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Players with the most WAR for their current club

We are looking at the players on each active roster who are making history for their franchises every time they step on the field. We're looking at the player who has compiled the highest WAR (per Baseball Reference) for his current team so far in his career.




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This is the D-backs prospect to watch in camp

The countdown to pitchers and catchers reporting is down to single digits for all 30 MLB clubs, but as exciting as it is to see the return of Major League stars, it's also a time to dream about the next wave of baseball talent.




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Get ready to watch: MLB.TV available for 2019

Spring Training is imminent, Opening Day is within sight and the big league season isn't complete for fans without a subscription to MLB.TV. The most comprehensive streaming service in professional sports is now available for the 2019 season.




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Widener among biggest prospect bargains

Considering the players that get the big bucks often get most of the attention when they are signed and drafted, let's take some time to look at the other end of the spectrum. Here are the biggest steals on the Top 100 Prospects list.




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10 players you forgot were once D-backs

When you think of the D-backs, what players spring to mind? Luis Gonzalez, Randy Johnson, Paul Goldschmidt and Matt Williams are probably some of the names that arise. But what names are familiar to baseball fans but might have even some D-backs fans saying, "He was a Diamondback?"




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Reloaded D-backs team set for new season

The D-backs will work to compete in 2019 while continuing to build up the farm system, which has some pitching at the top end with better position players at the lower levels.




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30 low-key acquisitions who could pay off big

Fans and analysts spend the entire offseason speculating where the top free agents could go, but sometimes an under-the-radar pickup can end up making a world of difference. As positional competitions begin to heat up at Spring Training camps this month, MLB.com's beat writers were asked to identify one potentially overlooked acquisition for each of the 30 clubs. Here's who they came up with.




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D-backs agree to 1-year deal with Joseph

The Arizona Diamondbacks agreed to terms with catcher Caleb Joseph on a one-year contract. To make room for Joseph on the roster, the D-backs placed right-hander Taijuan Walker on the 60-day injured list. The D-backs' 40-man roster remains at 40.




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Prospects who should vie for a roster spot

The 30 prospects below all are getting very long looks this spring with an eye toward breaking camp with the parent club. Even if they start the year in the Minors, they all should get the chance to contribute at some point in the very near future.




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Kelly already knows his way around ST facility

Yes, catcher Carson Kelly is new to the D-backs this spring, but this wasn't the first time he's gotten to see what the inside of Salt River Fields looks like.




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Marte confident transition to CF will be smooth

Ketel Marte does not lack for confidence when it comes to switching from second base/shortstop to center field, which is where he's expected to see a lot of time this season.




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Wide-open competition in D-backs' bullpen

For the final two spots in the D-backs' bullpen, good luck trying to figure that out just yet. In fact, manager Torey Lovullo has even declined to narrow it down to who could be in contention for those spots.




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The D-backs' Spring Training battle to watch

The next five weeks will see lots of shuffling on Major League rosters. Here are the most intriguing positional battles on each of the 30 MLB clubs.




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Tomas getting work in at first base

As the D-backs went through fielding drills Tuesday, Yasmany Tomas spent his time at first base rather than in the outfield.




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Covid-19: Nightingale hospitals set to shut down after seeing few patients

The mothballing of Britain’s Nightingale hospitals, some of which have yet to treat a single covid-19 patient, has raised questions about whether resources to fight the pandemic were...




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Adil El-Tayar: renowned NHS transplant surgeon who died from covid-19

bmj;369/may07_6/m1803/FAF1faPhoto credit: Abbas GhazanfarOn 25 March Adil El-Tayar, a renowned organ transplantation specialist, became the first working NHS surgeon to die from covid-19 in hospital...




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Covid-19: Health needs of sex workers are being sidelined, warn agencies

Agencies have criticised the lack of action to protect the health needs of sex workers during the pandemic, with the English Collective of Prostitutes (ECP) warning of a “ticking time bomb of health...




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Vitamin C in Human Health and Disease: Effects, Mechanisms of Action, and New Guidance on Intake




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Myocardial Blood Flow and Myocardial Flow Reserve After Cardiac Transplantation: Mistakes in Diagnostic Value and Prognosis




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Reply: Clarifying the Utility of Myocardial Blood Flow and Myocardial Flow Reserve After Cardiac Transplantation




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First Evidence for a Dose-Response Relationship in Patients Treated with 166Ho Radioembolization: A Prospective Study

166Ho-microspheres have recently been approved for clinical use for hepatic radioembolization in the European Union. The aim of this study was to investigate the absorbed dose–response relationship and its association with overall survival for 166Ho radioembolization in patients with liver metastases. Methods: Patients treated in the HEPAR I and II studies who underwent an 18F-FDG PET/CT scan at baseline, a posttreatment 166Ho SPECT/CT scan, and another 18F-FDG PET/CT scan at the 3-mo follow-up were included for analysis. The posttreatment 166Ho-microsphere activity distributions were estimated with quantitative SPECT/CT reconstructions using a quantitative Monte Carlo–based method. The response of each tumor was based on the change in total lesion glycolysis (TLG) between baseline and follow-up and was placed into 1 of 4 categories, according to the PERCIST criteria, ranging from complete response to progressive disease. Patient-level response was grouped according to the average change in TLG per patient. The absorbed dose–response relationship was assessed using a linear mixed model to account for correlation of tumors within patients. Median overall survival was compared between patients with and without a metabolic liver response, using a log-rank test. Results: Thirty-six patients with a total of 98 tumors were included. The relation between tumor-absorbed dose and both tumor-level and patient-level response was explored. At a tumor level, a significant difference in geometric mean absorbed dose was found between complete response (232 Gy; 95% confidence interval [CI], 178–303 Gy; n = 32) and stable disease (147 Gy; 95% CI, 113–191 Gy; n = 28) (P = 0.01) and between complete response and progressive disease (117 Gy; 95% CI, 87–159 Gy; n = 21) (P = 0.0008). This constitutes a robust absorbed dose–response relationship. At a patient level, a significant difference was found between patients with complete or partial response (210 Gy; 95% CI, 161–274 Gy; n = 13) and patients with progressive disease (116 Gy; 95% CI, 81–165 Gy; n = 9) (P = 0.01). Patients were subsequently grouped according to their average change in TLG. Patients with an objective response (complete or partial) exhibited a significantly higher overall survival than nonresponding patients (stable or progressive disease) (median, 19 mo vs. 7.5 mo; log-rank, P = 0.01). Conclusion: These results confirm a significant absorbed dose–response relationship in 166Ho radioembolization. Treatment response is associated with a higher overall survival.




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Preoperative Localization of Adenomas in Primary Hyperparathyroidism: The Value of 11C-Choline PET/CT in Patients with Negative or Discordant Findings on Ultrasonography and 99mTc-Sestamibi SPECT/CT

We aimed to assess the value of 11C-choline PET in patients with primary hyperparathyroidism and negative or discordant results on 99mTc-sestamibi imaging and neck ultrasound. Methods: Eighty-seven such patients were assessed and subsequently underwent parathyroidectomy. PET/CT image data were analyzed semiquantitatively using SUVmax and SUV ratios (target to contralateral thyroid gland and carotid artery). A positive PET/CT result was defined as focal uptake significantly higher than regular thyroid tissue. Ectopic foci were also considered positive. Inconclusive PET/CT cases were defined as a lesion with uptake equal to normal thyroid tissue. If no prominent or ectopic uptake was detectable, the PET/CT result was considered negative. Results: When dichotomizing the 11C-choline PET/CT imaging results by defining lesions with both positive and inconclusive uptake as positive, we found 84 of 92 lesions (91.3%) to have true-positive uptake whereas 8 lesions (8.7%) had false-positive uptake. One lesion showed false-negative uptake; the sensitivity was 98.8%. The corresponding positive predictive value for lesions was 91.3%. The mean SUVmax was 6.15 ± 4.92 in 72 lesions with positive uptake (70 patients) and 2.96 ± 2.32 in 20 lesions with inconclusive uptake (18 patients). Conclusion: These results in a large group of patients indicate that 11C-choline PET/CT is a promising tool for parathyroid adenoma localization when ultrasound and 99mTc-sestamibi imaging yield negative or discordant results.




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PET Imaging of Pancreatic Dopamine D2 and D3 Receptor Density with 11C-(+)-PHNO in Type 1 Diabetes

Type 1 diabetes mellitus (T1DM) has traditionally been characterized by a complete destruction of β-cell mass (BCM); however, there is growing evidence of possible residual BCM present in T1DM. Given the absence of in vivo tools to measure BCM, routine clinical measures of β-cell function (e.g., C-peptide release) may not reflect BCM. We previously demonstrated the potential utility of PET imaging with the dopamine D2 and D3 receptor agonist 3,4,4a,5,6,10b-hexahydro-2H-naphtho[1,2-b][1,4]oxazin-9-ol (11C-(+)-PHNO) to differentiate between healthy control (HC) and T1DM individuals. Methods: Sixteen individuals participated (10 men, 6 women; 9 HCs, 7 T1DMs). The average duration of diabetes was 18 ± 6 y (range, 14–30 y). Individuals underwent PET/CT scanning with a 120-min dynamic PET scan centered on the pancreas. One- and 2-tissue-compartment models were used to estimate pancreas and spleen distribution volume. Reference region approaches (spleen as reference) were also investigated. Quantitative PET measures were correlated with clinical outcome measures. Immunohistochemistry was performed to examine colocalization of dopamine receptors with endocrine hormones in HC and T1DM pancreatic tissue. Results: C-peptide release was not detectable in any T1DM individuals, whereas proinsulin was detectable in 3 of 5 T1DM individuals. Pancreas SUV ratio minus 1 (SUVR-1) (20–30 min; spleen as reference region) demonstrated a statistically significant reduction (–36.2%) in radioligand binding (HCs, 5.6; T1DMs, 3.6; P = 0.03). Age at diagnosis correlated significantly with pancreas SUVR-1 (20–30 min) (R2 = 0.67, P = 0.025). Duration of diabetes did not significantly correlate with pancreas SUVR-1 (20–30 min) (R2 = 0.36, P = 0.16). Mean acute C-peptide response to arginine at maximal glycemic potentiation did not significantly correlate with SUVR-1 (20–30 min) (R2 = 0.57, P = 0.05), nor did mean baseline proinsulin (R2 = 0.45, P = 0.10). Immunohistochemistry demonstrated colocalization of dopamine D3 receptor and dopamine D2 receptor in HCs. No colocalization of the dopamine D3 receptor or dopamine D2 receptor was seen with somatostatin, glucagon, or polypeptide Y. In a separate T1DM individual, no immunostaining was seen with dopamine D3 receptor, dopamine D2 receptor, or insulin antibodies, suggesting that loss of endocrine dopamine D3 receptor and dopamine D2 receptor expression accompanies loss of β-cell functional insulin secretory capacity. Conclusion: Thirty-minute scan durations and SUVR-1 provide quantitative outcome measures for 11C-(+)-PHNO, a dopamine D3 receptor–preferring agonist PET radioligand, to differentiate BCM in T1DM and HCs.




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Prostate-Specific Membrane Antigen PET/CT Combined with Sentinel Node Biopsy for Primary Lymph Node Staging in Prostate Cancer

Our objective was to determine the diagnostic capabilities of combined prostate-specific membrane antigen (PSMA) PET/CT and sentinel node (SN) biopsy in PSMA PET/CT–negative patients for primary lymph node (LN) staging in prostate cancer (PCa) patients. Methods: Between January 2017 and March 2019, retrospectively, all consecutive patients with diagnosed intermediate- or high-risk primary PCa who underwent preoperative PSMA PET/CT (68Ga or 18F-DCFPyL) followed by robot-assisted radical prostatectomy and extended pelvic LN dissection (ePLND) were included. All patients without suspected LN metastases on PSMA PET/CT were considered candidates for SN biopsy with indocyanine green–99mTc-nanocolloid or 99mTc-nanocolloid with free indocyanine green used as tracers. The ePLND was used as a reference standard. Results: Of 53 patients, 22 had positive PSMA PET/CT results and 31 underwent subsequent SN biopsy after negative PSMA PET/CT results. In total, 23 patients (43%) were pN1, of whom 6 (26%) had negative PSMA PET/CT results and underwent subsequent SN biopsy. The combined use of SN biopsy and PSMA PET/CT identified all pN1 patients (100% sensitivity; 95% confidence interval, 86%–100%) and performed correct nodal staging in 50 of 53 patients (94% diagnostic accuracy; 95% confidence interval, 84%–99%). SN biopsy identified significantly smaller LN metastases (median diameter, 2.0 mm; interquartile range, 1.0–3.8 mm) than PSMA PET/CT (median diameter, 5.5 mm; interquartile range, 2.6–9.3 mm; P = 0.007). Conclusion: Combining both modalities led to a 94% accuracy for nodal staging in diagnosed intermediate- and high-risk primary PCa. Adding SN biopsy in patients with negative PSMA PET/CT results increased the combined sensitivity to 100% for detecting nodal metastases at ePLND. This diagnostic accuracy may provide valuable information for directing further treatment in PCa patients, such as the use of PSMA PET/CT and SN biopsy rather than ePLND as the preferred approach for staging before radiotherapy.




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Head-to-Head Comparison of 68Ga-PSMA-11 with 18F-PSMA-1007 PET/CT in Staging Prostate Cancer Using Histopathology and Immunohistochemical Analysis as a Reference Standard

18F-PSMA-1007 is a novel prostate-specific membrane antigen (PSMA)–based radiopharmaceutical for imaging prostate cancer (PCa). The aim of this study was to compare the diagnostic accuracy of 18F-PSMA-1007 with 68Ga-PSMA-11 PET/CT in the same patients presenting with newly diagnosed intermediate- or high-risk PCa. Methods: Sixteen patients with intermediate- or high-risk PCa underwent 18F-PSMA-1007 and 68Ga-PSMA-11 PET/CT within 15 d. PET findings were compared between the 2 radiotracers and with reference-standard pathologic specimens obtained from radical prostatectomy. The Cohen -coefficient was used to assess the concordance between 18F-PSMA-1007 and 68Ga-PSMA-11 for detection of intraprostatic lesions. The McNemar test was used to assess agreement between intraprostatic PET/CT findings and histopathologic findings. Sensitivity, specificity, positive predictive value, and negative predictive value were reported for each radiotracer. SUVmax was measured for all lesions, and tumor-to-background activity was calculated. Areas under receiver-operating-characteristic curves were calculated for discriminating diseased from nondiseased prostate segments, and optimal SUV cutoffs were calculated using the Youden index for each radiotracer. Results: PSMA-avid lesions in the prostate were identified in all 16 patients with an almost perfect concordance between the 2 tracers ( ranged from 0.871 to 1). Aside from the dominant intraprostatic lesion, similarly detected by both radiotracers, a second less intense positive focus was detected in 4 patients only with 18F-PSMA-1007. Three of these secondary foci were confirmed as Gleason grade 3 lesions, whereas the fourth was shown on pathologic examination to represent chronic prostatitis. Conclusion: This pilot study showed that both 18F-PSMA-1007 and 68Ga-PSMA-11 identify all dominant prostatic lesions in patients with intermediate- or high-risk PCa at staging. 18F-PSMA-1007, however, may detect additional low-grade lesions of limited clinical relevance.




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First-in-Humans Imaging with 89Zr-Df-IAB22M2C Anti-CD8 Minibody in Patients with Solid Malignancies: Preliminary Pharmacokinetics, Biodistribution, and Lesion Targeting

Immunotherapy is becoming the mainstay for treatment of a variety of malignancies, but only a subset of patients responds to treatment. Tumor-infiltrating CD8-positive (CD8+) T lymphocytes play a central role in antitumor immune responses. Noninvasive imaging of CD8+ T cells may provide new insights into the mechanisms of immunotherapy and potentially predict treatment response. We are studying the safety and utility of 89Zr-IAB22M2C, a radiolabeled minibody against CD8+ T cells, for targeted imaging of CD8+ T cells in patients with cancer. Methods: The initial dose escalation phase of this first-in-humans prospective study included 6 patients (melanoma, 1; lung, 4; hepatocellular carcinoma, 1). Patients received approximately 111 MBq (3 mCi) of 89Zr-IAB22M2C (at minibody mass doses of 0.2, 0.5, 1.0, 1.5, 5, or 10 mg) as a single dose, followed by PET/CT scans at approximately 1–2, 6–8, 24, 48, and 96–144 h after injection. Biodistribution in normal organs, lymph nodes, and lesions was evaluated. In addition, serum samples were obtained at approximately 5, 30, and 60 min and later at the times of imaging. Patients were monitored for safety during infusion and up to the last imaging time point. Results: 89Zr-IAB22M2C infusion was well tolerated, with no immediate or delayed side effects observed after injection. Serum clearance was typically biexponential and dependent on the mass of minibody administered. Areas under the serum time–activity curve, normalized to administered activity, ranged from 1.3 h/L for 0.2 mg to 8.9 h/L for 10 mg. Biodistribution was dependent on the minibody mass administered. The highest uptake was always in spleen, followed by bone marrow. Liver uptake was more pronounced with higher minibody masses. Kidney uptake was typically low. Prominent uptake was seen in multiple normal lymph nodes as early as 2 h after injection, peaking by 24–48 h after injection. Uptake in tumor lesions was seen on imaging as early as 2 h after injection, with most 89Zr-IAB22M2C–positive lesions detectable by 24 h. Lesions were visualized early in patients receiving treatment, with SUV ranging from 5.85 to 22.8 in 6 target lesions. Conclusion: 89Zr-IAB22M2C imaging is safe and has favorable kinetics for early imaging. Biodistribution suggests successful targeting of CD8+ T-cell–rich tissues. The observed targeting of tumor lesions suggests this may be informative for CD8+ T-cell accumulation within tumors. Further evaluation is under way.




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Diagnostic Accuracy of PET Tracers for the Differentiation of Tumor Progression from Treatment-Related Changes in High-Grade Glioma: A Systematic Review and Metaanalysis

Posttreatment high-grade gliomas are usually monitored with contrast-enhanced MRI, but its diagnostic accuracy is limited as it cannot adequately distinguish between true tumor progression and treatment-related changes. According to recent Response Assessment in Neuro-Oncology recommendations, PET overcomes this limitation. However, it is currently unknown which tracer yields the best results. Therefore, a systematic review and metaanalysis were performed to compare the diagnostic accuracy of the different PET tracers in differentiating tumor progression from treatment-related changes in high-grade glioma patients. Methods: PubMed, Web of Science, and Embase were searched systematically. Study selection, data extraction, and quality assessment were performed independently by 2 authors. Metaanalysis was performed using a bivariate random-effects model when at least 5 studies were included. Results: The systematic review included 39 studies (11 tracers). 18F-FDG (12 studies, 171 lesions) showed a pooled sensitivity and specificity of 84% (95% confidence interval, 72%–92%) and 84% (95% confidence interval, 69%–93%), respectively. O-(2-18F-fluoroethyl)-l-tyrosine (18F-FET) (7 studies, 172 lesions) demonstrated a sensitivity of 90% (95% confidence interval, 81%–95%) and specificity of 85% (95% confidence interval, 71%–93%). For S-11C-methyl)-l-methionine (11C-MET) (8 studies, 151 lesions), sensitivity was 93% (95% confidence interval, 80%–98%) and specificity was 82% (95% confidence interval, 68%–91%). The numbers of included studies for the other tracers were too low to combine, but sensitivity and specificity ranged between 93%–100% and 0%–100%, respectively, for 18F-FLT; 85%–100% and 72%–100%, respectively, for 3,4-dihydroxy-6-18F-fluoro-l-phenylalanine (18F-FDOPA); and 100% and 70%–88%, respectively, for 11C-choline. Conclusion: 18F-FET and 11C-MET, both amino-acid tracers, showed a comparably higher sensitivity than 18F-FDG in the differentiation between tumor progression and treatment-related changes in high-grade glioma patients. The evidence for other tracers is limited; thus, 18F-FET and 11C-MET are preferred when available. Our results support the incorporation of amino-acid PET tracers for the treatment evaluation of high-grade gliomas.




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Patient Travel Concerns After Treatment with 177Lu-DOTATATE




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A Conversation with John Sunderland, Johannes Czernin, and Thomas Hope




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Newsbriefs




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SNMMI Newsline




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SNMMI Hosts FDA Workshop




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Immunomodulation Followed by Antigen-Specific Treg Infusion Controls Islet Autoimmunity

Optimal immune-based therapies for type 1 diabetes (T1D) should restore self-tolerance without inducing chronic immunosuppression. CD4+Foxp3+ regulatory T cells (Tregs) are a key cell population capable of facilitating durable immune tolerance. However, clinical trials with expanded Tregs in T1D and solid-organ transplant recipients are limited by poor Treg engraftment without host manipulation. We showed that Treg engraftment and therapeutic benefit in nonautoimmune models required ablative host conditioning. Here, we evaluated Treg engraftment and therapeutic efficacy in the nonobese diabetic (NOD) mouse model of autoimmune diabetes using nonablative, combinatorial regimens involving the anti-CD3 (αCD3), cyclophosphamide (CyP), and IAC (IL-2/JES6–1) antibody complex. We demonstrate that αCD3 alone induced substantial T-cell depletion, impacting both conventional T cells (Tconv) and Tregs, subsequently followed by more rapid rebound of Tregs. Despite robust depletion of host Tconv and host Tregs, donor Tregs failed to engraft even with interleukin-2 (IL-2) support. A single dose of CyP after αCD3 depleted rebounding host Tregs and resulted in a 43-fold increase in donor Treg engraftment, yet polyclonal donor Tregs failed to reverse diabetes. However, infusion of autoantigen-specific Tregs after αCD3 alone resulted in robust Treg engraftment within the islets and induced remission in all mice. This novel combinatorial therapy promotes engraftment of autoantigen-specific donor Tregs and controls islet autoimmunity without long-term immunosuppression.




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Artificial intelligence versus clinicians: systematic review of design, reporting standards, and claims of deep learning studies




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Manual acupuncture versus sham acupuncture and usual care for prophylaxis of episodic migraine without aura: multicentre, randomised clinical trial




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Clinical characteristics of 113 deceased patients with coronavirus disease 2019: retrospective study




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Comparison of dietary macronutrient patterns of 14 popular named dietary programmes for weight and cardiovascular risk factor reduction in adults: systematic review and network meta-analysis of randomised trials




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Prediction models for diagnosis and prognosis of covid-19 infection: systematic review and critical appraisal




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Use of electronic medical records in development and validation of risk prediction models of hospital readmission: systematic review




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Association between maternal and paternal mental illness and risk of injuries in children and adolescents: nationwide register based cohort study in Sweden




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Viral load dynamics and disease severity in patients infected with SARS-CoV-2 in Zhejiang province, China, January-March 2020: retrospective cohort study




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Estimated population wide benefits and risks in China of lowering sodium through potassium enriched salt substitution: modelling study




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Occurrence, prevention, and management of the psychological effects of emerging virus outbreaks on healthcare workers: rapid review and meta-analysis




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Association between tax on sugar sweetened beverages and soft drink consumption in adults in Mexico: open cohort longitudinal analysis of Health Workers Cohort Study




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Prognosis of unrecognised myocardial infarction determined by electrocardiography or cardiac magnetic resonance imaging: systematic review and meta-analysis




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UPDATE: SOS implements work rotation for staff

  Stationery & Office Supplies Limited, SOS, has implemented work rotation schedules, which sees only 50 per cent of its staff working from the office on a daily basis, as it tries to balance the needs of the business and the...




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Playa to cut Jamaican room count 40% with sale of two Jewels

The sale of two Jewel properties will inject US$60 million into loss-making Playa Resorts while reducing the hotel rooms it operates in Jamaica by more 40 per cent. Playa announced the sale of Jewel Runaway Bay Beach Resort...




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US Treasury says April-June borrowing will be a record US$2.99t

THE ECONOMIC paralysis triggered by the coronavirus pandemic is forcing the United States Treasury to borrow far more than it ever has before – US$2.99 trillion in the current quarter alone. The amount is more than five times the government’s...




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Dwayne Devonish | Smart virus testing necessary for economic reboot

OP-ED CONTRIBUTION: COVID-19 AND THE ECONOMY FOR MOST countries in the Caribbean, the current testing for COVID-19 has not reached levels suitable for ascertaining an accurate picture of the state of outbreak and spread of the infection. This...




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Digital Jamaica throws sales lifeline to furniture companies

DESPITE TUMBLING sales and challenges with hire-purchase accounts, two of the largest retailers of home furniture and appliances, Courts Jamaica and Singer Jamaica, have found glimmers of hope during the COVID-19 pandemic. That’s because work-from...