local therapy., (© 2023 Wiley Periodicals LLC.)

Background: Atherosclerotic cardiovascular disease (ASCVD) is the leading cause of death worldwide, driven primarily by coronary artery disease (CAD). ASCVD risk estimators such as the pooled cohort equations (PCE) facilitate risk stratification and primary prevention of ASCVD but their accuracy is still suboptimal., Methods: Using deep electronic health record data from 7,116,209 patients seen at 70+ hospitals and clinics across 5 states in the USA, we developed an artificial intelligence-based electrocardiogram analysis tool (ECG-AI) to detect CAD and assessed the additive value of ECG-AI-based ASCVD risk stratification to the PCE. We created independent ECG-AI models using separate neural networks including subjects without known history of ASCVD, to identify coronary artery calcium (CAC) score ≥300 Agatston units by computed tomography, obstructive CAD by angiography or procedural intervention, and regional left ventricular akinesis in ≥1 segment by echocardiogram, as a reflection of possible prior myocardial infarction (MI). These were used to assess the utility of ECG-AI-based ASCVD risk stratification in a retrospective observational study consisting of patients with PCE scores and no prior ASCVD. The study period covered all available digitized EHR data, with the first available ECG in 1987 and the last in February 2023., Findings: ECG-AI for identifying CAC ≥300, obstructive CAD, and regional akinesis achieved area under the receiver operating characteristic (AUROC) values of 0.88, 0.85, and 0.94, respectively. An ensembled ECG-AI identified 3, 5, and 10-year risk for acute coronary events and mortality independently and additively to PCE. Hazard ratios for acute coronary events over 3-years in patients without ASCVD that tested positive on 1, 2, or 3 versus 0 disease-specific ECG-AI models at cohort entry were 2.41 (2.14-2.71), 4.23 (3.74-4.78), and 11.75 (10.2-13.52), respectively. Similar stratification was observed in cohorts stratified by PCE or age., Interpretation: ECG-AI has potential to address unmet need for accessible risk stratification in patients in whom PCE under, over, or insufficiently estimates ASCVD risk, and in whom risk assessment over time periods shorter than 10 years is desired., Funding: Anumana., Competing Interests: SA, NS, RA, YG, AGA, SA, SB, SS, LH, NV, HA, MB, RB, and VS were employees of nference, inc. and/or Anumana, inc. at the time the work was conducted and held vested or unvested stock. MS is an employee and stockholder of Novartis Pharmaceuticals Corporation. PAF, ZIA, and FLJ are advisors to Anumana. In conjunction with Mayo Clinic, PAF, ZIA, FLJ, and JMRI have filed patents related to the application of AI to the ECG for diagnosis and risk stratification., (© 2023 Mayo Clinic Foundation.)

Craniosynostosis is characterised by the premature fusion of one or more cranial sutures, resulting in an abnormal head shape. The management of craniosynostosis requires early diagnosis, surgical intervention, and long-term monitoring. With the advancements in artificial intelligence (AI) technologies, there is great potential for AI to assist in various aspects of managing craniosynostosis. The main aim of this article is to review available literature describing the current uses of AI in craniosynostosis. The main applications highlighted include diagnosis, surgical planning, and outcome prediction. Many studies have demonstrated the accuracy of AI in differentiating subtypes of craniosynostosis using machine learning (ML) algorithms to classify craniosynostosis based on simple photographs. This demonstrates its potential to be used as a screening tool and may allow patients to monitor disease progression reducing the need for CT scanning. ML algorithms can also analyse CT scans to aid in the accurate and efficient diagnosis of craniosynostosis, particularly when training junior surgeons. However, the lack of sufficient data currently limits this clinical application. Virtual surgical planning for cranial vault remodelling using prefabricated cutting guides has been shown to allow more precise reconstruction by minimising the subjectivity of the clinicians' assessment. This was particularly beneficial in reducing operating length and preventing the need for blood transfusions. Despite the potential benefits, there are numerous challenges associated with implementing AI in craniosynostosis. The integration of AI in craniosynostosis holds significant promise for improving the management of craniosynostosis. Further collaboration between clinicians, researchers, and AI experts is necessary to harness its full potential., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2023, Qamar et al.)

Background: Carboplasty is a new minimally invasive technique for knee osteoarthritis (OA) that consists of injecting tibial marrow aspirate into the bone-cartilage interface as well as intra-articularly., Purpose: To compare the clinical and imaging outcomes, as well as the safety, of carboplasty for symptomatic knee OA in a placebo-controlled trial., Study Design: Randomized controlled trial; Level of evidence, 1., Methods: The authors conducted a randomized controlled trial to compare carboplasty with placebo for the treatment of symptomatic knee OA. Patients who had failed medical treatment and had bone edema on magnetic resonance imaging (MRI) were randomized in a 1:1 ratio to carboplasty or placebo. The primary outcome of the study was the Numeric Pain Rating Scale (NPRS) for the knee at 1 year (scores range from 0 to 10, with a higher score indicating worse pain). Secondary outcomes were the Knee injury and Osteoarthritis Outcome Score (KOOS), treatment responder rate (based on achieving the minimal clinically important difference of the NPRS), MRI bone edema reduction, and treatment safety., Results: In total, 50 patients (25 carboplasty vs 25 placebo) were enrolled and followed up with for an average of 18 months (range, 14-24 months). The average NPRS at baseline decreased from 7.1 ± 0.9 to 2.9 ± 2.1 ( P < .001) at 1 year in the carboplasty group and from 7.7 ± 0.9 to 4.9 ± 2.2 ( P < .001) in the placebo group. On average, patients after carboplasty improved 60% from their initial NPRS, and patients after placebo improved 37% ( P = .003). Patients had a statistically significantly greater improvement from baseline in all KOOS subscales in the carboplasty group compared with the placebo group ( P < .001). The responder rates were 96% for carboplasty and 76% for placebo ( P = .098). Bone edema was reduced in 72% of patients in the carboplasty group and 44% of patients in the placebo group ( P = .045). Neither group had adverse events related to treatment., Conclusion: Carboplasty resulted in greater pain reduction, a significantly greater improvement in all KOOS subscales, and a similar safety profile compared with placebo in patients with symptomatic knee OA and bone edema., Registration: ISRCTN69838191 (ISRCT Registry)., Competing Interests: One or more of the authors has declared the following potential conflict of interest or source of funding: This study was funded by the Vad Foundation. V.V. is the founder of the biotech company Vad Scientific, and R.B. is a shareholder of Vad Scientific. AOSSM checks author disclosures against the Open Payments Database (OPD). AOSSM has not conducted an independent investigation on the OPD and disclaims any liability or responsibility relating thereto., (© The Author(s) 2022.)

Objectives: To perform a mixed-methods study identifying motivators and deterrents to female doctors interested in core surgical training (CST). To provide tangible implementations based on the findings., Design: This study used quantitative (questionnaires) and qualitative (semistructured interviews (SSIs)) analyses. Participants completed online questionnaires on Qualtrics and SSIs were conducted remotely on Microsoft Teams. Questions were derived from previous studies and a novel term, the gender impact rating (GIR), was coined to assess the impact of gender on opportunities available during CST application., Setting: Participants were working in the UK National Health Service and data collected from December 2020 to January 2021., Participants: A total of 100 female surgical trainees in the UK ranging from Foundation Year 2 to Core Training Year 2., Main Outcome Measures: Participants ranked factors by their influence on their CST application. Of the 100 trainees, 21 were randomly selected for an SSI to explore their questionnaire responses. Statistical analyses were performed using MATLAB and SPSS, alongside a thematic analysis of the interviews., Results: A total of 44 out of 100 questionnaire respondents ranked early exposure to surgery as the most influential motivator, while 43% selected work-life balance as the greatest deterrent and 33% suggested mentoring schemes to encourage women to apply to CST. The median GIR was 3 out of 5, indicating a moderate perceived impact of gender on opportunities available during CST application. Qualitative analysis found four overarching themes: institutional factors (including mentorship schemes), organisational culture (including active engagement), social factors and personal factors., Conclusion: Thematic analysis suggested that seniors involving women in theatre and a supportive work environment would encourage entry of more female surgeons. Therefore, the proposed implementations are the active engagement of women in theatre and destigmatising less than full-time training. Further research into ethnicity and personality on motivations to enter surgery is advised., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Visceral artery aneurysms (VAAs) are associated with a very high mortality rate when ruptured and may present as a surgical emergency. Due to their rarity and varying pathophysiology, literature concerning the optimal management of VAAs is limited. This review evaluates the evolving management options for VAAs with a focus on open and endovascular repair., Methods: A combination of databases including OVID, PubMed and Medline were used to perform a literature search. Search terms employed include 'visceral artery aneurysms', 'angiography', '3D-volumetric rendering', 'management', 'open repair' and 'endovascular repair', amongst others., Results: 3D modelling in conjunction with existing diagnostic techniques, such as computed tomography and angiography, may improve diagnostic sensitivity. The literature surrounding operative management of VAAs highlights the effectiveness of endovascular repair for anatomically suitable aneurysms. Advances in endovascular technologies may expand the type and number of aneurysms amenable to catheter-based treatment approaches. For aneurysms not amenable to endovascular treatment, or those with an emergency indication, open repair remains an appropriate management choice., Conclusion: Although rare, VAAs pose a high mortality risk, especially when ruptured. Practical limitations that restrict current operative approaches may be overcome by recent developments including novel neurointerventional techniques that have been applied in VAA management., (Copyright © 2021. Published by Elsevier Inc.)

Understanding the relationships between pre-existing conditions and complications of COVID-19 infection is critical to identifying which patients will develop severe disease. Here, we leverage ~1.1 million clinical notes from 1803 hospitalized COVID-19 patients and deep neural network models to characterize associations between 21 pre-existing conditions and the development of 20 complications (e.g. respiratory, cardiovascular, renal, and hematologic) of COVID-19 infection throughout the course of infection (i.e. 0-30 days, 31-60 days, and 61-90 days). Pleural effusion was the most frequent complication of early COVID-19 infection (89/1803 patients, 4.9%) followed by cardiac arrhythmia (45/1803 patients, 2.5%). Notably, hypertension was the most significant risk factor associated with 10 different complications including acute respiratory distress syndrome, cardiac arrhythmia, and anemia. The onset of new complications after 30 days is rare and most commonly involves pleural effusion (31-60 days: 11 patients, 61-90 days: 9 patients). Lastly, comparing the rates of complications with a propensity-matched COVID-negative hospitalized population confirmed the importance of hypertension as a risk factor for early-onset complications. Overall, the associations between pre-COVID conditions and COVID-associated complications presented here may form the basis for the development of risk assessment scores to guide clinical care pathways., (© 2021. The Author(s).)

Technology to generate single cell RNA-sequencing (scRNA-seq) datasets and tools to annotate them have advanced rapidly in the past several years. Such tools generally rely on existing transcriptomic datasets or curated databases of cell type defining genes, while the application of scalable natural language processing (NLP) methods to enhance analysis workflows has not been adequately explored. Here we deployed an NLP framework to objectively quantify associations between a comprehensive set of over 20,000 human protein-coding genes and over 500 cell type terms across over 26 million biomedical documents. The resultant gene-cell type associations (GCAs) are significantly stronger between a curated set of matched cell type-marker pairs than the complementary set of mismatched pairs (Mann Whitney p = 6.15 × 10 -76 , r = 0.24; cohen's D = 2.6). Building on this, we developed an augmented annotation algorithm (single cell Annotation via Literature Encoding, or scALE) that leverages GCAs to categorize cell clusters identified in scRNA-seq datasets, and we tested its ability to predict the cellular identity of 133 clusters from nine datasets of human breast, colon, heart, joint, ovary, prostate, skin, and small intestine tissues. With the optimized settings, the true cellular identity matched the top prediction in 59% of tested clusters and was present among the top five predictions for 91% of clusters. scALE slightly outperformed an existing method for reference data driven automated cluster annotation, and we demonstrate that integration of scALE can meaningfully improve the annotations derived from such methods. Further, contextualization of differential expression analyses with these GCAs highlights poorly characterized markers of well-studied cell types, such as CLIC6 and DNASE1L3 in retinal pigment epithelial cells and endothelial cells, respectively. Taken together, this study illustrates for the first time how the systematic application of a literature-derived knowledge graph can expedite and enhance the annotation and interpretation of scRNA-seq data.

Background: Consecutive negative SARS-CoV-2 PCR test results are being considered to estimate viral clearance in COVID-19 patients. However, there are anecdotal reports of hospitalization from protracted COVID-19 complications despite such confirmed viral clearance, presenting a clinical conundrum., Methods: We conducted a retrospective analysis of 222 hospitalized COVID-19 patients to compare those that were readmitted post-viral clearance ( hospitalized post-clearance cohort, n  = 49) with those that were not re-admitted post-viral clearance ( non-hospitalized post-clearance cohort, n  = 173) between February and October 2020. In order to differentiate these two cohorts, we used neural network models for the 'augmented curation' of comorbidities and complications with positive sentiment in the Electronic Hosptial Records physician notes., Findings: In the year preceding COVID-19 onset, anemia ( n  = 13 [26.5%], p-value: 0.007), cardiac arrhythmias ( n  = 14 [28.6%], p-value: 0.015), and acute kidney injury ( n  = 7 [14.3%], p-value: 0.030) were significantly enriched in the physician notes of the hospitalized post-clearance cohort ., Interpretation: Overall, this retrospective study highlights specific pre-existing conditions that are associated with higher hospitalization rates in COVID-19 patients despite viral clearance and motivates follow-up prospective research into the associated risk factors., Funding: This work was supported by Nference, inc., Competing Interests: CP, AJV, ER, CK, GB, AP, NK, AA, RB, ADB, and VS have financial interests in nference, Inc. ADB is a consultant for Abbvie and Flambeau Diagnostics and is a DSMB member at Corvus and Equilium. ADB is on the scientific advisory boards for nference and Zentalis and is founder and President of Splissen therapeutics. JCO receives personal fees from Elsevier and Bates College, and receives small grants from nference, Inc, outside the submitted work. CP, AJV, ER, CK, GB, AP, NK, AA, RB and VS are nference employees. CP, NK, VS, CK, AA, AP, AJV, ER, GB and RB received personal fees from nference. The Mayo Clinic has a Financial Conflict of Interest in technology used in the research and may stand to gain financially from the successful outcome of the research. This research has been reviewed by the Mayo Clinic Conflict of Interest Review Board and is being conducted in compliance with Mayo Clinic Conflict of Interest policies., (© 2021 The Authors.)

Understanding temporal dynamics of COVID-19 symptoms could provide fine-grained resolution to guide clinical decision-making. Here, we use deep neural networks over an institution-wide platform for the augmented curation of clinical notes from 77,167 patients subjected to COVID-19 PCR testing. By contrasting Electronic Health Record (EHR)-derived symptoms of COVID-19-positive (COVID pos ; n = 2,317) versus COVID-19-negative (COVID neg ; n = 74,850) patients for the week preceding the PCR testing date, we identify anosmia/dysgeusia (27.1-fold), fever/chills (2.6-fold), respiratory difficulty (2.2-fold), cough (2.2-fold), myalgia/arthralgia (2-fold), and diarrhea (1.4-fold) as significantly amplified in COVID pos over COVID neg patients. The combination of cough and fever/chills has 4.2-fold amplification in COVID pos patients during the week prior to PCR testing, in addition to anosmia/dysgeusia, constitutes the earliest EHR-derived signature of COVID-19. This study introduces an Augmented Intelligence platform for the real-time synthesis of institutional biomedical knowledge. The platform holds tremendous potential for scaling up curation throughput, thus enabling EHR-powered early disease diagnosis., Competing Interests: TW, KM, SA, AV, SB, AP, MK, PA, ML, ZD, ES, HS, AA, RB, VS is an employee of nference and has financial interests in the company. FS, BP, JO, PB, RR, PV, ZT, SR, MM, WW, DC, GG, AW, WM, JH, AB has a Financial Conflict of Interest in technology used in the research and with Mayo Clinic may stand to gain financially from the successful outcome of the research. This research has been reviewed by the Mayo Clinic Conflict of Interest Review Board and is being conducted in compliance with Mayo Clinic Conflict of Interest policies., (© 2020, Wagner et al.)

The COVID-19 pandemic demands assimilation of all biomedical knowledge to decode mechanisms of pathogenesis. Despite the recent renaissance in neural networks, a platform for the real-time synthesis of the exponentially growing biomedical literature and deep omics insights is unavailable. Here, we present the nferX platform for dynamic inference from over 45 quadrillion possible conceptual associations from unstructured text, and triangulation with insights from single-cell RNA-sequencing, bulk RNA-seq and proteomics from diverse tissue types. A hypothesis-free profiling of ACE2 suggests tongue keratinocytes, olfactory epithelial cells, airway club cells and respiratory ciliated cells as potential reservoirs of the SARS-CoV-2 receptor. We find the gut as the putative hotspot of COVID-19, where a maturation correlated transcriptional signature is shared in small intestine enterocytes among coronavirus receptors (ACE2, DPP4, ANPEP). A holistic data science platform triangulating insights from structured and unstructured data holds potential for accelerating the generation of impactful biological insights and hypotheses., Competing Interests: AV, AP, AA, DZ, BR, TW, EG, HS, AG, RB, VS is affiliated with nference. The author has financial interests in nference. XY, XW, KS, AA, NK is affiliated with Janssen. The author has financial interests in Janssen. RC, DM is affiliated with nference. The author has financial interests in nference, (© 2020, Venkatakrishnan et al.)

We performed a transcriptome-wide meta-analysis and gene co-expression network analysis to identify genes and gene networks dysregulated in the peripheral blood of bipolar disorder (BD) cases relative to unaffected comparison subjects, and determined the specificity of the transcriptomic signatures of BD and schizophrenia (SZ). Nineteen genes and 4 gene modules were significantly differentially expressed in BD cases. Thirteen gene modules were shown to be differentially expressed in a combined case-group of BD and SZ subjects called "major psychosis", including genes biologically linked to apoptosis, reactive oxygen, chromatin remodeling, and immune signaling. No modules were differentially expressed between BD and SZ cases. Machine-learning classifiers trained to separate diagnostic classes based solely on gene expression profiles could distinguish BD cases from unaffected comparison subjects with an area under the curve (AUC) of 0.724, as well as BD cases from SZ cases with AUC = 0.677 in withheld test samples. We introduced a novel and straightforward method called "polytranscript risk scoring" that could distinguish BD cases from unaffected subjects (AUC = 0.672) and SZ cases (AUC = 0.607) significantly better than expected by chance. Taken together, our results highlighted gene expression alterations common to BD and SZ that involve biological processes of inflammation, oxidative stress, apoptosis, and chromatin regulation, and highlight disorder-specific changes in gene expression that discriminate the major psychoses., Competing Interests: Declaration of Competing Interest The authors have no conflicts of interest to declare., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Despite the burden of disease of CVD and DM, there is a lack of experimentally validated literature exploring their association with exacerbation of COVID-19. Target receptors of medications commonly used to treat CVD and DM may be involved in the viral entry mechanism of SARS-CoV-2. We propose the potential protective effects of these medications in COVID-19 infections, highlighting the need for further research. Firstly, AMPK mediated phosphorylation of ACE-2 by metformin as well as the drug's alkaline properties may interrupt the natural disease progression. Secondly, DPP4 receptor involvement in the putative viral entry of SARS-CoV-2 may be prevented by DPP4i. Finally, recent studies have shown that statins' ability to inhibit the cytokine storm may outweigh concerns of statin mediated ACE-2 upregulation in COVID-19. The complex interplay of factors affecting CVD and DM in COVID-19 patients makes the direct effects of medications difficult to examine. Therefore, further research is needed, in the context of SARS-CoV-2 and the molecular pathways it exploits, to potentially repurpose such pre-existing drugs for their use in COVID-19., Competing Interests: Conflict of InterestThe authors declare that they have no conflict of interest., (© The Author(s) 2020.)

Puberty/adolescence is a significant period of development and a time with a high emergence of psychiatric disorders. During this period, there is increased neuroplasticity and heightened vulnerability to stress and inflammation. The gut microbiome regulates stress and inflammatory responses and can alter brain chemistry and behaviour. However, the role of the gut microbiota during pubertal development remains largely uninvestigated. The current study examined gut manipulation with probiotics during puberty in CD1 mice on lipopolysaccharide (LPS)-induced immune responses and enduring effects on anxiety- and depression-like behaviours and stress-reactivity in adulthood. Probiotics reduced LPS-induced sickness behaviour at 12 h in females and at 48 h following LPS treatment in males. Probiotics also reduced LPS-induced changes in body weight at 48 h post-treatment in females. Probiotic treatment also prevented LPS-induced increases in pro- and anti-inflammatory peripheral cytokines at 8 h following LPS treatment, reduced central cytokine mRNA expression in the hypothalamus, hippocampus and PFC, and prevented LPS-induced changes to in the gut microbiota. A single exposure to LPS during puberty resulted in enduring depression-like behaviour in female mice, and anxiety-like behaviour in male mice in adulthood. However, pubertal exposure to probiotics prevented enduring LPS-induced depression-like behaviour in females and anxiety-like behaviors in males. Moreover, probiotics altered toll-like receptor-4 activity in the paraventricular nucleus of the hypothalamus (PVN) in males in response to a novel stressor in adulthood. Our results suggest that the gut microbiome plays an important role in pubertal neurodevelopment. These findings indicate that exposure to probiotics during puberty mitigates inflammation and decreases stress-induced vulnerabilities to emotional behaviours later in life, in a sex-specific manner., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Introduction: The aim of the study was to evaluate the outcomes of Arthroscopic ACL Reconstruction using Fixed suspensory device and Adjustable suspensory device for femoral side graft fixation., Material and Methods: We conducted a prospective study of sixty two patients with ACL deficient knees treated with arthroscopic ACL reconstruction. Consecutively patients were operated with fixed loop and adjustable loop suspensory devices for femoral side graft fixation and no randomization was done., Results: Functional assessment was performed with VAS score, IKDC score and Lyshom score before and after surgery with ACL reconstruction. The postoperative Lyshom score in fixed loop group and adjustable loop group was 94.23 and 94.32 respectively. The IKDC score in fixed group and adjustable group was 92.03 and 92.16 respectively. VAS in fixed loop group improved from score of 5-3, while in adjustable loop group from score of 4-3. There was significant improvement in stability of knee assessed by Lachman's test, anterior drawer test, and Pivot shiff's test and both methods of fixation provide stability to knee. The complications included; restriction of terminal flexion in 12 patients: 6 in each group. There was no implant breakage in both groups., Conclusion: Arthroscopic ACL reconstruction using fixed loop and adjustable loop suspensory devices are equally effective fixation methods.

Molecular and behavioral responses to opioids are thought to be primarily mediated by neurons, although there is accumulating evidence that other cell types play a prominent role in drug addiction. To investigate cell-type-specific opioid responses, we performed single-cell RNA sequencing (scRNA-seq) of the nucleus accumbens of mice following acute morphine treatment. Differential expression analysis uncovered unique morphine-dependent transcriptional responses by oligodendrocytes and astrocytes. We examined the expression of selected genes, including Cdkn1a and Sgk1, by FISH, confirming their induction by morphine in oligodendrocytes. Further analysis using RNA-seq of FACS-purified oligodendrocytes revealed a large cohort of morphine-regulated genes. The affected genes are enriched for roles in cellular pathways intimately linked to oligodendrocyte maturation and myelination, including the unfolded protein response. Altogether, our data illuminate the morphine-dependent transcriptional response by oligodendrocytes and offer mechanistic insights into myelination defects associated with opioid abuse., (Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.)

Blood-based microarray studies comparing individuals affected with autism spectrum disorder (ASD) and typically developing individuals help characterize differences in circulating immune cell functions and offer potential biomarker signal. We sought to combine the subject-level data from previously published studies by mega-analysis to increase the statistical power. We identified studies that compared ex vivo blood or lymphocytes from ASD-affected individuals and unrelated comparison subjects using Affymetrix or Illumina array platforms. Raw microarray data and clinical meta-data were obtained from seven studies, totaling 626 affected and 447 comparison subjects. Microarray data were processed using uniform methods. Covariate-controlled mixed-effect linear models were used to identify gene transcripts and co-expression network modules that were significantly associated with diagnostic status. Permutation-based gene-set analysis was used to identify functionally related sets of genes that were over- and under-expressed among ASD samples. Our results were consistent with diminished interferon-, EGF-, PDGF-, PI3K-AKT-mTOR-, and RAS-MAPK-signaling cascades, and increased ribosomal translation and NK-cell related activity in ASD. We explored evidence for sex-differences in the ASD-related transcriptomic signature. We also demonstrated that machine-learning classifiers using blood transcriptome data perform with moderate accuracy when data are combined across studies. Comparing our results with those from blood-based studies of protein biomarkers (e.g., cytokines and trophic factors), we propose that ASD may feature decoupling between certain circulating signaling proteins (higher in ASD samples) and the transcriptional cascades which they typically elicit within circulating immune cells (lower in ASD samples). These findings provide insight into ASD-related transcriptional differences in circulating immune cells. © 2016 Wiley Periodicals, Inc., (© 2016 Wiley Periodicals, Inc.)

Studies were carried out to assess the correlation between thermoluminescence (TL) and optically stimulated luminescence (OSL) of this phosphor. It was observed that the OSL and TL glow curve consists of a wide distribution of traps having different photo-ionization cross-sections, trap depths and frequency factors. In case of Al doped sample, some of the traps up to 200°C are assumed to act as a source traps for the observance of OSL due to thermal transfer of charge carriers into the deep traps beyond 480°C. This suggests that Al impurities play an important role in the thermal transfer OSL process. As most of the work on this phenomenon is done on natural materials (mainly quartz) in which aluminum is a natural impurity, this study will explain the role of Al in this phenomenon., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

The application of microarray technology in schizophrenia research was heralded as paradigm-shifting, as it allowed for high-throughput assessment of cell and tissue function. This technology was widely adopted, initially in studies of postmortem brain tissue, and later in studies of peripheral blood. The collective body of schizophrenia microarray literature contains apparent inconsistencies between studies, with failures to replicate top hits, in part due to small sample sizes, cohort-specific effects, differences in array types, and other confounders. In an attempt to summarize existing studies of schizophrenia cases and non-related comparison subjects, we performed two mega-analyses of a combined set of microarray data from postmortem prefrontal cortices (n=315) and from ex-vivo blood tissues (n=578). We adjusted regression models per gene to remove non-significant covariates, providing best-estimates of transcripts dysregulated in schizophrenia. We also examined dysregulation of functionally related gene sets and gene co-expression modules, and assessed enrichment of cell types and genetic risk factors. The identities of the most significantly dysregulated genes were largely distinct for each tissue, but the findings indicated common emergent biological functions (e.g. immunity) and regulatory factors (e.g., predicted targets of transcription factors and miRNA species across tissues). Our network-based analyses converged upon similar patterns of heightened innate immune gene expression in both brain and blood in schizophrenia. We also constructed generalizable machine-learning classifiers using the blood-based microarray data. Our study provides an informative atlas for future pathophysiologic and biomarker studies of schizophrenia., Competing Interests: The authors have no conflicts of interest to declare., (Published by Elsevier B.V.)

Background: High-risk patients with cholecystitis have conventionally been offered percutaneous gallbladder drainage (PGBD) for treatment. A growing experience of endoscopic gallbladder drainage (EGBD) has been reported to be effective and safe., Objective: To compare the short- and long-term outcomes of EGBD and PGBD., Design: A retrospective review., Setting: Single academic tertiary care center., Patients: Inpatients diagnosed with cholecystitis., Interventions: Any patient deemed a nonsurgical candidate and who has undergone either PGBD or EGBD was included in the analysis., Main Outcome Measurements: Patient demographics along with procedural and clinical outcomes were recorded for each group., Results: Forty-three patients underwent PGBD and 30 underwent EGBD (24 transpapillary, 6 transmural). Technical (97.6% vs 100%) and clinical (97.6% vs 86.7%) success rates of PGBD and EGBD were similar. However, postprocedure hospital length of stay (16.3 vs 7.6 days), time to clinical resolution (4.6 vs 3.0 days), adverse event rate (39.5% vs 13.3%), number of sessions (2.0 vs 1.0), number of repeat interventions (53.4% vs 13.3%), and postprocedure pain scores (3.8 vs 2.1) were significantly higher for PGBD than EGBD., Limitations: Retrospective analysis., Conclusion: Although EGBD has similar technical and clinical success compared with PGBD, it uses fewer hospital resources and results in fewer adverse events, improved pain scores, and decreased need for repeat gallbladder drainage. EGBD may provide a less-invasive, safer, cost-effective option for gallbladder drainage than PGBD with improved clinical outcomes., (Copyright © 2015 American Society for Gastrointestinal Endoscopy. Published by Elsevier Inc. All rights reserved.)

A new Al2O3:C,Cu,P phosphor is developed by the combustion synthesis technique which exhibits entirely different OSL properties as compared to that of the commercial alumina. No thermoluminescence (TL) is observed in this phosphor which also differentiates the present phosphor from the commercially available Al2O3:C (Landauer). The phosphor shows good optically stimulated luminescence (OSL) sensitivity for ionizing radiation with a fast OSL decay as compared to the commercial Al2O3:C. The phosphor heated in air followed by heating under the reactive atmosphere exhibits maximum sensitivity amongst several other phosphors. On the basis of area integration method; integrated over initial 3s, the sensitivity of this phosphor is about 67% of that of commercial Al2O3:C., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

A new Cu,P-doped, sodium fluorosilicate-based optically stimulated luminescence (OSL) phosphor is developed. This phosphor shows good OSL properties, and the sensitivity is comparable with that of the commercial Al(2)O(3):C (Landauer, Inc.) phosphor. For the luminescence averaged over initial 1 s, blue-stimulated luminescence and green-stimulated luminescence sensitivities were found to be 0.76 and 3.8 times, respectively, of Al(2)O(3):C (Landauer, Inc.) with 28 % of post-irradiation fading in 3 days and nil thereafter. The simple preparation procedure, fast decay, very good sensitivity and moderate fading will make this phosphor suitable for radiation dosimetry, using OSL., (© The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

When caught in the dilemma of career choice, a critical conversation helped the writer crystallize the decision to plunge into the field of mental health. The decision just not only kindled interest in psychiatry but passion to study the science of the mind despite the fact that in earlier times psychiatry mainly catered to patients with chronic schizophrenia and uncontrolled bipolar disorder. Weathering the curious glances of colleagues the writer pursued to explore the field of the science of the mind. Not restricting himself to classical trends in private practice, he explored every opportunity to reach out to the common man through writing articles in popular newspapers and also ran a TV Show to respond to people's queries on mental health. He further ventured into training and development of young MBA aspirants and trained himself into an international coach and facilitator. The science of Behavioural Economics beckons him now.