bluuebunny/crossref_metadata_2025_split huggingface dataset:
Estimates of the Lifetime Productivity Costs of Chlamydia, Gonorrhea, and Syphilis in the United States
Authors: Chesson Harrell , Spicknall Ian H. , Kreisel Kristen M. , Gift Thomas L. 
Published: April 2024

Background
Productivity costs of sexually transmitted infections (STIs) reflect the value of lost time due to STI morbidity and mortality, including time spent traveling to, waiting for, and receiving STI treatment. The purpose of this study was to provide updated estimates of the average lifetime productivity cost for chlamydia, gonorrhea, and syphilis, per incident infection.

Methods
We adapted published decision tree models from recent studies of the lifetime medical costs of chlamydia, gonorrhea, and syphilis in the United States. For each possible outcome of infection, we applied productivity costs that we obtained based on published health economic studies. Productivity costs included the value of patient time spent to receive treatment for STIs and for related sequelae such as pelvic inflammatory disease in women. We used a human capital approach and included losses in market (paid) and nonmarket (unpaid) productivity. We conducted 1-way sensitivity analyses and probabilistic sensitivity analyses.

Results
The average lifetime productivity cost per infection was $28 for chlamydia in men, $205 for chlamydia in women, $37 for gonorrhea in men, $212 for gonorrhea in women, and $411 for syphilis regardless of sex, in 2023 US dollars. The estimated lifetime productivity cost of these STIs acquired in the United States in 2018 was $795 million.

Conclusions
These estimates of the lifetime productivity costs can help in quantifying the overall economic burden of STIs in the United States beyond just the medical cost burden and can inform cost-effectiveness analyses of STI prevention activities.
Breakthrough Mpox Outbreak Investigation, the Delicate Balance Between Host Immune Response and Viral Immune Escape
Authors: Moretti Marco , Meuwissen Annelies , Rezende Antonio M. , Zange Sabine , Van Nedervelde Els , de Block Tessa , Vercauteren Koen , Demuyser Thomas , Allard Sabine D. 
Published: April 2024

Background
Limited data are available on Mpox breakthrough infections.

Purpose
The purpose of this study is to investigate a Mpox breakthrough outbreak in 3 vaccinated individuals.

Methods
Study participants provided informed consent. Serology testing was performed in one involved individual (ID-1) using an in-house assay detecting anti-orthopoxvirus IgG. Whole genome sequencing (WGS) was carried out and compared with the reference sequence ON563414.3 (https://www.ncbi.nlm.nih.gov/nuccore/ON563414.3/).

Results
Three individuals vaccinated with modified vaccinia Ankara–Bavaria Nordic contracted Mpox following one sexual intercourse event. One of them (ID-1) had received only one vaccine dose, while the other two were fully vaccinated. ID-1 presented to the sexual health clinic of the Universitair Ziekenhuis Brussel with proctitis related to Mpox. Despite one vaccination, serology testing Three months post vaccine showed absence of Mpox virus (MPXV) specific antibodies in ID-1. In contrast, 2 weeks after the sexual intercourse, seroconversion occurred. Whole genome sequencing of the isolated MPXV showed, compared with the reference sequence, a total of seven single nucleotide variants with four of them indicating protein amino-acid changes.

Conclusion
Incomplete MPXV vaccination as well as MPXV variants might result in breakthrough infections. Preventive measures, such as MPVX vaccination, could maintain immunity in individuals with higher risk of MPXV infection, and might lower disease severity.
JYNNEOS Vaccine Safety Surveillance During the 2022 Mpox Outbreak Using the Vaccine Adverse Event Reporting System and V-safe, United States, 2022 to 2023
Authors: Duffy Jonathan , Myers Tanya R. , Marquez Paige , Rouse Douglas , Brown Hannah , Zhang Bicheng , Shay David K. , Moro Pedro L. 
Published: April 2024

Background
In response to the 2022 mpox outbreak in the United States, people with higher potential for exposure to mpox were recommended to receive 2 doses of the JYNNEOS vaccine. Vaccine safety was monitored using 2 complementary systems.

Methods
The Vaccine Adverse Event Reporting System (VAERS) is a passive surveillance system that accepts reports of adverse events after vaccination. VAERS is capable of rapidly identifying rare adverse events and unusual reporting patterns. Medical records were requested and reviewed for adverse events of special interest, including myocarditis. Adverse event reporting rates were calculated as the number of verified adverse event cases divided by the number of JYNNEOS doses administered. V-safe for mpox was a voluntary smartphone-based vaccine safety surveillance system that sent enrolled persons text messages linked to health surveys asking about reactions and health impact events occurring after vaccination.

Results
There were 1,207,056 JYNNEOS doses administered in the United States. VAERS received 1927 reports for JYNNEOS. The myocarditis reporting rate per million doses was 2.69 after dose 1 and 8.64 after dose 2. V-safe had 213 participants complete at least one health survey. Rates of injection site and systemic reactions were similar in the first week after dose 1 and dose 2.

Conclusions
JYNNEOS vaccine safety surveillance findings from VAERS and v-safe did not identify any unexpected safety concerns. The VAERS reporting rate for myocarditis was similar to previously published population background rates.
Opt-Out Syphilis Screening at an Urgent Care Center in Atlanta: Evaluation of a Pilot Program
Authors: Sweitzer Stephanie , Sharp Joseph , Baker Dylan , Lynch Alexis , Stauch Meredith A. , Wheatley Matthew , Lora Meredith , Cantos Valeria D. , Gruen Judah 
Published: April 2024

Background
Human immunodeficiency virus (HIV) and syphilis disproportionately impact communities with low access to primary care, who often utilize urgent care centers (UCCs) for sexual health care. UCC visits represent an opportunity for identification and treatment of syphilis and linkage to HIV testing and prevention services. We describe a universal, opt-out syphilis screening program pilot at an Atlanta UCC.

Methods
A chart review was performed on patients 18 years and older who were offered opt-out syphilis screening and had a rapid plasma reagin (RPR) test collected from September 1, 2021 to December 31, 2021. Demographic data, syphilis stage and treatment, and HIV testing and serostatus were abstracted from the electronic health record. Patients with reactive RPRs were contacted by a study physician for syphilis staging and treatment, counseling, and referral for HIV preexposure prophylaxis (PrEP) or treatment.

Results
From September 1, 2021 to December 31, 2021, 5794 patients were triaged and 1381 underwent RPR screening (23.8%). Eighty (5.8%) had reactive RPRs, and 42 (52.5%) had active syphilis. Of those with active syphilis, 39 (92.9%) received any treatment, and 35 (83.3%) completed treatment. Patients with late syphilis were less likely to complete syphilis treatment (adjusted odds ratio, 0.03; P = 0.009; 95% confidence interval, 0.002–0.42). Among 955 offered PrEP, 41 (4.3%) expressed interest in PrEP, and 7 (0.7%) completed PrEP clinic intake. Univariate analysis did not identify any factors associated with interest in PrEP.

Conclusions
In a UCC setting, routine, opt-out syphilis testing resulted in increased syphilis identification and treatment. It also provided an opportunity for PrEP counseling and referral, although few patients completed PrEP clinic intake.
Exercise Training for Women With Fibromyalgia Syndrome
Authors: Silva Lais Carneiro , Dittgen Michelle , Meroni Roberto , Sanchez-Romero Eleuterio A. , Rossettini Giacomo , Villafañe Jorge Hugo , Corbellini Camilo 
Published: April 2024

Background:
To identify in the literature the exercise training therapies for females with fibromyalgia that may improve pain management and quality of life (QOL).

Methods:
A literature search was conducted in MEDLINE and PEDro databases for human studies up to June 2021. We considered studies if they investigated exercise therapies and their impact on pain, QOL, physical function, and mental health in female patients with fibromyalgia.

Results:
We identified 112 clinical trials. After posterior analyses, 15 articles were selected, and 8 were considered eligible.

Conclusions:
Selected studies demonstrated that high-intensity and moderate-intensity aerobic training combined or not with muscle strength anaerobic exercise reduces pain and improves QOL in females with fibromyalgia.
Suppressive Role of Pigment Epithelium-derived Factor in a Rat Model of Corneal Allograft Rejection
Authors: Chu Xiaoran , Yin Yilan , Chen Sijing , Chen Fu , Liu Hui , Zhao Shaozhen 
Published: April 2024

Background.
Immunological rejection is the most common reason for corneal transplantation failure. The importance of T cells in corneal allograft rejection is well demonstrated. Recent studies highlight that pigment epithelium-derived factor (PEDF) plays an immunoregulatory role in ocular diseases by enhancing the suppressive phenotype of regulatory T cells besides its other functions in neurotrophy and antiangiogenesis.

Methods.
The effects of PEDF on immune rejection were examined in rat models of corneal transplantation using slit-lamp microscope observation, immunohistochemistry, flow cytometry, and Western blot. In vitro, we demonstrated PEDF reduced alloreactive T-cell activation using real-time polymerase chain reaction, flow cytometry, and Western blot.

Results.
Topical administration of PEDF provided corneal transplantation rats with an improved graft survival rate of corneal allografts, reduced hemangiogenesis, and infiltration of immune cells in corneas, in particular, type 17 T helper cells while increased regulatory T cells. Moreover, nerve reinnervation within grafts was promoted in PEDF-treated recipient rats. In vitro, PEDF inhibited alloreactive T-cell activation via the c-Jun N-terminal kinase/c-Jun signaling pathway and upregulated the expressions of interleukin-10 and transforming growth factor-β, emphasizing the suppressive role of PEDF on immune responses.

Conclusions.
Our results underscore the feasibility of PEDF in alleviating corneal allograft rejection and further illustrate its potential in managing immune-related diseases.
Uncontrolled hypertension is associated with an increased risk of end-stage renal disease in patients with type 2 diabetes who underwent postpercutaneous coronary intervention: A nationwide population-based study
Authors: Kim Hyunglae , Park Yong-Moon , Ko Seung-Hyun , Cho Yun-Jung , Kim Hyung Wook , Kim Yong Kyun , Han Kyung-Do , Yun Jae-Seung , Kim Kyuho , Moon Donggyu 
Published: April 2024

AbstractBackgroundLittle is known about the use of hypertension to predict end-stage renal disease (ESRD) in patients with type 2 diabetes mellitus (T2DM) and established coronary artery disease who underwent percutaneous coronary intervention (PCI). Here, we evaluated the effect of differential blood pressure (BP) levels on future ESRD in this population.MethodsUsing nationwide health check-up data from the Korean National Health Insurance Service between 2015 and 2016, we obtained data for 80,187 patients with T2DM who underwent previous PCI. Patients were classified into four groups according to BP level measured within at least 2 years after PCI: systolic BP <120 (reference), <130, <140, <160, and ≥160 mm Hg; diastolic BP <80 (reference), <90, <100, and ≥100 mm Hg. The primary outcome was incident ESRD, defined as a combination of the relevant disease code and the initiation of renal replacement therapy. Multivariate Cox proportional hazard regression analysis was used to estimate the adjusted hazard ratio (HR) (95% CI) according to BP group.ResultsThe mean age was 67.7 years, and 80.9% of the participants were treated with antihypertensive medication. ESRD occurred in 1,362 (1.70%) patients during the 4.7-year follow-up. After adjustment for confounding factors, the HR of ESRD patients significantly and sequentially increased in the higher BP groups. Similar findings were noted regarding the relationship between incident ESRD and pulse pressure (PP). According to the subgroup analysis, this relationship was more significant for SBP in those aged <65 years than in those who were aged 65 years or older (Pfor interaction=0.0498). ESRD risk was linearly associated with systolic BP and had a J-shaped association with diastolic BP in patients with baseline values of 70 and 68 mm Hg.ConclusionsIn this nationwide population-based study, elevated systolic and diastolic BP and PP were associated with the risk of developing ESRD in a dose‒response manner among T2DM patients who underwent PCI. To prevent ESRD, more strict BP control is needed in T2DM patients who underwent PCI.
The Sodium/Glucose Cotransporter 2 Inhibitor Empagliflozin Inhibits Long QT 3 Late Sodium Currents in a Mutation Specific Manner
Authors: Lunsonga Lynn C. , Fatehi Mohammad , Long Wentong , Barr Amy J. , Gruber Brittany , Chattopadhyay Arkapravo , Barakat Khaled , Edwards Andrew G. , Light Peter E. 
Published: April 2024

AbstractBackgroundSodium/glucose cotransporter 2 inhibitors (SGLT2is) such as empagliflozin have demonstrated substantial cardioprotective effects in patients with or without diabetes. The SGLT2is have been shown to selectively inhibit the late component of cardiac sodium current (late INa). Induction of late INais also the primary mechanism involved in the pathophysiology of congenital long QT syndrome type 3 (LQT3) gain-of-function mutations in the SCN5A gene that encodes the major cardiac sodium channel isoform Nav1.5. Therefore, we investigated the effect of empagliflozin on late INain thirteen known LQT3 mutations located in distinct regions of the channel structure.MethodsThe whole-cell patch-clamp technique was used to investigate the effect of empagliflozin (10 µM) on late INain recombinantly expressed Nav1.5 channels containing different LQT3 mutations. Molecular modeling of human Nav1.5 and simulations in a mathematical model of human ventricular myocytes were used to extrapolate our experimental results to excitation contraction coupling.ResultsEmpagliflozin selectively inhibited late INain LQT3 mutations residing in the inactivation gate region of Nav1.5, with no effect on either peak current or channel kinetics. In contrast, empagliflozin caused inhibition of both peak and late INain mutations in the S4 voltage-sensing regions as well as changes in activation and inactivation kinetics and a slowing of recovery from inactivation. Empagliflozin had no effect on late/peak INaor channel kinetics in channels containing LQT3 mutations located in the putative empagliflozin binding region. Simulation of our experimental findings in a mathematical model of human ventricular myocytes predicts that empagliflozin may have a desirable therapeutic effect in LQT3 mutations located in the inactivation gate region.ConclusionsOur results show that empagliflozin selectively inhibits late INa, without affecting gating kinetics, in LQT3 mutations residing in the inactivation gate region. Patients with mutations in voltage-sensing regions are less suitable candidates as empagliflozin may prevent action potential firing. The SGLT2is may therefore be a promising novel precision medicine approach for patients with certain LQT3 mutations.
The evaluation of the clinical effect of primary insomnia treated with the manual acupuncture therapy: a study protocol for a parallel, randomized controlled trial
Authors: Zhu Kean , Zhou Chuanlong , Zhang Quanai , Han Dexiong , Chen Weiji , Wang Wenfang , Wu Bin , Lin Xianming , Liu Yingjun 
Published: April 2024

AbstractBackgroundClinically, primary insomnia (PI) manifests as difficulty falling asleep, difficulty maintaining sleep, or early waking up. The occurrence of PI is closely related to emotional disorders, social stress and environmental stress. According to current studies, acupuncture offers significant advantages in treating PI. The manual acupuncture has been used for the treatment of insomnia for decades. Different acupuncture strategies, including electroacupuncture, manual acupuncture, and multiple acupuncture, have been reported to treat insomnia. However, there are few standardized clinical reports to investigate the effect of the manual acupuncture and its mechanism.MethodsThis study was a parallel, randomized controlled trial designed to investigate the clinical efficacy of the manual acupuncture in treating PI, and to clarify the mechanism. The study included a 4-week treatment period and a 4-week follow-up period. All eligible 74 patients diagnosed with PI will be evaluated using scales before treatment, and then be randomly assigned to the acupuncture group and the placebo acupuncture group at a ratio of 1:1. Both groups choose the same acupoints. The patients will be evaluated at 4 weeks before treatment, after 4 weeks of treatment and 4 weeks after treatment respectively. The patients in the acupuncture group were treated with manual acupuncture and placebo acupuncture group received the tube of Park sham devices. All 12 sessions of treatment will last over 4 weeks (3 sessions per week). The main outcome measure will be the change in Pittsburgh sleep quality index before and after treatment, and the secondary outcome measures include Chalder-14 fatigue scale, Epworth sleepiness scale, self-rating depression scale, self-rating anxiety scale, polysomnography and heart rate variability.DiscussionThis study will evaluate the efficacy and safety of the manual acupuncture, and the results will provide a scientific theoretical basis for the clinical promotion.Trail registrationClinicalTrails.govIdentifier:NCT05830887. Registered 23 March 2023.
Integrating molecular and clinical variables to predict myocardial recovery
Authors: Visker Joseph R. , Brintz Ben J. , Kyriakopoulos Christos P. , Hillas Yanni , Taleb Iosif , Badolia Rachit , Shankar Thirupura S. , Amrute Junedh M. , Ling Jing , Hamouche Rana , Tseliou Eleni , Navankasattusas Sutip , Wever-Pinzon Omar , Ducker Gregory S. , Holland William L. , Summers Scott A. , Koenig Steven C. , Hanff Thomas C. , Lavine Kory , Murali Srinivas , Bailey Stephen , Alharethi Rami , Selzman Craig H. , Shah Palak , Slaughter Mark S. , Kanwar Manreet , Drakos Stavros G. 
Published: April 2024

ABSTRACTMechanical unloading and circulatory support with left ventricular assist devices (LVADs) mediate significant myocardial improvement in a subset of advanced heart failure (HF) patients. The clinical and biological phenomena associated with cardiac recovery are under intensive investigation. Left ventricular (LV) apical tissue, alongside clinical data, were collected from HF patients at the time of LVAD implantation (n=208). RNA was isolated and mRNA transcripts were identified through RNA sequencing and confirmed with RT-qPCR. To our knowledge this is the first study to combine transcriptomic and clinical data to derive predictors of myocardial recovery. We used a bioinformatic approach to integrate 59 clinical variables and 22,373 mRNA transcripts at the time of LVAD implantation for the prediction of post-LVAD myocardial recovery defined as LV ejection fraction (LVEF) ≥40% and LV end-diastolic diameter (LVEDD) ≤5.9cm, as well as functional and structural LV improvement independently by using LVEF and LVEDD as continuous variables, respectively. To substantiate the predicted variables, we used a multi-model approach with logistic and linear regressions. Combining RNA and clinical data resulted in a gradient boosted model with 80 features achieving an AUC of 0.731±0.15 for predicting myocardial recovery. Variables associated with myocardial recovery from a clinical standpoint included HF duration, pre-LVAD LVEF, LVEDD, and HF pharmacologic therapy, andLRRN4CL(ligand binding and programmed cell death) from a biological standpoint. Our findings could have diagnostic, prognostic, and therapeutic implications for advanced HF patients, and inform the care of the broader HF population.GRAPHICAL ABSTRACT
The entangled world of DNA quadruplex folds
Authors: Sundaresan Sruthi , Uttamrao Patil Pranita , Kovuri Purnima , Rathinavelan Thenmalarchelvi 
Published: April 2024

AbstractDNA quadruplexes take part in many biological functions. It takes up a variety of folds based on the sequence and environment. Here, a meticulous analysis of experimentally determined 392 quadruplex structures (388 PDB IDs) deposited in PDB is carried out. The analysis reveals the modular representation of the quadruplex folds. 48 unique quadruplex motifs (whose diversity arises out of the propeller, bulge, diagonal, and lateral loops that connect the quartets) are identified, leading to simple to complex inter-/intra-molecular quadruplex folds. These structural two-layered motifs are further classified into 33 continuous and 15 discontinuous motifs. The discontinuous motifs cannot further be classified into parallel, antiparallel, or hybrid as one or more guanines of the adjacent quartets are not connected. While the continuous motifs can be extended to a quadruplex fold, the discontinuous motif requires additional loop(s) to complete a fold, as illustrated here with examples. Similarly, the higher-order quadruplex folds can also be represented by continuous or discontinuous motifs or their combinations. Such a modular representation of the quadruplex folds may assist in custom engineering of quadruplexes, designing motif-based drugs, and the prediction of quadruplex structure. Further, it could facilitate understanding the role of quadruplexes in biological functions and diseases.