bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cerebrospinal Fluid and Brain Tissue Penetration of Tenofovir, Lamivudine, and Efavirenz in Postmortem Tissues with Cryptococcal Meningitis
Authors: Nicol Melanie R. , Pastick Katelyn A. , Taylor Joneé , Namuju Olivie C. , Rhein Joshua , Williams Darlisha A. , Meya David B. , Boulware David R. , Lukande Robert 
Published: June 2019

The central nervous system (CNS) is a known HIV reservoir, yet little is known about drug exposure in the brain. Our primary objective was to quantify exposure of three common antiretrovirals in brain tissue and compare exposures to plasma and cerebrospinal fluid (CSF). We also sought to identify pockets of brain most vulnerable to inadequate drug exposures and examine the role of meningitis in drug penetration into the CNS. Tenofovir, lamivudine, and efavirenz concentrations were measured using liquid chromatography and tandem mass spectrometry in plasma and CSF from 14 individuals with HIV, 7 with cryptococcal meningitis. In four individuals (three with meningitis) drug concentrations were also measured in 13 distinct brain tissue regions. In subjects with meningitis, geometric mean ratio (95% confidence interval) of tenofovir CSF to plasma was 66% (7–598%) and 14% (6–31%) in subjects without meningitis. Lamivudine CSF penetration was 100% (25–409%) in subjects with meningitis and 30% (24–37%) in subjects without meningitis. Tenofovir brain tissue concentrations were 36% (14–124%) of plasma and 49% (1–572%) of CSF. Lamivudine brain concentrations were 37% (23–64%) of plasma and 27% (1–104%) of CSF. Efavirenz brain tissue concentrations were 128% (108–179%) of plasma. Tissues collected postmortem provide a unique opportunity to assess drug distribution in tissues difficult to sample in living subjects. CSF is a poor surrogate for drug exposure throughout the CNS. Antiretrovirals differentially penetrate into the CNS and penetration may be enhanced by meningitis.
Cutaneous aneurysmal bone cyst—First report of a case and literature review
Authors: Chung Ivy Ah‐Yu , Petelin Kristina , Pižem Jože , Luzar Boštjan 
Published: June 2019

AbstractAneurysmal bone cyst (ABC) is a benign, expansile, multiloculated and blood‐filled cystic lesion most commonly involving bones. We report herein the case of a 78‐year‐old woman with a dermal ABC located in the skin of the right foot. Histologically, the lesion displayed characteristic features of ABC, including blood‐filled cystic spaces lined by loose connective tissue, admixed with solid areas composed of spindle cells and osteoclast‐like giant cells, associated with foci of woven bone formation and matrix calcification (“blue bone” formation). Fewer than 30 cases of extraosseous ABCs have been described in soft tissues and, to the best of our knowledge, ABC primarily occurring in the skin, not associated with an underlying lesion in the bone, has not so far been reported in the literature.
The utility of TTF‐1, napsin A, CK5 and p63 staining in the sub‐classification of non‐small cell carcinoma of the lung
Authors: van Zyl Adri , Schubert Pawel T. , Koegelenberg Coenraad F. N. 
Published: June 2019

AbstractBackgroundThe potentially curative and/or palliative therapy for non‐resectable lung cancer has evolved significantly over the past 2 decades. With the availability of targeted therapies, the need for precise sub‐typing of non‐small cell lung carcinoma (NCSLC) has become paramount.ObjectivesAs there are few data from South Africa, we aimed to determine utility of TTF‐1, napsin A, p63 and CK5 immunostaining on fine needle aspiration (FNA) cell block and formalin‐fixed paraffin‐embedded tissue biopsy specimens in subtyping NSCLC as adenocarcinoma and squamous cell carcinomas.MethodsAll cases of NSCLC diagnosed during a 3‐year period were retrospectively identified. All FNA biopsy and formalin‐fixed paraffin‐embedded cases that were stained with TTF‐1, napsin A, CK5 and p63 were collected. A lung cancer registry was used to access and correlate clinical and radiological data.ResultsWe included 271 cases with diagnoses of adenocarcinoma of the lung (n = 201), squamous cell carcinoma of the lung (n = 53), unspecified NSCLC (n = 8) and other carcinomas (n = 9). TTF‐1 and napsin A had sensitivities of 99.0% and 91.9%, respectively, positive predictive values (PPVs) of 90.8% and 90.3%, respectively, and accuracies of 91.0% for adenocarcinoma of the lung. Napsin A had a higher specificity than TTF‐1 (90.2% vs 62.8%). Both CK5 and P63 had high sensitivities (95.4% and 97.9%, respectively) and negative predictive values of 96.4% and 96.8%, respectively, for squamous cell carcinoma of the lung. CK5 had a higher specificity than p63 (84.4% and 61.2%, respectively), PPV (80.4% and 70.8%, respectively) and accuracy (88.8% and 79.2%, respectively) for squamous cell carcinoma.ConclusionAll four immunostaining methods had high sensitivities. TTF‐1 and napsin A both had high PPV and diagnostic accuracy for adenocarcinoma of the lung, whereas CK5 had an equally high PPV and accuracy for squamous cell carcinoma of the lung. The specificity of napsin A for adenocarcinoma was higher than that of TTF‐1. The specificity of CK5 for squamous cell carcinoma was higher than p63.
Preoperative indicators of misdiagnosis in invasion depth staging of esophageal cancer: Pitfalls of magnifying endoscopy with narrow‐band imaging
Authors: Kimura Hidenori , Yoshida Masao , Tanaka Masaki , Kawata Noboru , Kakushima Naomi , Takizawa Kohei , Kishida Yoshihiro , Imai Kenichiro , Ito Sayo , Hotta Kinichi , Ishiwatari Hirotoshi , Matsubayashi Hiroyuki , Ono Hiroyuki 
Published: June 2019

ObjectivesThe Japan Esophageal Society classification has been widely applied for predicting the invasion depth of superficial esophageal squamous cell carcinomas (SESCCs). Although Type B2 of the classification clinically corresponds to SESCCs with muscularis mucosa or slight submucosal invasion (MM/SM1), diagnostic yield based on Type B2 is insufficient. This study aimed to investigate risk factors for misdiagnosis in preoperative invasion depth staging.MethodsWe included a total of 104 SESCCs in which Type B2 was observed by magnifying endoscopy. SESCCs were classified as either correct diagnosis (pMM/SM1, 39 lesions), overdiagnosis (epithelium or the lamina propria [pEP/LPM], 34 lesions), or underdiagnosis (deep invasion into the submucosa [pSM2‐3], 31 lesions) based on pathological depth of invasion. The association between misdiagnosis and endoscopic features, including distinct features, was evaluated using logistic regression analysis. Distinct features were defined as nodular protrusion, thickness, and/or clearly depressed area. The diameter of type B2 area was endoscopically measured, and the cut‐off value was determined using a receiver operating characteristic curve.ResultsType B2 area <6 mm (area under the curve, 0.776) and Type B2 vessels around erosion were significantly associated with overdiagnosis (odds ratio, 16.6 and 11.0, respectively), while distinct features were significantly associated with underdiagnosis (odds ratio, 8.7). Adjusted by these misdiagnosis factors, positive predictive value of Type B2 significantly improved from 38% to 65% (P < 0.01).ConclusionsLesions with a small Type B2 area (<6 mm) and/or Type B2 vessels around erosion should be diagnosed as EP/LPM and lesions with distinct features as SM2‐3.
Universal drug coverage and income‐related disparities in glycaemic control
Authors: Branfield Day L. , Austin P. C. , Shah B. R. 
Published: June 2019

AbstractAimsTo examine whether income‐related disparities in glycaemic control decline after the age of 65 years, when publicly funded universal drug insurance is acquired in Ontario, Canada.MethodsWe conducted a population‐based cross‐sectional study using linked administrative healthcare databases. Adults with diabetes, aged 40–89 years, with available HbA1c data were included (N = 716 297). Income was based on median neighbourhood household income. Multiple linear regression was used to test for effect modification of age ≥65 years on the relationship between income and HbA1c.ResultsThere was a significant inverse association between income and HbA1c level. After adjusting for baseline factors, the effect of income on HbA1c level was significantly greater for individuals aged <65 years (mean difference HbA1c for lowest vs highest income group +2.5 mmol/mol, 95% CI +2.3 to +2.7 [+0.23%, 95% CI 0.21 to 0.24]) than for those aged ≥65 years (+1.2 mmol/mol, 95% CI +1.0 to +1.3 [+0.11%, 95% CI 0.10 to 0.12]; P < 0.0001 for interaction).ConclusionsDespite universal access to healthcare, people with diabetes with lower incomes had significantly worse glycaemic control compared with their counterparts on higher incomes. However, income gradients in glycaemic control were markedly reduced after the age of 65 years, possibly as a result of access to prescription drug coverage.
Extracellular matrix protein anosmin‐1 modulates olfactory ensheathing cell maturation in chick olfactory bulb development
Authors: Hu Youli , Butts Thomas , Poopalasundaram Subathra , Graham Anthony , Bouloux Pierre‐Marc 
Published: June 2019

AbstractOlfactory ensheathing cells (OECs) are a specialized class of glia, wrapping around olfactory sensory axons that target the olfactory bulb (OB) and cross the peripheral nervous system/central nervous system boundary during development and continue to do so post‐natally. OEC subpopulations perform distinct subtype‐specific functions dependent on their maturity status. Disrupted OEC development is thought to be associated with abnormal OB morphogenesis, leading to anosmia, a defining characteristic of Kallmann syndrome. Hence, anosmin‐1 encoded by Kallmann syndrome gene (KAL‐1) might modulate OEC differentiation/maturation in the OB. We performed in ovo electroporation of shRNA in the olfactory placode to knock‐down kal in chick embryos, resulting in abnormal OB morphogenesis and loss of olfactory sensory axonal innervation into OB. BLBP‐expressing OECs appeared to form a thinner and poorly organized outmost OB layer where SOX10 expressing OECs were completely absent with emergence of GFAP‐expressing OECs. Furthermore, in embryonic day 10 chick OB explant cultures, GFAP expression in OECs accumulating along the OB nerve layers was dramatically reduced by recombinant anosmin‐1. We then purified immature OECs from embryonic day 10 chick OB. These cells express GFAP after 7 days in vitro, exhibiting a multipolar morphology. Overexpression of chick anosmin, exogenous anosmin‐1 or FGF2 could inhibit GFAP expression with cells presenting elongated morphology, which was blocked by the FGF receptor inhibitor Su5402. These data demonstrate that anosmin‐1 functions via FGF signalling in regulating OEC maturation, thereby providing a permissive glial environment for axonal innervation into the OB during development.
Size‐abundance rules? Evolution changes scaling relationships between size, metabolism and demography
Authors: Malerba Martino E. , Marshall Dustin J. 
Published: June 2019

AbstractBody size often strongly covaries with demography across species. Metabolism has long been invoked as the driver of these patterns, but tests of causal links between size, metabolism and demography within a species are exceedingly rare. We used 400 generations of artificial selection to evolve a 2427% size difference in the microalga Dunaliella tertiolecta. We repeatedly measured size, energy fluxes and demography across the evolved lineages. Then, we used standard metabolic theory to generate predictions of how size and demography should covary based on the scaling of energy fluxes that we measured. The size dependency of energy remained relatively consistent in time, but metabolic theory failed to predict demographic rates, which varied unpredictably in strength and even sign across generations. Classic theory holds that size affects demography via metabolism – our results suggest that both metabolism and size act separately to drive demography and that among‐species patterns may not predict within‐species processes.
First record of Tuta absoluta (Meyrick) (Lepidoptera: Gelechiidae) in Burundi
Authors: Ndayizeye L. , Manirakiza O. , Ntashavu D. , Ndayikeza L. , Mbarushimana D. 
Published: June 2019

This study to detect Tuta absoluta was carried out at four sites in western Burundi from March to July 2018. Delta traps containing Tutrack pheromone and sticky paper were installed in tomato fields at 40 cm from the ground. Sample collection was carried out twice a week. The results confirmed the presence of T. absoluta in Burundi. Effective pest control is required to avoid heavy losses on tomato production.
Southern Lapwing Vanellus chilensis cooperative helpers at nests are older siblings
Authors: Cerboncini Ricardo A. S. , Braga Talita V. , Roper James J. , Passos Fernando C. 
Published: June 2019

Cooperative breeding is rare in shorebirds, and when found it is thought to be due to polygamous mating (cooperative polygamy). Here we describe the social structure of cooperatively breeding groups in Southern Lapwing Vanellus chilensis and test the prediction that offspring sex ratio is skewed towards the sex that helps. The social groups consisted of a breeding pair with one or two young (mostly males, 68%) from the previous breeding season, and offspring sex ratio was not skewed. Cooperative breeding in the Southern Lapwing is not the consequence of cooperative polygamy, but rather groups were formed by a mated pair and some of their offspring from previous nests as helpers.
Incidence, type and management of ureteric injury associated with vesicovaginal fistulas: Report of a series from a specialized center
Authors: Seth Jai , Kiosoglous Anthony , Pakzad Mahreen , Hamid Rizwan , Shah Julian , Ockrim Jeremy , Greenwell Tamsin 
Published: June 2019

ObjectivesTo report a large series of vesicovaginal fistula, and to assess the incidence of ureteric injury in association with vesicovaginal fistula.MethodsWe retrospectively reviewed a prospective database of patients with vesicovaginal fistula referred to our center between 2004 and 2016. Data on patient demographics, fistula etiology, mode of repair, and any associated ureteric injury and its treatment were noted.ResultsOverall, 116 patients (median age 49 years, range 23–88 years) were referred for management of vesicovaginal fistula during the study period. Four of these patients (3.4%) had associated ureteric injury, one of whom had bilateral injury. Ureteric obstruction alone was noted in two patients, ureterovaginal fistula alone in one patient, and bilateral ureteric obstruction and ureterovaginal fistula in one patient. All ureteric injuries were managed with simultaneous reimplantation into the bladder at the time of vesicovaginal fistula repair. Five patients had post‐radiotherapy vesicovaginal fistula, and the remainder were post‐surgical. Three patients with post‐radiotherapy vesicovaginal fistula proceeded to primary diversion.ConclusionsUreteric injury is far less common than previously reported, occurring in <5% of patients presenting with vesicovaginal fistula. It can be successfully managed, and it remains the major indication for abdominal repair of vesicovaginal fistula.
Do guidelines help us to deviate from their recommendations when appropriate for the individual patient? A systematic survey of clinical practice guidelines
Authors: Morgott Marc , Heinmüller Stefan , Hueber Susann , Schedlbauer Angela , Kühlein Thomas 
Published: June 2019

AbstractRationale, aims, and objectivesClinical practice guidelines (CPG) were introduced to summarize the best scientific evidence available. Thereby, CPG were meant to support evidence‐based medicine (EBM). However, besides evidence, EBM also asks for patients' preferences and physicians' experiences to be considered when coming to therapeutic decisions. Thus, deviations from CPG recommendations are sometimes necessary when practicing EBM. We wanted to examine whether CPG support deviations from their recommendations when appropriate. For operationalization, we asked whether absolute effect sizes (AES) for benefit and/or harm of suggested therapies were provided along with the respective CPG recommendation.MethodsThis systematic survey comprised the most common CPG on chronic coronary heart disease (CCHD) and type 2 diabetes mellitus (T2DM) from English‐ and German‐speaking countries. Only CPG recommendations on pharmacotherapy were evaluated. If AES of a recommended therapy were reported, we rated how easily findable they were within the CPG. Moreover, we assessed whether the CPG provided patient information material and whether this material supplied AES allowing patients to determine the effects to be expected.ResultsIn the 13 CPG surveyed, 144 recommendations on pharmacotherapy were identified. For 108 recommendations (75%), no AES for benefit and/or harm were reported. Thirty‐one recommendations (22%) were accompanied by one or more AES for either benefit or harm. Along with five recommendations (3%), one or more AES for both benefit and harm were given. AES were considered easy to find for three of these 36 recommendations (8%). Patient information material was provided in three of the 13 CPG (23%) accounting for AES in one occasion only.ConclusionCurrent CPG on T2DM and CCHD do not sufficiently offer AES for benefits and harms of recommended therapies. Thus, they lack satisfactory information to support deviations from CPG recommendations. Consequently, CPG in their present form do not adequately facilitate EBM.
Value‐based health care in obstetrics
Authors: Van Den Berg Kim , Dijksman Lea Magdalena , Keus Samyra Hermione Jessica , Scheele Fedde , Van Pampus Maria Gabriel 
Published: June 2019

AbstractRationale, Aims, and ObjectivesWe strive to maximize outcomes that are relevant to the women who deliver in our hospital. We demonstrate a practical method of using value‐based health care (VBHC) concepts to analyse how care can be improved.MethodUsing International Consortium of Health Outcome Measurements (ICHOM) set, a practical outcome set was constructed for women who go into spontaneous labour at term of a singleton in cephalic presentation and used for benchmarking. We included data on interventions that are major drivers of outcomes. Data from two hospitals in Amsterdam and for The Netherlands for 2011 to 2015 were collected.ResultsBenchmarking of readily available data helped identify a number of statistically significant and clinically relevant differences in obstetric outcomes. Caesarean section rate was significantly different at 13.7% in hospital 2 compared with 11.5% in hospital 1 with similar neonatal outcomes. Third and fourth degree tearing rates were significantly higher for hospital 1 at 5.5% compared with 3.6% for hospital 2 and the national average of 3.5%. On the basis of the guidelines, literature, and discussion, initiatives on how to improve these outcomes were then identified. These include caesarean section audit and guidelines regarding caesarean section decision making. In order to reduce the rate of third and fourth degree tearing, routine episiotomy on vaginal operative deliveries was introduced, and a training programme was set up to make care providers more aware of risk factors and potential preventive measures.ConclusionDefining, measuring, and comparing relevant outcomes enable care providers to identify improvements. Collection and comparison of readily available data can provide insights in where care can be improved. Insights from literature and comparison of care practices and processes can lead to how care can be improved. Continuous monitoring of outcomes and expanding the set of outcomes that is readily available are key in the process towards value‐based care provision.
Numerical study of the thermolysis of catechins in green tea
Authors: Carmona‐Jasso Jaime G. , Gallegos‐Infante José A. , Díaz‐Ovalle Christian O. , González‐Laredo Rubén , Valle‐Cervantes Sergio , Cruz‐Fierro Francisco , Lesso‐Arroyo Raúl 
Published: June 2019

AbstractTea contains health benefits due to its compounds such as catechins, which undergo thermolysis during heating. These complex reactions have been proposed as first order kinetic models at controlled conditions, and this work proposes a non‐first‐order kinetic model to cover a wide range of conditions. Afterward, these reactions were simulated via computational fluid dynamics in order to determine the concentration at different operative conditions. The system was a continuous heating reactor, where mesh and iteration tests were developed. The results indicated that the reactions presented a high thermal dependency, and a short residence time with low conversion due to the low values of the Damköhler number. Thus, the kinetic model proposed herein reached a well representation of the thermolysis of catechins, which suggests the applicability of this model and strategy in other thermal treatments of tea.Practical ApplicationThe high comsumption of green tea demands better process treatments in order to reduce the perishable compounds. Thermal processing of tea requires a thorough understanding of thermolysis in catechins. The basis of this paper can be extended into evaporation and drying of green tea under CFD simulation.
Evaluation of immersion‐contact type heat transfer for continuous pharmaceutical spin freeze‐drying process
Authors: Srinivasan Ganeshmurthy , Raja Balakrishnan 
Published: June 2019

AbstractSpin freeze‐drying process is a recently proposed method to achieve continuous processing of unit doses in freeze‐drying application. An experimental study is carried out to investigate the heat transfer and drying characteristics of a spin‐frozen liquid product. To enhance heat transfer, unlike freeze drying performed in shelves, the shell is immersed into a temperature‐controlled bath. The influence of different ramping condition of bath temperature on drying rate, time and variation of moisture content in spin‐frozen products (deionized water and skimmed milk) are analyzed and reported in this paper. Among different ramping conditions, ramping of bath temperature to 10°C resulted in higher drying rate (1.8 kg hr−1 m−2) and lesser drying time (44%). The overall heat transfer coefficient (Kv) between the bath and product is evaluated for the above condition in both the test liquids. This direct contact type heat transfer helps in reducing air gap resistance and radiation effect, which primarily helps in minimizing thermal resistances. The effect of dry layer resistance is minimal in the spin‐frozen product due to lower product thickness and larger ice‐vapor surface area.Practical ApplicationsThe spin‐frozen sample is dried either by using an infrared (IR) heater or by placing on a shelf. Limitations using IR heater include positioning of the vials (the distance between the vials and IR source) and selecting suitable IR window material and thickness. In the case of the shelf, conduction resistance between shelf and vial, radiation resistance inside the chamber and air gap resistance present between vial and shelf plays a major role. The thermal resistance is minimal in the immersion method due to the absence of air gap resistance and radiation effect. Hence, an alternative approach is discussed using immersion drying method to achieve continuous vial processing and uniformity among vials. Hence, freeze‐drying process can also be shifted to continuous production mode like prefilling and packaging.