bluuebunny/crossref_metadata_2025_split huggingface dataset:
Diverse Human Immunodeficiency Virus–1 Drug Resistance Profiles at Screening for ACTG A5288: A Study of People Experiencing Virologic Failure on Second-line Antiretroviral Therapy in Resource-limited Settings
Authors: Wallis Carole L , Hughes Michael D , Ritz Justin , Viana Raquel , de Jesus Carlos Silva , Saravanan Shanmugam , van Schalkwyk Marije , Mngqibisa Rosie , Salata Robert , Mugyenyi Peter , Hogg Evelyn , Hovind Laura , Wieclaw Linda , Gross Robert , Godfrey Catherine , Collier Ann C , Grinsztejn Beatriz , Mellors John W 
Published: November 2019

Abstract

Background
Human immunodeficiency virus (HIV) drug resistance profiles are needed to optimize individual patient management and to develop treatment guidelines. Resistance profiles are not well defined among individuals on failing second-line antiretroviral therapy (ART) in low- and middle-income countries (LMIC).

Methods
Resistance genotypes were performed during screening for enrollment into a trial of third-line ART (AIDS Clinical Trials Group protocol 5288). Prior exposure to both nucleoside reverse transcriptase inhibitors (NRTIs) and non-NRTIs and confirmed virologic failure on a protease inhibitor–containing regimen were required. Associations of drug resistance with sex, age, treatment history, plasma HIV RNA, nadir CD4+T-cell count, HIV subtype, and country were investigated.

Results
Plasma HIV genotypes were analyzed for 653 screened candidates; most had resistance (508 of 653; 78%) to 1 or more drugs. Genotypes from 133 (20%) showed resistance to at least 1 drug in a drug class, from 206 (32%) showed resistance to at least 1 drug in 2 drug classes, and from 169 (26%) showed resistance to at least 1 drug in all 3 commonly available drug classes. Susceptibility to at least 1 second-line regimen was preserved in 59%, as were susceptibility to etravirine (78%) and darunavir/ritonavir (97%). Susceptibility to a second-line regimen was significantly higher among women, younger individuals, those with higher nadir CD4+ T-cell counts, and those who had received lopinavir/ritonavir, but was lower among prior nevirapine recipients.

Conclusions
Highly divergent HIV drug resistance profiles were observed among candidates screened for third-line ART in LMIC, ranging from no resistance to resistance to 3 drug classes. These findings underscore the need for access to resistance testing and newer antiretrovirals for the optimal management of third-line ART in LMIC.
Isolation ofMycobacterium lepromatosisand Development of Molecular Diagnostic Assays to DistinguishMycobacterium lepraeandM. lepromatosis
Authors: Sharma Rahul , Singh Pushpendra , McCoy Rajiv C , Lenz Shannon M , Donovan Kelly , Ochoa Maria T , Estrada-Garcia Iris , Silva-Miranda Mayra , Jurado-Santa Cruz Fermin , Balagon Marivic F , Stryjewska Barbara , Scollard David M , Pena Maria T , Lahiri Ramanuj , Williams Diana L , Truman Richard W , Adams Linda B 
Published: November 2019

AbstractBackgroundMycobacterium leprae was thought to be the exclusive causative agent of leprosy until Mycobacterium lepromatosis was identified in a rare form of leprosy known as diffuse lepromatous leprosy (DLL).MethodsWe isolated M. lepromatosis from a patient with DLL and propagated it in athymic nude mouse footpads. Genomic analysis of this strain (NHDP-385) identified a unique repetitive element, RLPM, on which a specific real-time quantitative polymerase chain reaction assay was developed. The RLPM assay, and a previously developed RLEP quantitative polymerase chain reaction assay for M. leprae, were validated as clinical diagnostic assays according to Clinical Laboratory Improvement Amendments guidelines. We tested DNA from archived histological sections, patient specimens from the United States, Philippines, and Mexico, and US wild armadillos.ResultsThe limit of detection for the RLEP and RLPM assays is 30 M. leprae per specimen (0.76 bacilli per reaction; coefficient of variation, 0.65%–2.44%) and 122 M. lepromatosis per specimen (3.05 bacilli per reaction; 0.84%–2.9%), respectively. In histological sections (n = 10), 1 lepromatous leprosy (LL), 1 DLL, and 3 Lucio reactions contained M. lepromatosis; 2 LL and 2 Lucio reactions contained M. leprae; and 1 LL reaction contained both species. M. lepromatosis was detected in 3 of 218 US biopsy specimens (1.38%). All Philippines specimens (n = 180) were M. lepromatosis negative and M. leprae positive. Conversely, 15 of 47 Mexican specimens (31.91%) were positive for M. lepromatosis, 19 of 47 (40.43%) were positive for M. leprae, and 2 of 47 (4.26%) contained both organisms. All armadillos were M. lepromatosis negative.ConclusionsThe RLPM and RLEP assays will aid healthcare providers in the clinical diagnosis and surveillance of leprosy.
Predictive value of left ventricular diastolic chamber stiffness in patients with severe aortic stenosis undergoing aortic valve replacement
Authors: Anand Vidhu , Adigun Rosalyn O , Thaden Jeremy T , Pislaru Sorin V , Pellikka Patricia A , Nkomo Vuyisile T , Greason Kevin L , Pislaru Cristina 
Published: November 2019

Abstract

Aims
Despite improvements in cardiac haemodynamics and symptoms, long-term mortality remains increased in some patients after aortic valve replacement (AVR). Limited data exist on the prognostic role of left ventricular (LV) chamber stiffening in these patients.

Methods and results
We performed a retrospective analysis in 1893 patients with severe aortic stenosis (AS) referred for AVR. LV end-diastolic pressure–volume relations (EDPVR, P = αV^β) were reconstructed from echocardiographic measurements of end-diastolic volumes and estimates of end-diastolic pressure (EDP). The impact of EDPVR-derived LV chamber stiffness (CS30, at 30 mmHg EDP) on all-cause mortality after AVR was evaluated. Mean age was 76 ± 10 years, 39% were females, and ejection fraction (EF) was 61 ± 12%. The mean LV chamber stiffness (CS30) was 2.2 ± 1.3 mmHg/mL. A total of 877 (46%) patients had high LV stiffness (CS30 &gt;2 mmHg/mL). In these patients, the EDPVR curves were steeper and shifted leftwards, indicating higher stiffness at all pressure levels. These patients were slightly older, more often female, and had more prevalent comorbidities compared to patients with low stiffness. At follow-up [median 4.2 (interquartile range 2.8–6.3) years; 675 deaths], a higher CS30 was associated with lower survival (hazard ratio: 2.7 for severe vs. mild LV stiffening; P &lt; 0.0001), both in patients with normal or reduced EF. At multivariate analysis, CS30 remained an independent predictor, even after adjusting for age, sex, comorbidities, EF, LV remodelling, and diastolic dysfunction.

Conclusion
Higher preoperative LV chamber stiffening in patients with severe AS is associated with poorer outcome despite successful AVR.
The cardiac sympathetic co-transmitter neuropeptide Y is pro-arrhythmic following ST-elevation myocardial infarction despite beta-blockade
Authors: Kalla Manish , Hao Guoliang , Tapoulal Nidi , Tomek Jakub , Liu Kun , Woodward Lavinia ,   ‘Oxford Acute Myocardial Infarction (OxAMI) Study’, Dall’Armellina Erica , Banning Adrian P , Choudhury Robin P , Neubauer Stefan , Kharbanda Rajesh K , Channon Keith M , Ajijola Olujimi A , Shivkumar Kalyanam , Paterson David J , Herring Neil 
Published: November 2019

Abstract

Aims
ST-elevation myocardial infarction is associated with high levels of cardiac sympathetic drive and release of the co-transmitter neuropeptide Y (NPY). We hypothesized that despite beta-blockade, NPY promotes arrhythmogenesis via ventricular myocyte receptors.

Methods and results
In 78 patients treated with primary percutaneous coronary intervention, sustained ventricular tachycardia (VT) or fibrillation (VF) occurred in 6 (7.7%) within 48 h. These patients had significantly (P &lt; 0.05) higher venous NPY levels despite the absence of classical risk factors including late presentation, larger infarct size, and beta-blocker usage. Receiver operating curve identified an NPY threshold of 27.3 pg/mL with a sensitivity of 0.83 and a specificity of 0.71. RT-qPCR demonstrated the presence of NPY mRNA in both human and rat stellate ganglia. In the isolated Langendorff perfused rat heart, prolonged (10 Hz, 2 min) stimulation of the stellate ganglia caused significant NPY release. Despite maximal beta-blockade with metoprolol (10 μmol/L), optical mapping of ventricular voltage and calcium (using RH237 and Rhod2) demonstrated an increase in magnitude and shortening in duration of the calcium transient and a significant lowering of ventricular fibrillation threshold. These effects were prevented by the Y1 receptor antagonist BIBO3304 (1 μmol/L). Neuropeptide Y (250 nmol/L) significantly increased the incidence of VT/VF (60% vs. 10%) during experimental ST-elevation ischaemia and reperfusion compared to control, and this could also be prevented by BIBO3304.

Conclusions
The co-transmitter NPY is released during sympathetic stimulation and acts as a novel arrhythmic trigger. Drugs inhibiting the Y1 receptor work synergistically with beta-blockade as a new anti-arrhythmic therapy.
Clinical management of Type II Diabetes among the unstably housed: a qualitative study of primary care physicians
Authors: Henry Mariana L , Lichtman Judith H , Hanlon Kendra , Keene Danya E 
Published: November 2019

Abstract

Background
Housing is a growing challenge for US adults in an increasingly unaffordable housing market. These housing challenges can create barriers to effective management and control of Type II Diabetes. However, little is known about how housing challenges are perceived and navigated by clinicians who care for patients with Type II Diabetes.

Objective
To examine how primary care clinicians perceive and navigate their patients’ housing challenges in the context of Type II Diabetes management.

Methods
We conducted semi-structured interviews with 18 primary care clinicians practising in four clinical settings in New Haven, Connecticut. Two investigators systematically coded the interviews. Analysis of coded data was used to determine themes.

Results
Participants considered housing as significant to their patients’ health and a potential barrier to optimal diabetes management. Participants sought to improve their patients’ housing through advocacy, referrals and interdisciplinary collaborations. They also adjusted clinical decisions to adapt to patients’ housing challenges. In making clinical adjustments, participants struggled to find a balance between what they perceived to be feasible for unstably housed patients and maintaining a standard of care. Some participants navigated this balanced by employing creative strategies and individualized care.

Conclusion
In highlighting the challenges that clinicians face in maintaining a standard of care for unstably housed diabetes patients, our findings speak to the need for more guidance, resources and support to address housing in a clinical setting.
Cross-kingdom analysis of nymphal-stage Ixodes scapularis microbial communities in relation to Borrelia burgdorferi infection and load
Authors: Landesman William J , Mulder Kenneth , Fredericks L Page , Allan Brian F 
Published: November 2019

ABSTRACTThe tick microbiota may influence the colonization of Ixodes scapularis by Borrelia burgdorferi, the Lyme disease bacterium. Using conserved and pathogen-specific primers we performed a cross-kingdom analysis of bacterial, fungal, protistan and archaeal communities of I. scapularis nymphs (N = 105) collected from southern Vermont, USA. The bacterial community was dominated by a Rickettsia and several environmental taxa commonly reported in I. scapularis, as well as the human pathogens B. burgdorferi and Anaplasma phagocytophilum, agent of human granulocytic anaplasmosis. With the fungal primer set we detected primarily plant- and litter-associated taxa and >18% of sequences were Malassezia, a fungal genus associated with mammalian skin. Two 18S rRNA gene primer sets, intended to target protistan communities, returned mostly Ixodes DNA as well as the wildlife pathogen Babesia odocoilei (7% of samples), a Gregarines species (14%) and a Spirurida nematode (18%). Data from pathogen-specific and conserved primers were consistent in terms of prevalence and identification. We measured B. burgdorferi presence/absence and load and found that bacterial beta diversity varied based on B. burgdorferi presence/absence. Load was weakly associated with bacterial community composition. We identified taxa associated with B. burgdorferi infection that should be evaluated for their role in vector colonization by pathogens.
Electromagnetic wave propagation based upon spectral-element methodology in dispersive and attenuating media
Authors: Morency Christina 
Published: November 2019

SUMMARYWe build on mathematical equivalences between Maxwell’s wave equations for an electromagnetic medium and elastic seismic wave equations. This allows us to readily model Maxwell’s wave propagation in the spectral-element codes SPECFEM2D and SPECFEM3D, written for acoustic, viscoelastic and poroelastic seismic wave propagation, providing the ability to handle complex geometries, inherent to finite-element methods and retaining the strength of exponential convergence and accuracy due to the use of high-degree polynomials to interpolate field functions on the elements, characteristic to spectral-element methods (SEMs). Attenuation and dispersion processes related to the frequency dependence of dielectric permittivity and conductivity are also included using a Zener model, similar to shear attenuation in viscoelastic media or viscous diffusion in poroelastic media, and a Kelvin–Voigt model, respectively. Ability to account for anisotropic media is also discussed. Here, we limit ourselves to certain dielectric permittivity tensor geometries, in order to conserve a diagonal mass matrix after discretization of the system of equations. Doing so, simulation of Maxwell’s wave equations in the radar frequency range based on SEM can be solved using explicit time integration schemes well suited for parallel computation. We validate our formulation with analytical solutions. In 2-D, our implementation allows for the modelling of both a transverse magnetic (TM) mode, suitable for surface based reflection ground penetration radar type of applications, and a transverse electric (TE) mode more suitable for crosshole and vertical radar profiling setups. Two 2-D examples are designed to demonstrated the use of the TM and TE modes. A 3-D example is also presented, which allows for the full TEM solution, different antenna orientations, and out-of-plane variations in material properties.
From Spinning Silk to Spreading Saliva: Mouthpart Remodeling inManduca sexta(Lepidoptera: Sphingidae)
Authors: Mikó István , Rahman Sarthok Rasique , Jones Anne C , Townley Mark A , Gominho Brandon , Paudel Sulav , Stupski S David , Hines Heather M , Schilder Rudolf J 
Published: November 2019

AbstractAs a model organism, the tobacco hornworm Manduca sexta (Linnaeus 1763) has contributed much to our knowledge of developmental processes in insects, and major developmental changes between different larval instars are generally well understood. Second and later instars of M. sexta do not produce silk, and their spinneret and accessory labial glands (=Lyonet’s glands), structures thought to be key players in silk production in other lepidopterans, are highly reduced. To our knowledge, mouthparts and labial gland morphology of the silk-producing first instar have never been described. In this study, we compared the mouthpart morphology and transcriptome profile of first and later instars of M. sexta to determine whether the loss of silk production correlates with changes in the structure of the spinneret and the labial glands, and with changes in expression of silk-related genes. We found that the first instar, unlike later instars, has a typical, silk-producing spinneret with a tube-like spigot and well developed Lyonet’s glands. Moreover, three known silk protein genes are highly expressed in the first instar but exhibit little to no expression in the embryo or later instars. Thus, the changes in morphology and gene expression presented here, coinciding with changes in larval behavior from silk production to saliva spreading, further our understanding of the developmental processes underlying this transition in this model organism.
Revision of the Highly Specialized Ant Genus Discothyrea (Hymenoptera: Formicidae) in the Afrotropics with X-Ray Microtomography and 3D Cybertaxonomy
Authors: Hita-Garcia Francisco , Lieberman Ziv , Audisio Tracy L , Liu Cong , Economo Evan P 
Published: November 2019

AbstractDiscothyrea Roger, 1863 is a small genus of proceratiine ants with remarkable morphology and biology. However, due to cryptic lifestyle, Discothyrea are poorly represented in museum collections and their taxonomy has been severely neglected. We perform the first comprehensive revision of Discothyrea in the Afrotropical region through a combination of traditional and three-dimensional (3D) cybertaxonomy based on microtomography (micro-CT). Species diagnostics and morphological character evaluations are based on examinations of all physical specimens and virtual analyses of 3D surface models generated from micro-CT data. Additionally, we applied virtual dissections for detailed examinations of cephalic structures to establish terminology based on homology for the first time in Discothyrea. The complete datasets comprising micro-CT data, 3D surface models and videos, still images of volume renderings, and colored stacked images are available online as cybertype datasets (Hita Garcia et al. 2019, http://doi.org/10.5061/dryad.3qm4183). We define two species complexes (D. oculata and D. traegaordhi complexes) and revise the taxonomy of all species through detailed illustrated diagnostic character plates, a newly developed identification key, species descriptions, and distribution maps. In total, we recognize 20 species; of which, 15 are described as new. We also propose D. hewitti Arnold, 1916 as junior synonym of D. traegaordhi Santschi, 1914 and D. sculptior Santschi, 1913 as junior synonym of D. oculata Emery, 1901. Also, we designate a neotype for D. traegaordhi to stabilize its status and identity, and we designate a lectotype for D. oculata. The observed diversity and endemism are discussed within the context of Afrotropical biogeography and the oophagous lifestyle.
Role of the N-terminus in human 4-hydroxyphenylpyruvate dioxygenase activity
Authors: Feng An-Ning , Huang Chih-Wei , Lin Chi-Huei , Chang Yung-Lung , Ni Meng-Yuan , Lee Hwei-Jen 
Published: November 2019

Abstract4-Hydroxyphenylpyruvate dioxygenase (HPPD) is a key enzyme in tyrosine catabolism, catalysing the oxidation of 4-hydroxyphenylpyruvate to homogentisate. Genetic deficiency of this enzyme causes type III tyrosinaemia. The enzyme comprises two barrel-shaped domains formed by the N- and C-termini, with the active site located in the C-terminus. This study investigated the role of the N-terminus, located at the domain interface, in HPPD activity. We observed that the kcat/Km decreased ∼8-fold compared with wild type upon removal of the 12 N-terminal residues (ΔR13). Interestingly, the wild-type level of activity was retained in a mutant missing the 17 N-terminal residues, with a kcat/Km 11-fold higher than that of the ΔR13 mutant; however, the structural stability of this mutant was lower than that of wild type. A 2-fold decrease in catalytic efficiency was observed for the K10A and E12A mutants, indicating synergism between these residues in the enzyme catalytic function. A molecular dynamics simulation showed large RMS fluctuations in ΔR13 suggesting that conformational flexibility at the domain interface leads to lower activity in this mutant. These results demonstrate that the N-terminus maintains the stability of the domain interface to allow for catalysis at the active site of HPPD.
Ultrasound-Guided Lateral Femoral Cutaneous Nerve Cryoneurolysis for Analgesia in Patients With Burns
Authors: Finneran John J , Swisher Matthew W , Gabriel Rodney A , Fiallo Alfredo , Hamilton Jeffrey R , Lee Jeanne G , Ilfeld Brian M 
Published: November 2019

AbstractAutologous skin grafting from the thigh is frequently required for treatment of burns and is associated with intense pain at the donor site. Local anesthetic–based (LA) nerve blocks of the lateral femoral cutaneous nerve (LFCN) have been demonstrated to provide analgesia when the graft is taken from the lateral thigh. However, the duration of these single injection blocks has been reported to average only 9 hours, whereas the pain from the procedure lasts days or weeks. Continuous LA nerve blocks can also be used to provide analgesia during serial debridement of burns, although this requires placement of a perineural catheter which may increase infection risk in a population with an increased susceptibility to infection. Cryoneurolysis of the LFCN can potentially provide analgesia of the lateral thigh for skin graft harvesting or serial burn debridement that lasts far longer than conventional LA nerve blocks. Here, we present a series of three patients who received a combination of a LA nerve block and cryoneurolysis nerve block of the LFCN for analgesia of the lateral thigh. Two of these patients had the blocks placed before harvesting a split thickness skin graft. The third received the blocks for outpatient wound care of a burn to the lateral thigh. In all cases, the resulting analgesia lasted more than 1 week. A single cryoneurolysis block of the LFCN successfully provided extended duration analgesia of the lateral thigh for autologous skin graft donor site or wound care of a burn in three patients.
Investment Wars: Contestation and Confusion in Debate About Investment Liberalization
Authors: Bonnitcha Jonathan 
Published: November 2019

ABSTRACT
Questions of investment governance are central to current trade wars. The USA complains of China’s use of restrictions on US investment as a lever to force technology transfer, while China complains of the review of investment in the USA on national security grounds. This article examines the place of these debates about investment liberalization within the trade wars. The focus is on US conduct, as the instigator of the trade wars. I argue that the USA is pursuing diverse and partially inconsistent in relation to investment liberalization. In some contexts, the USA is continuing to pursue the objective of removing impediments to outward investment, which was the principal objective of US investment policy for the decades prior to the Trump administration. In other contexts, the USA is seeking to encourage the repatriation of US outward investment and to regulate inward and outward investment according to ill-defined security rationales. I argue that prevailing materialist accounts of the trade wars struggle to explain these inconsistencies. Instead, I suggest that constructivist political economy provides a more promising explanatory framework. According to this view, inconsistency in policy objectives stems from foundational uncertainty about the nature of the ‘problem’ of investment liberalization.