bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Estimated Lifetime Medical Cost of Syphilis in the United States
Authors: Chesson Harrell W. , Peterman Thomas A. 
Published: January 2021

Background
The purpose of this study was to estimate the cost of syphilis in the United States, in terms of the average lifetime direct medical cost per infection.

Methods
We used a decision tree model of the natural history of syphilis. The model allowed for numerous possible outcomes of infection, including treatment for syphilis at various stages, inadvertent treatment, and late syphilis outcomes in those who are alive and still infected 30 years after acquisition. Future costs were discounted at 3% annually. Model inputs, such as the cost and probability of each outcome, were based on published sources. The probabilities we applied yielded outcomes consistent with reported cases of syphilis by stage from national surveillance data and number of deaths due to late syphilis from national mortality data.

Results
The estimated, discounted lifetime cost per infection was $1190 under base case assumptions (2019 dollars). Treatment costs associated with late syphilis outcomes, such as cardiovascular syphilis, accounted for only $26 of the average lifetime cost per infection. Results were most sensitive to assumptions regarding the treatment cost per case of unknown duration or late syphilis. In the probabilistic sensitivity analyses, the 2.5th and 97.5th percentiles of the 10,000 simulations of the lifetime cost per infection were $729 and $1884, respectively.

Conclusions
Our estimate of the lifetime cost per infection is about 50% higher than in a previous study, a difference due in large part to our higher cost assumptions for benzathine penicillin G.
The Estimated Number and Lifetime Medical Cost of HIV Infections Attributable to Sexually Transmitted Infections Acquired in the United States in 2018: A Compilation of Published Modeling Results
Authors: Chesson Harrell W. , Song Ruiguang , Bingham Adrienna , Farnham Paul G. 
Published: January 2021

Background
The purpose of this study was to estimate the number and lifetime medical cost of HIV infections attributable to incident sexually transmitted infections (STIs) in the United States in 2018.

Methods
We combined data from published models regarding the number or percentage of HIV infections attributable to STIs with updated estimates of the lifetime medical cost per HIV infection. We used 2 distinct calculation methods. Our first calculation used recent estimates of the percentage of HIV infections in men who have sex with men (MSM) attributable to gonorrhea and chlamydia. Our second calculation, based on older studies, used estimates of the expected number of STI-attributable HIV infections per new STI infection, for gonorrhea, chlamydia, syphilis, and trichomoniasis.

Results
Our first calculation method suggested that 2489 (25th–75th percentiles, 1895–3000) HIV infections in 2018 among MSM could be attributed to gonorrhea and chlamydia, at an estimated lifetime medical cost of $1.05 billion (25th–75th percentiles, $0.79–$1.26 billion). Our second calculation method suggested that 2349 (25th–75th percentiles, 1948–2744) HIV infections in the general population (including MSM) could be attributed to chlamydia, gonorrhea, syphilis, and trichomoniasis acquired in 2018, at an estimated lifetime medical cost of $0.99 billion (25th–75th percentiles, $0.80–$1.16 billion).

Conclusions
Despite ambiguity regarding the degree to which STIs affect HIV transmission, our combination of data from published STI/HIV transmission models and an HIV lifetime medical cost model can help to quantify the estimated burden of STI-attributable HIV infections in the United States.
Incidence and Prevalence of Sexually Transmitted Hepatitis B, United States, 2013–2018
Authors: Roberts Henry , Jiles Ruth , Harris Aaron M. , Gupta Neil , Teshale Eyasu 
Published: January 2021

Background
Sexual transmission of hepatitis B virus (HBV) is common in the United States. In 2008, an estimated 50% of HBV infections were attributed to sexual transmission. Among 21,600 acute infections that occurred in 2018, the proportion attributable to sexual transmissions is unknown.

Methods
Objectives of this study were to estimate incidence and prevalence of hepatitis B attributable to sexual transmission among the US population 15 years and older for 2013 to 2018. Incidence estimates were calculated for confirmed cases submitted to Centers for Disease Control and Prevention from 14 states. A hierarchical algorithm defining sexually transmitted acute HBV infections as the absence of injection drug use among persons reporting sexual risk factors was applied to determine proportion of hepatitis B infections attributable to sexual transmission nationally. National Health and Nutrition Examination Survey public use data files were analyzed to calculate prevalence estimates of hepatitis B among US households and proportion attributed to sexual transmission was conservatively determined for HBV-infected non–US-born Americans who migrated from HBV endemic countries.

Results
During 2013 to 2018, an estimated 47,000 (95% confidence interval [CI], 27,000–116,000) or 38.2% of acute HBV infections in the United States were attributable to sexual transmission. During 2013 to 2018, among the US noninstitutionalized population, an estimated 817,000 (95% CI, 613,000–1,100,000) persons 15 years and older were living with hepatitis B, with an estimated 103,000 (95% CI, 89,000–118,000) infections or 12.6% attributable to sexual transmission.

Conclusions
These findings provide evidence sexually transmitted HBV infections remain a public health problem and underscore the importance of interventions to improve vaccination among at-risk populations.
Distinguishing Features of Patients Evaluated for Multisystem Inflammatory Syndrome in Children
Authors: Kelly Michael S. , Fernandes Neil D. , Carr Audrey V. , Lahoud-Rahme Manuella , Cummings Brian M. , Chiu Joanne S. 
Published: January 2021

Objectives
Given the significant overlap of multisystem inflammatory syndrome in children (MIS-C) with other common childhood illnesses presenting to the emergency department, extensive workup of this syndrome has become necessary. Nevertheless, little has been published on the factors differentiating MIS-C from other conditions in the acute care setting. We investigated differences in presentation and laboratory studies between suspected versus confirmed MIS-C patients.

Methods
This was a retrospective cohort study on patients 21 years or younger undergoing investigation for possible MIS-C at a single institution between April 21 and July 1, 2020. The primary outcome was diagnosis of MIS-C or an alternative final diagnosis. Clinical features and laboratory findings from initial presentation were collected and analyzed.

Results
A total of 106 patients (median, 4 years; 55.7% male) were included, of whom 17 (16%) of 106 met the criteria for MIS-C. Multisystem inflammatory syndrome in children patients were significantly more likely to report a coronavirus disease 2019 exposure (odds ratio (OR), 13.17 [3.87–44.9]), have gastrointestinal symptoms (OR, 3.81 [1.02–14.19]), and have a significantly higher odds of having abnormal laboratory values including high-sensitivity troponin T (OR, 13 [4.0–42.2]), N-terminal B-type natriuretic peptide (OR, 8.4 [2.3–30.1]), D-dimer (OR, 13 [1.6–103]), and ferritin (OR, 7.8 [2.2–27.2]). There were also differences between groups in inflammatory markers: C-reactive protein (median, 134.45 mg/L vs 12.6 mg/L; P < 0.05) and procalcitonin (1.71 ng/mL vs 0.14 ng/mL; P < 0.001).

Conclusions
Higher elevations in key laboratory studies may help to distinguish between MIS-C patients and non–MIS-C patients presenting to the emergency department.
Brief Report: Lower Socioeconomic Status Associates With Greater Systemic and Arterial Inflammation in HIV
Authors: Zhang Lili , Abohashem Shady , Osborne Michael T. , Naddaf Nicki , Park Rebecca , Moore Kelvin , Patrich Tomas , Deeks Steven G. , Hsue Priscilla Y. , Tawakol Ahmed A. 
Published: January 2021

Objectives:
In the general population, the lower socioeconomic status (SES) associates with greater systemic and arterial inflammation and a greater risk of cardiovascular disease. Because arterial inflammation is heightened in individuals living with HIV, we tested the hypothesis that SES associates with arterial inflammation in this population.

Settings:
Prospective cohort study.

Methods:
Men living with HIV were recruited. Arterial inflammation and leukopoietic activity (ie, bone marrow activity) were measured using 18F-fluorodeoxyglucose positron emission tomography/computed tomography. Zip code-level SES measures were derived from the US Census Bureau. Linear regression and mediation analyses were used to assess associations between SES, arterial inflammation, leukopoietic activity, C-reactive protein (CRP), and interleukin-6.

Results:
Thirty-nine virologically suppressed men living with HIV were studied (mean ± SD age 50.5 ± 11.1 years). The median CD4 count was 663 cells/mm3 (interquartile range: 399–922); 82% were receiving antiretroviral therapies. Local median income inversely associated with arterial inflammation [standardized β (95% confidence interval): −0.42 (−0.76 to −0.08)] after adjusting for age, Framingham risk score, statin use, antiretroviral use, and nadir CD4 count. The high-school graduation rate independently associated with arterial inflammation [−0.45 (−0.78 to −0.12)] and CRP [−0.49 (−0.86 to −0.012)]. Mediation analysis demonstrated the impact of SES on arterial inflammation was partially mediated by heightened circulating inflammatory levels: ↓SES (as high school graduation rate) →↑CRP →↑arterial inflammation accounting for 44% of the total effect (P < 0.05).

Conclusion:
In individuals living with HIV, lower SES independently associated with higher leukopoietic activity, circulating markers of inflammation, and arterial inflammation. Furthermore, the link between SES and arterial inflammation was mediated by increased systemic inflammation.
FDG PET/CT of an Advanced Case of Malignant Nerve Sheath Tumor of Pleura
Authors: Saidi Bahare , Fallahi Babak , Abdi Anahid , Rakhshani Nasser , Eftekhari Mohammad 
Published: January 2021

Abstract
We present a rare case of malignant nerve sheath tumor of pleura referred for the evaluation of metastases and local invasion. FDG PET/CT demonstrated a hypermetabolic tumoral lesion extensively involving the right pleura with no involvement of mediastinal structures or pulmonary parenchyma and no clear evidence of distant metastasis. Malignant nerve sheath tumor of pleura is an extremely rare entity, and FDG PET/CT is valuable in demonstrating the extent of disease and can have potential role for postsurgical as well as postchemotherapy assessment of possible residual disease.
Oncologic Outcomes Associated With MRI-detected Extramural Venous Invasion (mrEMVI) in Rectal Cancer
Authors: Rouleau Fournier François , Motamedi Mohammad Ali K. , Brown Carl J. , Phang Terry , Raval Manoj J. , Hague Cameron J. , Karimuddin Ahmer A. 
Published: January 2021

Background:
The role of MRI-detected EMVI (mrEMVI) as a reliable prognostic factor in rectal cancer has been emphasized in recent years but this finding remains underreported by many institutions.

Objective:
This review aimed to demonstrate the importance of pre- and post-treatment MRI-detected EMVI as independent prognostic factors of adverse oncologic outcomes in patients undergoing neoadjuvant therapy followed by total mesorectal excision.

Methods:
This review was designed using the PRISMA guidelines. The following electronic databases were searched from January 2002 to January 2020: CENTRAL, Ovid MEDLINE, PubMed, and Ovid Embase. Main outcomes included DFS and overall survival (OS). Other outcomes of interest comprised positive resection margin and synchronous metastases.

Results:
Seventeen studies involving a total of 3821 patients were included for data synthesis. For preneoadjuvant treatment mrEMVI, pooled hazard ratio (HR) estimate for DFS was 2.30 (95% confidence intervals (CI) 1.54–3.44) for higher recurrence in mrEMVI-positive patients. mrEMVI-positive patients were found to have a lower OS with a pooled HR of 1.68 (95%CI 1.27–2.22). Pooled risk ratio for synchronous metastasis was 4.11 (95%CI 2.80–6.02) for mrEMVI-positivity. For postneoadjuvant treatment EMVI (ymrEMVI), positive status showed a lower DFS with a pooled HR of 2.04 (95%CI 1.55–2.69). Risk ratio of having a positive resection margin status was 2.95 (95%CI 1.75–4.98) for ymrEMVI-positive patients.

Conclusions:
This review showed that oncologic outcomes are significantly worse for both pre- and post-neoadjuvant treatment mrEMVI-positive patients. MRI-detected EMVI should be consistently reported in rectal cancer staging and may provide guidance for the targeted use of additional systemic therapy.
Valuing what happens: a biogenic approach to valence and (potentially) affect
Authors: Lyon Pamela , Kuchling Franz 
Published: January 2021

Valence is half of the pair of properties that constitute core affect, the foundation of emotion. But what is valence, and where is it found in the natural world? Currently, this question cannot be answered. The idea that emotion is the body's way of driving the organism to secure its survival, thriving and reproduction runs like a leitmotif from the pathfinding work of Antonio Damasio through four book-length neuroscientific accounts of emotion recently published by the field's leading practitioners. Yet while Damasio concluded 20 years ago that the homeostasis–affect linkage is rooted in unicellular life, no agreement exists about whether even non-human animals with brains experience emotions. Simple neural animals—those less brainy than bees, fruit flies and other charismatic invertebrates—are not even on the radar of contemporary affective research, to say nothing of aneural organisms. This near-sightedness has effectively denied the most productive method available for getting a grip on highly complex biological processes to a scientific domain whose importance for understanding biological decision-making cannot be underestimated. Valence arguably is the fulcrum around which the dance of life revolves. Without the ability to discriminate advantage from harm, life very quickly comes to an end. In this paper, we review the concept of valence, where it came from, the work it does in current leading theories of emotion, and some of the odd features revealed via experiment. We present a biologically grounded framework for investigating valence in any organism and sketch a preliminary pathway to a computational model.This article is part of the theme issue ‘Basal cognition: conceptual tools and the view from the single cell’.
From environmental sensing to developmental control: cognitive evolution in dictyostelid social amoebas
Authors: Schaap Pauline 
Published: January 2021

Dictyostelid social amoebas respond to starvation by self-organizing into multicellular slugs that migrate towards light to construct spore-bearing structures. These behaviours depend on excitable networks that enable amoebas to produce propagating waves of the chemoattractant cAMP, and to respond by directional movement. cAMP additionally regulates cell differentiation throughout development, with differentiation and cell movement being coordinated by interaction of the stalk inducer c-di-GMP with the adenylate cyclase that generates cAMP oscillations. Evolutionary studies indicate how the manifold roles of cAMP in multicellular development evolved from a role as intermediate for starvation-induced encystation in the unicellular ancestor. A merger of this stress response with the chemotaxis excitable networks yielded the developmental complexity and cognitive capabilities of extant Dictyostelia.This article is part of the theme issue ‘Basal cognition: conceptual tools and the view from the single cell’.
Adaptive behaviour and learning in slime moulds: the role of oscillations
Authors: Boussard Aurèle , Fessel Adrian , Oettmeier Christina , Briard Léa , Döbereiner Hans-Günther , Dussutour Audrey 
Published: January 2021

The slime mouldPhysarum polycephalum, an aneural organism, uses information from previous experiences to adjust its behaviour, but the mechanisms by which this is accomplished remain unknown. This article examines the possible role of oscillations in learning and memory in slime moulds. Slime moulds share surprising similarities with the network of synaptic connections in animal brains. First, their topology derives from a network of interconnected, vein-like tubes in which signalling molecules are transported. Second, network motility, which generates slime mould behaviour, is driven by distinct oscillations that organize into spatio-temporal wave patterns. Likewise, neural activity in the brain is organized in a variety of oscillations characterized by different frequencies. Interestingly, the oscillating networks of slime moulds are not precursors of nervous systems but, rather, an alternative architecture. Here, we argue that comparable information-processing operations can be realized on different architectures sharing similar oscillatory properties. After describing learning abilities and oscillatory activities ofP. polycephalum, we explore the relation between network oscillations and learning, and evaluate the organism's global architecture with respect to information-processing potential. We hypothesize that, as in the brain, modulation of spontaneous oscillations may sustain learning in slime mould.This article is part of the theme issue ‘Basal cognition: conceptual tools and the view from the single cell’.
The “throwaways”. Conflicts of interest in dermatology publications
Authors: Roman Jorge , Elpern David J. 
Published: January 2021

AbstractImportanceConflict of interest as it relates to medical education is a topic of concern. Dermatology journals, periodicals, editorials, and news magazines are influential resources that are not uniformly regulated and subject to influence from the pharmaceutical industry.ObjectiveThis study evaluates industry payments to physician editorial board members of common dermatology publications, including “throwaway” publications.DesignA list of editorial board members was compiled from a collection of clinical dermatology publications received over a 3-month period. To analyze the nature and extent of industry payments to this cohort, payments data from the Open Payments database from 2013 to 2019 were collected. Analysis of the total payments, number of transactions, categories of payments, payment sources, and physician specific characteristics was performed.ResultsTen publications were evaluated, and payments data for 466 physicians were analyzed. The total compensation across all years was $75,622,369.64. Services other than consulting, consulting, and travel/lodging payments comprised most of the payments. A faction of dermatologists received the majority of payments. The top payers were manufacturers of biologic medications. Payment amounts were higher for throwaway publications compared to peer-reviewed journals.ConclusionsEditorial board members of dermatology publications received substantial payments from the pharmaceutical industry. A minority of physicians receive the lion’s share of payments from industry. “Throwaway” publications have more financial conflict of interest than peer-reviewed journals. The impact of these conflicts of interest on patient care, physicians practice patterns, and patient perception of physicians is noteworthy.
Validation of the new pathology staging system for progressive supranuclear palsy
Authors: Briggs Mayen , Allinson Kieren SJ , Malpetti Maura , Spillantini Maria Grazia , Rowe James Benedict , Kaalund Sanne Simone 
Published: January 2021

AbstractProgressive supranuclear palsy (PSP) is a neurodegenerative disorder associated with neuroglial accumulation of 4-repeat tau protein. Kovacs et al. have recently proposed a new semi-quantitative staging system to categorise the severity of PSP pathology, using the distribution of tau aggregates as it progresses from subcortical to cerebellar and cortical regions. Here, we test the new PSP pathology staging system in an independent series of PSP, and test the potential association between pathology stage and clinical severity at death. We include tissue from 35 people with a clinical diagnosis of PSP (including N=25 with Richardson’s syndrome and N=10 with other phenotypes). Donors had attended longitudinal clinical studies at the Cambridge Centre Parkinson-plus including assessment of clinical severity by the PSP rating scale (PSPRS) and cognitive performance by the revised Addenbrooke’s Cognitive Examination (ACE-R). We rated tau pathology from none-to-severe in six regions. We focused on (I) astrocytic tau inclusions in striatum, frontal and occipital regions, and (II) neuronal and oligodendroglia tau inclusions in globus pallidus, subthalamic nucleus, and cerebellum. Thirty-two cases (91%) readily conformed to the new staging system, ranging from stage 2 to 6. Staging system applied to brains from people with different clinical phenotypes of PSP. Neuropathology stages correlated with clinical severity at death using both PSPRS and ACE-R, weighted for the interval between last assessment and donation. Our study supports the proposed sequential distribution of tau aggregates in PSP pathology, and the hypothesised relationship between clinical and neuropathological severity. For future studies, in order to standardise rating between centres, we propose a set of operational criteria for region-specific thresholds or tau burden, and a visual guide.
Diagnosing pulmonary tuberculosis using sequence-specific purification of urine cell-free DNA
Authors: Oreskovic Amy , Panpradist Nuttada , Marangu Diana , Ngwane M. William , Magcaba Zanele P. , Ngcobo Sindiswa , Ngcobo Zinhle , Horne David J. , Wilson Douglas P.K. , Shapiro Adrienne E. , Drain Paul K. , Lutz Barry R. 
Published: January 2021

ABSTRACTTransrenal urine cell-free DNA (cfDNA) is a promising tuberculosis (TB) biomarker, but is challenging to detect because of the short length (<100 bp) and low concentration of TB-specific fragments. We aimed to improve the diagnostic sensitivity of TB urine cfDNA by increasing recovery of short fragments during sample preparation. We developed a highly sensitive sequence-specific purification method that uses hybridization probes immobilized on magnetic beads to capture short TB cfDNA (50 bp) with 91.8% average efficiency. Combined with short-target PCR, the assay limit of detection was ≤5 copies of cfDNA in 10 mL urine. In a clinical cohort study in South Africa, our urine cfDNA assay had 83.7% sensitivity (95% CI: 71.0– 91.5%) and 100% specificity (95% CI: 86.2–100%) for diagnosis of active pulmonary TB when using sputum Xpert MTB/RIF as the reference standard. The detected cfDNA concentration was 0.14–2804 copies/mL (median 14.6 copies/mL) and was inversely correlated with CD4 count and days to culture positivity. Sensitivity was non-significantly higher in HIV-positive (88.2%) compared to HIV-negative patients (73.3%), and was not dependent on CD4 count. Sensitivity remained high in sputum smear-negative (76.0%) and urine LAM-negative (76.5%) patients. With improved sample preparation, urine cfDNA is a viable biomarker for TB diagnosis. Our assay has the highest reported accuracy of any TB urine cfDNA test to date and has the potential to enable rapid non-sputum-based TB diagnosis across key underserved patient populations.