bluuebunny/crossref_metadata_2025_split huggingface dataset:
Quantifying the dynamics of viral recombination during free virus and cell-to-cell transmission in HIV-1 infection
Authors: Kreger Jesse , Garcia Josephine , Zhang Hongtao , Komarova Natalia L , Wodarz Dominik , Levy David N 
Published: March 2021

AbstractRecombination has been shown to contribute to human immunodeficiency virus-1 (HIV-1) evolution in vivo, but the underlying dynamics are extremely complex, depending on the nature of the fitness landscapes and of epistatic interactions. A less well-studied determinant of recombinant evolution is the mode of virus transmission in the cell population. HIV-1 can spread by free virus transmission, resulting largely in singly infected cells, and also by direct cell-to-cell transmission, resulting in the simultaneous infection of cells with multiple viruses. We investigate the contribution of these two transmission pathways to recombinant evolution, by applying mathematical models to in vitro experimental data on the growth of fluorescent reporter viruses under static conditions (where both transmission pathways operate), and under gentle shaking conditions, where cell-to-cell transmission is largely inhibited. The parameterized mathematical models are then used to extrapolate the viral evolutionary dynamics beyond the experimental settings. Assuming a fixed basic reproductive ratio of the virus (independent of transmission pathway), we find that recombinant evolution is fastest if virus spread is driven only by cell-to-cell transmission and slows down if both transmission pathways operate. Recombinant evolution is slowest if all virus spread occurs through free virus transmission. This is due to cell-to-cell transmission 1, increasing infection multiplicity; 2, promoting the co-transmission of different virus strains from cell to cell; and 3, increasing the rate at which point mutations are generated as a result of more reverse transcription events. This study further resulted in the estimation of various parameters that characterize these evolutionary processes. For example, we estimate that during cell-to-cell transmission, an average of three viruses successfully integrated into the target cell, which can significantly raise the infection multiplicity compared to free virus transmission. In general, our study points towards the importance of infection multiplicity and cell-to-cell transmission for HIV evolution.
Jurisdiction, Civilization, and the Ends of Native American Citizenship: The View from 1866
Authors: Kantrowitz Stephen 
Published: March 2021

Abstract
Most nineteenth-century political debates over U.S. citizenship revolved around the claims of people, often African Americans or immigrants, who aspired to that status. But Native American citizenship’s genealogy began instead with the United States assertion of the right to purchase or conquer the territory of its Indigenous neighbors, to replace them as its sole or primary inhabitants, and to make policy for the people thereby dispossessed. These very different histories of citizenship collided in 1866, when the U.S. Senate considered how to codify that status in the Civil Rights Act and Fourteenth Amendment. This article interprets these debates as the collision of an array of distinct and divergent settler colonial processes and experiences. It argues that the ultimate resolution—a half-articulated commitment to let local settler communities decide—both contradicted the ostensible purposes of the Civil Rights Act and accurately reflected how the era’s settler colonial society understood the purposes and functions of Native citizenship.
Perioperative Methadone and Ketamine for Postoperative Pain Control in Spinal Surgical Patients: A Randomized, Double-blind, Placebo-controlled Trial
Authors: Murphy Glenn S. , Avram Michael J. , Greenberg Steven B. , Benson Jessica , Bilimoria Sara , Maher Colleen E. , Teister Kevin , Szokol Joseph W. 
Published: March 2021

Background
Despite application of multimodal pain management strategies, patients undergoing spinal fusion surgery frequently report severe postoperative pain. Methadone and ketamine, which are N-methyl-d-aspartate receptor antagonists, have been documented to facilitate postoperative pain control. This study therefore tested the primary hypothesis that patients recovering from spinal fusion surgery who are given ketamine and methadone use less hydromorphone on the first postoperative day than those give methadone alone.

Methods
In this randomized, double-blind, placebo-controlled trial, 130 spinal surgery patients were randomized to receive either methadone at 0.2 mg/kg (ideal body weight) intraoperatively and a 5% dextrose in water infusion for 48 h postoperatively (methadone group) or 0.2 mg/kg methadone intraoperatively and a ketamine infusion (0.3 mg · kg−1 · h−1 infusion [no bolus] intraoperatively and then 0.1 mg · kg−1 · h−1 for next 48 h [both medications dosed at ideal body weight]; methadone/ketamine group). Anesthetic care was standardized in all patients. Intravenous hydromorphone use on postoperative day 1 was the primary outcome. Pain scores, intravenous and oral opioid requirements, and patient satisfaction with pain management were assessed for the first 3 postoperative days.

Results
Median (interquartile range) intravenous hydromorphone requirements were lower in the methadone/ketamine group on postoperative day 1 (2.0 [1.0 to 3.0] vs. 4.6 [3.2 to 6.6] mg in the methadone group, median difference [95% CI] 2.5 [1.8 to 3.3] mg; P < 0.0001) and postoperative day 2. In addition, fewer oral opioid tablets were needed in the methadone/ketamine group on postoperative day 1 (2 [0 to 3] vs. 4 [0 to 8] in the methadone group; P = 0.001) and postoperative day 3. Pain scores at rest, with coughing, and with movement were lower in the methadone/ketamine group at 23 of the 24 assessment times. Patient-reported satisfaction scores were high in both study groups.

Conclusions
Postoperative analgesia was enhanced by the combination of methadone and ketamine, which act on both N-methyl-d-aspartate and μ-opioid receptors. The combination could be considered in patients having spine surgery.

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What We Already Know about This Topic

What This Article Tells Us That Is New
Factors Associated With Failure of Superior Pubic Ramus Screws
Authors: Comadoll Shea M. , Matuszewski Paul E. , Liu Boshen , Scott Alesha , Cooper Colin , Scott Brandon , Wright Raymond D. 
Published: March 2021

Objective:
Examine factors associated with fixation failure in patients treated with superior intramedullary ramus screws.

Design:
Retrospective.

Setting:
Single, Level 1 trauma center.

Patients:
Unstable pelvic ring fractures amenable fixation that included superior intramedullary ramus screws.

Intervention:
Percutaneously inserted intramedullary superior ramus screw fixation of superior pubic ramus (SPR) fractures.

Main Outcome Measurements:
Loss of reduction (LOR) of the SPR fracture defined as >2 mm displacement on pelvic radiographs at any time point in follow-up.

Results:
Two hundred eighty-five fractures in 211 patients (age 44, 95% confidence interval 40.8%–46.4%, 59.3% women, 55.1% retrograde screws) were included in the analysis. 14 (4.9%) of fractures had LOR. Patients were significantly more likely to have LOR as age increased (P = 0.01), body mass index (BMI) increased (P = 0.01), and if they were women (P < 0.01). There was a significantly decreased LOR (P < 0.01) as fractures moved further from the pubis symphysis. Retrograde screws were significantly (P < 0.01) more likely to have LOR. In SPR fractures treated with retrograde screws, failure was significantly associated with increasing BMI (P = 0.02), the presence of an inferior ramus fracture (P = 0.02), and trended toward significance with increasing age (P = 0.06), and decreased distance from the symphysis (P = 0.07).

Conclusions:
Superior ramus screws are associated with a low failure rate (4.9%), which is lower than previously reported. Retrograde screw insertion, distance from the symphysis, increasing age, increasing BMI, decreased distance from the symphysis, and ipsilateral inferior ramus fractures were predictors of failure. In these patients, alternative modalities should be considered, although low rates of failure can still be expected.

Level of Evidence:
Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence.
Genitourinary syndrome of menopause: a systematic review on prevalence and treatment
Authors: Mili Nikoletta , Paschou Stavroula A. , Armeni Anastasia , Georgopoulos Neoklis , Goulis Dimitrios G. , Lambrinoudaki Irene 
Published: March 2021

Abstract

Importance:
Genitourinary syndrome of menopause (GSM) consists of genitourinary tract symptoms that occur due to physical changes caused by estrogen concentrations decline after menopause. Unlike menopausal symptoms, which subside with time, GSM symptoms persist throughout a woman's life.

Objective:
This article aimed to systematically review the literature to investigate the prevalence of GSM and its treatment.

Evidence Review:
The search was conducted in the electronic databases PubMed, CENTRAL, and EMBASE until October 2020. Eligible for the systematic review were studies and surveys conducted via questionnaires or medical interviews evaluating the existence of GSM symptoms with or without gynecological examination in postmenopausal women or women >40 years of age.

Findings:
After the application of predefined inclusion/exclusion criteria, 27 studies were included in the systematic review. The prevalence of GSM-related symptoms, such as vaginal dryness, irritation, itching, and dyspareunia, ranged from 13% to 87%. The use of GSM-specific treatment varied from 13% to 78%. Over-the-counter lubricants and moisturizers were the most popular therapeutic options (24.0%-85.5%), followed by low-dose vaginal estrogens (4.8%-35.0%). Vaginal health is not frequently discussed during doctor visits and awareness about the condition and the number of treatment options is low. Women are concerned about the long-term safety and side effects of hormonal treatment. The majority of women who suffer from genitourinary symptoms are dissatisfied by the treatment they have used.

Conclusions and Relevance:
GSM is a highly prevalent condition among women. Nevertheless, women are frequently not aware of its cause and its treatment options. The findings of this review underline the need for education of patients and healthcare professionals regarding GSM diagnosis and treatment options.

Video Summary:

http://links.lww.com/MENO/A720.
Experiences of menopause during incarceration
Authors: Jaffe Elana F. , Palmquist Aunchalee E.L. , Knittel Andrea K. 
Published: March 2021

Abstract

Objective:
Despite increasing representation of older women in US jail and prison facilities, their menopause experiences and access to related care remain uncharacterized. Our objective is to explore the menopause experiences of women incarcerated in jail and prison facilities.

Methods:
We conducted a pilot study of four semi-structured in-depth interviews with women in the community who experienced menopause symptoms while incarcerated in either a prison or jail facility.

Results:
Preliminary findings suggest critical gaps in access to menopause-related resources and medical care. Participants described that lifestyle and medical interventions for menopause in prison were inaccessible, and that untreated symptoms contributed to significant distress. Participants reported feeling as though medical staff did not believe their concerns and were dismissive of their complaints. In some cases, menopause symptoms and symptom management exacerbated the ways in which institutional barriers reproduce criminalization within the carceral system.

Conclusions:
Individuals going through the menopause transition while experiencing incarceration have significant unmet needs and poor access to relieving lifestyle changes or medical interventions. Policy and practice changes should address menopause-related needs of individuals experiencing incarceration.

Video Summary:

http://links.lww.com/MENO/A730.
International Association for the Study of Pain Presidential Task Force on Cannabis and Cannabinoid Analgesia: research agenda on the use of cannabinoids, cannabis, and cannabis-based medicines for pain management
Authors: Haroutounian Simon , Arendt-Nielsen Lars , Belton Joletta , Blyth Fiona M. , Degenhardt Louisa , Di Forti Marta , Eccleston Christopher , Finn David P. , Finnerup Nanna B. , Fisher Emma , Fogarty Alexandra E. , Gilron Ian , Hohmann Andrea G. , Kalso Eija , Krane Elliot , Mohiuddin Mohammed , Moore R. Andrew , Rowbotham Michael , Soliman Nadia , Wallace Mark , Zinboonyahgoon Nantthasorn , Rice Andrew S.C. 
Published: March 2021

Abstract:
The President of the International Association for the Study of Pain established a task force on cannabis and cannabinoid analgesia to systematically examine the evidence on (1) analgesic pharmacology of cannabinoids and preclinical evidence on their efficacy in animal models of injury-related or pathological persistent pain; (2) the clinical efficacy of cannabis, cannabinoids, and cannabis-based medicines for pain; (3) harms related to long-term use of cannabinoids; as well as (4) societal issues and policy implications related to the use of these compounds for pain management. Here, we summarize key knowledge gaps identified in the task force outputs and propose a research agenda for generating high-quality evidence on the topic. The systematic assessment of preclinical and clinical literature identified gaps in rigor of study design and reporting across the translational spectrum. We provide recommendations to improve the quality, rigor, transparency, and reproducibility of preclinical and clinical research on cannabis and cannabinoids for pain, as well as for the conduct of systematic reviews on the topic. Gaps related to comprehensive understanding of the endocannabinoid system and cannabinoid pharmacology, including pharmacokinetics and drug formulation aspects, are discussed. We outline key areas where high-quality clinical trials with cannabinoids are needed. Remaining important questions about long-term and short-term safety of cannabis and cannabinoids are emphasized. Finally, regulatory, societal, and policy challenges associated with medicinal and nonmedicinal use of cannabis are highlighted, with recommendations for improving patient safety and reducing societal harms in the context of pain management.
Willingness to Pay for Select Tick-Borne Disease Prevention Measures in Endemic Areas
Authors: Niesobecki Sara , Rutz Heather , Niccolai Linda , Hook Sarah , Feldman Katherine , Hinckley Alison 
Published: March 2021

Tick-borne diseases (TBDs) are increasing despite prevention recommendations. We explored whether cost is a barrier to prevention use in Connecticut and Maryland, using a cross-sectional survey. Respondents were queried regarding their willingness to pay for chemical, natural, and rodent-targeted yard pesticide treatments and permethrin-treated clothing. We evaluated associations between demographics, TBD knowledge and attitudes, and willingness to pay for prevention methods.
Most respondents would pay for yard treatments (85%); 95% preferring natural pesticide, and 82% would pay for permethrin-treated clothing. Most did not want to pay more than $99 for any of the yard treatments. Having a household income of $100 000 was associated with willingness to pay $100 or more for chemical, natural, or rodent-targeted treatments and $25 or more for permethrin self-treated and pretreated clothing. Yard treatments, especially natural pesticides, were acceptable for TBD prevention; however, current pricing may be cost-prohibitive. Permethrin-treated clothing may be an affordable and acceptable prevention method.
Changes in CD163+, CD11b+, and CCR2+ peripheral monocytes relate to Parkinson’s disease and cognition
Authors: Nissen Sara Konstantin , Farmen Kristine , Carstensen Mikkel , Schulte Claudia , Goldeck David , Brockmann Kathrin , Romero-Ramos Marina 
Published: March 2021

1.AbstractAlpha-synuclein pathology is associated with immune activation and neurodegeneration in Parkinson’s disease. The immune activation involves not only microglia but also peripheral immune cells, such as mononuclear phagocytes found in blood and infiltrated in the brain. Understanding peripheral immune involvement is essential for developing immunomodulatory treatment. Therefore, we aimed to study circulating mononuclear phagocytes in early- and late-stage Parkinson’s disease, defined by disease duration of less or more than five years, respectively, and analyze their association with clinical phenotypes. We performed a cross-sectional multi-color flow cytometry study on 78 sex-balanced individuals with sporadic Parkinson’s disease, 28 controls, and longitudinal samples from seven patients and one control. Cell frequencies and surface marker expressions on natural killer cells, monocyte subtypes, and dendritic cells were compared between groups and correlated with standardized clinical scores. We found elevated frequencies and surface levels of migration-(CCR2, CD11b) and phagocytic-(CD163) markers, particularly on classical and intermediate monocytes in early Parkinson’s disease. HLA-DR expression was increased in advanced stages of the disease, whereas TLR4 expression was decreased in women with Parkinson’s Disease. The disease-associated immune changes on CCR2 and CD11b correlated with worse cognition. Increased TLR2 expression was related to worse motor symptoms. In conclusion, our data highlights the TLR2 relevance in the symptomatic motor presentation of the disease and a role for peripheral CD163+ and migration-competent monocytes in Parkinson’s disease cognitive defects. Our study suggests that the peripheral immune system is dynamically altered in Parkinson’s disease stages and directly related to both symptoms and the sex bias of the disease.HighlightsTLR2 expression increased in patients with worse motor symptoms.Increased CD163 and HLA-DR monocytic expression in patients with long PD duration.Sexual-dimorphism for CCR2, CD11b, and TLR4 expression on PD monocytes.CCR2 and CD11b expression are associated with cognitive impairment in PD.
Rapid base-specific calling of SARS-CoV-2 variants of concern using combined RT-PCR melting curve screening and SIRPH technology
Authors: Sascha Tierling , Kathrin Kattler , Markus Vogelgesang , Thorsten Pfuhl , Stefan Lohse , Christina Lo Porto , Beate Schmitt , Abdulrahman Salhab , Sigrun Smola , Jörn Walter 
Published: March 2021

ABSTRACTThe emergence of novel variants of concern of SARS-CoV-2 demands a fast and reliable detection of such variants in local populations. Here we present a cost-efficient and fast workflow combining a pre-screening of SARS-CoV-2 positive samples using RT-PCR melting curve analysis with multiplexed IP-RP-HPLC-based single nucleotide primer extensions (SIRPH). The entire workflow from positive SARS-CoV-2 testing to base-specific identification of variants requires about 24 h. We applied the sensitive method to monitor the local VOC outbreaks in a few hundred positive samples collected in a confined region of Germany.
JAX-CNV: A whole genome sequencing-based algorithm for copy number detection at clinical grade level
Authors: Lee Wan-Ping , Zhu Qihui , Yang Xiaofei , Liu Silvia , Cerveira Eliza , Ryan Mallory , Mil-Homens Adam , Bellfy Lauren , Ye Kai , Zhang Chengsheng , Lee Charles 
Published: March 2021

AbstractWe aimed to develop a whole genome sequencing (WGS)-based copy number variant (CNV) calling algorithm with the potential of replacing chromosomal microarray assay (CMA) for clinical diagnosis. JAX-CNV is thus developed for CNV detection from WGS. The performance of this CNV calling algorithm was evaluated in a blinded manner on 31 samples and compared to the results of clinically-validated CMAs. Comparing to 112 CNVs reported by clinically-validated CMAs of the 31 samples, JAX-CNV is 100% recalling them. Besides, JAX-CNV identified an average of 30 CNVs per individual that is an approximately seven-fold increase compared to calls of clinically-validated CMAs. Experimental validation of 24 randomly selected CNVs, showed one false positive (i.e., a false discovery rate of 4.17%). A robustness test on lower-coverage data revealed a 100% sensitivity for CNVs greater than 300 kb (the current threshold for College of American Pathologists) down to 10x coverage. For CNVs greater than 50 kb, sensitivities were 100% for coverages deeper than 20x, 97% for 15x, and 95% for 10x. We developed a WGS-based CNV pipeline, including this newly developed CNV caller JAX-CNV, and found it capable of detecting CMA reported CNVs at 100% sensitivity with about 4% false discovery rate. We propose that JAX-CNV could be further examined in a multi-institutional study to justify the transition of first-tier genetic testing from CMAs to WGS. JAX-CNV is available on https://github.com/TheJacksonLaboratory/JAX-CNV.
Post-stroke fatigue is linked to resting state posterior hypoactivity and prefrontal hyperactivity
Authors: Cotter Georgia , Khlif Mohamed Salah , Bird Laura , Howard Mark E , Brodtmann Amy , Egorova Natalia 
Published: March 2021

AbstractBackground and PurposeFatigue is associated with poor functional outcomes and increased mortality following stroke. Survivors identify fatigue as one of their key unmet needs. Despite the growing body of research into post-stroke fatigue, the specific neural mechanisms remain largely unknown.MethodsThis observational study included 63 stroke survivors (22 women; age 30-89 years; mean 67.5±13.4 years) from the Cognition And Neocortical Volume After Stroke (CANVAS) study, a cohort study examining cognition, mood, and brain volume in stroke survivors following ischaemic stroke. Participants underwent brain imaging 3 months post-stroke, including a 7-minute resting state fMRI echoplanar sequence. We calculated the fractional amplitude of low-frequency fluctuations, a measure of resting state brain activity at the whole-brain level.ResultsForty-five participants reported experiencing post-stroke fatigue as measured by an item on the Patient Health Questionnaire-9. A generalised linear regression model analysis with age, sex, and stroke severity covariates was conducted to compare resting state brain activity in the 0.01-0.08 Hz range, as well as its subcomponents - slow-5 (0.01-0.027 Hz), and slow-4 (0.027-0.073 Hz) frequency bands between fatigued and non-fatigued participants. We found no significant associations between post-stroke fatigue and ischaemic stroke lesion location or stroke volume. However, in the overall 0.01-0.08 Hz band, participants with post-stroke fatigue demonstrated significantly lower resting-state activity in the calcarine cortex (p<0.001, cluster-corrected pFDR=0.009, k=63) and lingual gyrus (p<0.001, cluster-corrected pFDR=0.025, k=42) and significantly higher activity in the medial prefrontal cortex (p<0.001, cluster-corrected pFDR=0.03, k=45), attributed to slow-4 and slow-5 oscillations, respectively.ConclusionsPost-stroke fatigue is associated with posterior hypoactivity and prefrontal hyperactivity, reflecting dysfunction within large-scale brain systems such as fronto-striatal-thalamic and frontal-occipital networks. These systems in turn might reflect a relationship between post-stroke fatigue and abnormalities in executive and visual functioning. This first whole-brain resting-state study provides new targets for further investigation of post-stroke fatigue beyond the lesion approach.