bluuebunny/crossref_metadata_2025_split huggingface dataset:
The use of extrapolation based on modeling and simulation to support high‐dose regimens of ceftaroline fosamil in pediatric patients with complicated skin and soft‐tissue infections
Authors: Chan Phylinda L.S. , McFadyen Lynn , Quaye Andrea , Leister‐Tebbe Heidi , Hendrick Victoria M. , Hammond Jennifer , Raber Susan 
Published: March 2021

AbstractA model‐informed drug development approach was used to select ceftaroline fosamil high‐dose regimens for pediatric patients with complicated skin and soft‐tissue infections caused by Staphylococcus aureus with a ceftaroline minimum inhibitory concentration (MIC) of 2 or 4 mg/L. Steady‐state ceftaroline concentrations were simulated using a population pharmacokinetics (PK) model for ceftaroline fosamil and ceftaroline including data from 304 pediatric subjects and 944 adults. Probability of target attainment (PTA) for various simulated pediatric high‐dose regimens and renal function categories were calculated based on patients achieving 35% fT>MIC (S. aureus PK/pharmacodynamic target for 2‐log10 bacterial killing). For extrapolation of efficacy, simulated exposures and PTA were compared to adults with normal renal function receiving high‐dose ceftaroline fosamil (600 mg 2‐h infusions every 8 h). For safety, predicted ceftaroline exposures were compared with observed pediatric and adult data. Predicted ceftaroline exposures for the approved pediatric high‐dose regimens (12, 10, or 8 mg/kg by 2‐h infusions every 8 h for patients aged >2 to <18 years with normal/mild, moderate, or severe renal impairment, respectively; 10 mg/kg by 2‐h infusions every 8 h for patients aged ≥2 months to <2 years with normal renal function/mild impairment) were well matched to adults with normal renal function. Median predicted maximum concentration at steady state (Cmax,ss) and area under the plasma concentration‐time curve over 24 h at steady state pediatric to adult ratios were 0.907–1.33 and 0.940–1.41, respectively. PTAs (>99% and ≥81% for MICs of 2 and 4 mg/L, respectively) matched or exceeded the adult predictions. Simulated Cmax,ss values were below the maximum observed data in other indications, including a high‐dose pediatric pneumonia trial, which reported no adverse events related to high exposure.
A family history of Hermansky–Pudlak syndrome complicated with pulmonary fibrosis: a case series and review
Authors: Liendo Martinez Katiuska , Pedraza Fernando , Fuentes Alonso Marta , Puente Maestu Luis , Rodriguez Naranjo Carla , De Miguel‐Diez Javier 
Published: March 2021

AbstractThe Hermansky–Pudlak syndrome (HPS) is a rare genetic disorder. We report three cases from a family of 12 siblings, with six albinos, of whom four and the father had pulmonary fibrosis (PF). Case 1 was admitted to our hospital due to increasing dyspnoea and history of gynaecological bleeding. Pulmonary function test showed a restrictive airflow pattern, high‐resolution computed tomographic scan demonstrated interstitial lung disease (ILD), and platelet aggregation was compromised with a reduced number of platelet dense bodies. The family history revealed endogamy and 11 members with suspected HPS. One of the albino sisters and the father had passed away with unidentified ILD, an albino brother died 14 years earlier, his autopsy had shown collections of ceroid pigments in the lungs, consistent with HPS, and another brother was followed up at our hospital for ILD and compromised platelet aggregation. This family probably has the highest number of members affected by HPS in Spain.
Dynamic trade‐offs in granulocyte colony‐stimulating factor (G‐CSF) administration during chemotherapy
Authors: İrsoy Orkun , Güz Şanser , Akan Naz Beril , Yücel Gönenç 
Published: March 2021

AbstractChemotherapeutic treatment of cancer comes with side effects on the immune system, such as Chemotherapy‐Induced Neutropenia (CIN). A recombinant form of Granulocyte Colony‐Stimulating Factor (G‐CSF) has been used to alleviate CIN. This is a challenging task due to the feedback complexity of the hematological system. A System Dynamics model is constructed to study this system and to derive practical insights for the management of CIN. Stimulation of neutrophil production via G‐CSF is observed to propose crucial trade‐offs. On one hand, production by stem cells and mobilization from bone marrow should be stimulated to compensate for the impairment caused by chemotherapy. On the other hand, it is important to avoid overstimulation, which reduces the regenerative capacity, as well as draining the much‐needed bone‐marrow reservoir. Our analysis supports the intuition that the response to G‐CSF administration is conditional to patient characteristics, and “one for all” treatment protocols are impractical. © 2021 System Dynamics Society
CdS/MoS2 Nanoparticles on Nanoribbon Heterostructures with Boosted Photocatalytic H2 Evolution under Visible‐light Irradiation
Authors: Ma Di , Lu Qifang , Guo Enyan , Tao Furong , Wei Mingzhi 
Published: March 2021

AbstractThe construction of the heterostructures with intimate contacts and prominent sunlight absorption capacity are essential for achieving the highly effective photocatalytic H2 evolution. Here, the CdS/MoS2 heterostructures constituted by CdS nanoparticals loaded on uniform MoS2 nanoribbons were synthesized through solid‐gas reaction and hydrothermal treatments. In the as‐prepared CdS/MoS2 heterostructures, there are large‐area contact interfaces between the external highly dispersed small CdS nanoparticals and MoS2 nanoribbons. Impressively, the optimized CdS/MoS2‐8 photocatalyst delivered the highest hydrogen production rate of 91.2 μmol h−1, which is 9 times that of CdS. It demonstrates that the formation of the heterostructures could eﬀectively promote the separation and transfer of photogenerated charge carriers due to the intimate contacts between CdS nanoparticals and MoS2 nanoribbons. This work would provide a new method to develop efficient photocatalysts for photocatalytic H2 evolution.
Concise Synthesis of Some New Benzothiazole‐Based Heterocycles as Probable Anticancer and Antioxidant Agents
Authors: El‐Mekabaty Ahmed , Sofan Mamdouh A. , Hasel Ali M. , Said Samy B. 
Published: March 2021

AbstractBenzothiazole is the basic skeleton of multi‐target drugs with remarkable anticancer and antioxidant characteristics. In this research, new sets of benzothiazole derivatives carrying different pharmacophores and heterocyclic rings (e. g. 1,2,3‐triazole, pyrazole, thiazolidinone, thiophene, benzothiazole, 1,3‐dithiane, chromene, and pyrimidine) were efficiently synthesized through different synthetic routes from the newly synthesized ethyl 3‐(benzo[d]thiazol‐2‐ylamino)‐3‐oxopropanoate (1). These compounds were assessed in vitro as cytotoxic agents against two human cell lines, HCT‐116 (colon carcinoma) and WI‐38 (normal lung fibroblast) employing the MTT (3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide) assay, in which doxorubicin was used as a positive standard. Among the synthesized compounds, 1,2,3‐triazole 3 and pyrazoles 6 and 12 inhibited the growth of HCT‐116 cell line with high potency (IC50=7.54±0.7, 9.89±0.8, and 8.45±0.7 μM, respectively), along with low toxicity to normal cells, indicated their selectivity. Further, they were screened for their antioxidant performance using the ABTS (2,2′‐azino‐bis(3‐ethylbenzothiazoline‐6‐sulfonic acid)) bioassay and the results coincided with those of the cytotoxicity test, where the most powerful anticancer candidates displayed promising antioxidant activities with % inhibition 80.98 %, 84.12 %, and 88.82 %, respectively, comparable or superior to those of ascorbic acid (88.63 %).
Model Lipid Membranes Assembled from Natural Plant Thylakoids into 2D Microarray Patterns as a Platform to Assess the Organization and Photophysics of Light‐Harvesting Proteins
Authors: Meredith Sophie A. , Yoneda Takuro , Hancock Ashley M. , Connell Simon D. , Evans Stephen D. , Morigaki Kenichi , Adams Peter G. 
Published: March 2021

AbstractNatural photosynthetic “thylakoid” membranes found in green plants contain a large network of light‐harvesting (LH) protein complexes. Rearrangement of this photosynthetic machinery, laterally within stacked membranes called “grana”, alters protein–protein interactions leading to changes in the energy balance within the system. Preparation of an experimentally accessible model system that allows the detailed investigation of these complex interactions can be achieved by interfacing thylakoid membranes and synthetic lipids into a template comprised of polymerized lipids in a 2D microarray pattern on glass surfaces. This paper uses this system to interrogate the behavior of LH proteins at the micro‐ and nanoscale and assesses the efficacy of this model. A combination of fluorescence lifetime imaging and atomic force microscopy reveals the differences in photophysical state and lateral organization between native thylakoid and hybrid membranes, the mechanism of LH protein incorporation into the developing hybrid membranes, and the nanoscale structure of the system. The resulting model system within each corral is a high‐quality supported lipid bilayer that incorporates laterally mobile LH proteins. Photosynthetic activity is assessed in the hybrid membranes versus proteoliposomes, revealing that commonly used photochemical assays to test the electron transfer activity of photosystem II may actually produce false‐positive results.
Preparation of Hollow Cobalt–Iron Phosphides Nanospheres by Controllable Atom Migration for Enhanced Water Oxidation and Splitting
Authors: Chen Qiming , Zhang Qicheng , Liu Huibin , Liang Junmei , Peng Wenchao , Li Yang , Zhang Fengbao , Fan Xiaobin 
Published: March 2021

AbstractTransition metal phosphides (TMPs), especially the dual‐metal TMPs, are highly active non‐precious metal oxygen evolution reaction (OER) electrocatalysts. Herein, an interesting atom migration phenomenon induced by Kirkendall effect is reported for the preparation of cobalt–iron (Co–Fe) phosphides by the direct phosphorization of Co–Fe alloys. The compositions and distributions of the Co and Fe phosphides phases on the surfaces of the electrocatalysts can be readily controlled by CoxFey alloys precursors and the phosphorization process with interesting atom migration phenomenon. The optimized Co7Fe3 phosphides exhibit a low overpotential of 225 mV at 10 mA cm−2 in 1 m KOH alkaline media, with a small Tafel slope of 37.88 mV dec−1 and excellent durability. It only requires a voltage of 1.56 V to drive the current density of 10 mA cm−2 when used as both anode and cathode for overall water splitting. This work opens a new strategy to controllable preparation of dual‐metal TMPs with designed phosphides active sites for enhanced OER and overall water splitting.
Engineering of electrocatalyst/electrolyte interface for ambient ammonia synthesis
Authors: Du Lei , Xing Lixin , Zhang Gaixia , Liu Xianhu , Rawach Diane , Sun Shuhui 
Published: March 2021

AbstractAmmonia is not only an important platform chemical for industrial and agricultural use but is also a novel energy‐carrying molecule. The electrochemical reduction method for ambient ammonia synthesis is emerging as a promising strategy for the replacement of the current Haber–Bosch ammonia synthesis method, which consumes a large amount of energy and natural gas (hydrogen resource) while releasing substantial greenhouse gases (eg, carbon dioxide). The challenges in electrochemical ammonia synthesis, also known as nitrogen reduction reaction, primarily include the cleavage of extremely stable N≡N bonds and the competitive hydrogen evolution reaction in routine aqueous media, which significantly leads to a low production rate and Faradaic efficiency. The rational design and engineering of the electrocatalyst/electrolyte interface are crucial to address these challenges. Herein, recent achievements for catalyst/electrolyte interface engineering are reviewed to provide insights into enhancing the production rate and Faradaic efficiency. Perspectives on future research and development of the electrochemical ammonia synthesis from theory to practice will be provided.
Experimental and numerical study of unbonded post‐tensioned precast concrete connections with controllable post‐decompression stiffness
Authors: Huang Linjie , Zhou Zhen , Clayton Patricia M. 
Published: March 2021

SummaryA new unbonded post‐tensioned precast concrete (PTPC) frame with controllable post‐decompression stiffness (CPDS), achieved by employing novel variable friction energy dissipaters (VFEDs), is proposed in this paper. A steel corbel (SC) is used in the CPDS‐PTPC connection to enhance the shear capacity. The VFED incorporates grooved steel plates and a combination of Bellville washers to provide variable energy dissipation and load‐resisting capacity to achieve target structural performance at different seismic intensity levels. A series of cyclic tests of a full‐scale beam‐to‐column specimen were carried out with different design parameters to investigate the hysteretic behavior of the proposed CPDS‐PTPC connection. The specimen was subjected to cyclic loading up to 9.0% drift to observe different levels of structural damage. Finally, a numerical model is proposed and validated with experimental data, and parametric analyses were performed by varying geometric properties of the VFEDs in the model. Both experimental and numerical analyses confirm the unique capabilities of the proposed CPDS‐PTPC connections to achieve tunable seismic behavior, especially in controlling post‐decompression stiffness while also providing desirable ductile damage at very large seismic demands. The post‐decompression stiffness and load‐carrying capacity are mainly controlled by the stiffness of post‐tensioned (PT) elements and configuration of VFEDs.
Accumulation of heavy metals and bacteriological contaminations in carrots and okra irrigated with tertiary wastewater
Authors: Letshwenyo Moatlhodi Wise 
Published: March 2021

AbstractThe present study investigates the accumulation of heavy metals (mg L−1) and bacteriological contaminations (log10 coliform forming units (CFU) 100 mL−1) in Daucus carota subsp. Sativus (carrot) and Abelmoschus esculentus (okra) irrigated with tertiary effluent. Chromium (Cr), copper (Cu), manganese (Mn), and nickel (Ni) concentrations in the leaves of carrots were higher than the concentrations in the roots. Arsenic (As), iron (Fe), lead (Pb), and zin (Zn) had higher concentrations in the roots than in leaves. Arsenic, chromium, lead, and zinc bioaccumulation factors in the roots were 6.4 ± 1.20, 1.8 ± 0.25, 1.23 ± 0.07, and 2.16 ± 0.76, respectively. The highest bioaccumulation factors were 1.03 ± 0.05 and 2.38 ± 1.40 for chromium and zinc, respectively, in the okra fruit. The health risk indices in adults and children were 1.4E−01 and 2.0E−01, respectively, for consuming carrots and 5.2E−02 and 7.9E−02, respectively, for okra consumption by adults and children. Average log10 counts of the bacteriological contaminations in irrigation water were 1.3, 1.6, and 1.4 log10 CFU 100 mL−1 for E. coli, total coliforms, and fecal coliforms, respectively. The corresponding counts in the edible inner carrot flesh were 0.78 log10, 0.95, and 0 log10 CFU 100 m L−1, respectively. Monitoring of both irrigation water and vegetables should be conducted regularly.
Gauge invariance, polar coordinates and inflation
Authors: Akil Ali , Tong Xi 
Published: March 2021

Abstract
We point out the necessity of resolving the apparent gauge dependence in the quantum corrections of cosmological observables for Higgs-like inflation models. We highlight the fact that this gauge dependence is due to the use of an asymmetric background current which is specific to a choice of coordinate system in the scalar manifold. Favoring simplicity over complexity, we further propose a practical shortcut to gauge-independent inflationary observables by using effective potential obtained from a polar-like background current choice. We demonstrate this shortcut for several explicit examples and present a gauge-independent prediction of inflationary observables in the Abelian Higgs model. Furthermore, with Nielsen’s gauge dependence identities, we show that for any theory to all orders, a gauge-invariant current term gives a gauge-independent effective potential and thus gauge-invariant inflationary observables.
Topological defects and SUSY RG flow
Authors: Brunner I. , Mayer I. , Schmidt-Colinet C. 
Published: March 2021

AbstractWe study the effect of bulk perturbations of N=(2) superconformal minimal models on topological defects. In particular, symmetries and more general topological defects which survive the flow to the IR are identified. Our method is to consider the topological subsector and make use of the Landau-Ginzburg formulation to describe RG flows and topological defects in terms of matrix factorizations.
Rotons in anyon superfluids
Authors: Du Yi-Hsien , Mehta Umang , Son Dam Thanh 
Published: March 2021

Abstract
We consider the problem of calculating the excitation spectrum of a gas of nonrelativistic anyons. When the anyons have statistics close to fermionic and the statistical angle has the form θ = π(1 −$$ \frac{1}{k} $$

1
k

) where k is a large integer, the problem can be solved by employing the method of bosonization, which maps the problem to that of an infinite number of bosonic excitations coupled to a U(1) Chern-Simons gauge field. The spectrum consists of a Goldstone boson branch and a large number of massive branches, each having roton minima and maxima. The dispersion curves asymptote to the Landau levels at large momentum.
The complement system in age-related macular degeneration
Authors: Armento Angela , Ueffing Marius , Clark Simon J. 
Published: March 2021

AbstractAge-related macular degeneration (AMD) is a chronic and progressive degenerative disease of the retina, which culminates in blindness and affects mainly the elderly population. AMD pathogenesis and pathophysiology are incredibly complex due to the structural and cellular complexity of the retina, and the variety of risk factors and molecular mechanisms that contribute to disease onset and progression. AMD is driven by a combination of genetic predisposition, natural ageing changes and lifestyle factors, such as smoking or nutritional intake. The mechanism by which these risk factors interact and converge towards AMD are not fully understood and therefore drug discovery is challenging, where no therapeutic attempt has been fully effective thus far. Genetic and molecular studies have identified the complement system as an important player in AMD. Indeed, many of the genetic risk variants cluster in genes of the alternative pathway of the complement system and complement activation products are elevated in AMD patients. Nevertheless, attempts in treating AMD via complement regulators have not yet been successful, suggesting a level of complexity that could not be predicted only from a genetic point of view. In this review, we will explore the role of complement system in AMD development and in the main molecular and cellular features of AMD, including complement activation itself, inflammation, ECM stability, energy metabolism and oxidative stress.
Tandem communication improves ant foraging success in a highly competitive tropical habitat
Authors: Glaser S. M. , Feitosa R. M. , Koch A. , Goß N. , do Nascimento F. S. , Grüter C. 
Published: March 2021

AbstractTropical ants experience intense intra- and interspecific competition for food sources, which influences their activity pattern and foraging strategies. Even though different ant species can coexist through spatial and temporal niche partitioning, direct competition for food cannot be avoided. Recruitment communication is assumed to help colonies to monopolize and exploit food sources successfully, but this has rarely been tested under field conditions. We studied if recruitment communication helps colonies of the Neotropical antPachycondyla harpaxto be more successful in a highly competitive tropical environment. Additionally, we explored if temporal and spatial niche differentiation helps focal colonies to avoid competition.Pachycondyla harpaxcompeted with dozens of ant species for food. Mass-recruiting competitors were often successful in displacingP. harpaxfrom food baits. However, when foragers ofP. harpaxwere able to recruit nestmates they had a 4-times higher probability to keep access to the food baits. Colonies were unlikely to be displaced during our observations after a few ants arrived at the food source. Competition was more intense after sunset, but a disproportionate increase in activity after sunset allowed focal colonies to exploit food sources more successfully after sunset. Our results support the hypothesis that recruitment communication helps colonies to monopolize food sources by helping them to establish a critical mass of nestmates at large resources. This indicates that even species with a small colony size and a slow recruitment method, such as tandem running, benefit from recruitment communication in a competitive environment.
Efficacy and safety of PEGylated exenatide injection (PB-119) in treatment-naive type 2 diabetes mellitus patients: a Phase II randomised, double-blind, parallel, placebo-controlled study
Authors: Ji Linong , Du Ying , Xu Min , Zhou Xiangjun , Mo Zhaohui , Ma Jianhua , Li Jiarui , Li Yufeng , Lin Jingna , Wang Yanjun , Yang Jing , Song Weihong , Jin Hui , Pang Shuguang , Liu Hui , Li Ping , Liu Jie , Yao Minxiu , Li Wenhui , Jiang Xiaohong , Shen Feixia , Geng Houfa , Zhou Haifeng , Ran Jianmin , Lei Minxiang , Du Yinghong , Ye Shandong , Guan Qingbo , Lv Wenshan , Tan Huiwen , Chen Tao , Yang Jinkui , Qin Guijun , Li Shiyun , Chen Lei 
Published: March 2021

Abstract
Aims/hypothesis
Glucagon-like peptide 1 receptor agonists (GLP-1 RA) such as exenatide are used as monotherapy and add-on therapy for maintaining glycaemic control in patients with type 2 diabetes mellitus. The current study investigated the safety and efficacy of once-weekly PB-119, a PEGylated exenatide injection, in treatment-naive patients with type 2 diabetes.

Methods
In this Phase II, randomised, placebo-controlled, double-blind study, we randomly assigned treatment-naive Chinese patients with type 2 diabetes in a 1:1:1:1 ratio to receive subcutaneous placebo or one of three subcutaneous doses of PB-119 (75, 150, and 200 μg) for 12 weeks. The primary endpoint was the change in HbA1c from baseline to week 12, and other endpoints were fasting plasma glucose, 2 h postprandial glucose (PPG), and proportion of patients with HbA1c < 53 mmol/mol (<7.0%) and ≤48 mmol/mol (≤6.5%) at 2, 4, 8 and 12 weeks of treatment. Safety was assessed in all patients who received at least one dose of study drug.

Results
We randomly assigned 251 patients to one of the four treatment groups (n = 62 in placebo and 63 each in PB-119 75 μg, 150 μg and 200 μg groups). At the end of 12 weeks, mean differences in HbA1c in the treatment groups were −7.76 mmol/mol (95% CI −9.23, −4.63, p < 0.001) (−0.72%, 95% CI −1.01, −0.43), −12.89 mmol/mol (95% CI −16.05, −9.72, p < 0.001) (−1.18%, 95% CI −1.47, −0.89) and −11.14 mmol/mol (95% CI −14.19, −7.97, p <0 .001) (−1.02%, 95% CI −1.30, −0.73) in the 75 μg, 150 μg and 200 μg PB-119 groups, respectively, compared with that in the placebo group after adjusting for baseline HbA1c. Similar results were also observed for other efficacy endpoints across different time points. There was no incidence of treatment-emergent serious adverse event, severe hypoglycaemia or death.

Conclusions/interpretation
All tested PB-119 doses had superior efficacy compared with placebo and were safe and well tolerated over 12 weeks in treatment-naive Chinese patients with type 2 diabetes.

Trial registration
ClinicalTrials.gov NCT03520972

Funding
The study was funded by National Major Scientific and Technological Special Project for Significant New Drugs Development and PegBio.

Graphical abstract