bluuebunny/crossref_metadata_2025_split huggingface dataset:
Comparing digital to analog prostate-specific membrane antigen-targeted piflufolastat 18F PET/CT in prostate cancer patients in early biochemical failure
Authors: Maliha Peter George , Nolet Benoit , Ebrahim Anwar , Abikhzer Gad , Chaussé Guillaume , Bahoric Boris , Niazi Tamim , Probst Stephan 
Published: December 2022

Purpose
Prostate-specific membrane antigen (PSMA) positron emission tomography/computer tomography (PET/CT) in prostate cancer patients with biochemical failure(BCF) showslimited sensitivity when the prostate-specific antigen(PSA) <0.5 ng/mL. The development of digital PET/CT has greatly improved smaller lesion detection. This study’s goal was to compare the performance and clinical value of PSMA-targeted piflufolastat PET/CT for prostate cancer BCF with digital versus analog PET/CT.

Methods
In this retrospective study, all piflufolastat PET/CT scans in subjects with PSA ≤ 3.0 ng/mL who were referred for prostate cancer BCF were included. The performance characteristics of 171 analog PET/CT studies in 155 subjects from May 2017 to January 2020 and 106 digital PET/CT studies in 103 subjects from February 2020 to December 2020 were compared. Lesions were considered malignant if they did not match the known physiological distribution of piflufolastat and did not represent uptake in benign lesions. PSMA PET/CT studies were considered positive if at least one malignant lesion was detected and negative if none were detected.

Results
Digital piflufolastat PET/CT outperformed analog piflufolastat PET/CT in subjects with PSA < 0.5 ng/mL with a positivity rate of 69% versus 37%, respectively. In patients with PSA ≥ 0.5 ng/mL, both technologies performed similarly. There was no statistically significant difference between the number or size of piflufolastat-avid lesions detected per PET/CT study.

Conclusion
In prostate cancer patients with BCF and PSA < 0.5 ng/mL, digital piflufolastat PET/CT has a higher detection rate of malignant lesions than analog piflufolastat PET/CT.
Bacterial contamination is involved in the etiology of soft tissue filler, late-onset inflammatory adverse events
Authors: Decates Tom S. , Budding Andries E. , Velthuis Peter J. , Bachour Yara , Wolters Lisanne W. , Schelke Leonie W. , Nijsten Tamar E.C. , Niessen Frank B. 
Published: December 2022

Background:
The treatment algorithm in late-onset inflammatory adverse events on soft tissue fillers depends primarily on the assumed causative factor, being either immunological or bacterial.

Methods:
We included 29 patients, of whom 13 experienced late-onset inflammatory adverse events to fillers (Inflammatory group) and 16 who did not (Reference group). We acquired biopsies from both groups with an 18 G needle. Before taking the biopsy, we acquired skin swabs in 25 of the 29 patients. We used a new and very sensitive method to detect microbiota, the IS-pro method. This is a novel broad-range PCR technique based on length and sequence variations of the 16S-23S ribosomal interspacer (IS) region. IS-pro can detect bacteria at low abundances and identify them up to species level. To exclude contamination from skin microbiota we compared the microbiota found on skin swabs with that found in the corresponding biopsies

Results:
A high level of Gram-positive bacteria was found in biopsies of soft tissue fillers, predominantly in patients from the inflammation group. This suggests that these bacteria were introduced during the primary filler injection treatment. The composition of the microbiota on the skin differed markedly from that in the filler indicating that contamination during our sampling process did not influence results.

Conclusion:
Bacteria adherent to soft tissue fillers or bacteremia probably play a causative role in adverse events. Contamination of samples in the biopsies with skin microbiota was excluded.
Ideal cardiovascular health, biomarkers, and coronary artery disease in persons with HIV
Authors: Douglas Pamela S. , McCallum Sara , Lu Michael T. , Umbleja Triin , Fitch Kathleen V. , Foldyna Borek , Zanni Markella V. , Fulda Evelynne S. , Bloomfield Gerald S. , Fichtenbaum Carl J. , Overton Edgar T. , Aberg Judith A. , Malvestutto Carlos D. , Burdo Tricia H. , Arduino Roberto C. , Ho Ken S. , Yin Michael T. , Ribaudo Heather J. , Grinspoon Steven K. 
Published: December 2022

Objective:
To investigate relationships between Life's Simple 7 (LS7), an assessment of cardiovascular health (CVH), and coronary plaque among people with HIV (PWH).

Design:
Cross-sectional.

Methods:
Coronary computed tomography angiography, immune/inflammatory biomarkers, and characterization of LS7 were collected among a subset of ART-treated PWH enrolled in REPRIEVE, a primary prevention trial. Analyses adjusted for cardiovascular disease risk (ASCVD score).

Results:
Median age of the 735 participants was 51(±6) years, 16% female, and median (Q1–Q3) CVD risk was 4.5% (2.6–6.9). Forty percent had poor (≤2 ideal components), 51% had intermediate (three or four ideal components), and only 9% had ideal CVH (≥5). Coronary plaque was present in 357 (49%); 167 (23%) had one or more vulnerable plaque features, 293 (40%) had noncalcified plaque, and 242 (35%) had a coronary artery calcium score >0. All three phenotypes were increasingly more prevalent with poorer CVH and these relationships remained after adjusting for ASCVD risk. Poor CVH was associated with higher high-sensitivity C-reactive protein, oxidized low-density cholesterol, and interleukin-6. The relationship of LS7 to plaque remained after adjusting for these biomarkers.

Conclusions:
Among PWH, poor CVH as measured by LS7 was associated with coronary plaque presence, vulnerable features, and calcification. LS7 was also associated with selected biomarkers; adjustment for these and ASCVD score reduced but did not eliminate LS7's association with plaque, suggesting the possibility of additional protective mechanisms against atherogenesis and plaque remodeling. Clinical use of LS7 and further exploration of its relationships with coronary artery disease may enhance efforts to reduce cardiovascular morbidity and mortality in PWH.

Clinical Trials Registration:
NCT02344290
The Cost-effectiveness of Transplanting Hearts From Hepatitis C-infected Donors Into Uninfected Recipients
Authors: Woolley Ann E. , Gandhi Aditya R. , Jones Michelle L. , Kim Jane J. , Mallidi Hari R. , Givertz Michael M. , Baden Lindsey R. , Mehra Mandeep R. , Neilan and Anne M. 
Published: December 2022

Background.
The DONATE HCV trial demonstrated the safety and efficacy of transplanting hearts from hepatitis C viremic (HCV+) donors. In this report, we examine the cost-effectiveness and impact of universal HCV+ heart donor eligibility in the United States on transplant waitlist time and life expectancy.

Methods.
We developed a microsimulation model to compare 2 waitlist strategies for heart transplant candidates in 2018: (1) status quo (SQ) and (2) SQ plus HCV+ donors (SQ + HCV). From the DONATE HCV trial and published national datasets, we modeled mean age (53 years), male sex (75%), probabilities of waitlist mortality (0.01–0.10/month) and transplant (0.03–0.21/month) stratified by medical urgency, and posttransplant mortality (0.003–0.052/month). We assumed a 23% increase in transplant volume with SQ + HCV compared with SQ. Costs (2018 United States dollar) included waitlist care ($2200–190 000/month), transplant ($213 400), 4-wk HCV treatment ($26 000), and posttransplant care ($2500–11 300/month). We projected waitlist time, quality-adjusted life-years (QALYs), lifetime costs, and incremental cost-effectiveness ratios (ICERs [$/QALY, discounted 3%/year]; threshold ≤$100 000/QALY).

Results.
Compared with SQ, SQ + HCV decreased waitlist time from 8.7 to 6.7 months, increased undiscounted life expectancy from 8.9 to 9.2 QALYs, and increased discounted lifetime costs from $671 400/person to $690 000/person. Four-week HCV treatment comprised 0.5% of lifetime costs. The ICER of SQ + HCV compared with SQ was $74 100/QALY and remained ≤$100 000/QALY with up to 30% increases in transplant and posttransplant costs.

Conclusions.
Transplanting hearts from HCV-infected donors could decrease waitlist times, increase life expectancy, and be cost-effective. These findings were robust within the context of current high HCV treatment costs.
Utility of Digital Single-operator Video Cholangioscopy for the Endoscopic Management of Biliary Complications After Liver Transplantation—A Single-center Experience
Authors: Bokemeyer Arne , Lenze Frank , Stoica Viorelia , Selcuk Sensoy Timur , Huesing-Kabar Anna , Kabar Iyad , Schmidt Hartmut , Ullerich Hansjoerg 
Published: December 2022

Background.
Liver transplant recipients (LTRs) frequently develop biliary complications, and endoscopy is crucial for their subsequent management. Recently, single-operator video cholangioscopy (SOVC) with digital imaging quality was introduced. This study evaluated the utility of digital SOVC for the management of biliary complications in LTRs.

Methods.
This observational study retrospectively analyzed all LTRs undergoing digital SOVC between 2015 and 2019 at a tertiary referral center. Endpoints included the assessment of biliary strictures, performance of selective guidewire passage across biliary strictures, and diagnosis and treatment of biliary stone disease.

Results.
In total, 79 digital SOVCs performed in 50 LTRs were identified. Fifty-eight percent of the procedures were performed for biliary stricture assessment, and using visual signs or guided biopsies, SOVC excluded malignancy in all cases (100%). Of all the examinations, 29.1% (23/79) were performed solely because of a previous failure of conventional endoscopic methods to pass a guidewire across a biliary stricture. Using SOVC, guidewire passage was successfully performed in 73.9% of these examinations, enabling subsequent endoscopic therapy. Furthermore, biliary stones were found in 16.5% (13/79) of the examinations. In 38.5% of these cases, standard fluoroscopy failed to detect stones, which were only visualized using digital SOVC. Biliary stone treatment was successful in 92% (12/13) of the examinations. Complications occurred in 11.4% of all SOVCs. No procedure-associated mortalities were observed.

Conclusions.
Digital SOVC is effective and safe for the endoscopic management of biliary complications in LTRs and offers unique diagnostic and therapeutic opportunities that strongly impact the clinical course in selected cases.
Jaccard dissimilarity in stochastic community models based on the species-independence assumption
Authors: Iritani Ryosuke , Ontiveros Vicente J. , Alonso David , Capitán José A. , Godsoe William , Tatsumi Shinichi 
Published: December 2022

AbstractA fundamental problem in ecology is understanding the causes of change in species composition among sites (i.e. beta diversity). At present it is unclear how spatial heterogeneity in species occupancy across sites shapes these patterns. To address this question, we develop probabilistic models that consider two spatial or temporal sites, where presence probabilities vary both among species and between the sites. We derive analytical and approximate formulae for the expectation of pairwise beta-diversity. Using a novel graphical tool, Stochastic Incidence Plots (SIPs), which depict the presence probabilities in two sites across species labels, we develop a means to conceptualize the heterogeneity in presence probabilities: the steepness or unevenness of SIPs reflects species-level heterogeneity, while the degree of overlap between SIPs indicates site-level heterogeneity. Utilizing SIPs and a combinatorial approach in a two-species scenario, we demonstrate that beta-diversity is lower when SIPs are parallel compared to when they are anti-parallel. We also find that this prediction is testable with the well-known checkerboard pattern in incidence matrices. Finally, we applied the method to the species distribution models for five woodpecker species in Switzerland, showing that their spatial distributions will change significantly in the future. Overall, this work improves our understanding of how pairwise beta-diversity responds to occupancy heterogeneity.
Lung tumor-infiltrating Treghave divergent transcriptional profiles and function linked to checkpoint blockade response
Authors: Dykema Arbor G. , Zhang Jiajia , Zhang Boyang , Cheung Laurene S. , Zeng Zhen , Cherry Christopher M. , Li Taibo , Caushi Justina X. , Nishimoto Marni , Connor Sydney , Ji Zhicheng , Munoz Andrew J. , Hou Wenpin , Zhan Wentao , Singh Dipika , Rashid Rufiaat , Mitchell-Flack Marisa , Bom Sadhana , Tam Ada , Ionta Nick , Wang Yi , Sawosik Camille A. , Tirado Lauren E. , Tomasovic Luke M. , VanDyke Derek , Spangler Jamie B. , Anagnostou Valsamo , Yang Stephen , Spicer Jonathan , Rayes Roni , Taube Janis , Brahmer Julie R. , Forde Patrick M. , Yegnasubramanian Srinivasan , Ji Hongkai , Pardoll Drew M. , Smith Kellie N. 
Published: December 2022

AbstractRegulatory T cells (Treg) are conventionally viewed to suppress endogenous and therapyinduced anti-tumor immunity; however, their role in modulating responses to immune checkpoint blockade (ICB) is unclear. In this study, we integrated single-cell RNAseq/TCRseq of >73,000 tumor-infiltrating Treg(TIL-Treg) from anti-PD-1-treated and treatment naive non-small cell lung cancers (NSCLC) with single cell analysis of tumor-associated antigen (TAA)-specific Tregderived from a murine tumor model. We identified 10 subsets of human TIL-Treg, most of which have high concordance with murine TIL-Tregsubsets. Notably, one subset selectively expresses high levels of OX40 and GITR, whose engangement by cognate ligand mediated proliferative programs and NF-kB activation, as well as multiple genes involved in Tregsuppression, in particular LAG3. Functionally, the OX40hiGITRhisubset in the most highly suppressiveex vivoand Tregexpression of OX40, GITR and LAG3, correlated with resistance to PD-1 blockade. Surprisingly, in the murine tumor model, we found that virtually all TIL-Tregexpressing T cell receptors that are specific for TAA fully develop a distinct Th1-like signature over a two-week period after entry into the tumor, down-regulating FoxP3 and up-regulating expression ofTBX21 (Tbet), IFNγ and certain pro-inflammatory granzymes. Application of a gene score from the murine TAA-specific Th1-like Tregsubset to the human single-cell dataset revealed a highly analogous subcluster that was enriched in anti-PD-1 responding tumors. These findings demonstrate that TIL-Tregpartition into multiple distinct transcriptionally-defined subsets with potentially opposing effects on ICB-induced anti-tumor immunity and suggest that TAA-specific TIL-Tregmay positively contribute to anti-tumor responses.One-Sentence SummaryWe define 10 subsets of lung cancer-infiltrating regulatory T cells, one of which is highly suppressive and enriched in anti-PD-1 non-responders and the other is Th1-like and is enriched in PD-1 responders.
Analyzing patterns of tyrosine sulfation in naive antibody repertoires
Authors: Pospelova Maria , Safonova Yana 
Published: December 2022

AbstractHIV-1 infects a subset of immune cells identified by the receptor CD4 and a coreceptor, CCR5 or CXCR4. Previous studies revealed bnAbs against HIV-1 with antigen-binding sites mimicking binding sites of CCR5. Such antibodies are characterized by post-translationally sulfated tyrosines and anionic motifs in long complementarity determining regions 3 (CDR3s) of the heavy chains. Despite the great therapeutic potential of human antibodies mimicking CCR5, their immunogenetic signatures remain unknown. In this study, we analyzed human naïve heavy chain antibody repertoires and described the most common VDJ recombination scenarios generating CDR3s with sulfated tyrosines and anionic motifs. We showed ~77% of such CDR3s are generated using seven D genes from two families, IGHD3 and IGHD4. We also demonstrated that sulfated tyrosines and anionic motifs are a common feature of mammalian germline D genes.
A novel multi-epitope peptide vaccine candidate targeting Hepatitis E virus: an in-silico approach
Authors: Kumar Anoop , Sahu Utkarsha , Agnihotri Geetanjali , Dixit Anshuman , Khare Prashant 
Published: December 2022

AbstractHEV is a foodborne virus transmitted through the fecal-oral route that causes viral hepatitis in humans worldwide. Ever since its discovery as a zoonotic agent, HEV was isolated from several species with an expanding range of hosts. HEV possesses several features of other RNA viruses but also has certain HEV-specific traits that make its viral-host interactions inimitable. HEV leads to severe morbidity and mortality in immunocompromised people and pregnant women across the world. The situation in underdeveloped countries is even more alarming. Even after creating a menace across the world, we still lack an effective vaccine against HEV. Till date, there is only one licensed vaccine for HEV available only in China. The development of an anti-HEV vaccine that can reduce HEV-induced morbidity and mortality is required. Live attenuated and killed vaccines against HEV are not accessible due to the lack of a tolerant cell culture system, slow viral replication kinetics and varying growth conditions. Thus, the main focus for anti-HEV vaccine development is now on the molecular approaches. In the current study, we have designed a multi-epitope vaccine against HEV through a reverse vaccinology approach(Figure 1). For the first time, we have used viral ORF3, capsid protein and polyprotein altogether for epitope prediction. These are crucial for viral replication and persistence and are major vaccine targets against HEV. The proposedin-silicovaccine construct comprises of highly immunogenic and antigenic T-cell and B-cell epitopes of HEV proteins and ORF3. The construct is capable of inducing an effective and long-lasting host immune response as evident from the simulations results. In addition, the construct is stable, non-allergic and antigenic for the host. Altogether, our findings suggest that thein-silicovaccine construct may be useful as a vaccine candidate for preventing HEV infections.
The Impact of Freeze-Thaw Cycles on the Integrity of SARS-COV-2 Viral Culture Fluids and Clinical Remnant Samples in Antigen or Nucleic Acid Testing
Authors: Hussain Hajirah Noor , Weeks Hali , Zhou Derek , Joseph Divya , Lam Brooke , Xu Haidong , Zhang Chushi , Gregg Keqin , Zhou Wenli 
Published: December 2022

AbstractPreservation at ultra-low temperatures has been a gold standardfor long-term storage of many types of clinical specimens including the SARS-CoV-2 virus. The frozen specimens can be easily transported and tested later. In addition, de-identified frozen remnant samples are resources for many preclinical or clinical studies. It is therefore crucial to understand whether freeze and thaw cycles (FTCs) can adversely affect SARS-CoV-2 test performance when frozen samples are tested. Some early studies suggest that the FTCs increased the cycles threshold (Ct) of RT-PCR indicating the potential degradation of the SARS-CoV-2 nucleic acid after FTCs, while the others did not report any significant changes in the SARS-CoV-2 nucleic acids after the FTCs. Moreover, the impact of FTCs on the performance of the SARS-CoV-2 antigen test is scarcely reported.In this study, we performed paired nucleic acid and rapid antigen testson the same samples to investigate and directly compare how FTCs affect the performance of two types of tests. Both inactivated viral culture fluid samples and clinical remnant samples were studied. Our results showed that FTCs had minimal negative effects on the performance of the rapid SARS-CoV-2 antigen test, and the test results remained largely consistent throughout the FTCs, whereas the Ct values of RT-PCR increased with the increase of the FTC numbers. In addition, our data also demonstrated that the SARS-CoV-2 is preserved better in VTM than PBS during FTCs in regard to nucleic acid testing.
Effects of mindfulness meditation and Acceptance and Commitment Therapy in patients with obstructive sleep apnea with residual excessive sleepiness: A randomized controlled pilot study
Authors: Hellrigel-Holderbaum Max , Romanczuk-Seiferth Nina , Glos Martin , Fietze Ingo 
Published: December 2022

AbstractObjectiveAssessing the effects of Mindfulness-Based Stress Reduction (MBSR) and Acceptance and Commitment Therapy (ACT) on symptoms of OSA, especially on the main outcome, excessive daytime sleepiness (EDS).MethodsParallel randomized controlled trial. 16 OSA patients with residual EDS (rEDS) were randomized and assigned to the two programs via a central computer system using REDCap. Participants completed a standardized 8-week MBSR program or a time-matched program on Acceptance and Commitment Therapy (ACT). Both programs were conducted online. Participants answered questionnaires online at baseline (pre), post-intervention (post), three months after the intervention (follow-up) and were blinded to whether their group was the treatment or control group but not to group allocation. Three participants dropped out early. Most analyses are based on the remaining 13 patients.ResultsThere was a significant difference between the MBSR (n=7) and ACT group (n=6) in changes of EDS between pre and post (p=.043) and a significant reduction of EDS for patients in the ACT group at post (p=.034). This EDS reduction averaging 2.17 points on the Epworth Sleepiness Scale reached the prespecified bar for clinical significance of two points on that scale. Insomnia symptoms reduced significantly following ACT (p=.017). In MBSR, both participants and the MBSR-trainer judged movement-based exercises to be most efficacious.ConclusionACT shows potential as adjunctive therapy for OSA with rEDS, although further studies are needed. It seems promising to develop therapeutic approaches for OSA with rEDS using ACT, especially if they are tailored to patients’ needs.Trial registrationdrks.de; Identifier: DRKS00026812
Fastest may not maximize gait quality: differential and individual-specific immediate effects of gait speed on biomechanical variables post-stroke
Authors: Rosenberg Michael C. , Christianson Hannah , Liu Justin , Santucci Vincent , Sims Payton , Schilder Alex , Zajac-Cox Laura , Winner Taniel S. , Ting Lena H. , Kesar Trisha M. 
Published: December 2022

ABSTRACTA common perspective in post-stroke gait training is that walking at the fastest safe speed maximizes the quality of gait biomechanics, but effects on compensatory biomechanics and inter-limb asymmetry have not been widely characterized. It is unclear whether walking at the fastest speed maximizes the quality of (i.e., optimizes) post-stroke biomechanics across variables, individuals, and walking function levels. In low- (n=9) and high-functioning (n=9) stroke survivors walking at six individualized speeds, we determined if walking at the fastest speed optimized 16 biomechanical variables. Across participants, 46% of magnitude and 17% of asymmetry variables were optimized at the fastest speed, but the optimized variables differed across individuals. Some inter-limb asymmetry variables sustained large biomechanical costs, (i.e., biomechanical quality lost by walking at the fastest vs. the optimal speed; difference in Cohen’sd=0.1-0.7). In both groups, faster speeds were associated with increased (improved) paretic-leg trailing limb angle, peak ankle moment, and peak hip and ankle power magnitudes (all p<0.001), but changes in inter-limb asymmetry were individual-specific. Our findings suggest that treadmill training at the fastest safe speed does not maximize gait quality across individuals or biomechanical variables. More holistic, individual-specific gait quality metrics are needed to guide gait speed optimization during rehabilitation.