bluuebunny/crossref_metadata_2025 huggingface dataset:
Association between priapism and HIV disease and treatment
Authors: Mulloy Evan , Li Shufeng , Belladelli Federico , Del Giudice Francesco , Glover Frank , Eisenberg Michael L
Published: March 2023

Background

Priapism, a urologic emergency, has known associations with certain medical conditions. Many cases are idiopathic, suggesting an opportunity to identify novel risk factors.

Aim

We sought to identify medical conditions and pharmaceutical treatments that are associated with priapism using data-mining techniques.

Methods

Using deidentified data in a large insurance claims database, we identified all men (age ≥20 years) with a diagnosis of priapism from 2003 to 2020 and matched them to cohorts of men with other diseases of male genitalia: erectile dysfunction, Peyronie disease, and premature ejaculation. All medical diagnoses and prescriptions used prior to first disease diagnosis were examined. Predictors were selected by random forest, and conditional multivariate logistic regressions were applied to assess the risks of each predictor.

Outcomes

We identified novel relationships of HIV and some HIV treatments with priapism and confirmed existing associations.

Results

An overall 10 459 men with priapism were identified and matched 1:1 to the 3 control groups. After multivariable adjustment, men with priapism had high associations of hereditary anemias (odds ratio [OR], 3.99; 95% CI, 2.73-5.82), use of vasodilating agents (OR, 2.45; 95% CI, 2.01-2.98), use of HIV medications (OR, 1.95; 95% CI, 1.36-2.79), and use of antipsychotic medications (OR, 1.90; 95% CI, 1.52-2.38) as compared with erectile dysfunction controls. Similar patterns were noted when compared with premature ejaculation and Peyronie disease controls.

Clinical Implications

HIV and its treatment are associated with priapism, which may affect patient counseling.

Strengths and Limitations

To our knowledge, this is the first study to identify risk factors for priapism utilizing machine learning. All men in our series were commercially insured, which limits the generalizability of our findings.

Conclusion

Using data-mining techniques, we confirmed existing associations with priapism (eg, hemolytic anemias, antipsychotics) and identified novel relationships (eg, HIV disease and treatment).
Oil of Gladness and the Immortal High Priest in Hebrews
Authors: Duff Justin
Published: March 2023

The anointment of Jesus with the ‘oil of gladness’ in Hebrews 1 is a puzzling feature of Hebrews’ argument. The anointment—which is drawn from Psalm 45 and connected to Christ’s messianic enthronement—is often regarded as a royal investiture that transpired after the death of Christ. The relationship with royal messianism and heavenly enthronement, however, may overshadow another significant function of the oil of gladness: high priestly consecration and bodily immortalization. In this article, the function of Christ’s anointment is explored against uses of Psalm 45 in early Judaism and Greco-Roman and Second Temple traditions that depict heavenly oil as an agent of bodily transformation. These traditions suggest that Jesus’ anointment in Hebrews may signify a priestly consecration that transforms and immortalizes the human body for the heavenly realms. The anointment of Jesus in Hebrews may therefore be connected to the incarnate Son’s inheritance of ‘indestructible life’ (7:16) and clarifies when Jesus ‘became’ a royal-priestly Messiah ‘for the ages’.
A point mutation in the kinase domain of CRK10 leads to xylem vessel collapse and activation of defence responses in Arabidopsis
Authors: Piovesana Maiara , Wood Ana K M , Smith Daniel P , Deery Michael J , Bayliss Richard , Carrera Esther , Wellner Nikolaus , Kosik Ondrej , Napier Johnathan A , Kurup Smita , Matthes Michaela C
Published: March 2023

Cysteine-rich receptor-like kinases (CRKs) are a large family of plasma membrane-bound receptors ubiquitous in higher plants. However, despite their prominence, their biological roles have remained largely elusive so far. In this study we report the characterization of an Arabidopsis mutant named crk10-A397T in which alanine 397 has been replaced by a threonine in the αC helix of the kinase domain of CRK10, known to be a crucial regulatory module in mammalian kinases. The crk10-A397T mutant is a dwarf that displays collapsed xylem vessels in the root and hypocotyl, whereas the vasculature of the inflorescence develops normally. In situ phosphorylation assays with His-tagged wild type and crk10-A397T versions of the CRK10 kinase domain revealed that both alleles are active kinases capable of autophosphorylation, with the newly introduced threonine acting as an additional phosphorylation site in crk10-A397T. Transcriptomic analysis of wild type and crk10-A397T mutant hypocotyls revealed that biotic and abiotic stress-responsive genes are constitutively up-regulated in the mutant, and a root-infection assay with the vascular pathogen Fusarium oxysporum demonstrated that the mutant has enhanced resistance to this pathogen compared with wild type plants. Taken together our results suggest that crk10-A397T is a gain-of-function allele of CRK10, the first such mutant to have been identified for a CRK in Arabidopsis.
Evaluation of Vitamin D Status and the Analysis of Risk Factors of Vitamin D Deficiency in Twin Pregnancies
Authors: Le Juan , Lv Zhi-Hua , Peng Rui , Li Yan , Wang Shao-Ting
Published: March 2023

Objective

Optimization of maternal vitamin D (VD) status has beneficial effects on pregnancies, but little is known about it of twin pregnancies (TP). Our aim was to promote the current understanding of VD status and its associated factors in TP.

Methods

We performed liquid chromatography-tandem mass spectrometry to quantify 25-hydroxyvitamin D [25(OH)D] and used the enzyme-linked immunosorbent assay method to detect vitamin D binding protein (VDBP) in 218 singleton pregnancies (SP) and 236 TP.

Results

Levels of 25(OH)D and VDBP were higher in TP than SP. The 25(OH)D, free 25(OH)D, C-3 epimer of 25-hydroxyvitamin D [epi-25(OH)D], and VDBP all increased with gestational progress. Age, body  mass index, and hemoglobin level were associated with VD deficiency (VDD). Analysis of covariance demonstrated that the 25(OH)D and VDBP of TP and SP still showed differences after adjusting for the above associated factors.

Conclusion

Differences in VD status were found in SP and TP, suggesting that the assessment of VD status in TP should be treated with caution. High VDD prevalence is observed among pregnant Chinese women, and it is recommended to promote evaluation for VDD.
Tissue-Like 3D Standard and Protocols for Microscope Quality Management
Authors: Abrams Benjamin , Pengo Thomas , Wee Tse-Luen , Deagle Rebecca C , Vuillemin Nelly , Callahan Linda M , Smith Megan A , Kubow Kristopher E , Girard Anne-Marie , Rappoport Joshua Z , Bayles Carol J , Cameron Lisa A , Cole Richard , Brown Claire M
Published: March 2023

This article outlines a global study conducted by the Association of Biomedical Resource Facilities (ABRF) Light Microscopy Research Group (LMRG). The results present a novel 3D tissue-like biologically relevant standard sample that is affordable and straightforward to prepare. Detailed sample preparation, instrument-specific image acquisition protocols and image analysis methods are presented and made available to the community. The standard consists of sub-resolution and large well characterized relative intensity fluorescence microspheres embedded in a 120 µm thick 3D gel with a refractive index of 1.365. The standard allows the evaluation of several properties as a function of depth. These include the following: 1) microscope resolution with automated analysis of the point-spread function (PSF), 2) automated signal-to-noise ratio analysis, 3) calibration and correction of fluorescence intensity loss, and 4) quantitative relative intensity. Results demonstrate expected refractive index mismatch dependent losses in intensity and resolution with depth, but the relative intensities of different objects at similar depths are maintained. This is a robust standard showing reproducible results across laboratories, microscope manufacturers and objective lens types (e.g., magnification, immersion medium). Thus, these tools will be valuable for the global community to benchmark fluorescence microscopes and will contribute to improved scientific rigor and reproducibility.
Hunting for C-rich long-period variable stars in the Milky Way’s bar-bulge using unsupervised classification ofGaiaBP/RP spectra
Authors: Sanders Jason L , Matsunaga Noriyuki
Published: March 2023

The separation of oxygen- and carbon-rich asymptotic giant branch sources is crucial for their accurate use as local and cosmological distance and age/metallicity indicators. We investigate the use of unsupervised learning algorithms for classifying the chemistry of long-period variables from Gaia DR3’s BP/RP spectra. Even in the presence of significant interstellar dust, the spectra separate into two groups attributable to O-rich and C-rich sources. Given these classifications, we utilize a supervised approach to separate O-rich and C-rich sources without blue and red photometers (BP/RP) spectra but instead given broadband optical and infrared photometry finding a purity of our C-rich classifications of around 95 per cent. We test and validate the classifications against other advocated colour–colour separations based on photometry. Furthermore, we demonstrate the potential of BP/RP spectra for finding S-type stars or those possibly symbiotic sources with strong emission lines. Although our classification suggests the Galactic bar-bulge is host to very few C-rich long-period variable stars, we do find a small fraction of C-rich stars with periods $\gt 250\, \mathrm{day}$ that are spatially and kinematically consistent with bar-bulge membership. We argue the combination of the observed number, the spatial alignment, the kinematics, and the period distribution disfavour young metal-poor star formation scenarios either in situ or in an accreted host, and instead, these stars are highly likely to be the result of binary evolution and the evolved versions of blue straggler stars already observed in the bar-bulge.
Using the star-forming main sequence to explore quiescent galaxies across cosmic time
Authors: Houston Tyler , Croton Darren J , Sinha Manodeep
Published: March 2023

In this letter, we explore the quiescent lives of central galaxies using the Semi-Analytical Galaxy Evolution galaxy model and Uchuu dark matter simulation. We ask three questions: (1) How much of a galaxy’s life is spent in quiescence? (2) How often do galaxies transit off the main sequence? (3) What is the typical duration of a quiescent phase? We find that the low- and high-mass galaxies spend the highest fraction of their lives in quiescence: 45 ± 19 per cent for log10(Mstar) < 9.0 (3.68 ± 1.80 Gyr) and 26 ± 25 per cent for log10(Mstar) > 11.5 (3.46 ± 3.30 Gyr), falling to 7 ± 13 per cent for galaxies in-between (0.82 ± 1.57 Gyr). Low-mass galaxies move in and out of quiescence frequently, 2.8 ± 1.3 times on average, though only for short periods, 1.49 ± 1.04 Gyr. This can be traced to the influence of supernova feedback on their quite stochastic evolution. Galaxies of higher mass have fewer quiescent periods, ∼0.7 ± 0.9, and their length increases with mass, peaking at 1.97 ± 2.27 Gyr. However, our high-mass population comprises star-forming and quiescent galaxies with diverging evolutionary paths, so the actual time may be even longer. These high-mass trends are driven by radio-mode feedback from supermassive black holes, which, once active, tend to remain active for extended periods.
Limited Song Mixing Without Genomic Gene Flow in a Contact Zone Between Two Songbird Species
Authors: Wu Lei , Dang Jing , Tang Linfang , Cheng Yalin , Song Gang , Sun Yuehua , Martens Jochen , Päckert Martin , Alström Per , Zhang Dezhi , Jia Chenxi , Lei Fumin
Published: March 2023

Song is considered to play an important role in the maintenance of prezygotic reproductive isolation between closely related songbird species. Therefore, song mixing in a contact zone between closely related species is often considered as evidence of hybridization. The Sichuan Leaf Warbler Phylloscopus forresti and the Gansu Leaf Warbler Phylloscopus kansuensis, which diverged 2 million years ago, have formed a contact zone in the south of the Gansu Province of China, where mixed songs have been observed. In this study, we investigated the potential causes and consequences of song mixing by integrating bioacoustic, morphological, mitochondrial, and genomic data with field ecological observations. We found that the two species display no apparent morphological differences, whereas their songs differ dramatically. We demonstrated that ∼11% of the males in the contact zone sang mixed songs. Two males singing mixed song were genotyped, and both were found to be P. kansuensis. Despite the presence of mixed singers, population genomic analyses detected no signs of recent gene flow between the two species, although two possible cases of mitochondrial introgression were identified. We conclude that the rather limited song mixing does not lead to, or result from, hybridization, and hence does not result in the breakdown of reproductive barriers between these cryptic species.
Similarity and difference between systemic lupus erythematosus and NZB/W F1 mice by multi-omics analysis
Authors: Okuma Kenji , Oku Takuma , Sasaki Chiyomi , Kitagori Koji , Mimori Tsuneyo , Aramori Ichiro , Hirayama Yoshitaka , Yoshifuji Hajime
Published: March 2023

Objectives

Several animal disease models have been used to understand the mechanisms of systemic lupus erythematosus (SLE); however, the translation of findings from animals to humans has not been sufficiently examined in drug development. To confirm the validity of New Zealand black x New Zealand white (NZB/W) F1 mice as an SLE model, we extensively characterized SLE patients and NZB/W F1 mice by omics analysis.

Methods

Peripheral blood from patients and mice and spleen and lymph node tissue from mice were analysed using cell subset analysis, cytokine panel assays, and transcriptome analysis.

Results

CD4+ effector memory T cells, plasmablasts, and plasma cells were increased in both SLE patients and NZB/W F1 mice. Levels of tumor necrosis factor-α, interferon gamma induced protein-10, and B cell activating factor in plasma were significantly higher in SLE patients and NZB/W F1 mice than in their corresponding controls. Transcriptome analysis revealed an upregulation of genes involved in the interferon signalling pathway and T-cell exhaustion signalling pathway in both SLE patients and the mouse model. In contrast, death receptor signalling genes showed changes in the opposite direction between patients and mice.

Conclusion

NZB/W F1 mice are a generally suitable model of SLE for analysing the pathophysiology and treatment response of T/B cells and monocytes/macrophages and their secreted cytokines.
Weak tension accelerates hybridization and dehybridization of short oligonucleotides
Authors: Hart Derek J , Jeong Jiyoun , Gumbart James C , Kim Harold D
Published: March 2023

The hybridization and dehybridization of DNA subject to tension is relevant to fundamental genetic processes and to the design of DNA-based mechanobiology assays. While strong tension accelerates DNA melting and decelerates DNA annealing, the effects of tension weaker than 5 pN are less clear. In this study, we developed a DNA bow assay, which uses the bending rigidity of double-stranded DNA (dsDNA) to exert weak tension on a single-stranded DNA (ssDNA) target in the range of 2–6 pN. Combining this assay with single-molecule FRET, we measured the hybridization and dehybridization kinetics between a 15 nt ssDNA under tension and a 8–9  nt oligonucleotide, and found that both the hybridization and dehybridization rates monotonically increase with tension for various nucleotide sequences tested. These findings suggest that the nucleated duplex in its transition state is more extended than the pure dsDNA or ssDNA counterpart. Based on coarse-grained oxDNA simulations, we propose that this increased extension of the transition state is due to steric repulsion between the unpaired ssDNA segments in close proximity to one another. Using linear force-extension relations verified by simulations of short DNA segments, we derived analytical equations for force-to-rate conversion that are in good agreement with our measurements.
Identification and characterization of thousands of bacteriophage satellites across bacteria
Authors: de Sousa Jorge A Moura , Fillol-Salom Alfred , Penadés José R , Rocha Eduardo P C
Published: March 2023

Bacteriophage–bacteria interactions are affected by phage satellites, elements that exploit phages for transfer between bacteria. Satellites can encode defense systems, antibiotic resistance genes, and virulence factors, but their number and diversity are unknown. We developed SatelliteFinder to identify satellites in bacterial genomes, detecting the four best described families: P4-like, phage inducible chromosomal islands (PICI), capsid-forming PICI, and PICI-like elements (PLE). We vastly expanded the number of described elements to ∼5000, finding bacterial genomes with up to three different families of satellites. Most satellites were found in Proteobacteria and Firmicutes, but some are in novel taxa such as Actinobacteria. We characterized the gene repertoires of satellites, which are variable in size and composition, and their genomic organization, which is very conserved. Phylogenies of core genes in PICI and cfPICI indicate independent evolution of their hijacking modules. There are few other homologous core genes between other families of satellites, and even fewer homologous to phages. Hence, phage satellites are ancient, diverse, and probably evolved multiple times independently. Given the many bacteria infected by phages that still lack known satellites, and the recent proposals for novel families, we speculate that we are at the beginning of the discovery of massive numbers and types of satellites.
PRRC2 proteins impact translation initiation by promoting leaky scanning
Authors: Bohlen Jonathan , Roiuk Mykola , Neff Marilena , Teleman Aurelio A
Published: March 2023

Roughly half of animal mRNAs contain upstream open reading frames (uORFs). These uORFs can represent an impediment to translation of the main ORF since ribosomes usually bind the mRNA cap at the 5′ end and then scan for ORFs in a 5′-to-3′ fashion. One way for ribosomes to bypass uORFs is via leaky scanning, whereby the ribosome disregards the uORF start codon. Hence leaky scanning is an important instance of post-transcriptional regulation that affects gene expression. Few molecular factors regulating or facilitating this process are known. Here we show that the PRRC2 proteins PRRC2A, PRRC2B and PRRC2C impact translation initiation. We find that they bind eukaryotic translation initiation factors and preinitiation complexes, and are enriched on ribosomes translating mRNAs with uORFs. We find that PRRC2 proteins promote leaky scanning past translation start codons, thereby promoting translation of mRNAs containing uORFs. Since PRRC2 proteins have been associated with cancer, this provides a mechanistic starting point for understanding their physiological and pathophysiological roles.
SelectBCM tool: a batch evaluation framework to select the most appropriate batch-correction methods for bulk transcriptome analysis
Authors: Mishra Madhulika , Barck Lucas , Moreno Pablo , Heger Guillaume , Song Yuyao , Thornton Janet M , Papatheodorou Irene
Published: March 2023

Bulk transcriptomes are an essential data resource for understanding basic and disease biology. However, integrating information from different experiments remains challenging because of the batch effect generated by various technological and biological variations in the transcriptome. Numerous batch-correction methods to deal with this batch effect have been developed in the past. However, a user-friendly workflow to select the most appropriate batch-correction method for the given set of experiments is still missing. We present the SelectBCM tool that prioritizes the most appropriate batch-correction method for a given set of bulk transcriptomic experiments, improving biological clustering and gene differential expression analysis. We demonstrate the applicability of the SelectBCM tool on analyses of real data for two common diseases, rheumatoid arthritis and osteoarthritis, and one example to characterize a biological state, where we performed a meta-analysis of the macrophage activation state. The R package is available at https://github.com/ebi-gene-expression-group/selectBCM.
cgRNASP: coarse-grained statistical potentials with residue separation for RNA structure evaluation
Authors: Tan Ya-Lan , Wang Xunxun , Yu Shixiong , Zhang Bengong , Tan Zhi-Jie
Published: March 2023

Knowledge-based statistical potentials are very important for RNA 3-dimensional (3D) structure prediction and evaluation. In recent years, various coarse-grained (CG) and all-atom models have been developed for predicting RNA 3D structures, while there is still lack of reliable CG statistical potentials not only for CG structure evaluation but also for all-atom structure evaluation at high efficiency. In this work, we have developed a series of residue-separation-based CG statistical potentials at different CG levels for RNA 3D structure evaluation, namely cgRNASP, which is composed of long-ranged and short-ranged interactions by residue separation. Compared with the newly developed all-atom rsRNASP, the short-ranged interaction in cgRNASP was involved more subtly and completely. Our examinations show that, the performance of cgRNASP varies with CG levels and compared with rsRNASP, cgRNASP has similarly good performance for extensive types of test datasets and can have slightly better performance for the realistic dataset—RNA-Puzzles dataset. Furthermore, cgRNASP is strikingly more efficient than all-atom statistical potentials/scoring functions, and can be apparently superior to other all-atom statistical potentials and scoring functions trained from neural networks for the RNA-Puzzles dataset. cgRNASP is available at https://github.com/Tan-group/cgRNASP.
BaM-seq and TBaM-seq, highly multiplexed and targeted RNA-seq protocols for rapid, low-cost library generation from bacterial samples
Authors: Johnson Grace E , Parker Darren J , Lalanne Jean-Benoit , Parker Mirae L , Li Gene-Wei
Published: March 2023

The ability to profile transcriptomes and characterize global gene expression changes has been greatly enabled by the development of RNA sequencing technologies (RNA-seq). However, the process of generating sequencing-compatible cDNA libraries from RNA samples can be time-consuming and expensive, especially for bacterial mRNAs which lack poly(A)-tails that are often used to streamline this process for eukaryotic samples. Compared to the increasing throughput and decreasing cost of sequencing, library preparation has had limited advances. Here, we describe bacterial-multiplexed-seq (BaM-seq), an approach that enables simple barcoding of many bacterial RNA samples that decreases the time and cost of library preparation. We also present targeted-bacterial-multiplexed-seq (TBaM-seq) that allows for differential expression analysis of specific gene panels with over 100-fold enrichment in read coverage. In addition, we introduce the concept of transcriptome redistribution based on TBaM-seq that dramatically reduces the required sequencing depth while still allowing for quantification of both highly and lowly abundant transcripts. These methods accurately measure gene expression changes with high technical reproducibility and agreement with gold standard, lower throughput approaches. Together, use of these library preparation protocols allows for fast, affordable generation of sequencing libraries.
De-novoreconstruction and identification of transcriptional gene regulatory network modules differentiating single-cell clusters
Authors: Oubounyt Mhaned , Elkjaer Maria L , Laske Tanja , Grønning Alexander G B , Moeller Marcus J , Baumbach Jan
Published: March 2023

Single-cell RNA sequencing (scRNA-seq) technology provides an unprecedented opportunity to understand gene functions and interactions at single-cell resolution. While computational tools for scRNA-seq data analysis to decipher differential gene expression profiles and differential pathway expression exist, we still lack methods to learn differential regulatory disease mechanisms directly from the single-cell data. Here, we provide a new methodology, named DiNiro, to unravel such mechanisms de novo and report them as small, easily interpretable transcriptional regulatory network modules. We demonstrate that DiNiro is able to uncover novel, relevant, and deep mechanistic models that not just predict but explain differential cellular gene expression programs. DiNiro is available at https://exbio.wzw.tum.de/diniro/.
Genital Herpes Simplex Virus Type 2 Suppression With Valacyclovir Is Not Associated With Changes in Nugent Score or Absolute Abundance of Key Vaginal Bacteria
Authors: Babu Tara M , Srinivasan Sujatha , Magaret Amalia , Proll Sean , Karita Helen Stankiewicz , Wallis Jacqueline M , Selke Stacy , Varon Dana , Pholsena Thepthara , Fredricks David , Marrazzo Jeanne , Wald Anna , Johnston Christine
Published: March 2023

Background

In women, genital herpes simplex virus type 2 (HSV-2) infection is associated with increased risk for recurrent bacterial vaginosis (BV), but causal relationships are unclear.

Methods

Women with a self-reported history of BV and HSV-2 seropositivity self-collected vaginal and anogenital swabs for 2 nonconsecutive 28-day periods, in the absence or presence of valacyclovir suppressive therapy (500 mg daily). HSV polymerase chain reaction was performed on anogenital swabs; vaginal swabs were used for assessment of BV by Nugent score and quantification of vaginal microbiota. Days with BV, defined by Nugent score ≥7, were compared during the observational period and valacyclovir treatment.

Results

Forty-one women collected swabs for a median of 28 days (range, 20–32 days) each study period. The HSV-2 shedding rate decreased from 109 of 1126 days (9.7%) presuppression to 6 of 1125 days (0.05%) during valacyclovir (rate ratio [RR], 0.06 [95% confidence interval {CI}, .02–.13]). BV occurred on 343 of 1103 days (31.1%) during observation and 302 of 1091 days (27.7%) during valacyclovir (RR, 0.90 [95% CI, .68–1.20]). The median per-person Nugent score was 3.8 during observation and 4.0 during valacyclovir. Average log10 concentrations of vaginal bacterial species did not change significantly during valacyclovir treatment.

Conclusions

Short-term HSV-2 suppression with valacyclovir did not significantly affect the Nugent score or the vaginal microbiome despite potent suppression of HSV-2 shedding.
Effectiveness of Noncertified Pharmacist–Led Antimicrobial Stewardship Programs in a Medium-Sized Hospital Without an Infectious Disease Specialist: A Retrospective Pre–Post Study
Authors: Sawada Keisuke , Inose Ryo , Goto Ryota , Nakatani Takeshi , Kono Shuji , Muraki Yuichi
Published: March 2023

Background

Few studies have reported the outcomes of antimicrobial stewardship programs (ASPs) implemented without infectious disease (ID) physician or pharmacist specialists. We implemented interventions that included providing antimicrobial optimization recommendations through a pharmacist-led team using prospective audit and feedback. This study evaluated different types of interventions and their impact on the outcomes of ASPs in a medium-sized hospital without ID specialists.

Methods

This retrospective pre–post study included adult inpatients treated with intravenous antimicrobials between April 2016 and March 2020. Outcome (eg, length of hospital stay [LOS], drug cost) and process measures (eg, type of intervention, length of therapy) were compared between 2 time periods: pre-ASP (April 2016–March 2018) and post-ASP (April 2018–March 2020).

Results

We included 5419 and 5634 patients in the pre- and post-ASP periods, respectively. The most common types of interventions were adjusting length of therapy (49.5%), additional laboratory tests (27.1%), antimicrobial change (16.2%), and dosage of antimicrobial (7.1%). After ASP implementation, LOS significantly decreased (14.8 vs 13.8 days, P < .01), along with the length of therapy, empirical use of antipseudomonal and anti–methicillin-resistant Staphylococcus aureus drugs, and number of days to de-escalation. No significant differences were noted in 30-day mortality, 30-day readmission, or de-escalation rates. On average, the antimicrobial cost per hospitalization decreased from US$173.03 to US$120.66.

Conclusions

Pharmacist-led ASP interventions that focus on the length of therapy have the potential to reduce LOS in hospitals without ID specialists. Overall, this study showed that ASPs can be effectively implemented in medium-sized hospitals without ID specialists.
Factors Associated With Adherence to First-line Antiviral Therapy Among Commercially Insured Patients With Chronic Hepatitis B
Authors: Alpern Jonathan D , Joo Heesoo , Bahr Nathan C , Leventhal Thomas M
Published: March 2023

Background

Nonadherence to antiviral therapy can lead to poor clinical outcomes among patients with chronic hepatitis B (CHB). We used a claims database to evaluate risk factors for nonadherence to antiviral therapy among commercially insured patients with CHB in the United States.

Methods

We obtained data for commercially insured adult patients with CHB prescribed entecavir or tenofovir disoproxil fumarate (TDF) in 2019. Primary outcomes were adherence to entecavir and adherence to TDF. Enrollees with a proportion of days covered (PDC) ≥80% were considered adherent. We presented adjusted odds ratios (AORs) from multivariate logistic regressions.

Results

Eighty-three percent (n = 640) of entecavir patients were adherent, and 81% (n = 687) of TDF patients were adherent. Ninety-day supply (vs 30-day supply; AOR, 2.21; P < .01), mixed supply (vs 30-day supply; AOR, 2.19; P = .04), and ever using a mail order pharmacy (AOR, 1.92, P = .03) were associated with adherence to entecavir. Ninety-day supply (vs 30-day supply; AOR, 2.51; P < .01), mixed supply (vs 30-day supply; AOR, 1.82; P = .04), and use of a high-deductible health plan (vs no high-deductible health plan; AOR, 2.29; P = .01) were associated with adherence to TDF. Out-of-pocket spending of >$25 per 30-day supply of TDF was associated with reduced odds of adherence to TDF (vs <$5 per 30-day supply of TDF; AOR, 0.34; P < .01).

Conclusions

Ninety-day and mixed-duration supplies of entecavir and TDF were associated with higher fill rates as compared with 30-day supplies among commercially insured patients with CHB.
Tenosynovial Giant Cell Tumor Observational Platform Project (TOPP) Registry: A 2-Year Analysis of Patient-Reported Outcomes and Treatment Strategies
Authors: Palmerini Emanuela , Healey John H , Bernthal Nicholas M , Bauer Sebastian , Schreuder Hendrik , Leithner Andreas , Martin-Broto Javier , Gouin Francois , Lopez-Bastida Julio , Gelderblom Hans , Staals Eric L , Mercier Florence , Laeis Petra , Ye Xin , van de Sande Michiel
Published: March 2023

Background

The Tenosynovial giant cell tumor Observational Platform Project (TOPP) registry is an international prospective study that ­previously described the impact of diffuse-type tenosynovial giant cell tumour (D-TGCT) on patient-reported outcomes (PROs) from a baseline snapshot. This analysis describes the impact of D-TGCT at 2-year follow-up based on treatment strategies.

Material and Methods

TOPP was conducted at 12 sites (EU: 10; US: 2). Captured PRO measurements assessed at baseline, 1-year, and 2-year follow-ups were Brief Pain Inventory (BPI), Pain Interference, BPI Pain Severity, Worst Pain, EQ-5D-5L, Worst Stiffness, and ­Patient-Reported Outcomes Measurement Information System. Treatment interventions were no current/planned treatment (Off-Treatment) and systemic treatment/surgery (On-Treatment).

Results

A total of 176 patients (mean age: 43.5 years) were included in the full analysis set. For patients without active treatment strategy ­(Off-Treatment) at baseline (n = 79), BPI Pain Interference (1.00 vs. 2.86) and BPI Pain Severity scores (1.50 vs. 3.00) were numerically favorable in patients remaining Off-Treatment compared with those who switched to an active treatment strategy at year 1. From 1-year to 2-year ­follow-ups, patients who remained Off-Treatment had better BPI Pain Interference (0.57 vs. 2.57) and Worst Pain (2.0 vs. 4.5) scores compared with patients who switched to an alternative treatment strategy. In addition, EQ-5D VAS scores (80.0 vs. 65.0) were higher in patients who remained ­Off-Treatment between 1-year and 2-year follow-ups compared with patients who changed treatment strategy. For patients receiving systemic treatment at baseline, numerically favorable scores were seen in patients remaining on systemic therapy at 1-year follow-up: BPI Pain Interference (2.79 vs. 5.93), BPI Pain Severity (3.63 vs. 6.38), Worst Pain (4.5 vs. 7.5), and Worst Stiffness (4.0 vs. 7.5). From 1-year to 2-year follow-up, EQ-5D VAS scores (77.5 vs. 65.0) were higher in patients who changed from systemic treatment to a different treatment strategy.

Conclusion

These findings highlight the impact D-TGCT has on patient quality of life, and how treatment strategies may be influenced by these outcome measures. (ClinicalTrials.gov number: NCT02948088)
Exercising Caution: A Case for Ethics Analysis in Physical Activity Promotion
Authors: Esmonde Katelyn
Published: March 2023

Despite the important role of physical activity in population health and well-being, it has received less focus in public health ethics as compared to other modifiable lifestyle factors such as smoking and diet. However, when considering the current and potential role of physical activity within public health—including interventions and policies to encourage physical activity in schools and workplaces, changes to the built environment and the equity issues associated with access to physical activity—it is a ripe territory for ethical analysis. This paper makes a case for a more sustained focus on physical activity within public health ethics by reviewing two ethical issues within physical activity and public health: physical activity inequity as a structural injustice issue, and stigma in physical activity promotion. While the benefits of physical activity for every age group and demographic are numerous, ethics oversight is encouraged to ensure that these efforts do not impose unnecessary risks or stigmatize marginalized populations.
Reducing Item Nonresponse to Vote-Choice Questions: Evidence from a Survey Experiment in Mexico
Authors: Cohen Mollie J , Cassell Kaitlen J
Published: March 2023

Retrospective vote choice is a critical question asked in political science surveys. Yet, this question suffers from persistently high item nonresponse rates, which can bias estimates and limit scholars’ ability to make sound inferences. In this paper, we develop a sensitive survey technique to decrease nonresponse to the vote-choice question in a representative, face-to-face survey in Mexico City and Mexico State in 2018–2019. Respondents received different iterations of three treatments: an anonymity guarantee, a confidentiality reminder, and audio-assisted interviewing technology. The use of audio technology combined with a credible anonymity guarantee significantly improved item response. Both anonymity and confidentiality assurances improved the accuracy of response, which more closely resembled official results in the treatment conditions. We then evaluate two non-rival mechanisms that might drive our findings: beliefs about response anonymity and re-engagement with the survey. We find that increased perceptions of response anonymity are associated with improved item response.
Do Physical Therapists Practice a Behavioral Medicine Approach? A Comparison of Perceived and Observed Practice Behaviors
Authors: Fritz Johanna , Overmeer Thomas
Published: March 2023

Objective

A behavioral medicine approach, incorporating a biopsychosocial view and behavior change techniques, is recommended in physical therapy for the management of musculoskeletal pain. However, little is known about physical therapists’ actual practice behavior regarding the behavioral medicine approach. The aim of this study was to examine how physical therapists in primary health care judge their own practice behavior of a behavioral medicine approach in the assessment and treatment of patients with persistent musculoskeletal pain versus how they practice a behavioral medicine approach as observed by independent experts in video recordings of patient consultations.

Methods

A prospective cohort study was conducted. Video recordings of 23 physical therapists’ clinical behavior in 139 patient consultations were observed by independent experts and compared with the physical therapists’ self-reported practice behavior, using a protocol including 24 clinical behaviors. The difference between observed and self-reported clinical behaviors was analyzed with a Chi-square test and a Fisher exact test.

Results

The behavioral medicine approach was, in general, practiced to a small extent and half of the self-reported clinical behaviors were overestimated when compared with the observed behaviors. According to the observations, the physical perspective dominated in assessment and treatment, the functional behavioral analysis was never performed, and the mean number of behavior change techniques used was 0.7.

Conclusion

There was a discrepancy between how physical therapists perceived the extent to which they practiced a behavioral medicine approach in their clinical behavior compared with what the independent researchers observed in the video recordings.

Impact

This study demonstrates the importance of using observations instead of using self-reports when evaluating professionals’ clinical behavior. The results also suggest that—to ensure that physical therapy integrates the biopsychosocial model of health—physical therapists need to increase their focus on psychosocial factors in clinical practice.
Rehabilitation Characteristics and Outcomes for Lung Transplantation for COVID-19: A Case Series
Authors: Clancy Malachy J , Adler Joe , Tevald Michael A , Zaleski Derek , Fluehr Lindsay , Wamsley Carol , Bermudez Christian A , Crespo Maria M , Balar Priya , Oyster Michelle L , Courtwright Andrew M , Diamond Joshua M
Published: March 2023

Objective

Severe coronavirus disease 2019 (COVID-19) can result in irreversible lung damage, with some individuals requiring lung transplantation. The purpose of this case series is to describe the initial experience with the rehabilitation and functional outcomes of 9 patients receiving a lung transplant for COVID-19.

Methods

Nine individuals, ranging in age from 37 to 68 years, received bilateral orthotopic lung transplantation (BOLT) for COVID-19 between December 2020 and July 2021. Rehabilitation was provided before and after the transplant, including in-hospital rehabilitation, postacute care inpatient rehabilitation, and outpatient rehabilitation.

Results

Progress with mobility was limited in the pretransplant phase despite rehabilitation efforts. Following transplantation, 2 individuals expired before resuming rehabilitation, and 2 others had complications that delayed their progress. The remaining 5 experienced clinically important improvements in mobility and walking capacities.

Conclusion

Considerable rehabilitation resources are required to care for individuals both before and after BOLT for COVID-19. Rehabilitation can have a profound impact on both functional and clinical outcomes for this unique patient population.

Impact

There is limited literature on the rehabilitation efforts and outcomes for patients who received BOLT for COVID-19. Occupational therapists and physical therapists play an important role during the pretransplant and posttransplant recovery process for this novel patient population.

Lay Summary

Patients with a bilateral orthotopic lung transplant due to COVID-19 require a unique rehabilitation process. They have significant difficulties with activities of daily living and functional mobility across the pretransplant and posttransplant continuum of care, but progressive gains in functional performance may be possible with a comprehensive multidisciplinary rehabilitation program.
Comparison of High-Intensity Interval Training to Moderate-Intensity Continuous Training for Functioning and Quality of Life in Survivors of COVID-19 (COVIDEX): Protocol for a Randomized Controlled Trial
Authors: Gomes Vinicius Afonso , Fontoura Fabiane , Saquetto Micheli Bernardone , Ramos Thaiana , Santos Samara , Coutinho de Araujo William Suzart , Rivas Paulo , Martinez Bruno Prata , Barreto Ana Paula , Coelho Lima Marcelo Chalhoub , Gomes-Neto Mansueto
Published: March 2023

Objective

The purpose of this study was to compare high-intensity interval training (HIIT) with moderate-intensity continuous training (MICT) for feasibility, safety, adherence, and short- and long-term efficacy in improving functioning and health-related quality of life in survivors of coronavirus disease 2019 (COVID-19).

Methods

COVIDEX is a two-pronged, parallel-group, randomized controlled trial with an 8-week training intervention. The study participants will be 94 patients aged >18 years, admitted to a specialized post-COVID center. Participants will be randomized to HIIT (4 × 4 minutes of high-intensity work periods at 85% to 90% of peak heart rate) and MICT (47 minutes at 70% to 75% peak heart rate) groups for biweekly sessions for 8 weeks. The participants will undergo 2 phases of supervised training (phases 1 and 2) of 4 weeks each, in a public, specialized, post-COVID center. In phase 1, we will assess and compare the feasibility, acceptability, and short-term efficacy of HIIT and MICT intervention. In phase 2, the long-term efficacy of HIIT and MICT will be assessed and compared regarding function and health-related quality of life. To prevent any expectation bias, all study participants and assessors will be blinded to the study hypotheses. Group allocation will be masked during the analysis. All statistical analyses will be conducted following intention-to-treat principles.

Impact

This study is the first randomized controlled trial that will compare the feasibility, safety, adherence, and efficacy of the HIIT and MICT intervention programs in this population. The findings will potentially provide important information and assist in clinical decision making on exercise to optimize the benefits of clinical health care in survivors of COVID-19.
Association Between Frailty and Free-Living Walking Performance in People With Multiple Sclerosis
Authors: Zanotto Tobia , Galperin Irina , Mirelman Anat , Chen Lingjun , Regev Keren , Karni Arnon , Schmitz-Hübsch Tanja , Paul Friedemann , Lynch Sharon G , Akinwuntan Abiodun E , Devos Hannes , Hausdorff Jeffrey M , Sosnoff Jacob J
Published: March 2023

Objective

The purpose of this study was to examine the association between frailty and the quantity and quality of free-living walking and the mediating effect of frailty on the relationship between disability and walking performance in people with multiple sclerosis (MS).

Methods

Ninety-nine people with relapsing–remitting MS (mean age = 49.3 [SD = 9.8] years; 73.7% women; Expanded Disability Status Scale [EDSS] score range = 2.0–6.0) wore a triaxial accelerometer for 7 days. Recorded measures reflected the quantity (daily step counts, number of 30-second walking bouts, and signal vector magnitude [SVM]) and quality (gait speed, step cadence, step and stride regularity, and sample entropy) of walking. For each walking quality measure, the typical (median), best (90th percentile), and worst (10th percentile) values were calculated. Frailty was evaluated through a 38-item frailty index.

Results

Participants were classified as not frail (n = 31), moderately frail (n = 34), and severely frail (n = 34) on the basis of established procedures. Patients who were moderately and severely frail exhibited poorer performance in all measures of walking quantity and quality, except for sample entropy, than individuals who were not frail. No differences in free-living walking performance were observed between the moderately and severely frail groups. Frailty did not mediate the relationship between disability (EDSS) and measures of walking quality. Conversely, frailty had a significant mediating effect on the relationship between disability and measures of walking quantity, such as daily step counts (indirect effect: b = −220.42, 95% CI = −452.03 to −19.65) and SVM (indirect effect: b = −1.00, 95% CI = −1.86 to −0.30).

Conclusion

Frailty is associated with poorer free-living walking performance in people with MS. The study findings suggest that frailty, rather than disability, may be primarily responsible for the lower amount of physical activity performed by people with MS in the real world.

Impact

The observation that frailty and disability are differently related to measures of walking quality and quantity underscores the importance of a targeted approach to rehabilitation in people with MS.
RADIATION DOSE REDUCTION AT LOW TUBE VOLTAGE WITH CORONARY ARTERY BYPASS GRAFT COMPUTED TOMOGRAPHY ANGIOGRAPHY BASED ON THE CONTRAST NOISE RATIO INDEX
Authors: Masuda Takanori , Nakaura Takeshi , Funama Yoshinori , Sato Tomoyasu , Masuda Shouko , Gotanda Rumi , Arao Keiko , Imaizumi Hiromasa , Arao Shinichi , Ono Atsushi , Hiratsuka Junichi , Awai Kazuo
Published: March 2023

To compare the radiation dose and diagnostic ability of the 100-kVp protocol, based on the contrast noise ratio (CNR) index, during coronary artery bypass graft (CABG) vessels with those of the 120-kVp protocol. For the 120-kVp scans (150 patients), the targeted image level was set at 25 Hounsfield units (HU) (CNR120 = iodine contrast/25 HU). For the 100-kVp scans (150 patients), the targeted noise level was set at 30 HU to obtain the same CNR as in the 120-kVp scans (i.e. using 1.2-fold higher iodine contrast, CNR100 = 1.2 × iodine contrast/(1.2 × 25 HU) = CNR120). We compared the CNRs, radiation doses, detection of CABG vessels and visualisation scores of the scans acquired at 120 and 100 kVp, respectively. At the same CNR, the 100-kVp protocol may help reduce the radiation dose by ⁓30% compared with the 120-kVp protocol, without degradation of diagnostic ability during CABG.
A SURVEY OF THE RADIOFREQUENCY ELECTROMAGNETIC ENERGY ENVIRONMENT IN MELBOURNE, AUSTRALIA
Authors: Henderson Stuart , Bhatt Chhavi , Loughran Sarah
Published: March 2023

A wide variety of modern technologies make use of radiofrequency (RF) electromagnetic energy (EME) to provide convenient functions and services to users. The rise in the use of RF EME-enabled devices has led to public perception of increasing exposures and concerns about potential health effects. During March and April 2022, the Australian Radiation Protection and Nuclear Safety Agency conducted an intensive campaign to measure and characterise ambient RF EME levels within the Melbourne metropolitan area. Fifty locations across the city were visited, and a wide variety of signals in the frequency range 100 kHz to 6 GHz were detected and recorded including broadcast radio and television (TV), Wi-Fi and mobile telecommunications services. The highest measured total RF EME level was 2.85 mW/m2, which is equivalent to 0.14% of the relevant limit specified by the Australian Standard (RPS S-1). The results showed that broadcast radio signals were the largest contributor to measured RF EME levels at 30 locations across the suburbs, whereas downlink signals from mobile phone towers were the main contributor at the other 20 sites. Broadcast TV and Wi-Fi were the only other sources found to contribute more than 1% of the total RF EME exposure recorded at any site. All measured RF EME levels were well below the permitted limit for general public exposure given by RPS S-1 and therefore do not present a health hazard.