bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pharmacovirological analyses of blood and male genital compartment in patients receiving dolutegravir + lamivudine dual therapy as a switch strategy (ANRS 167 LAMIDOL trial)
Authors: Charpentier Charlotte , Peytavin Gilles , Raffi François , Burdet Charles , Landman Roland , Lê Minh P , Katlama Christine , Collin Gilles , Benalycherif Aida , Cabie André , Mentré France , Yazdanpanah Yazdan , Descamps Diane , Joly Véronique 
Published: January 2020

Abstract

Objectives
To describe plasma residual HIV viraemia, cellular HIV reservoir size, blood plasma drug concentrations and their male genital tract penetration during the maintenance dual therapy dolutegravir + lamivudine.

Patients and methods
ANRS167 LAMIDOL enrolled 104 virologically suppressed patients to switch to dolutegravir + lamivudine. In this pharmacovirological substudy, ultrasensitive plasma viral load (USpVL) and plasma drug concentrations were measured at Day 0 (D0), Week 24 (W24) and W48 of dolutegravir + lamivudine, and HIV-DNA was measured at W−8 and W48. Semen samples were collected at D0 and W24 from 18 participants. Total and unbound blood and seminal plasma drug concentrations were measured using UPLC–MS/MS.

Results
Median HIV-DNA was 2.5 log10 copies/106 PBMC (IQR = 2.2–3.0, n = 100) at W−8 and 2.4 log10 copies/106 PBMC (IQR = 2.1–2.9, n = 100) at W48 (P = 0.17). The proportion of patients with undetected USpVL was 38% (n = 98), 43% (n = 98) and 49% (n = 97) at D0, W24 and W48, respectively (P = 0.08). Total and unbound plasma dolutegravir concentrations were stable between timepoints (P = 0.13) and all total plasma dolutegravir concentrations except one were adequate. Median free fraction of dolutegravir in plasma was 0.21%. Median blood plasma and seminal plasma concentrations of total dolutegravir at 24 h were 1812 ng/mL and 206 ng/mL, respectively. Median seminal plasma/blood plasma total concentration ratios were 11.6% and 2478% for dolutegravir and lamivudine, respectively. HIV-RNA (365 to 475 copies/mL) was detected in seminal plasma of one patient at D0 (5.9%) and of two patients at W24 (11.8%).

Conclusions
These findings add further important information regarding the effectiveness of dolutegravir + lamivudine maintenance dual therapy in terms of plasma residual viraemia, cellular reservoir size and drug penetration in the male genital tract.
Whole-genome analysis of vancomycin-resistant Enterococcus faecium causing nosocomial outbreaks suggests the occurrence of few endemic clonal lineages in Bavaria, Germany
Authors: Eisenberger David , Tuschak Christian , Werner Markus , Bogdan Christian , Bollinger Thomas , Hossain Hamid , Friedrich Petra , Hussein Ziyad , Pöhlmann Christoph , Würstl Benjamin , Nickel Silke , Lehner-Reindl Verena , Höller Christiane , Liebl Bernhard , Valenza Giuseppe 
Published: January 2020

Abstract

Objectives
Infections caused by vancomycin-resistant Enterococcus faecium (VREfm) represent a major public health concern due to limited treatment options. Among invasive isolates of VREfm, ST117, ST80 and ST78 represent the most frequently detected STs by MLST in Germany. In this study, we investigated the genetic diversity of isolates of VREfm recovered from different nosocomial outbreaks in Bavaria, Germany, by WGS.

Methods
Between January 2018 and April 2019, 99 non-replicate isolates of VREfm originating from nosocomial outbreaks at eight different hospitals in Bavaria were investigated for genetic diversity by WGS. In detail, complex types (CTs) were identified by core-genome MLST. Furthermore, an SNP analysis was performed for all VREfm strains.

Results
Most of the isolates of this study (76%) belonged to three major clonal groups, which occurred in at least three hospitals: ST80/CT1065 vanB (n = 45; six hospitals), ST117/CT71 vanB (n = 11; four hospitals) and ST78/CT894like vanA (n = 19; three hospitals). Moreover, isolates of the predominant lineage ST80/CT1065 vanB showed a maximum difference of 36 SNPs as revealed by SNP analysis.

Conclusions
Whole-genome analysis of VREfm causing nosocomial outbreaks suggests the occurrence of few endemic clonal lineages in Bavarian hospital settings, namely ST80/CT1065 vanB, ST117/CT71 vanB and ST78/CT894like vanA. Further studies are needed for a better understanding of the factors affecting the successful spread of the above-mentioned lineages.
Evaluation of Resistance Management for the Oriental Fruit Moth (Lepidoptera: Tortricidae) to Insecticides in Brazilian Apple Orchards
Authors: Monteiro Lino Bittencourt , Witt Luis Gustavo , Guiloski Izonete Cristina , dos Santos Regis Silvori Silva , Silva de Assis Helena C 
Published: January 2020

AbstractThe oriental fruit moth, Grapholita molesta (Busk, 1916), is one of the most important pests in apple orchards in southern Brazil. Chemical control is still the most commonly used strategy for pest control. The aim of this study was to determine the resistance evolution of seven South Brazilian populations to four insecticides (chlorantraniliprole, lufenuron, chlorpyrifos, and fenitrothion). Bioassays were paired with metabolic analyses of glutathione-S-transferase (GST), carboxylesterases (α-NA and β-NA), and acetylcholinesterase (AChE) to understand the possible role with phytosanitary strategies in the insects’ susceptibility. Insect populations were collected in the municipalities of Campo do Tenente, Lapa and Porto Amazonas, Fraiburgo, São Joaquim, and Vacaria and multiplied in the laboratory. Two susceptible and two resistant populations were used as references. The bioassays showed that five populations were considered more resistant to organophosphates, six to lufenuron and two to chlorantraniliprole when compared with the sensitive population. None of the field populations had greater resistance than the resistant laboratory population. The enzymatic activity of AChE and GST was elevated in most of the populations that were less susceptible to organophosphates and lufenuron. The populations originating from orchards that used sexual confusion techniques had the greatest susceptibility based on toxicological and biochemical bioassays. Populations under pressure from various compounds had high GST, α and β-NA activity. There is evidence that a diversity of control strategies can provide better resistance management.
A benign, low-grade myofibroblastic lesion mimicking a sarcoma
Authors: Patel Veena Abigale , Naqvi Ambareen , Koshal Sonita 
Published: January 2020

AbstractBenign myofibroblastic lesions can clinically and histologically be mistaken for sarcoma. Excessive and potentially disfiguring surgical treatment can be avoided by ruling out malignancy. We present the case of a low-grade, myofibroblastic lesion of the lip, which shows how detailed clinical examination rather than reliance on histopathological information alone helped to achieve this. Differential diagnoses of myofibroblastic lesions are also discussed.
Traveller exposures to animals: a GeoSentinel analysis
Authors: Muehlenbein Michael P , Angelo Kristina M , Schlagenhauf Patricia , Chen Lin , Grobusch Martin P , Gautret Philippe , Duvignaud Alexandre , Chappuis François , Kain Kevin C , Bottieau Emmanuel , Epelboin Loïc , Shaw Marc , Hynes Noreen , Hamer Davidson H ,   GeoSentinel Surveillance Network
Published: January 2020

AbstractBackgroundHuman coexistence with other animals can result in both intentional and unintentional contact with a variety of mammalian and non-mammalian species. International travellers are at risk for such encounters; travellers risk injury, infection and possibly death from domestic and wild animal bites, scratches, licks and other exposures. The aim of the present analysis was to understand the diversity and distribution of animal-related exposures among international travellers.MethodsData from January 2007 through December 2018 from the GeoSentinel Surveillance Network were reviewed. Records were included if the exposure was non-migration travel with a diagnosis of an animal (dog, cat, monkey, snake or other) bite or other exposure (non-bite); records were excluded if the region of exposure was not ascertainable or if another, unrelated acute diagnosis was reported.ResultsA total of 6470 animal exposures (bite or non-bite) were included. The majority (71%) occurred in Asia. Travellers to 167 countries had at least one report of an animal bite or non-bite exposure. The majority (76%) involved dogs, monkeys and cats, although a wide range of wild and domestic species were involved. Almost two-thirds (62.6%) of 4395 travellers with information available did not report a pretravel consultation with a healthcare provider.ConclusionsMinimizing bites and other animal exposures requires education (particularly during pretravel consultations) and behavioral modification. These should be supplemented by the use of pre-exposure rabies vaccination for travellers to high-risk countries (especially to those with limited access to rabies immunoglobulin), as well as encouragement of timely (in-country) post-exposure prophylaxis for rabies and Macacine alphaherpesvirus 1 (herpesvirus B) when warranted.
The contribution of cis- and trans-acting variants to gene regulation in wild and domesticated barley under cold stress and control conditions
Authors: Haas Matthew , Himmelbach Axel , Mascher Martin 
Published: January 2020

AbstractBarley, like other crops, has experienced a series of genetic changes that have impacted its architecture and growth habit to suit the needs of humans, termed the domestication syndrome. Domestication also resulted in a concomitant bottleneck that reduced sequence diversity in genes and regulatory regions. Little is known about regulatory changes resulting from domestication in barley. We used RNA sequencing to examine allele-specific expression in hybrids between wild and domesticated barley. Our results show that most genes have conserved regulation. In contrast to studies of allele-specific expression in interspecific hybrids, we find almost a complete absence of trans effects. We also find that cis regulation is largely stable in response to short-term cold stress. Our study has practical implications for crop improvement using wild relatives. Genes regulated in cis are more likely to be expressed in a new genetic background at the same level as in their native background.
Jean Toomer’s Cane and the Borderlands of Encounter and Contradiction
Authors: Robles Francisco E 
Published: January 2020

AbstractThis article looks at Jean Toomer’s Cane (1923) through the theoretical framework of Anzaldúa’s Borderlands/La Frontera: The New Mestiza (1987) and Eve Kosofsky Sedgwick’s Touching Feeling: Affect, Pedagogy, Performativity (2003), arguing that Cane might best be understood as a text focused on borders. In doing so, the article puts forth the claim that the ideas of “contradiction” and “beside” offer important insights into understanding the formal innovations and thematic qualities of Cane. Specifically, by focusing on the text’s use of migration as a meaningful aesthetic category, the essay unsettles recent literary historical questions about Toomer’s personal identifications, instead looking at how contradiction and paradox generate a text whose flows, moves, and shifts insist on multiplicity and movement.
The maximum accretion rate of hot gas in dark matter haloes
Authors: Stern Jonathan , Fielding Drummond , Faucher-Giguère Claude-André , Quataert Eliot 
Published: January 2020

ABSTRACT
We revisit the question of ‘hot mode’ versus ‘cold mode’ accretion on to galaxies using steady-state cooling flow solutions and idealized 3D hydrodynamic simulations. We demonstrate that for the hot accretion mode to exist, the cooling time is required to be longer than the free-fall time near the radius where the gas is rotationally supported, Rcirc, i.e. the existence of the hot mode depends on physical conditions at the galaxy scale rather than on physical conditions at the halo scale. When allowing for the depletion of the halo baryon fraction relative to the cosmic mean, the longer cooling times imply that a virialized gaseous halo may form in halo masses below the threshold of $\sim 10^{12}\, {\rm M_{\odot }}$ derived for baryon-complete haloes. We show that for any halo mass there is a maximum accretion rate for which the gas is virialized throughout the halo and can accrete via the hot mode of ${\dot{M}}_{\rm crit}\approx 0.7(v_{\rm c}/100\, \rm km\ s^{-1})^{5.4}(R_{\rm circ}/10\, {\rm kpc})(Z/\, {\rm Z_{\odot }})^{-0.9}\, {\rm M_{\odot }}\, {\rm yr}^{-1}$, where Z and vc are the metallicity and circular velocity measured at Rcirc. For accretion rates $\gtrsim {\dot{M}}_{\rm crit}$ the volume-filling gas phase can in principle be ‘transonic’ – virialized in the outer halo but cool and free-falling near the galaxy. We compare ${\dot{M}}_{\rm crit}$ to the average star formation rate (SFR) in haloes at 0 &lt; z &lt; 10 implied by the stellar-mass–halo-mass relation. For a plausible metallicity evolution with redshift, we find that ${\rm SFR}\lesssim {\dot{M}}_{\rm crit}$ at most masses and redshifts, suggesting that the SFR of galaxies could be primarily sustained by the hot mode in halo masses well below the classic threshold of $\sim 10^{12}\, {\rm M_{\odot }}$.
Wind collision and accretion simulations of the massive binary system HD 166734
Authors: Kashi Amit 
Published: January 2020

ABSTRACTI have run hydrodynamic simulations that follow the colliding wind structure of the massive binary system HD 166734 along its binary orbit. I show that close to periastron passage the secondary wind is suppressed and the secondary accretes mass from the primary wind. The system consists of two blue supergiants with masses of $M_1 \approx 39.5 ~\rm {M_{\odot }}$ and $M_2 \approx 30.5 ~\rm {M_{\odot }}$, on an orbit of $P \simeq 34.538\, {\rm d}$ with an eccentricity of e ≈ 0.618. This close O–O binary with high eccentricity is observed through its orbit in X-rays, where it shows an unusually long minimum close to periastron passage. I use advanced simulations with wind acceleration and a prescription treatment of accretion and I simulate the entire orbit at high resolution, which captures the instabilities in the winds. I find that the colliding wind structure is unstable even at apastron. As the stars approach periastron passage, the secondary wind is quenched by the primary wind and the accretion on to the secondary begins. The accretion phase lasts for ${\simeq}12 \,{\rm d}$, and the amount of accreted mass obtained per cycle is $M_{\rm {acc}} \simeq 1.3 \times 10^{-8} \,{\rm M}_{\odot }$. The accretion phase can account for the observed decline in X-ray emission from the system.
Percutaneous Cordotomy for Pain Palliation in Advanced Cancer: A Randomized Clinical Trial Study Protocol
Authors: Viswanathan Ashwin , Vedantam Aditya , Williams Loretta A , Koyyalagunta Dhanalakshmi , Abdi Salahadin , Dougherty Patrick M , Mendoza Tito , Bassett Roland L , Hou Ping , Bruera Eduardo 
Published: January 2020

Abstract

BACKGROUND
Cancer pain, one of the most common symptoms for patients with advanced cancer, is often refractory to maximal medical therapy. A controlled clinical trial is needed to provide definitive evidence to support the use of ablative procedures such as cordotomy for patients with medically refractory cancer pain.

OBJECTIVE
To assess the efficacy of cordotomy for patients with unilateral advanced cancer pain using a controlled clinical trial study design. The secondary objectives are to define the patient experience of cordotomy for medically refractory cancer pain as well as to determine the utility of magnetic resonance imaging as a non-invasive biomarker for successful cordotomy.

METHODS
We will undertake a single-institution, double-blind, sham-controlled clinical trial of cordotomy in patients with refractory cancer pain. Patients in the cordotomy arm will undergo a percutaneous computed tomography-guided cordotomy at C1-C2, while patients in the control arm will undergo a similar procedure where the needle will not penetrate the thecal sac. The primary endpoint will be the reduction in pain intensity, as measured by the Edmonton Symptoms Assessment Scale.

EXPECTED OUTCOMES
We expect that patients randomized to cordotomy will have a significantly greater reduction in pain intensity than those patients randomized to the control surgical intervention.

DISCUSSION
This randomized clinical trial comparing cordotomy with a control intervention will provide the level of evidence necessary to determine whether cordotomy should be the standard of care intervention for patients with advanced cancer pain.
Peripherally acting μ-opioid receptor antagonists for treatment of opioid-induced constipation in children
Authors: Novak Chris , Hogg Amanda , Sue Kyle , Davies Dawn 
Published: January 2020

Abstract

Background and Objective
Opioid-induced constipation (OIC) is a common and important problem in paediatric palliative care, critical care, and postoperative settings. Treatment for OIC is often ineffective and limited by enteral intake. A new class of drugs called peripherally acting mu-opioid receptor antagonists (PAMORAs) have been shown to be effective treatments of OIC in adults, including the agents methylnaltrexone and naloxegol. Data in children are limited to several small case reports, mostly in the palliative care setting. The goal of this study was to evaluate the effectiveness and safety of methylnaltrexone and naloxegol in hospitalized children, including those with critical illness.

Methods
We conducted a retrospective study of all children admitted to the Stollery Children’s Hospital in Edmonton (Canada) who received either methylnaltrexone or naloxegol for OIC. The primary outcome was median time to first bowel movement (BM) after the first dose of PAMORA.

Results
A total of 27 patients were included in the study. Kaplan–Meier survival analysis showed the median time to the first BM after the first dose of PAMORA was 15.5 hours. Seventeen (63%) patients had laxation within 24 hours of first dose. No significant adverse events were observed.

Conclusion
This study is the largest to date to evaluate efficacy and safety of PAMORAs in children. Future studies should be prospective and include larger numbers of patients with critical illness and postoperative OIC as indications for treatment.
Cell Wall Composition and Ultrastructural Immunolocalization of Pectin and Arabinogalactan Protein during Olea europaea L. Fruit Abscission
Authors: Parra Ruben , Paredes Miguel A , Labrador Juana , Nunes Cláudia , Coimbra Manuel A , Fernandez-Garcia Nieves , Olmos Enrique , Gallardo Mercedes , Gomez-Jimenez Maria C 
Published: January 2020

AbstractCell wall modification is integral to many plant developmental processes where cells need to separate, such as abscission. However, changes in cell wall composition during natural fruit abscission are poorly understood. In olive (Olea europaea L.), some cultivars such as ‘Picual’ undergo massive natural fruit abscission after fruit ripening. This study investigates the differences in cell wall polysaccharide composition and the localization of pectins and arabinogalactan protein (AGP) in the abscission zone (AZ) during cell separation to understand fruit abscission control in ‘Picual’ olive. To this end, immunogold labeling employing a suite of monoclonal antibodies to cell wall components (JIM13, LM5, LM6, LM19 and LM20) was investigated in olive fruit AZ. Cell wall polysaccharide extraction revealed that the AZ cell separation is related to the de-esterification and degradation of pectic polysaccharides. Moreover, ultrastructural localization showed that both esterified and unesterified homogalacturonans (HGs) localize mainly in the AZ cell walls, including the middle lamella and tricellular junction zones. Our results indicate that unesterified HGs are likely to contribute to cell separation in the olive fruit AZ. Similarly, immunogold labeling demonstrated a decrease in both galactose-rich and arabinose-rich pectins in AZ cell walls during ripe fruit abscission. In addition, AGPs were localized in the cell wall, plasma membrane and cytoplasm of AZ cells with lower levels of AGPs during ripe fruit abscission. This detailed temporal profile of the cell wall polysaccharide composition, and the pectins and AGP immunolocalization in the olive fruit AZ, offers new insights into cell wall remodeling during ripe fruit abscission.
Antibody humanization—the Influence of the antibody framework on the CDR-H3 loop ensemble in solution
Authors: Fernández-Quintero Monica L , Heiss Martin C , Liedl Klaus R 
Published: January 2020

AbstractAntibody engineering of non-human antibodies has focused on reducing immunogenicity by humanization, being a major limitation in developing monoclonal antibodies. We analyzed four series of antibody binding fragments (Fabs) and a variable fragment (Fv) with structural information in different stages of humanization to investigate the influence of the framework, point mutations and specificity on the complementarity determining region (CDR)-H3 loop dynamics. We also studied a Fv without structural information of the anti-idiotypic antibody Ab2/3H6, because it completely lost its binding affinity upon superhumanization, as an example of a failed humanization. Enhanced sampling techniques in combination with molecular dynamics simulations allow to access micro- to milli-second timescales of the CDR-H3 loop dynamics and reveal kinetic and thermodynamic changes involved in the process of humanization. In most cases, we observe a reduced conformational diversity of the CDR-H3 loop when grafted on a human framework and find a conformational shift of the dominant CDR-H3 loop conformation in solution. A shallow side minimum of the conformational CDR-H3 loop ensemble attached to the murine framework becomes the dominant conformation in solution influenced by the human framework. Additionally, we observe in the case of the failed humanization that the potentially binding competent murine CDR-H3 loop ensemble in solution shows nearly no kinetical or structural overlap with the superhumanized variant, thus explaining the loss of binding.
Cortical fNIRS Responses Can Be Better Explained by Loudness Percept than Sound Intensity
Authors: Weder Stefan , Shoushtarian Mehrnaz , Olivares Virginia , Zhou Xin , Innes-Brown Hamish , McKay Colette 
Published: January 2020

Objectives:
Functional near-infrared spectroscopy (fNIRS) is a brain imaging technique particularly suitable for hearing studies. However, the nature of fNIRS responses to auditory stimuli presented at different stimulus intensities is not well understood. In this study, we investigated whether fNIRS response amplitude was better predicted by stimulus properties (intensity) or individually perceived attributes (loudness).

Design:
Twenty-two young adults were included in this experimental study. Four different stimulus intensities of a broadband noise were used as stimuli. First, loudness estimates for each stimulus intensity were measured for each participant. Then, the 4 stimulation intensities were presented in counterbalanced order while recording hemoglobin saturation changes from cortical auditory brain areas. The fNIRS response was analyzed in a general linear model design, using 3 different regressors: a non-modulated, an intensity-modulated, and a loudness-modulated regressor.

Results:
Higher intensity stimuli resulted in higher amplitude fNIRS responses. The relationship between stimulus intensity and fNIRS response amplitude was better explained using a regressor based on individually estimated loudness estimates compared with a regressor modulated by stimulus intensity alone.

Conclusions:
Brain activation in response to different stimulus intensities is more reliant upon individual loudness sensation than physical stimulus properties. Therefore, in measurements using different auditory stimulus intensities or subjective hearing parameters, loudness estimates should be examined when interpreting results.