bluuebunny/crossref_metadata_2025_split huggingface dataset:
α‐Triazolylboronic Acids: A Promising Scaffold for Effective Inhibitors of KPCs
Authors: Introvigne Maria Luisa , Taracila Magdalena A. , Prati Fabio , Caselli Emilia , Bonomo Robert A. 
Published: May 2020

AbstractBoronic acids are known reversible covalent inhibitors of serine β‐lactamases. The selectivity and high potency of specific boronates bearing an amide side chain that mimics the β‐lactam's amide side chain have been advanced in several studies. Herein, we describe a new class of boronic acids in which the amide group is replaced by a bioisostere triazole. The boronic acids were obtained in a two‐step synthesis that relies on the solid and versatile copper‐catalyzed azide–alkyne cycloaddition (CuAAC) followed by boronate deprotection. All of the compounds show very good inhibition of the Klebsiella pneumoniae carbapenemase KPC‐2, with Ki values ranging from 1 nM to 1 μM, and most of them are able to restore cefepime activity against K. pneumoniae harboring blaKPC‐2. In particular, compound 1 e, bearing a sulfonamide substituted by a thiophene ring, proved to be an excellent KPC‐2 inhibitor (Ki=30 nM); it restored cefepime susceptibility in KPC‐Kpn cells (MIC=0.5 μg/mL) with values similar to that of vaborbactam (Ki=20 nM, MIC in KPC‐Kpn 0.5 μg/mL). Our findings suggest that α‐triazolylboronates might represent an effective scaffold for the treatment of KPC‐mediated infections.
Validation of the 7‐item Functional Assessment of Cancer Therapy‐General (FACT‐G7) as a short measure of quality of life in patients with advanced cancer
Authors: Mah Kenneth , Swami Nadia , Le Lisa W. , Chow Ronald , Hannon Breffni L. , Rodin Gary , Zimmermann Camilla 
Published: May 2020

BackgroundAssessing quality of life is essential for individuals with advanced cancer, but lengthy assessments can be burdensome. The authors investigated the psychometric characteristics of the FACT‐G7, a 7‐item quality‐of‐life measure derived from the Functional Assessment of Cancer Therapy‐General (FACT‐G) scale, in advanced cancer.MethodsData were obtained from outpatients with advanced cancer who were enrolled in a randomized controlled trial of early palliative care. At baseline, 228 intervention participants and 233 control participants (N = 461) completed the FACT‐G and measures of symptom severity, quality of life near the end of life, problematic medical communication, and satisfaction with care. Follow‐up measures were administered monthly for 4 months.ResultsThe FACT‐G7 showed good internal consistency (Cronbach α = .72‐.80), and its single‐factor structure was supported. It correlated strongly with the FACT‐G total, physical, and functional indices and with symptom severity (absolute r = 0.73‐0.92); more moderately with the FACT‐G emotional index and with symptom impact and preparation for the end of life (r = .40‐.71); and least with the FACT‐G social/family index and with relationship with health care provider, life completion, problematic medical communication, and care satisfaction measures (absolute r = .26‐.44). Eastern Cooperative Oncology Group performance status groups differed on FACT‐G7 scores, as expected (all P < .001). Improvements in FACT‐G7 scores in the intervention group compared with the control group at 3‐month (P = .049) and 4‐month (P = .034) follow‐up supported responsiveness to change and somewhat greater sensitivity than the FACT‐G scores.ConclusionsThe FACT‐G7 is a valid, brief measure particularly of the physical and functional facets of quality of life. It may enable rapid quality‐of‐life assessments in patients with advanced cancer.
Population Pharmacokinetics and Exposure‐Response Analysis of nab‐Paclitaxel in Pediatric Patients With Recurrent or Refractory Solid Tumors
Authors: Li Yan , Kassir Nastya , Chen Nianhang , Wang Xiaomin , Palmisano Maria , Zhou Simon 
Published: May 2020

AbstractPediatric malignancies are most commonly of primary central nervous system or hematopoietic origin. The main reason for cancer death in pediatrics is refractory and relapsed disease, and improved therapeutic options are needed in the pediatric population. Nanoparticle albumin‐bound (nab)‐paclitaxel (Abraxane) is a human albumin‐stabilized formulation of paclitaxel and was designed to improve the chemotherapeutic effects of paclitaxel and to reduce toxicities. Although nab‐paclitaxel pharmacokinetics (PK) has been extensively studied in adults, no information is available on its PK in children. ABI‐007‐PST‐001 was the first nab‐paclitaxel clinical trial conducted in pediatrics, and the current analysis is the first study of nab‐paclitaxel PK in pediatrics. Our analyses suggested that ontogeny and maturation play a role in nab‐paclitaxel PK disposition, as demonstrated by the finding that both blood clearance and volume of distribution increased from younger to older pediatric age groups and from pediatrics to adults. A 3‐compartment population PK (PPK) model with saturable elimination was developed to describe the paclitaxel whole blood concentrations in pediatrics. The PPK model was customized by estimating the allometric function on PK parameters to take into account the ontogeny/maturation of patients. PPK estimates are consistent with the fast and deep distribution of paclitaxel that was previously observed in adults. Finally, the exposure‐safety analysis showed an increased probability of drug‐related adverse events (>grade 2) in cycle 1 and the first cycle of neutropenia (>grade 2) associated with higher doses. However, there is no statistically significant association between exposures (measured by area under the concentration‐time curve) and the probabilities of either safety event.
Performance analysis of QoS in IoT based cognitive radio Ad Hoc network
Authors: Afzal Humaira , Rafiq Mufti Muhammad , Raza Aamir , Hassan Abbas 
Published: May 2020

AbstractSince the advent of Internet of Things (IoT), there is a dramatic increase in the number of devices being connected to networks. This increase causes spectrum shortage for devices competing to share the limited spectrum. Wireless IoT devices mostly utilize unlicensed radio spectrum. Soon, the bands in this spectrum will become overcrowded causing collisions among subscribers that will result in scarcity of spectrum. Therefore, in order to ease the smooth running and frequent proliferation in IoT objects, the efficient use of radio spectrum is necessary. One of the solutions to this problem is cognitive radio (CR) that has gained the attention among researchers. The network, formed by CRs, allows an unlicensed user to occupy and use the spectrum of a licensed user/primary user (PU) when the spectrum is found to be free. In this work, these two technologies are combined to get the advantages of both in ad hoc manner while relating this concept with trunking theory. The distances of CRs from nearby PUs are calculated using radio frequency identifications (RFIDs), and then based on these distances, some quality‐of‐service (QoS) parameters of CR network are analyzed. The main objective of this study is to go through the performance analysis of CR network integrated with IoT in the non‐queued system. Numerical results show that this integration is beneficial for the survival of future wireless technologies.
Biological sensitivity to context in Pakistani preschoolers: Hair cortisol and family wealth are interactively associated with girls’ cognitive skills
Authors: Armstrong‐Carter Emma , Finch Jenna E. , Siyal Saima , Yousafzai Aisha K. , Obradović Jelena 
Published: May 2020

AbstractMany young children in low‐ and middle‐income countries (LMICs) face heightened risk for experiencing environmental adversity, which is linked with poorer developmental outcomes. Children's stress physiology can shed light on why children are differentially susceptible to adversity. However, no known studies have examined whether links between adversity and children's development are moderated by children's stress physiology in LMICs. The present study revealed significant interactive effects of hair cortisol concentrations, an index of chronic physiological stress regulation, and family wealth on preschoolers’ cognitive skills in rural Pakistan. In a sample of 535 4‐year‐old children (n = 342 girls), we found significant associations between family wealth and direct assessments of verbal intelligence, pre‐academic skills, and executive functions only in girls with lower hair cortisol concentrations. Specifically, girls with lower cortisol concentrations displayed greater cognitive skills if they came from relatively wealthier families, but lower cognitive skills if they came from very poor families. There were no significant associations among boys. Results provide evidence of biological sensitivity to context among young girls in a LMIC, perhaps reflecting, in part, sex differences in daily experiences of environmental adversity.
Combining stable isotopes, morphological, and molecular analyses to reconstruct the diet of free‐ranging consumers
Authors: Bonin Michaël , Dussault Christian , Taillon Joëlle , Lecomte Nicolas , Côté Steeve D. 
Published: May 2020

Abstract

Accurate estimates of animal diet composition are essential to untangle complex interactions in food webs. Biomarkers and molecular tools are increasingly used to estimate diet, sometimes alongside traditional dietary tracing methods. Yet only a few empirical studies have compared the outcomes and potential gains of using a combination of these methods, especially using free‐ranging animals with distinct foraging preferences.

We used stable isotopes, morphological, and molecular analyses to investigate the diet of free‐ranging consumers with two distinct diet types, that is, carnivore and omnivore. By combining the three analytical methods to assess the diet of consumers during the same period, we aimed to identify the limits of each method and to assess the potential benefits of their combined use to derive diet estimates.

Our results showed that the different methods led to a consistent diet description for carnivores, which have a relatively simple diet mixture, but their outcomes somewhat differed for omnivore, which have a more complex diet. Still, the combined use of morphological and molecular analyses enhanced the diversity of food sources detected compared to the use of a single method independently of diet types. Precision of diet estimates derived from stable isotope analyses was improved by the addition of priors obtained from morphological and molecular diet analyses of the same population.

Although we used free‐ranging animals without a known diet, our empirical testing of three of the most widely used methods of diet determination highlights the limits of relying over a single approach, especially in systems with few or no a priori information about the foraging habits of consumers. The choice of an appropriate approach of diet description should be a key step when planning dietary studies of free‐ranging populations. We recommend using more than one dietary determination methods especially for species with complex diet mixtures.
Fetal‐derived macrophages persist and sequentially maturate in ovaries after birth in mice
Authors: Jokela Heli , Lokka Emmi , Kiviranta Miikka , Tyystjärvi Sofia , Gerke Heidi , Elima Kati , Salmi Marko , Rantakari Pia 
Published: May 2020

AbstractMacrophages, which are highly diverse in different tissues, play a complex and vital role in tissue development, homeostasis, and inflammation. The origin and heterogeneity of tissue‐resident monocytes and macrophages in ovaries remains unknown. Here we identify three tissue‐resident monocyte populations and five macrophage populations in the adult ovaries using high‐dimensional single cell mass cytometry. Ontogenic analyses using cell fate mapping models and cell depletion experiments revealed the infiltration of ovaries by both yolk sac and fetal liver‐derived macrophages already during the embryonic development. Moreover, we found that both embryonic and bone marrow‐derived macrophages contribute to the distinct ovarian macrophage subpopulations in the adults. These assays also showed that fetal‐derived MHC II‐negative macrophages differentiate postnatally in the maturing ovary to MHC II‐positive cells. Our analyses further unraveled that the developmentally distinct macrophage types share overlapping distribution and scavenging function in the ovaries under homeostatic conditions. In conclusion, we report here the first comprehensive analyses of ovarian monocytes and macrophages. In addition, we show that the mechanisms controlling monocyte immigration, the phenotype of different pools of interstitial macrophages, and the interconversion capacity of fetal‐derived macrophages in ovaries are remarkably different from those seen in other tissue niches.
Chromatin remodelers in oligodendroglia
Authors: Parras Carlos , Marie Corentine , Zhao Chuntao , Lu Qing Richard 
Published: May 2020

AbstractOligodendrocytes, the myelinating cells in the vertebrate central nervous system, produce myelin sheaths to enable saltatory propagation of action potentials. The process of oligodendrocyte myelination entails a stepwise progression from precursor specification to differentiation, which is coordinated by a series of transcriptional and chromatin remodeling events. ATP‐dependent chromatin remodeling enzymes, which utilize ATP as an energy source to control chromatin dynamics and regulate the accessibility of chromatin to transcriptional regulators, are critical for oligodendrocyte lineage development and regeneration. In this review, we focus on the latest insights into the spatial and temporal specificity of chromatin remodelers during oligodendrocyte development, myelinogenesis, and regeneration. We will also bring together various plausible mechanisms by which lineage specific transcriptional regulators coordinate with chromatin remodeling factors for programming genomic landscapes to specifically modulate these different processes during developmental myelination and remyelination upon injury.
Prediction of regional‐scale groundwater recharge and nitrate storage in the vadose zone: A comparison between a global model and a regional model
Authors: Turkeltaub Tuvia , Ascott Matthew. J. , Gooddy Daren C. , Jia Xiaoxu , Shao Ming‐An , Binley Andrew 
Published: May 2020

AbstractExtensive nitrogen loads at the soil surface exceed plant uptake and soil biochemical capacity, and therefore lead to nitrogen accumulation in the deep vadose zone. Studies have shown that stored nitrogen in the vadose zone can eventually reach the water table and affect the quality of groundwater resources. Recently, global scale models have been implemented to quantify nitrate storage and nitrate travel time in the vadose zone. These global models are simplistic and relatively easy to implement and therefore facilitate analysis of the considered transport processes at a regional scale with no further requirements. However, the suitability of applying these models at a regional scale has not been tested. Here, we evaluate, for the first time, the performance and utility of global scale models at the regional scale. Applied to the Loess Plateau of China, we compare estimates of groundwater recharge and nitrate storage derived from global scale models with results from a regional scale approach utilizing the Richards and advection‐dispersion equations. The estimated nitrate storage was compared to nitrate observations collected in the deep vadose zone (>50 m) at five sites across the Loess Plateau. Although both models predict similar spatial patterns of nitrate storage, the recharge fluxes were three times smaller and the nitrate storage was two times higher compared with the regional model. The results suggest that global scale models are a potentially useful screening tool, but require refinement for local scale applications.
Examining the use of electronic money and technology by the diaspora in international remittance system: A case of Somali remittances from Canada
Authors: Elmi Mohamed A. , Ngwenyama Ojelanki 
Published: May 2020

AbstractThe diaspora, particularly through ICT‐enabled remittances, are an important lifeline to many in the developing world. This study aims to better understand the usefulness of ICTs in the role played by the remittance sending diasporans in developing countries' economic and social system. Through a mixed‐method approach, we explore the institution behind the Somali Hawala system and how it is enabled by technology. Guided by the question: What is the role of electronic money, technology, and the diaspora in the international remittance system? Using Somalia and the Somali diaspora, we create an inventory of the Hawala businesses based in the Canada gathered from secondary sources and online business listings. Next, surveys of 143 Somalis, who have remitted internationally in 2017, were conducted. We observed that social ties are strong motivators as to why individuals in Canada send money to people in Somalia. People who communicate less frequently were more likely to send less than $500. However, those who frequently communicate with their family members were more likely to send more than $500. Drawing on Social Network Theory and Altruism theory, we establish the role of ICTs in the Somali money transfer sector, confirming the crucial role served by ICTs in remittances.
Physical and biological properties of blend‐electrospun polycaprolactone/chitosan‐based wound dressings loaded with N‐decyl‐N, N‐dimethyl‐1‐decanaminium chloride: An in vitro and in vivo study
Authors: Zafari Mahdi , Mansouri Milad , Omidghaemi Shadi , Yazdani Amid , Pourmotabed Samiramis , Hasanpour Dehkordi Ali , Nosrati Hamed , Validi Majid , Sharifi Esmaeel 
Published: May 2020

AbstractDual‐pump electrospinning of antibacterial N‐decyl‐N, N‐dimethyl‐1‐decanaminium‐chloride (DDAC)‐loaded polycaprolactone (PCL) nanofibers, and chitosan (CS)/polyethylene‐oxide (PEO)‐based wound dressings with hydrophilic and hydrophobic properties to eliminate and absorb pathogenic bacteria from wound surface besides antibacterial action and to support wound healing and accelerate its process. Physicochemical properties of the prepared nanofibrous mat as well as antibacterial, cytotoxicity, and cell compatibility were studied. The full‐thickness excisional wound healing properties up to 3 weeks using hematoxylin and eosin and Masson‐trichrome staining were investigated. Addition of DDAC to CS/PEO‐PCL mats decreased the diameter of the nanofibers, which is a crucial property for wound healing as large surface area per volume ratio of nanofibers, in addition to proper cell adhesion, increases loading of DDAC in mats and leads to increased cell viability and eliminating Gram‐positive bacteria at in vitro studies. In vivo studies showed DDAC‐loaded CS/PEO‐PCL mats increased epithelialization and angiogenesis and decreased the inflammation according to histological results. We demonstrated that hydrophobic PCL/DDAC mats, besides antibacterial properties of DDAC, absorbed and eliminated the hydrophobic pathological microorganisms, whereas the hydrophilic nanofibers consisted of CS/PEO, increased the cell adhesion and proliferation due to positive charge of CS. Finally, we were able to increase the wound healing quality by using multifunctional wound dressing. CS/PEO‐PCL containing 8 wt % of DDAC nanofibrous mats is promising as a wound dressing for wound management due to the favorable interactions between the pathogenic bacteria and PCL/CS‐based wound dressing.
Treatment with Zoledronate Subsequent to Denosumab in Osteoporosis: a Randomized Trial
Authors: Sølling Anne Sophie , Harsløf Torben , Langdahl Bente 
Published: May 2020

ABSTRACT
Discontinuing denosumab is associated with bone loss and possibly increased fracture risk. We investigated if treatment with zoledronate (ZOL) could prevent bone loss and if the timing of the ZOL infusion influenced the outcome. We report on a 2-year randomized, open label, interventional study including 61 patients with osteopenia, discontinuing denosumab after 4.6 ± 1.6 years. We administrated ZOL 6 months (6M group, n = 20) or 9 months (9M group, n = 20) after the last denosumab injection or when bone turnover had increased (OBS group, n = 21). We monitored the patients with DXA and bone turnover markers. Our primary endpoints were change in lumbar spine BMD (LSBMD) 6 months after ZOL and the proportion of patients who failed to maintain BMD. The study is ongoing (clinicaltrials.gov; NCT03087851). We included 61 participants and 59 patients completed follow-up 12 months after ZOL. Six months after ZOL, LSBMD had decreased significantly by (mean ± SE) 2.1% ± 0.9%, 4.3% ± 1.1%, and 3.0% ± 1.1% in the 6M, 9M, and OBS groups, respectively, and by 4.8% ± 0.7%, 4.1% ± 1.1%, and 4.7% ± 1.2% 12 months after ZOL in the 6M, 9M, and OBS groups, respectively (p &lt; .02, no between-group differences). BMD loss above the least significant change was seen in all groups; at the spine: 6M, n = 6 (30%); 9M, n = 9 (45%); and OBS, n = 9 (47%); and at the total hip: 6M, n = 1 (5%); 9M, n = 5 (25%); and OBS, n = 2 (11%). In the 6M group p-crosslinked C-terminal telopeptide (p-CTX) decreased initially, but increased rapidly thereafter, and 6 months after ZOL, p-CTX was 0.60 ± 0.08 g/L. p-CTX increased rapidly in the 9M and OBS groups, was suppressed by ZOL but increased again thereafter; p-CTX was 0.47 ± 0.05 μg/L and 0.47 ± 0.05 μg/L in the 9M and OBS groups 6 months after ZOL, respectively. Incident vertebral fractures were seen in two women in the 9M group. Treatment with ZOL irrespective of the timing did not fully prevent loss of BMD in patients discontinuing denosumab. © 2020 American Society for Bone and Mineral Research.
Effect of Rooibos (Aspalathus linearis) extract on atorvastatin‐induced toxicity in C3A liver cells
Authors: Millar Danielle A. , Bowles Sandra , Windvogel Shantal Lynn , Louw Johan , Muller Christo J. F. 
Published: May 2020

AbstractRooibos (Aspalathus linearis) has various health benefits. Two case studies have associated chronic Rooibos consumption with conventional prescription medications, including atorvastatin (ATV), with hepatotoxicity. Statins act by inhibiting hydroxymethylglutaryl‐coenzyme A reductase, a rate‐limiting enzyme in cholesterol synthesis. Although rare, statins are potentially hepatotoxic. The aim was to investigate interactions between aspalathin‐rich Rooibos extract GRT™ and ATV‐induced hepatotoxicity in C3A liver cells cultured with and without palmitate. Effects of co‐treatment of GRT + ATV on cell viability, oxidative stress, apoptosis, mitochondrial integrity, and cellular reactive oxygen species (ROS) production were assessed. Significantly increased ROS production was observed in cells exposed to ATV and palmitate. Combination therapy of GRT + ATV also showed significant increases in ROS production. Under palmitate‐treated conditions, ATV‐induced significant apoptosis which was not ameliorated by GRT + ATV co‐treatment. Despite studies purporting hepatoprotection from Rooibos, our study showed that GRT was unable to modulate ATV‐induced hepatotoxic effects in this model.