bluuebunny/crossref_metadata_2025_split huggingface dataset:
The value of intravenous contrast medium in PSMA PET/CT imaging in patients with biochemical recurrence of prostate cancer
Authors: Winiger Alain , Pérez Lago Maria del Sol , Lehnick Dirk , Roos Justus E. , Strobel Klaus 
Published: June 2021

Purpose
To investigate the added value of diagnostic abdominal contrast-enhanced computed tomography (ceCT) in Ga-68 PSMA PET/CT in prostate cancer patients with biochemical recurrence (BCR).

Methods
Eighty-two consecutive patients (median age, 69 years; range, 45–86 years) with BCR underwent Ga-68 PSMA PET/CT with low-dose nonenhanced (ne) whole-body CT and diagnostic ceCT. Imaging results were retrospectively reviewed by two readers (R1, R2) for diagnostic certainty, local recurrence, lymph node metastasis (LNM) and bone metastasis. Interobserver agreement was assessed. Histopathology served as reference standard in 7, imaging and clinical follow-up in 65 and clinical follow-up alone in 10 patients.

Results
Certain local recurrence, LNM and bone metastasis diagnoses increased substantially from ceCT (R1: 5%/18%/32%; R2: 37%/50%/82%) to nePET/CT (R1: 78%/87%/93%; R2: 81%/87%/95%) for both readers, but the difference between nePET/CT and cePET/CT (R1: 77%/96%/92%; R2: 89%/94%/96%) was marginal. Interobserver agreement was minimal with ceCT (Krippendorff’s alpha: 0.04–0.26), substantial with nePET/CT (0.60–0.86) and best with cePET/CT (0.76–0.86). The areas under the receiver operating characteristic curve (AUCs) for local recurrence for R1/R2 were 0.60/0.65 for ceCT, 0.81/0.79 for nePET/CT and 0.81/0.82 for cePET/CT. AUCs for LNMs for R1/R2 were 0.67/0.77 for ceCT, 0.91/0.82 for nePET/CT and 0.92/0.87 for cePET/CT. AUCs for BMs for R1/R2 were 0.60/0.53 for ceCT, 0.93/0.84 for nePET/CT and 0.93/0.86 for cePET/CT.

Conclusion
Diagnostic abdominal ceCT increases the diagnostic certainty and interobserver agreement in Ga-68 PSMA PET/CT in BCR of prostate cancer. The diagnostic performance of cePET/CT is significantly better than ceCT alone but not nePET/CT.
Febrile Neutropenia Syndromes in Children: Risk Factors and Outcomes of Primary, Prolonged, and Recurrent Fever
Authors: Alali Muayad , David Michael Z. , Ham Sandra A. , Danziger-Isakov Lara , Pisano Jennifer 
Published: June 2021

Background:
The approach to recurrent febrile neutropenia (FN) in children with cancer has not been sufficiently addressed and was cited as a research gap in the International Pediatric Fever and Neutropenia (IPFNP) Guideline 2017.

Methods:
Retrospective medical record review for all pediatric cancer patients with a diagnosis of FN was performed. Variables were collected at 2 different time sets (at day 1 and day 4 of presentation). Three FN syndromes have been defined based on the duration and time course of the fever: (1) primary: fever resolved before 96 hours and did not follow with recurrent fever; (2) prolonged fever: episodes failing to defervesce after at least 96 hours of antibacterial therapy; (3) recurrent fever: a new episode of fever >72 hours after resolution of the initial fever when a patient remained neutropenic and on antibiotics or if a fever developed within 1 week after antibiotic discontinuation. These entities were compared with define risk factors and adverse outcomes associated with recurrent fever.

Results:
A total of 633 FN episodes (FNEs) were identified in 268 patients. Each FNE was classified as primary (n=453, 71.5%), prolonged (n=119, 18.7%), or recurrent (n=61, 9.7%). In multivariable analysis, acute myelogenous leukemia (odds ratio [OR]=4.6, 95% confidence interval [CI]: 2.95-7.24), allogeneic stem cell transplant (SCT) (OR=4.9, 95% CI: 2.61-7.35), absolute lymphocyte count <300/mm3 (OR=3.8, 95% CI: 1.30-5.02), prior neutropenia of ≥10 days, (OR=3.95, 95% CI: 1.70-5.93) and hypotension (OR=3.65, 95% CI: 1.30-5.86) on day 1 of presentation were all associated with an increased risk of recurrent fever when compared with primary fever. In subset analysis for only the high-risk FN group, hypotension (OR=3.2, 95% CI: 1.80-4.96), prior neutropenia ≥10 days (OR=2.55, 95% CI: 1.40-6.22), and absolute lymphocyte count <300/mm3 at presentation (OR=2.6, P=0.03, 95% CI: 2.65-7.12) were associated with an increased risk of recurrent fever when compared with high-risk FN not developing recurrent fever. Allogeneic SCT (OR=5.9, 95% CI: 2.65-7.12) and prior neutropenia ≥10 days (OR=2.11, 95% CI: 1.25-9.32) were significantly associated with recurrent fever when compared with prolonged fever. Invasive fungal disease was a more common etiology with recurrent fever compared with primary and prolonged fever (P=0.001 and 0.01, respectively). Recurrent fever episodes were more likely to be admitted to the pediatric intensive care unit (OR=3, 95% CI: 1.27-6.23) and had a higher 30-day mortality (OR=8, 95% CI: 1.87-71.85) when compared with primary fever.

Conclusions:
Knowledge of risk factors for recurrent fever may enable the early detection infection-related complications of this high-risk group, and possible improved approaches to treatment resulting in decreased morbidity and mortality.
Unilateral Breast Uptake of 99mTc-MIBI in a Lactating Woman During Myocardial Perfusion Imaging
Authors: Malhotra Gaurav , Phadke Milind S. , Rakshit Sutapa , Bagul Swati D. , Verma Priyanka , Asopa Ramesh V. 
Published: June 2021

Abstract
A 34-year-old woman, who was 11 months postpartum, underwent 99mTc-MIBI myocardial perfusion SPECT imaging for atypical symptomatology with normal baseline electrocardiogram and 2-dimensional echocardiography. She was lactating on and off, preferentially from the right breast. Analysis of the raw images revealed unilateral intense tracer uptake in the right breast region that persisted in the delayed spot views (24-hour postinjection). Although bilateral breast uptake of 99mTc-MIBI may be seen in postpartum scenario, unilateral breast uptake can also occur in patients with preferential lactation from 1 breast as seen in this case and should not be mistaken for pathology.
What Is the Optimal Method on Myocardial Suppression in FDG PET/CT Evaluation of Cardiac Sarcoidosis?
Authors: Lu Yang , Sweiss Nadera J. , Macapinlac Homer A. 
Published: June 2021

Abstract
Based on the recent publications, including large cohort retrospective study and prospective clinical trial data, we are commenting on the optimal methods on myocardial suppression in FDG PET/CT evaluation of patients with suspected cardiac sarcoidosis.
Failure to Rescue After Pancreatoduodenectomy
Authors: Gleeson Elizabeth M. , Pitt Henry A. , Mackay Tara. M. , Wellner Ulrich F. , Williamsson Caroline , Busch Olivier R. , Koerkamp Bas Groot , Keck Tobias , van Santvoort Hjalmar C. , Tingstedt Bobby , Besselink Marc G. 
Published: June 2021

Objective:
This analysis aimed to compare failure to rescue (FTR) after pancreatoduodenectomy across the Atlantic.

Summary Background Data:
FTR, or mortality after development of a major complication, is a quality metric originally created to compare hospital results. FTR has been studied in North American and Northern European patients undergoing pancreatoduodenectomy (PD). However, a direct comparison of FTR after PD between North America and Northern Europe has not been performed.

Methods:
Patients who underwent PD in North America, the Netherlands, Sweden and Germany (GAPASURG dataset) were identified from their respective registries (2014–17). Patients who developed a major complication defined as Clavien-Dindo ≥3 or developed a grade B/C postoperative pancreatic fistula (POPF) were included. Preoperative, intraoperative, and postoperative variables were compared between patients with and without FTR. Variables significant on univariable analysis were entered into a logistic regression for FTR.

Results:
Major complications occurred in 6188 of 22,983 patients (26.9%) after PD, and 504 (8.1%) patients had FTR. North American and Northern European patients with complications differed, and rates of FTR were lower in North America (5.4% vs 12%, P < 0.001). Fourteen factors from univariable analysis contributing to differences in patients who developed FTR were included in a logistic regression. On multivariable analysis, factors independently associated with FTR were age, American Society of Anesthesiology ≥3, Northern Europe, POPF, organ failure, life-threatening complication, nonradiologic intervention, and reoperation.

Conclusions:
Older patients with severe systemic diseases are more difficult to rescue. Failure to rescue is more common in Northern Europe than North America. In stable patients, management of complications by interventional radiology is preferred over reoperation.
Chemotherapy Versus Chemotherapy Plus Chemoradiation as Neoadjuvant Therapy for Resectable Gastric Adenocarcinoma
Authors: Allen Casey J. , Pointer David T. , Blumenthaler Alisa N. , Mehta Rutika J. , Hoffe Sarah E. , Minsky Bruce D. , Smith Grace L. , Blum Mariela , Mansfield Paul F. , Ikoma Naruhiko , Das Prajnan , Ajani Jaffer , Dineen Sean P. , Fleming Jason B. , Badgwell Brian D. , Pimiento Jose M. 
Published: June 2021

Objective:
We compare neoadjuvant chemotherapy (CT) to neoadjuvant chemotherapy plus chemoradiation (CRT) for patients with gastric adenocarcinoma (GA).

Summary of Background Data:
The optimal neoadjuvant therapy regimen for resectable GA is not defined.

Methods:
Utilizing data from 2 high-volume cancer centers, we analyzed patients who underwent surgery for localized GA from 1/1/2000-12/31/2017. Standard CT regimens were used according to treatment period. We compared propensity matched cohorts based on age, sex, race, histology, and clinical stage.

Results:
Four-hundred five patients (age 62 ± 12 year, 58% male, 56% White) were analyzed. 231 (57%) received CRT and 174 (43%) received CT. Groups differed based on histopathologic characteristics including preoperative stage (p = 0.013). To control for these differences, propensity matched cohorts of 113 CT and 113 CRT patients were compared. CRT had similar frequencies of microscopically negative resections to CT (93% vs 91%, p = 0.81), but higher rates of complete pathologic response (15% vs 4%, p = 0.003) and lower pathologic stage (p = 0.002). Completion of intended perioperative therapy occurred in 63% of CT and 91% of CRT patients (p < 0.001). Median DFS was 45mo (95%CI: 20–70) in the CT group and 113mo (95%CI: 75–151) in the CRT group (p = 0.018). Median OS was 53mo (95%CI: 30–77) versus 120mo (95%CI: 101–138); p = 0.015.

Conclusions:
In this multi-institutional comparison of neoadjuvant CT and CRT for resectable GA, CRT is associated with higher rates of completed perioperative therapy, higher rates of complete pathologic response, lower pathologic stage, and improved survival.

Level of Evidence: Level III
Large-scale trans-ethnic replication and discovery of genetic associations for rare diseases with self-reported medical data
Authors: Shringarpure Suyash S. , Wang Wei , Jiang Yunxuan , Acevedo Alison , Dhamija Devika , Cameron Briana , Jubb Adrian , Yue Peng ,   The 23andMe Research Team, Sarov-Blat Lea , Gentleman Robert , Auton Adam 
Published: June 2021

AbstractA key challenge in the study of rare disease genetics is assembling large case cohorts for well-powered studies. We demonstrate the use of self-reported diagnosis data to study rare diseases at scale. We performed genome-wide association studies (GWAS) for 33 rare diseases using self-reported diagnosis phenotypes and re-discovered 29 known associations to validate our approach. In addition, we performed the first GWAS for Duane retraction syndrome, vestibular schwannoma and spontaneous pneumothorax, and report novel genome-wide significant associations for these diseases. We replicated these novel associations in non-European populations within the 23andMe, Inc. cohort as well as in the UK Biobank cohort. We also show that mixed model analyses including all ethnicities and related samples increase the power for finding associations in rare diseases. Our results, based on analysis of 19,084 rare disease cases for 33 diseases from 7 populations, show that large-scale online collection of self-reported data is a viable method for discovery and replication of genetic associations for rare diseases. This approach, which is complementary to sequencing-based approaches, will enable the discovery of more novel genetic associations for increasingly rare diseases across multiple ancestries and shed more light on the genetic architecture of rare diseases.
Unrepresentative Big Surveys Significantly Overestimate US Vaccine Uptake
Authors: Bradley Valerie C. , Kuriwaki Shiro , Isakov Michael , Sejdinovic Dino , Meng Xiao-Li , Flaxman Seth 
Published: June 2021

AbstractSurveys are a crucial tool for understanding public opinion and behavior, and their accuracy depends on maintaining statistical representativeness of their target populations by minimizing biases from all sources. Increasing data size shrinks confidence intervals but magnifies the impact of survey bias – an instance of the Big Data Paradox1. Here we demonstrate this paradox in estimates of first-dose COVID-19 vaccine uptake in US adults: Delphi-Facebook2,3(about 250,000 responses per week) and Census Household Pulse4(about 75,000 per week). By May 2021, Delphi-Facebook overestimated uptake by 17 percentage points and Census Household Pulse by 14, compared to a benchmark from the Centers for Disease Control and Prevention (CDC). Moreover, their large data sizes led to minuscule margins of error on the incorrect estimates. In contrast, an Axios-Ipsos online panel5with about 1,000 responses following survey research best practices6provided reliable estimates and uncertainty. We decompose observed error using a recent analytic framework1to explain the inaccuracy in the three surveys. We then analyze the implications for vaccine hesitancy and willingness. We show how a survey of 250,000 respondents can produce an estimate of the population mean that is no more accurate than an estimate from a simple random sample of size 10. Our central message is that data quality matters far more than data quantity, and compensating the former with the latter is a mathematically provable losing proposition.
A Warm-start Digital CRISPR-based Method for the Quantitative Detection of Nucleic Acids
Authors: Wu Xiaolin , Lee Yie Hou , Lu Timothy K. , Yu Hanry 
Published: June 2021

ABSTRACTNucleic acids-based molecular diagnostic tools incorporating the CRISPR/Cas system are being developed as rapid and sensitive methods for pathogen detection. However, most CRISPR/Cas-based diagnostics lack quantitative detection ability. Here, we report Warm-Start RApid DIgital Crispr Approach (WS-RADICA), which uses commercially available digital chips for the rapid, sensitive, and quantitative detection of nucleic acids. WS-RADICA detected as little as 1 copy/μl SARS-CoV-2 RNA in 40 min (qualitative detection) or 60 min (quantitative detection). WS-RADICA can be easily adapted to various digital devices: two digital devices were evaluated for both DNA and RNA quantification, with linear dynamic ranges of 0.8-12777 copies/µL for DNA and 1.2-18391 copies/µL for RNA (both R2 values > 0.99). Moreover, WS-RADICA had greater sensitivity and inhibitor tolerance than a bulk RT-LAMP-Cas12b reaction and similar performance to RT-qPCR and RT-dPCR. Given its speed, sensitivity, quantification capability, and inhibitor tolerance, WS-RADICA shows great promise for a variety of applications requiring nucleic acid quantification.
SARS-CoV-2 is associated with changes in brain structure in UK Biobank
Authors: Douaud Gwenaëlle , Lee Soojin , Alfaro-Almagro Fidel , Arthofer Christoph , Wang Chaoyue , McCarthy Paul , Lange Frederik , Andersson Jesper L.R. , Griffanti Ludovica , Duff Eugene , Jbabdi Saad , Taschler Bernd , Keating Peter , Winkler Anderson M. , Collins Rory , Matthews Paul M. , Allen Naomi , Miller Karla L. , Nichols Thomas E. , Smith Stephen M. 
Published: June 2021

AbstractThere is strong evidence for brain-related abnormalities in COVID-191–13. It remains unknown however whether the impact of SARS-CoV-2 infection can be detected in milder cases, and whether this can reveal possible mechanisms contributing to brain pathology. Here, we investigated brain changes in 785 UK Biobank participants (aged 51–81) imaged twice, including 401 cases who tested positive for infection with SARS-CoV-2 between their two scans, with 141 days on average separating their diagnosis and second scan, and 384 controls. The availability of pre-infection imaging data reduces the likelihood of pre-existing risk factors being misinterpreted as disease effects. We identified significant longitudinal effects when comparing the two groups, including: (i) greater reduction in grey matter thickness and tissue-contrast in the orbitofrontal cortex and parahippocampal gyrus, (ii) greater changes in markers of tissue damage in regions functionally-connected to the primary olfactory cortex, and (iii) greater reduction in global brain size. The infected participants also showed on average larger cognitive decline between the two timepoints. Importantly, these imaging and cognitive longitudinal effects were still seen after excluding the 15 cases who had been hospitalised. These mainly limbic brain imaging results may be the in vivo hallmarks of a degenerative spread of the disease via olfactory pathways, of neuroinflammatory events, or of the loss of sensory input due to anosmia. Whether this deleterious impact can be partially reversed, or whether these effects will persist in the long term, remains to be investigated with additional follow up.
Evidence for lower threshold for diagnosis of hypertension: inferences from an urban-slum cohort in India
Authors: Awadhiya Onkar , Tiwari Ankit , Solanki Premlata , Lahiri Anuja , Shrivastava Neelesh , Joshi Ankur , Pakhare Abhijit P , Joshi Rajnish 
Published: June 2021

AbstractBackgroundHypertension (HTN) is a key risk-factor for cardiovascular diseases (CVDs). Blood-pressure (BP) categorizations between systolic blood pressure (SBP) of 120 and 140 remain debatable. In the current study we aim to evaluate if individuals with a baseline SBP between 130-140 mm Hg (hypertension as per AHA 2017 guidelines) have a significantly higher proportion of incident hypertension on follow-up, as compared to those with SBP between 120-130 mm Hg.MethodsSecondary data analysis was performed in a community-based cohort, instituted, and followed since 2017. Participants were aged ≥30 years, residents of urban slums in Bhopal. BP was measured at or near home by Community Health Workers (CHWs). Two-year follow up was completed in 2019. We excluded participants who were on BP reduction therapy, had fewer than two out-of-office BP measurements and who could not be followed. Eligible participants were re-classified based on baseline BP in four categories: Normal (Category-A), Elevated-BP (Category-B), Variable-BP (Category-C) and reclassified HTN based on AHA-2017 (Category-D). Proportion of individuals who developed incident hypertension on follow up was primary outcome.ResultOut of 2649 records, 768 (28.9%), 647 (24.4%), 586 (22.1%), 648 (24.4%) belonged to Categories A, B, C and D respectively. Incident HTN with cut-off of 140/90 mm Hg was, 1.6%, 2.6%, 6.7%, 12% in categories A, B, C and D respectively. Incidence of incident hypertension in individuals with a baseline SBP between 130-140 mm Hg (Category D) was significantly higher as compared to those with SBP between 120-130 mm Hg (Category B).ConclusionWe conclude that biological basis for AHA-2017 definition of hypertension is relatively robust also for low income and resource-limited settings. Evidence from our longitudinal study will be useful for policy makers for harmonizing national guidelines with AHA-2017.
A New Saliva-Based Lateral-Flow SARS-CoV-2 IgG Antibody Test for mRNA Vaccination
Authors: Shan Dingying , Hsiung Jessica , Bliden Kevin P. , Zhao Su , Liao Tao , Wang Guoxing , Tan Shuanglin , Liu Tiancheng , Sreedhar Deepika , Kost Jessica , Chang Shin Ting , Yuan Wei Po , Tantry Udaya , Gurbel Paul , Tang Meijie , Dai Hongjie 
Published: June 2021

AbstractSensitive detection of IgG antibodies against SARS-CoV-2 is important to assessing immune responses to viral infection or vaccination and immunity duration. Antibody assays using non-invasive body fluids such as saliva could facilitate mass testing including young children, elderly and those who resist blood draws, and easily allowing longitudinal testing/monitoring of antibodies over time. Here, we developed a new lateral flow (nLF) assay that sensitively detects SARS-CoV-2 IgG antibodies in the saliva samples of vaccinated individuals and previous COVID-19 patients. The 25-minute nLF assay detected anti-spike protein (anti-S1) IgG in saliva samples with 100% specificity and high sensitivity from both vaccinated (99.51% for samples ≥ 19 days post 1st Pfizer/BioNTech or Moderna mRNA vaccine dose) and infected individuals. Antibodies against nucleocapsid protein (anti-NCP) was detected only in the saliva samples of COVID-19 patients and not in vaccinated samples, allowing facile differentiation of vaccination from infection. SARS-CoV-2 anti-S1 IgG antibody in saliva measured by nLF demonstrated similar evolution trends post vaccination to that in matching dried blood spot (DBS) samples measured by a quantitative pGOLD lab-test, enabling the nLF to be a valid tool for non-invasive personalized monitoring of SARS-CoV-2 antibody persistence. The new salivary rapid test platform can be applied for non-invasive detection of antibodies against infection and vaccination in a wide range of diseases.
Poor Readability of COVID-19 Vaccine Information for the General Public: A Lost Opportunity
Authors: Bothun Luke S. , Feeder Scott E. , Poland Gregory A. 
Published: June 2021

ABSTRACTBackgroundAll adults in the Unites States now have access to COVID-19 vaccines. During the vaccination process, Emergency Use Authorization (EUA) fact sheets are provided.ObjectiveTo analyze the ease of reading (i.e., readability) of the EUA-approved fact sheets for the vaccines currently available in the United States, the V-Safe adverse event survey script, and the Centers for Disease Control and Prevention (CDC) website on COVID-19 vaccines.DesignWe analyzed the readability of Pfizer, Moderna, and Janssen EUA fact sheets, as well as the V-Safe survey script and the vaccine-related information on the CDC website.MeasurementsReadability factors include the following: average length of paragraphs, sentences, and words; font size and style; use of passive voice; the Gunning-Fog index; the Flesch Reading Ease index; and the Flesch-Kincaid Grade Level index.ResultsOnly the V-Safe adverse event survey script met readability standards for adequate comprehension. The mean readability scores of the EUA fact sheets and the CDC website were as follows: Flesch Reading Ease score (mean 44.35); Flesch-Kincaid Grade Level (mean 10.48); and Gunning-Fog index (mean 11.8). These scores indicate that a 10th-12thgrade-level education is necessary to comprehend these documents.ConclusionThe average person in the United States would have difficulty understanding the information provided in the EUA fact sheets and CDC COVID-19 vaccine website; however, the V-Safe survey was written at an appropriate reading level. To ensure that the public fully understands information regarding COVID-19 vaccines, simplified information material should be developed.