bluuebunny/crossref_metadata_2025_split huggingface dataset:
Global estimates for the lifetime cost of managing HIV
Authors: Tran Huynh , Saleem Kanwal , Lim Megumi , Chow Eric P.F. , Fairley Christopher K. , Terris-Prestholt Fern , Ong Jason J. 
Published: March 2021

Objective:
There are an estimated 38 million people with HIV (PWH), with significant economic consequences. We aimed to collate global lifetime costs for managing HIV.

Design:
We conducted a systematic review (PROSPERO: CRD42020184490) using five databases from 1999 to 2019.

Methods:
Studies were included if they reported primary data on lifetime costs for PWH. Two reviewers independently assessed the titles and abstracts, and data were extracted from full texts: lifetime cost, year of currency, country of currency, discount rate, time horizon, perspective, method used to estimate cost and cost items included. Descriptive statistics were used to summarize the discounted lifetime costs [2019 United States dollars (USD)].

Results:
Of the 505 studies found, 260 full texts were examined and 75 included. Fifty (67%) studies were from high-income, 22 (29%) from middle-income and three (4%) from low-income countries. Of the 65 studies, which reported study perspective, 45 (69%) were healthcare provider and the remainder were societal. The median lifetime costs for managing HIV differed according to: country income level: $5221 [interquartile range (IQR)]: 2978–11 177) for low-income to $377 820 (IQR: 260 176–541 430) for high-income; study perspective: $189 230 (IQR: 14 794–424 069) for healthcare provider, to $508 804 (IQR: 174 781–812 418) for societal; and decision model: $190 255 (IQR: 13 588–429 772) for Markov cohort, to $283 905 (IQR: 10 558–453 779) for microsimulation models.

Conclusion:
Estimating the lifetime costs of managing HIV is useful for budgetary planning and to ensure HIV management is affordable for all. Furthermore, HIV prevention strategies need to be strengthened to avert these high costs of managing HIV.
Tesamorelin improves fat quality independent of changes in fat quantity
Authors: Lake Jordan E. , La Kristen , Erlandson Kristine M. , Adrian Stefan , Yenokyan Gayane , Scherzinger Ann , Dubé Michael P. , Stanley Takara , Grinspoon Steven , Falutz Julian , Mamputu Jean-Claude , Marsolais Christian , McComsey Grace A. , Brown Todd T. 
Published: March 2021

Objectives:
Fat quality and quantity may affect health similarly or differently. Fat quality can be assessed by measuring fat density on CT scan (greater density = smaller, higher quality adipocytes). We assessed the effects of tesamorelin, a growth hormone-releasing hormone analogue that reduces visceral fat (VAT) quantity in some people living with HIV (PWH), on fat density.

Design:
Participants from two completed, placebo-controlled, randomized trials of tesamorelin for central adiposity treatment in PWH were included if they had either a clinical response to tesamorelin (VAT decrease ≥8%, ≈70% of participants) or were placebo-treated.

Methods:
CT VAT and subcutaneous fat (SAT) density (Hounsfield Units, HU) were measured by a central blinded reader.

Results:
Participants (193 responders, 148 placebo) were 87% male and 83% white. Baseline characteristics were similar across arms, including VAT (−91 HU both arms, P = 0.80) and SAT density (−94 HU tesamorelin, −95 HU placebo, P = 0.29). Over 26 weeks, mean (SD) VAT and SAT density increased in tesamorelin-treated participants only [VAT: +6.2 (8.7) HU tesamorelin, +0.3 (4.2) HU placebo, P < 0.0001; SAT: +4.0 (8.7) HU tesamorelin, +0.3 (4.8) HU placebo, P < 0.0001]. The tesamorelin effects persisted after controlling for baseline VAT or SAT HU and area, and VAT [+2.3 HU, 95% confidence interval (4.5–7.3), P = 0.001) or SAT (+3.5 HU, 95% confidence interval (2.3–4.7), P < 0.001] area change.

Conclusion:
In PWH with central adiposity who experienced VAT quantity reductions on tesamorelin, VAT and SAT density increased independent of changes in fat quantity, suggesting that tesamorelin also improves VAT and SAT quality in this group.
Broadly neutralizing HIV-1 antibody reactivity in HIV tests: implications for diagnostics
Authors: Smith Tara , Masciotra Silvina , Luo Wei , Sullivan Vickie , Switzer William M. , Johnson Jeffrey A. , Heneine Walid 
Published: March 2021

Objective:
Passive immunization with broadly neutralizing antibodies (bNAbs) is under evaluation for HIV prevention. BNAbs target gp120 or gp41, two HIV envelope antigens commonly present in diagnostic tests. Depending on bNAb type and dose administered to humans, serum levels can reach nearly 1 mg/ml and wane over several weeks to months. We investigated the reactivity of bNAbs in HIV serological tests to inform diagnostic testing practices for persons treated with these products.

Design and methods:
The antigp120 bNAbs VRCO1, PGT121, PGT145, 3BNC117, 10–1074 and N6 and antigp41 bNAbs 10E8 and 10E8v4 were tested with the laboratory-based Bio-Rad Ag/Ab Combo assay, the point-of-care single-use Determine Combo, OraQuick, Reveal G4, SureCheck, Uni-Gold, INSTI and DPP HIV-1/2 assays, and the supplemental Geenius and HIV-1 Western Blot assays.

Results:
At 1 mg/ml, all bNAbs were nonreactive in four screening tests. OraQuick, SureCheck, Reveal G4 and INSTI detected at least two bNAbs each; SureCheck exhibited reactivity to six bNAbs. Geenius was HIV-1 indeterminate (gp160+) with all bNAbs except PGT121, which was HIV antibody-negative. HIV-1 Western Blot was indeterminate (gp41+/gp160+) with 10E8 and 10E8v4 and negative with the remaining bNAbs. There was no correlation between the test antigen construct(s) and bNAb reactivity.

Conclusion:
We identified a laboratory-based Ag/Ab EIA and three single-use rapid HIV tests that are nonreactive against a panel of bNAbs supporting some diagnostic tests can distinguish HIV-1 infection events among persons receiving bNAb immunoprophylaxis. Evaluation of HIV diagnostic tests prior to clinical use may identify suitable serologic assays for persons administered bNAbs.
Modulation of the Permeability-Inducing Factor Angiopoietin-2 Through Bifonazole in Systemic Inflammation
Authors: Pape Thorben , Idowu Temitayo Opemipo , Etzrodt Valerie Maritta , Stahl Klaus , Seeliger Benjamin , Haller Hermann , David Sascha 
Published: March 2021

ABSTRACT

Background:
Vascular barrier breakdown in sepsis represents a key component of the maladaptive host response to infection and the release of endothelial Angiopoietin-2 (Angpt-2) is a mechanistic driver of endothelial hyperpermeability. Angpt-2 is associated with morbidity and mortality but a targeted therapeutic approach is not available. We screened for U.S. Food and Drug Administration (FDA) approved drugs that might have off-target effects decreasing Angpt-2 and therefore, ameliorating capillary leakage.

Methods:
Endothelial cells were isolated from human umbilical veins (HUVECs) and used for in vitro studies at baseline and after stimulation (FDA-library screening, RT-PCR, ELISA, immunocytochemistry, MTT assay). On the functional level, we assessed real-time transendothelial electrical resistance (TER) using an electric cell-substrate impedance sensing device.

Results:
We found that the anti-fungal Bifonazole (BIFO) reduces spontaneous Angpt-2 release in a time- and dose-dependent manner after 8, 12, and 24 h (24 h: veh: 15.6 ± 0.7 vs. BIFO: 8.6 ± 0.8 ng/mL, P < 0.0001). Furthermore, we observed a reduction in its intra-cellular content by 33% (P < 0.001). Stimulation with tumor necrosis factor α induced a strong release of Angpt-2 that could analogously be blocked by additional treatment with BIFO (veh: 1.58 ± 0.2 vs. BIFO: 1.02 ± 0.1, P < 0.0001). Quantification of endothelial permeability by TER revealed that BIFO was sufficient to reduce Thrombin-induced barrier breakdown (veh: 0.82 ± 0.1 vs. BIFO: 1.01 ± 0.02, P < 0.05).

Conclusion:
The antifungal BIFO reduces both release and biosynthesis of the endothelial-destabilizing factor Angpt-2 in vitro thereby improving vascular barrier function. Additional studies are needed to further investigate the underlying mechanism and to translate these findings to in vivo models.
Evaluation of Evidence, Pharmacology, and Interplay of Fluid Resuscitation and Vasoactive Therapy in Sepsis and Septic Shock
Authors: Barlow Brooke , Bissell Brittany D. 
Published: March 2021

ABSTRACT
We sought to review the pharmacology of vasoactive therapy and fluid administration in sepsis and septic shock, with specific insight into the physiologic interplay of these agents. A PubMed/MEDLINE search was conducted using the following terms (vasopressor OR vasoactive OR inotrope) AND (crystalloid OR colloid OR fluid) AND (sepsis) AND (shock OR septic shock) from 1965 to October 2020. A total of 1,022 citations were reviewed with only relevant clinical data extracted. While physiologic rationale provides a hypothetical foundation for interaction between fluid and vasopressor administration, few studies have sought to evaluate the clinical impact of this synergy. Current guidelines are not in alignment with the data available, which suggests a potential benefit from low-dose fluid administration and early vasopressor exposure. Future data must account for the impact of both of these pharmacotherapies when assessing clinical outcomes and should assess personalization of therapy based on the possible interaction.
Characteristics and Outcomes of Heart Transplant Recipients With Coronavirus-19 Disease in a High-volume Transplant Center
Authors: Marcondes-Braga Fabiana G. , Murad Ciro M. , Belfort Deborah S.P. , Dantas Rafael C.T. , Lira Maria Tereza S.S. , Aragão Carlos A.S. , Siciliano Rinaldo F. , Mangini Sandrigo , Seguro Luis Fernando B.C. , Campos Iáscara W. , Avila Mônica S. , Bello Mariana V.O. , dos Santos Fernanda B.A. , Strabelli Tânia M.V. , Gaiotto Fabio A. , Bacal Fernando 
Published: March 2021

Background.
Heart transplant (HT) recipients may be at higher risk of acquiring SARS-CoV-2 infection and developing critical illness. The aim of this study is to describe characteristics and outcomes of HT recipients infected by SARS-COV-2, from a high-volume transplant center.

Methods.
We have described data of all adult HT recipients with confirmed coronavirus disease 2019 by RT-PCR in nasopharyngeal samples from April 5, 2020, to January 5, 2021. Outcomes and follow-up were recorded until February 5, 2021.

Results.
Forty patients were included. Twenty-four patients (60%) were men; the median age was 53 (40–60) y old; median HT time was 34 mo; and median follow-up time 162 d. The majority needed hospitalization (83%). Immunosuppressive therapy was reduced/withdrawn in the majority of patients, except from steroids, which were maintained. Seventeen patients (42.5%) were classified as having severe disease according to the ordinal scale developed by the World Health Organization Committee. They tended to have lower absolute lymphocyte count (P < 0.001) during follow-up when compared with patients with mild disease. Thirty-day mortality was 12.5%. However, a longer follow-up revealed increased later mortality (27.5%), with median time to death around 35 d. Bacterial nosocomial infections were a leading cause of death. Cardiac allograft rejection (10%) and ventricular dysfunction (12.5%) were also not negligible.

Conclusions.
Major findings of this study corroborate other cohorts’ results, but it also reports significant rate of later events, suggesting that a strict midterm surveillance is advisable to HT recipients with coronavirus disease 2019.
Entangled radicals may explain lithium effects on hyperactivity
Authors: Zadeh-Haghighi Hadi , Simon Christoph 
Published: March 2021

ABSTRACTIt is known that bipolar disorder and its lithium treatment involve the modulation of oxidative stress. Moreover, it has been observed that lithium’s effects are isotope-dependent. Based on these findings, here we propose that lithium exerts its effects by influencing the recombination dynamics of a naturally occurring radical pair involving oxygen. We develop a simple model inspired by the radical-pair mechanism in cryptochrome in the context of avian magnetoreception and xenon-induced anesthesia. Our model reproduces the observed isotopic dependence in the lithium treatment of hyperactivity in rats. It predicts a magnetic-field dependence of the effectiveness of lithium, which provides one potential experimental test of our hypothesis. Our findings show that Nature might harness quantum entanglement for the brain’s cognitive processes.
Off-resonance saturation as an MRI method to quantify ferritin-bound iron in the post-mortem brain
Authors: Bossoni Lucia , Hegeman-Kleinn Ingrid , van Duinen Sjoerd G. , Vroegindeweij Lena H. P. , Langendonk Janneke G. , Hirschler Lydiane , Webb Andrew , van der Weerd Louise 
Published: March 2021

AbstractPurposeTo employ an Off-Resonance Saturation (ORS) method to measure the ferritin-bound iron pool, which is an endogenous contrast agent which can give information on cellular iron status.MethodsAn ORS acquisition protocol was implemented on a 7T preclinical scanner and the contrast maps were fitted to an established analytical model. The method was validated by correlation and Bland-Altman analysis on a ferritin-containing phantom. Ferritin-iron maps were obtained from post-mortem tissue of patients with neurological diseases characterized by brain iron accumulation, i. e. Alzheimer’s disease, Huntington’s disease and aceruloplasminemia, and validated with histology. Transverse relaxation rate and magnetic susceptibility values were also obtained for comparison.ResultsIn post-mortem tissue, the ferritin-iron contrast strongly co-localizes with histological iron staining, in all the cases. Quantitative iron values obtained via the ORS method are in agreement with literature.ConclusionsOff-resonance saturation is an effective way to detect iron in grey matter structures, while mitigating for the presence of myelin. If a reference region with little iron is available in the tissue, the method can produce quantitative iron maps. This method is applicable in the study of brain diseases characterized by brain iron accumulation and complement existing iron-sensitive parametric methods.
Recognition of familiar objects in tortoise hatchlings (Testudo spp.)
Authors: Damini Silvia , Stancher Gionata , Versace Elisabetta 
Published: March 2021

ABSTRACTTortoises do not show parental care and live solitary except for the context of reproduction. Despite their limited need to interact with conspecifics, we previously observed that young tortoises, at their first experiences with conspecifics, can discriminate between familiar and unfamiliar conspecifics after just one encounter with another tortoise. Tortoise hatchlings ignored familiar conspecifics, while they first explored and then actively avoided unfamiliar conspecifics. It remains to be established whether the different reactions to unfamiliar and familiar individuals in tortoise hatchlings are reactions to novelty, or whether they are specific to the interactions with living animals. To test this, we familiarized one-month-old tortoise hatchlings with an object (a brown conevs. a blue sphere) and then tested them in a novel arena once with the familiar object and once with an unfamiliar one. To measure the reactions toward familiar and unfamiliar objects, we measured the distance between the tortoise and the object throughout the test. Differently from what happened with unfamiliar and familiar conspecifics, we found no difference in behavior toward familiar and unfamiliar objects. This shows that the different reactions toward familiar and unfamiliar conspecifics previously observed are specific for social interactions and are not a mere reaction to the novelty effect. The behavioral responses displayed by young tortoises for unfamiliar conspecifics, but not for unfamiliar objects, show the relevance of social behavior from the beginning of life, even for solitary species.
Contemporary clinical isolates ofStaphylococcus aureusfrom pediatric osteomyelitis patients display unique characteristics in a mouse model of hematogenous osteomyelitis
Authors: Roper Philip M , Eichelberger Kara R , Cox Linda , O’Connor Luke , Shao Christine , Ford Caleb A , Fritz Stephanie A , Cassat James E , Veis Deborah J 
Published: March 2021

AbstractOsteomyelitis can result from the direct inoculation of pathogens into bone during injury or surgery, or from spread via the bloodstream, a condition called hematogenous osteomyelitis (HOM). HOM disproportionally affects children, and more than half of cases are caused byStaphylococcus (S.) aureus. Laboratory models of osteomyelitis mostly utilize direct injection of bacteria into the bone or the implantation of foreign material, and therefore do not directly interrogate the pathogenesis of pediatric hematogenous osteomyelitis. In this study, we inoculated mice intravenously and characterized resultant musculoskeletal infections using two strains isolated from adults (USA300-LAC and NRS384) and five new methicillin-resistantS. aureusisolates from pediatric osteomyelitis patients. All strains were capable of creating stable infections over five weeks, although the incidence varied. Micro-computed tomography (microCT) analysis demonstrated decreases in trabecular bone volume fraction but little effect on bone cortices. Histologic assessment revealed differences in the precise focus of musculoskeletal infection, with varying mixtures of bone-centered osteomyelitis and joint-centered septic arthritis. Whole genome sequencing of three new isolates demonstrated distinct strains, two within the USA300 lineage and one USA100 isolate. Interestingly, the USA100 strain showed a distinct predilection for septic arthritis, compared to the USA300 strains, including NRS384 and LAC, which more frequently led to osteomyelitis or mixed bone and joint infections. Collectively, these data outline the feasibility of using pediatric osteomyelitis clinical isolates to study the pathogenesis of HOM in murine models and lay the groundwork for future studies investigating strain-dependent differences in musculoskeletal infection.ImportanceThe inflammation of bone tissue is called osteomyelitis, and more than half of cases are caused by an infection with the bacteriumStaphylococcus aureus. In children, the most common route of infection is hematogenous, wherein bacteria seed the bone from the bloodstream without another known site of infection. Although these infections pose a significant health problem, they are understudied in the laboratory because of a dearth of robust animal models. In this study, we utilized several previously uncharacterized clinical isolates ofS. aureusderived from children with bone infections to generate reproducible and stable musculoskeletal infection in mice with many features seen in human osteomyelitis, making them a valuable resource for future mechanistic and therapeutic studies.
A New Monocyte Epigenetic Clock Reveals Effects of Alcohol Consumption on Epigenetic Aging in Three Independent Cohorts
Authors: Liang Xiaoyu , Sinha Rajita , Justice Amy C. , Cohen Mardge H. , Aouizerat Bradley E. , Xu Ke 
Published: March 2021

AbstractBackgroundExcessive alcohol consumption increases the risk of aging-related comorbidities and mortality. Assessing the impact of alcohol consumption on biological age is important for clinical decision-making and prevention. Evidence shows that alcohol alters monocyte function, and age is associated with DNA methylome and transcriptomic changes among monocytes. However, no monocyte-based epigenetic clock is currently available. In this study, we developed a new monocyte-based DNA methylation clock (MonoDNAmAge) by using elastic net regularization. The MonoDNAmAge was validated by benchmarking using epigenetic age acceleration (EAA) in HIV infection. Using MonoDNAmAge clock as well as four established clocks (i.e., HorvathDNAmAge, HannumDNAmAge, PhenoDNAmAge, GrimDNAmAge), we then evaluated the effect of alcohol consumption on biological aging in three independent cohorts (N=2,242).ResultsMonoDNAmAge, comprised of 186 CpG sites, was highly correlated with chronological age (rtraining=0.96, p<2.20E-16; rtesting=0.86, p=1.55E-141). The MonoDNAmAge clock predicted an approximately 10-year age acceleration from HIV infection in two cohorts. Quadratic regression analysis showed a nonlinear relationship between MonoDNAmAge and alcohol consumption in the Yale Stress Center Community Study (YSCCS,pmodel=4.55E-08,px2=7.80E-08) and in the Veteran Aging Cohort Study (VACS,pmodel=1.85E-02,px2=3.46E-02). MonoDNAmAge and light alcohol consumption showed a negative linear relationship in the Women’s Interagency HIV Study (WIHS,β=-2.63,px=2.82E-06). Heavy consumption increased EAAMonoDNAmAge up to 1.60 years in the VACS while light consumption decreased EAAMonoDNAmAge to 2.66 years in the WIHS. These results were corroborated by the four established epigenetic clocks.ConclusionsWe observed a nonlinear effect of alcohol consumption on epigenetic age that is estimated by a novel monocyte-based “clock” in three distinct cohorts, highlighting the complex effects of alcohol consumption on biological age.
Diverse arsenic-containing lipids in the surface ocean
Authors: Heal Katherine R. , Maloney Ashley E. , Ingalls Anitra E. , Bundy Randelle M. 
Published: March 2021

AbstractArsenic is present at nanomolar levels throughout the surface ocean, and microbes assimilate this toxic element due to its similarity to inorganic phosphorus. Although the concentration and characterization of dissolved arsenic has been a focus of ocean studies, the size of the particulate arsenic pool and its partitioning into organic molecules within the microbial community is not known. We measured the particulate pool of arsenic in five surface samples from the open ocean and determined the contribution of arsenic-containing lipids to this pool. Here we show that the accumulation of arsenic into lipids is a widespread phenomenon in the surface ocean. Particulate arsenic concentrations were 15 to 42 pmol L−1with 7–20% of the particulate arsenic pool in the form of arsenolipids. We characterized these arsenolipids and found that arsenosugar phospholipids dominated the arsenolipid pools in our samples with a minor component of arsenohydrocarbons and other unidentified lipids. A significant portion of the arsenosugar phospholipids (up to 35%) were present as previously undescribed mixed acyl ether lipids, suggesting a bacterial source.Scientific significance statementMarine microbes experience constant exposure to the toxic element arsenic. However, there are no baseline measurements of how much arsenic accumulates in microbial communities nor do we know the full spectrum of arsenic containing biomolecules produced in marine systems. In culture-based studies there is strong evidence that phytoplankton synthesize arsenic-containing lipids, but these lipids have not been observed in natural communities of marine microbes. Here we make measurements of bulk particulate arsenic at five sites in the surface open ocean and show that a significant portion of this particulate arsenic is present as complex arsenic-containing lipids. We characterize this arsenolipid pool chemically and quantitatively to show a variety of chemically distinct and quantitatively significant lipids that expand our understanding of marine arsenic biogeochemistry.Data availability statementMass spectrometry data and its associated metadata will be available on Dryad with publication. Scripts for data processing and figure generation found on github athttps://github.com/kheal/particulate_As_data_analysis.