bluuebunny/crossref_metadata_2025 huggingface dataset:
Ampicillin & Gentamicin V/S 3rd Generation Cephalosporin for the Management of Community-Acquired Pneumonia in Children; A Comparative Analysis
Authors: Kumar Aneel , Rais Heena , Prakash Arit , Ali Amin , Jung Sandeep , Siddiqui Fatima Ghayas
Published: January 2022

Background: Community acquired pneumonia (CAP) is a common cause of childhood morbidity, attributed to every 1 in 500 hospitalization of children under the age of 5 years. While science made therapeutic advancements to battle CAP, the pathogens too have acquired resistance to many drugs. In this fight for dominance, Ampicillin plus Gentamicin and 3rd Gen Cephalosporins are nowadays the cornerstone of treatment. However, their efficacy varies in different parts of the world owing to differing levels of drug resistance.

Objective: To compare the effect of Ampicillin and Gentamicin vs. third generation cephalosporin in treatment of severe community acquired pneumonia.

Methodology: This Randomized Controlled Trial was conducted at the Dept. of Pediatrics (Ziauddin University Hospital) upon a sample of 74 patients (in two equal groups) of either gender, aged 2 months to 5 years, presenting with CAP. After taking written informed consent, data was recorded onto a pre-structured questionnaire containing inquiries pertaining to basic biodata, sociodemographic details, presenting complaints, immunization status of the pneumococcal and HIB vaccine, laboratory values, and treatment outcome.

Results: The mean age of the sample stood at 15 months (SD ± 3) with a majority of the sample comprising of male children (52.7%). The mean weight stood at 8.7 kg (SD ± 0.9) and the mean height was recorded to be 74.2 cm (SD ± 11). The commonest symptoms included fever, fast breathing, chest in-drawing and added sounds. It was revealed that both treatments achieved successful treatment outcomes in all patients with no mortality. The resolution of symptoms however varied with faster resolution observed in the Cephalosporin group.

Conclusion: After careful consideration, it can be concluded that 3rd generation cephalosporins is more efficacious at treatment of CAP with significantly faster resolution of disease symptoms.
Study of Morphofunctional Parameters of Blood Cells in Ischemic Stroke Using a Genome-wide Research
Authors: Matveeva Ulyana Viktorovna , Askhanova Malika Ruslanovna , Saydaev Shamsi Aisayevich , Bakasheva Alina Said-Alvievna , Nauruzova Diana Magomedovna , Muzaeva Z. I. , Bazaeva Nuryan Ruslanovna , Maslova Alina Yurievna , Magomedkhadjieva Marem Makhmudovna , Mezhidova Khadizhat Isaevna
Published: January 2022

Biomarkers can play many useful roles in modern neurology. Early diagnosis and immediate therapy are important factors for reducing the degree of brain tissue damage in ischemic stroke, reduces the risk of death from stroke. In the current study, apolipoprotein CIII (ApoCIII), a biomarker of ischemic stroke, was found.
Extent of and Reasons for Discontinuation and Nonpublication of Interventional Trials on Connective Tissue Diseases: An Observational Study
Authors: Brigante Alejandro , Russo Barbara , Mongin Denis , Lauper Kim , Allali Danièle , Courvoisier Delphine S. , Iudici Michele
Published: January 2022

Objective

To assess the proportion, the reasons, and the factors associated with the discontinuation or nonpublication of randomized controlled trials (RCTs) on connective tissue diseases (CTDs).

Methods

We searched all interventional RCTs on CTDs registered in ClinicalTrials.gov since 2000. Two reviewers selected studies according to prespecified eligibility criteria. Completion status, publication status, and reported reasons for discontinuation or nonpublication were retrieved on ClinicalTrials.gov, through literature search, and by contacting investigators. Multivariable logistic regression was used to identify factors associated with study noncompletion and nonpublication.

Results

We included 175 studies, mostly phase III, placebo‐controlled trials on pharmacologic treatments recruiting patients with systemic lupus erythematosus (51%), systemic sclerosis (20%), Sjögren's syndrome (12%), or other CTDs. Fifty‐eight (33%) had been discontinued, mainly for insufficient patient accrual, with no differences in discontinuation rates across the CTDs (P > 0.5). Forty‐six (35%) of 130 studies having included at least 1 patient were unpublished, and 86 (65%) were published in a peer‐reviewed journal after a median of 24 months (interquartile range 15–41) from completion, with a significantly higher publication rate in completed versus discontinued studies (81% versus 22%; P < 0.001). We were able to obtain reasons for nonpublication in one‐third of cases. Small sample size (<100 participants) was the only factor associated with study noncompletion and nonpublication.

Conclusion

One of 3 registered RCTs on CTDs fails to be completed or published. This represents a waste of resources and raises ethical concerns regarding hidden clinical data and unfruitful participation by patients.
Broadband Asymmetric Transmission of Linearly Polarized Mid‐Infrared Light Based on Quasi‐3D Metamaterials
Authors: Whiting Eric B. , Goldflam Michael D. , Kang Lei , Sinclair Michael B. , Musick Katherine M. , Campbell Sawyer D. , Burckel D. Bruce , Werner Douglas H.
Published: January 2022

Metamaterials consisting of subwavelength resonators offer an exciting opportunity for realizing asymmetric transmission (AT) of linearly polarized light. However, to date, only moderate/narrow‐band AT responses have been obtained in metadevices based on stacked planar nanostructures. Here, leveraging a combination of a genetic algorithm (GA) based optimization method and a membrane projection lithography (MPL) fabrication approach, a quasi‐3D metamaterial for broadband AT of linearly polarized mid‐infrared light is demonstrated. Facilitated by the customized GA, an efficient exploration of 3D plasmonic meta‐atoms with broken mirror symmetry in the light propagation direction allows the satisfaction of the rigorous conditions for AT of linearly polarized waves over a broad wavelength range. Confirmed by surface current analysis, the observed AT behavior is attributed to the resonant coupling between the plasmonic nanostructures located on the two orthogonal walls of the MPL cavities. Incorporating an advanced inverse‐design method and a state‐of‐art fabrication technique, the methodology used in the present study provides a promising route for exploiting 3D metamaterials with sophisticated functionalities via effectively exploring the high‐dimensional parametric space offered by true 3D meta‐atoms.
Ultrathin Si Nanosheets Dispersed in Graphene Matrix Enable Stable Interface and High Rate Capability of Anode for Lithium‐ion Batteries
Authors: Ren Yang , Xiang Lizhi , Yin Xucai , Xiao Rang , Zuo Pengjian , Gao Yunzhi , Yin Geping , Du Chunyu
Published: January 2022

Owing to the thinness and large lateral size, 2D Si materials exhibit very promising prospects as the high‐performance anodes of lithium‐ion batteries (LIBs). However, the facile synthesis of ultrathin 2D Si nanosheets (Si‐NSs) and their efficient application still remain a great challenge. Herein, the fabrication of ultrathin Si‐NSs with the average thickness of <2 nm is demonstrated using a unique etching‐reduction protocol. After hybridizing with graphene, the as‐prepared Si‐NSs@rGO material delivers ultrahigh rate capability (2395.8 mAh g−1 at 0.05 A g−1 and 1727.3 mAh g−1 at 10 A g−1), long cycling lifespan (1000 cycles at 2 A g−1 with a capacity decay rate of 0.05% per cycle) and high average Coulombic efficiency (99.85% during 1000 cycles). The superior performance is attributed to the ultrathinness of Si‐NSs that greatly improves the diffusivity and reversibility of Li+ ions. This work provides a strategy for fabricating a high‐rate‐capability anode material to meet the growing demand for high power density LIBs.
Electric Field‐Driven Control of Cholesteric Cellulose Nanocrystal Orientation and Morphology
Authors: Qu Dan , Zussman Eyal
Published: January 2022

A new insight into the control of the helix axis direction and pitch of an aqueous suspension of cellulose nanocrystal‐derived lyotropic liquid crystals by electric field strength and frequency is presented. At low frequency, liquid crystalline cellulose nanocrystals exhibit anomalous negative birefringence, with the helix axis lying parallel to the electric field, followed by a helix pitch decrease upon increasing the field strength. In contrast, they initially show a positive birefringence at high frequency, with the helix axis perpendicular to the electric field and increasing helix pitch with increasing field strength. When the electric field strength is further increased, the helix axis rotates orthogonally to align parallel to the electric field, producing negative birefringence. Such electric field‐induced manipulation of liquid crystalline cellulose nanocrystal helix axis orientation and pitch can set the stage for various fascinating soft matter nanotechnology applications.
Family perspectives on gaps in health care for people with Down syndrome
Authors: King Emily , Remington Mason , Berger Heidi
Published: January 2022

Patients with Down syndrome (DS) have significant specialized healthcare needs. Our objective was to understand what families of patients with DS perceive to be the most pressing gaps in health care, barriers to attendance at a DS specialty clinic, and what they thought a specialty healthcare clinic for people with DS ought to include as part of the clinical package. A qualitative survey was distributed nationally through the online platform SurveyMonkey. We divided respondents into two groups: those who attended a DS specialty clinic (n = 141) and those who did not (n = 100). Data were cleaned and analyzed in RStudio 3.6.3. Results demonstrate that families value mental health services, therapies (e.g., physical therapy, occupational therapy, and speech therapy), developmental specialists, dietitians, and educational advocates. Lack of clear advertisement, especially within low‐income communities, a lack of awareness of DS specialty clinics, and travel time to clinics constituted significant barriers to care. These findings are arguably of benefit to those who direct DS specialty clinics because they offer direction for resource allocation in a time of increasing healthcare costs and financial scrutiny.
Longitudinal analysis of symptoms in the Ehlers‐Danlos syndromes
Authors: Schubart Jane R. , Mills Susan E. , Schaefer Eric W. , Bascom Rebecca , Francomano Clair A.
Published: January 2022

Our study extends a cross‐sectional dataset on the Ehlers‐Danlos syndromes (EDS) assembled by the National Institute on Aging (NIA), under a protocol entitled Clinical and Molecular Manifestations of Heritable Disorders of Connective Tissue. We were successful in contacting 171 of the original 252 participants with EDS. Our study cohort included 91 participants who completed at least one of the following surveys: Brief Pain Inventory (BPI), Pittsburgh Sleep Quality Index (PSQI), Multidimensional Fatigue Inventory (MFI‐20), and Short Form (SF‐36) Health Survey, at both baseline and follow‐up. Follow‐up surveys occurred a median of 11.6 years after the baseline survey. We used mixed effects linear regression models to examine the change in scores for multiple indices reported by participants. There were small mean changes reflected in our estimates for the EDS population as a whole. There was wide heterogeneity between reported individual experiences, with some participants markedly improved and some dramatically worse. Men had a greater increase in mean pain severity over time than women. This is the first study to report a decade of longitudinal data in EDS.
Direct Lactamization of β‐Arylated δ‐Aminopentanoic Acid Carboxamides: En Route to 4‐aryl‐2‐Piperidones, Piperidines, Antituberculosis Molecule Q203 (Telacebec) and its Analogues
Authors: Tomar Radha , Bhattacharya Debabrata , Arulananda Babu Srinivasarao
Published: January 2022

We report the synthesis of 4‐aryl‐2‐piperidone, 4‐arylpiperidine motifs, antituberculosis molecule Q203 (Telacebec) and its analogues. Direct lactamization of β‐C−H arylated N‐phthaloyl δ‐aminopentanoic acid carboxamides yielded 4‐aryl‐2‐piperidone (4‐aryl‐δ‐valerolactam) scaffolds. The required β‐C−H arylated N‐phthaloyl δ‐aminopentanoic acid carboxamides were assembled via the Pd(II)‐catalyzed, 8‐aminoquinoline‐aided, sp3 β‐C−H activation and arylation method. The β‐C−H arylated N‐phthaloyl δ‐aminopentanoic acid carboxamides containing both 8‐aminoquinoline and N‐phthaloyl protecting groups directly underwent the hydrazine‐mediated lactamization to afford 4‐aryl‐2‐piperidones. 4‐Aryl‐2‐piperidone scaffolds were then converted into N‐functionalized 4‐aryl‐2‐piperidones, 4‐arylpiperidines, which are structurally closer to bio‐active 4‐aryl‐ 2‐piperidone and piperidine motifs. A synthetic route for assembling antituberculosis molecule Q203 and its analogues from the corresponding 4‐aryl‐2‐piperidones was also shown.
TFA/DMSO‐Promoted Cross‐Dehydrogenative Coupling of Hetaryl Thiols with Indoles: Access to 3‐(Hetarylsulfenyl)indole under Mild Conditions
Authors: Truong Tan Sang , Retailleau Pascal , Nguyen Thanh Binh
Published: January 2022

TFA/DMSO combination was found to efficiently promote the cross‐dehydrogenative coupling of a wide range of hetaryl thiols with indole derivatives, leading to 3‐(hetarylsulfenyl)indoles in good‐to excellent yields under mild heating conditions. Two‐fold hetarylsulfenylation of indoles in 2‐ and 3‐positions could be conveniently achieved by simply adapting the molar ratio of the starting materials.
In Situ Self‐Assembly of Bispecific Peptide for Cancer Immunotherapy
Authors: Wang Man‐Di , Lv Gan‐Tian , An Hong‐Wei , Zhang Ni‐Yuan , Wang Hao
Published: January 2022

Precise and effective manipulation of protein functions still faces tremendous challenges. Herein we report a programmable peptide molecule, consisted of targeting and self‐assembly modules, that enables specific and highly efficient assembly governed by targeting receptor proteins. Upon binding to the cell membrane receptor, peptide conformation is somewhat stabilized along with decreased self‐assembly activation energy, promoting peptide‐protein complex oligomerization. We first design a GNNQQNY‐RGD peptide (G7‐RGD) to recognize integrin αVβ3 receptor for proof‐of‐concept study. In the presence of αVβ3 protein, the critical assembly concentration of free G7‐RGD decreases from 525 to 33 μM and the resultant G7‐RGD cluster drives integrin receptor oligomerization. Finally, a bispecific assembling peptide antiCD3‐G7‐RGD is rationally designed for cancer immunotherapy, which validates CD3 oligomerization and concomitant T cell activation, leading to T cell‐mediated cancer cell cytolysis.
Synthesis of Cyclopropenols Enabled by Visible‐Light‐Induced Organocatalyzed [2+1] Cyclization
Authors: Zhou Gang , Shen Xiao
Published: January 2022

Although the synthesis of common cyclopropenes has been well studied, the access to cyclopropenols is rather limited. Herein, we report the first synthesis of α‐trifluoromethylated cyclopropenols via 2+1 cycloaddition reactions between alkynes and trifluoroacylsilanes, enabled by visible‐light‐induced organocatalysis. The novel ambiphilic donor–acceptor carbenes derived from trifluoroacetylsilanes reacted efficiently with both activated and non‐activated alkynes. The reaction features simple operation, mild conditions, broad substrate scope and good functional group tolerance. The synthetic potential of the reaction is highlighted by the gram‐scale reactions and first synthesis of α‐trifluoromethylated cyclopropanols through the combination of the 2+1 cyclization and high diastereoselective hydrogenation reaction in one pot.
Causal inference in case of near‐violation of positivity: comparison of methods
Authors: Léger Maxime , Chatton Arthur , Le Borgne Florent , Pirracchio Romain , Lasocki Sigismond , Foucher Yohann
Published: January 2022

In causal studies, the near‐violation of the positivity may occur by chance, because of sample‐to‐sample fluctuation despite the theoretical veracity of the positivity assumption in the population. It may mostly happen when the exposure prevalence is low or when the sample size is small. We aimed to compare the robustness of g‐computation (GC), inverse probability weighting (IPW), truncated IPW, targeted maximum likelihood estimation (TMLE), and truncated TMLE in this situation, using simulations and one real application. We also tested different extrapolation situations for the sub‐group with a positivity violation. The results illustrated that the near‐violation of the positivity impacted all methods. We demonstrated the robustness of GC and TMLE‐based methods. Truncation helped in limiting the bias in near‐violation situations, but at the cost of bias in normal conditions. The application illustrated the variability of the results between the methods and the importance of choosing the most appropriate one. In conclusion, compared to propensity score‐based methods, methods based on outcome regression should be preferred when suspecting near‐violation of the positivity assumption.
Effect of various aqueous extracting agents on fluorescence properties of waste tea residue derived carbon dots (WTR‐CDs): Comparative spectroscopic analysis
Authors: Mote Umesh S. , Gore Anil H. , Panja Sumit Kumar , Kolekar Govind B.
Published: January 2022

Fluorescent carbon dots (CDs) are one of the important carbonaceous nanomaterials in the area of nanoscience and nanotechnology because of their interesting physical as well as chemical properties. Herein we studied the effect of various aqueous extracting agents on fluorescence properties of waste tea residue‐based carbon dots (WTR‐CDs). WTR‐CDs are firstly synthesized by utilizing kitchen waste‐based carbonaceous biomass. To check the role of various aqueous media during the course of WTR‐CDs synthesis from carbonized carbon powder, extraction of WTR‐CDs was carried out in various kinds of aqueous media viz., only aqueous (100% water, WT), aqueous‐alcoholic (10% ethanol, ET), aqueous‐acidic (10% acetic acid, AA), and aqueous‐basic (10% ammonia, AM). The consequences of extracting agents on the photophysical properties of final WTR‐CDs‐WT, WTR‐CDs‐ET, WTR‐CDs‐AA and WTR‐CDs‐AM were also discussed in detail. We have observed interesting blue shift fluorescence spectra in acidic medium for WTR‐CDs‐AA and polar protic solvents compared to polar aprotic medium. The solvatochromic behaviour of WTR‐CDs‐WT in model polar and non‐polar solvent was also studied. The effect of cationic, anionic and non‐anionic surfactants on the fluorescence of WTR‐CDs‐WT was also evaluated. The proposed findings may help researchers in the near future to obtain fast, easy and direct synthesize CDs from a variety of biomass‐based precursors under different aqueous conditions.
Quantification of rosiglitazone in rat plasma and tissues via LC–MS/MS: Method development, validation, and application in pharmacokinetic and tissue distribution studies
Authors: Garikapati Kusuma Kumari , Ammu V. V. V. Ravi Kiran , Krishnamurthy Praveen Thaggikuppe , S. T. Narenderan , B. Babu , Nagappan Krishnaveni
Published: January 2022

A bioanalytical method for the quantification of rosiglitazone in rat plasma and tissues (adipose tissue, heart, brain, bone, and kidney) using LC–MS/MS was developed and validated. Chromatographic separation was achieved on a Gemini C18 column (50 × 4.6 mm, 3 μm) using a mobile phase consisting of 10 mM ammonium formate (pH 4.0) and acetonitrile (10:90, v/v) at a flow rate of 0.8 mL/min and injection volume of 10 μL (internal standard: pioglitazone). LC–MS detection was performed with multiple reaction monitoring mode using target ions at m/z → 358.0 and m/z → 357.67 for rosiglitazone and pioglitazone (internal standard), respectively. The calibration curve showed a good correlation coefficient (r2) over the concentration range of 1–10,000 ng/mL. The mean percentage recoveries of rosiglitazone were found to be over the range of 92.54–96.64%, with detection and lower quantification limit of 0.6 and 1.0 ng/mL, respectively. The developed method was validated per U.S. Food and Drug Administration guidelines and successfully utilized to measure rosiglitazone in plasma and tissue samples. Further, the developed method can be utilized for validating specific organ‐targeting delivery systems of rosiglitazone in addition to conventional dosage forms.
Pharmacokinetics and tissue distribution of trans‐ferulic acid‐4‐β‐glucoside in rats using UPLC–MS/MS
Authors: Xia Tongchao , Yang Yuqi , Li Le , Tan Yuting , Chen Yuan , Wang Shengyan , Ye Liming , Bao Xu , Yang Junyi
Published: January 2022

Trans‐ferulic acid‐4‐β‐glucoside (FAG) is a monomer extracted from Radix Aconiti Lateralis Preparata, which is a potential candidate for the prevention and treatment of cold injury. To determine the concentration of FAG in rats, it is essential to develop an ultra‐performance liquid chromatography coupled with MS/MS method. Chromatographic separation was achieved by an Acquity UPLC BEH C18 column (2.1 × 50 mm, 1.7 μm). A Xevo triple quadrupole tandem mass spectrometer was used to quantitatively determine FAG in the negative‐ion mode. The standard calibration curve was linear over the concentration range of 0.1–100 μg/mL and 0.0626–31.28 μg/g for rat plasma and liver tissue homogenate samples, respectively. The inter‐ and intra‐batch precision (% relative standard deviation) of the assay was ≤8.29%, and accuracy (% relative error) ranged from −7.41 to 10.99%. The matrix effect was between 92.99 and 102.39%. The oral absolute bioavailability of FAG was obtained as 1.80%. The results of tissue distribution suggested that FAG spread rarely in the liver and brown adipose, which was not propitious to exert its ability to treat cold injury. In general, these studies were significant to provide necessary information for further study.
Stability‐indicating liquid chromatography method development and validation for impurity profiling of montelukast sodium in bulk drug and tablet dosage form
Authors: Pasham Mohan , Haridasyam Sharath Babu , Boppy N. V. V. D. Praveen , Venkatanarayana Muvvala , Palakurthi Ashok Kumar
Published: January 2022

Montelukast sodium (MLS) is a leukotriene receptor antagonist drug used in the treatment of asthma, bronchospasm, allergic rhinitis and urticaria. A reversed‐phase high performance liquid chromatography method was developed to separate, identify and quantitative determination of MLS and its eight known organic impurities in tablet dosage form using a C18 column and mobile phases consisting of a gradient mixture of pH 2.5 phosphate buffer and acetonitrile. The stability‐indicating character of the developed method was proven using stress testing (1 m HCl at 80°C/30 min, 1 m NaOH at 80°C/30 min, H2O at 80°C/30 min, 3% H2O2 at 25°C/1 min, dry heat at 105°C/10 h and UV–vis light/4 days) and was validated for specificity, quantitation limit, linearity, precision, accuracy and robustness. For MLS and its eight known impurities, the quantitation limits, linearity and recoveries were 0.015–0.03 μg/ml, correlation coefficient > 0.997 (R2 > 0.995) and 85.5–107.0%, respectively. The developed chromatographic method is suitable for impurity profiling and also for assay determination of MLS in bulk drugs and pharmaceutical formulations. The mass values (m/z) of newly formed degradation products (DP1 and DP2) of montelukast sodium were identified using liquid chromatography–mass spectrometry.
Serious adverse events related to transcatheter aortic valve replacement are infrequent: FORWARD 3‐years
Authors: Belardi Jorge , Lamelas Pablo
Published: January 2022

Key Points

Long‐term information about clinical events related to transcatheter aortic valve replacement (TAVR) is needed to be considered in younger populations.

The overall rate of endocarditis, reintervention, and clinical valve thrombosis was low at 3 years.

These results highlight that adverse events related to TAVR are infrequent at intermediate follow‐up and support the use of TAVR in clinical practice.
Left ventricular aneurysm: What is the role of surgical or percutaneous interventions?
Authors: Grines Cindy L. , Voeltz Michele
Published: January 2022

Key Points

The chance of developing left ventricular (LV) aneurysm after anterior ST‐segment myocardial infarction is reduced with ACE inhibitors, beta‐blockers early (within 24 h of symptom onset) and rapid reperfusion.

Anterior LV aneurysm increases the risk of angina, heart failure, arrhythmia, stroke, and death.

LV partitioning with surgery or percutaneous devices improve LV volumes and ejection fraction, but trials have not yet proven sustained clinical benefits.
Transcatheter valve in valve replacement in stentless prosthetic aortic valves compared to a surgical approach: The lunch is good, but not free!
Authors: Inci Errol , Block Peter C.
Published: January 2022

Key Points

Particularly in a higher risk population, transcatheter aortic valve in valve replacement is a suitable alternative to repeat surgical valve replacement—with possibly better short term outcomes.

Challenges remain: Valve‐in‐valve TAVR may require a second valve placement and has more residual valve leak than surgery.

Long‐term clinical outcomes comparing transcatheter and surgical replacements for degraded stentless aortic valves are still needed.
Repurposing of 8‐Hydroxyquinoline‐Based Butyrylcholinesterase and Cathepsin B Ligands as Potent Nonpeptidic Deoxyribonuclease I Inhibitors
Authors: Gajic Mihajlo , Knez Damijan , Sosič Izidor , Mravljak Janez , Meden Anže , Košak Urban , Leitzbach Luisa , George Sven , Hofmann Bettina , Zivkovic Aleksandra , Steinhilber Dieter , Stark Holger , Gobec Stanislav , Smelcerovic Andrija , Anderluh Marko
Published: January 2022

A library of 31 butyrylcholinesterase (BChE) and cathepsin B (CatB) inhibitors was screened in vitro for inhibition of deoxyribonuclease I (DNase I). Compounds 22, 8 and 7 are among the most potent synthetic non‐peptide DNase I inhibitors reported to date. Three 8‐hydroxyquinoline analogues inhibited both DNase I and BChE with IC50 values below 35 μM and 50 nM, respectively, while two nitroxoline derivatives inhibited DNase I and Cat B endopeptidase activity with IC50 values below 60 and 20 μM. Selected derivatives were screened for various co‐target binding affinities at dopamine D2 and D3, histamine H3 and H4 receptors and inhibition of 5‐lipoxygenase. Compound 8 bound to the H3 receptor and is highlighted as the most promising multifunctional ligand with a favorable pharmacokinetic profile and one of the most potent non‐peptide DNase I inhibitors. The present study demonstrates that 8‐hydroxyquinoline is a structural fragment critical for DNase I inhibition in the presented series of compounds.
Use of Modeling and Simulation to Predict the Influence of Triazole Antifungal Agents on the Pharmacokinetics of Crizotinib
Authors: Chen Lu , Li Lixian , Chen Wanyi
Published: January 2022

Crizotinib is used for the treatment of c‐ros oncogene 1–positive advanced non–small‐cell lung cancer. Triazole antifungal agents are widely used for invasive fungal infections in clinical practice. To predict the potential influence of different triazoles (voriconazole, fluconazole, and itraconazole) on the pharmacokinetics of crizotinib by modeling and simulation the physiologically based pharmacokinetic models were established and validated in virtual cancer subjects through Simcyp software based on the essential physicochemical properties and pharmacokinetic data collected. The validated physiologically based pharmacokinetic models were applied to predict the drug‐drug interactions between crizotinib and different triazoles (voriconazole, fluconazole, or itraconazole) in patients with cancer. Crizotinib and triazole antifungal agents were administered orally. The predicted plasma concentration vs time profiles of crizotinib, voriconazole, fluconazole, and itraconazole showed good agreement with observed, respectively. The geometric mean area under the plasma concentration–time curve (AUC) of crizotinib was increased by 84%, 58%, and 79% when coadministered with voriconazole, fluconazole, or itraconazole at multiple doses, respectively. The drug‐drug interaction results showed increased pharmacokinetic exposure (maximum plasma concentration and area under the plasma concentration–time curve) of crizotinib when coadministrated with different triazoles (voriconazole > itraconazole > fluconazole). Among the 3 triazoles, voriconazole exhibited the most significant influence on the pharmacokinetic exposure of crizotinib. In clinic, adverse drug reactions and toxicity related to crizotinib should be carefully monitored, and therapeutic drug monitoring for crizotinib is recommended to guide dosing and optimize treatment when coadministered with voriconazole, fluconazole, or itraconazole.
Schooling practices, curriculum, and educational opportunities of the children in the fisherman' neighbourhoods in Indonesia archipelago
Authors: Aletheiani Dinny Risri
Published: January 2022

This paper focuses on the schooling practices, curriculum, and educational opportunities available to children in the fishermen's neighbourhoods of the Indonesian archipelago. The study investigates what schooling practices, curriculum, and educational opportunities are thought important for the education of children in fishermen's neighbourhoods of the Indonesian archipelago. The study utilises archival and policy texts, created teaching and learning materials from the Indonesian Ministry of Education and Culture, and various texts derived from the community‐based foundations and non‐profit organisations spread out in the Indonesian archipelago related to the education of children in Indonesian fishermen's neighbourhoods. Through an archival investigation of curricula, the study hopes to examine the languages of instrumentality and criticality and how they have shaped the educational practices and experiences in these fishermen's neighbourhood contexts.
Direct sequence confirmation of qPCR products for gene doping assay validation in horses
Authors: Maniego Jillian , Pesko Bogusia , Hincks Pamela , Taylor Polly , Stewart Graham , Proudman Christopher , Scarth James , Ryder Edward
Published: January 2022

The misuse of gene therapy by the introduction of transgenes via plasmid or viral vectors as a doping agent is an increasing concern in human and animal sports, not only in consideration to fair competition but also in potential detrimental effects to welfare. Doping events can be detected by polymerase chain reaction (PCR) amplification of a transgene‐specific region of DNA. Quantitative real‐time PCR (qPCR) is particularly suited to confirmatory investigations where precise limits of detection can be calculated. To fully validate a qPCR experiment, it is highly desirable to confirm the identity of the amplicon. Although post‐PCR techniques such as melt curve and fragment size analysis can provide strong evidence that the amplicon is as expected, sequence identity confirmation may be beneficial as part of regulatory proceedings. We present here our investigation into two alternative processes for the direct assessment of qPCR products for five genes using next‐generation sequencing: ligation of sequence‐ready adapters to qPCR products and qPCR assays performed with primers tailed with Illumina flow cell binding sites. To fully test the robustness of the techniques at concentrations required for gene doping detection, we also calculated a putative limit of detection for the assays. Both ligated adapters and tailed primers were successful in producing sequence data for the qPCR products without further amplification. Ligated adapters are preferred, however, as they do not require re‐optimisation of existing qPCR assays.
Autophony in inpatients with anorexia nervosa or avoidant restrictive food intake disorder
Authors: Hollis Jeff , Mann Scott , Watters Ashlie , Oakes Judy , Mehler Philip S.
Published: January 2022

Objective

To assess for the prevalence of autophony, a distressing auditory symptom commonly attributed to patulous eustachian tube, in a cohort of individuals with severe malnourishment due to an eating disorder.

Method

A cross‐sectional survey study was performed. Patients admitted for inpatient medical stabilization of an eating disorder, who were also at low body weight, were asked to complete a survey assessing aural symptoms present in the previous 24 hr, including autophony. Anthropometric data and prealbumin levels were collected.

Results

Of 101 patients enrolled, 43 (42.6%) reported symptoms of autophony. The presence of autophony was associated with lower serum prealbumin levels and lower body weight as measured by percentage of ideal body weight.

Discussion

Autophony is a commonly reported, albeit rarely discussed, symptom in individuals with severe eating disorders and correlates with degree of malnutrition.
A comprehensive study of different objectives and solutions of controller placement problem in software‐defined networks
Authors: Dhar Mili , Debnath Arindam , Bhattacharyya Bidyut K. , Debbarma Mrinal Kanti , Debbarma Swapan
Published: January 2022

Software‐defined network (SDN) is a programmable networking paradigm that enables logically centralized network management. In order to overcome the shortcomings of traditional networks, SDN has come into the picture. SDN is a recent and fast‐forwarding technique that involves separating the network's control plane from the data plane. This network also allows us to directly communicate with the applications through application programming interfaces. A network administrator can directly modify and update the routing policies and rules in SDN. Apart from the advantages given by the SDN, it has also been found that separation of control plane directly affects the network performance. Finding the optimum number of controllers and their locations to improve the performance is one of the fundamental research problems in SDN which is also commonly known as the controller placement problem (CPP). In this article, we have addressed the CPP in SDN in detail and investigated the optimization objectives that influence CPP. The state‐of‐the‐art of this article is to review almost all the optimization objective along with their mathematical formulation and survey the CPP solutions proposed by the other researchers'. Classified the CPP into three parts based on the objectives and solutions of CPP and reviewed the impact of these objectives on network performance. This article gives a comprehensive overview of current strategies on CPP in SDN and at last, we give some research issues that can be further explored by the researchers.
Wave propagation in inhomogeneous media via FE/PML method
Authors: Savidis Stavros , Bergmann Mathias , Schepers Winfried , Fontara Ioanna‐Kleoniki
Published: January 2022

The Perfectly Matched Layer (PML) method is an efficient approach to imposing radiation conditions at the bounded region of interest in case of wave propagation in unbounded domains. This paper presents and validates 3D FE/PML numerical schemes based on two different PML formulations for homogeneous and inhomogeneous geological media exhibiting discrete or continuous inhomogeneity. In the equation of motion for the PML domain the applied stretching behavior is expressed either as complex material properties or as complex coordinates. Both PML formulations are implemented in the FEM and verified against analytical solutions. Three different types of material inhomogeneity are considered: layered half‐space, continuously inhomogeneous half‐space with linear velocity profile and continuously inhomogeneous half‐space with nonlinear velocity profile. Sensitivity analyses are conducted, and the performance of the developed numerical schemes is investigated taking into account a broad variation of the PML parameters. Recommendations are given for the optimal values of the PML parameters for the case of homogeneous and inhomogeneous geological media.
The productive efficiency of community health service stations in China: Taking Shandong province as a case
Authors: Qiu Leijie , Yang Linsheng , Li Hairong , Wang Li
Published: January 2022

The present study evaluated the efficiencies of community health service (CHS) stations based on a survey of 1246 CHS stations, covering nine subcategories in 16 cities in Shandong province. Data envelopment analysis (DEA) was applied to investigate the overall efficiency, the technical and the scale efficiency of community health care resources. The results are, the overall efficiency was 9.47%, and the overall efficiency was generally higher in the central‐west region than in the east. There were 23.27% of CHS stations showing technically efficient. The technical efficiency was higher in the east (31.11%) relative to the central‐west (19.72%), and 72.71% of CHS stations had a technical efficiency higher than the regional average efficiency. The scale efficiency was 9.31% for CHS stations in Shandong province, being the decisive factor for overall efficiency, and 68.96% of CHS stations showed a scale efficiency above the regional average. Stations held by enterprises and universities, and extended by tertiary hospitals had lower efficiencies than other types of CHS stations. In conclusion, the CHS stations had low efficiencies in general, and scale inefficiencies were the main cause. Related suggestions to improve the efficiency are provided accordingly.
Disparities in demand for COVID‐19 hospital care in the United States: Insights from a longitudinal hierarchical study
Authors: Messner Wolfgang
Published: January 2022

Background and aims

This study examined disparities in hospitalization for COVID‐19 within the U.S. by racial and ethnic groups, health insurance status, and social support structure.

Methods

Using publicly available ecological case and contextual data from July 2020 to April 2021, a longitudinal hierarchical model for the 51 U.S. states was constructed.

Results

Racial/ethnic disparities were observed, such as that hospitalization rates were higher in states with a higher percentage of Black (β = .002, P = .009) and American Indian or Alaska Native persons (β = .003, P = .03). Conversely, lack of health insurance was related to a lower hospitalization rate (β = −.005, P = .002), and so was a stronger social support system (β = −.015, P = .05).

Conclusion

These differences suggest disparities in COVID‐19 incidence, symptom severity, and demand for hospital care. Understanding how they contribute to geographic differences in hospitalization can help guide public health decisions and resource allocation to address COVID‐19‐related health inequalities.
Optimizing large‐scale autologous human keratinocyte sheets for major burns—Toward an animal‐free production and a more accessible clinical application
Authors: Frese Laura , Darwiche Salim Elias , Gunning Myrna Elisabeth , Hoerstrup Simon Philipp , von Rechenberg Brigitte , Giovanoli Pietro , Calcagni Maurizio
Published: January 2022

Background and Aims

Autologous keratinocyte sheets constitute an important component of the burn wound treatment toolbox available to a surgeon and can be considered a life‐saving procedure for patients with severe burns over 50% of their total body surface area. Large‐scale keratinocyte sheet cultivation still fundamentally relies on the use of animal components such as inactivated murine 3T3 fibroblasts as feeders, animal‐derived enzymes such as trypsin, as well as media components such as fetal bovine serum (FBS). This study was therefore aimed to optimize autologous keratinocyte sheets by comparing various alternatives to critical components in their production.

Methods

Human skin samples were retrieved from remnant operative tissues. Cell isolation efficiency and viability were investigated by comparing the efficacy of porcine‐derived trypsin and animal‐free enzymes (Accutase and TrypLESelect). The subsequent expansion of the cells and the keratinocyte sheet formation was analyzed, comparing various cell culture substrates (inactivated murine 3T3 fibroblasts, inactivated human fibroblasts, Collagen I or plain tissue culture plastic), as well as media containing serum or chemically defined animal‐free media.

Results

The cell isolation step showed clear cell yield advantages when using porcine‐derived trypsin, compared to animal‐free alternatives. The keratinocyte sheets produced using animal‐free serum were similar to those produced using 3T3 feeder layer and FBS‐containing medium, particularly in mechanical integrity as all grafts were liftable. In addition, sheets grown on collagen in an animal‐free medium showed indications of advantages in homogeneity, speed, reduced variability, and differentiation status compared to the other growth conditions investigated. Most importantly, the procedure was compatible with the up‐scaling requirements of major burn wound treatments.

Conclusion

This study demonstrated that animal‐free components could be used successfully to reduce the risk profile of large‐scale autologous keratinocyte sheet production, and thereby increase clinical accessibility.
What will be the future of dinoprostone in labor induction?
Authors: Ragusa Antonio , De Luca Caterina , Zucchelli Emma , Svelato Alessandro
Published: January 2022

A productive debate is needed about the use of dinoprostone in labor induction.
Trial of labor after cesarean in twin gestation with no prior vaginal delivery – evidence from largest cohort reported
Authors: Levin Gabriel , Yagel Simcha , Schwartz Anat , Many Ariel , Rosenbloom Joshua I. , Yinon Yoav , Meyer Raanan
Published: January 2022

Objective

To investigate trial of labor after cesarean (TOLAC) success rates in twin gestations with no prior vaginal delivery.

Methods

A retrospective study of women with twin gestations who underwent a TOLAC and had no prior vaginal delivery during 2011–2020. TOLAC success and failure groups were compared.

Results

Of 675 twin gestations with a history of cesarean delivery and no prior vaginal delivery, 83 (12.3%) elected to undergo a TOLAC and 26 (31.3%) succeeded. Two (7.7%) women delivered by cesarean for the second twin after vaginal delivery of the first twin. Epidural analgesia was positively associated with TOLAC success (odds ratio [OR] 4.31, 95% confidence interval [CI] 1.56–11.94, P = 0.004). Uterine rupture occurred in two patients (3.5%) of the TOLAC failure group. The proportion of cases with low Apgar score (<7) at 5 min was higher in the TOLAC success group (4 [15.4%] versus 1 [1.8%]; OR 10.1, 95% CI 1.07–96.22, P = 0.032) and the neonatal composite adverse outcome rate was lower in this group (OR 0.22, 95% CI 0.07–0.69, P = 0.009).

Conclusion

TOLAC in women with twins with no prior vaginal delivery is associated with a low success rate. No independent predictors of successful TOLAC were identified.
Acute exposure to abuse‐like concentrations of toluene induces inflammation in mouse lungs and brain
Authors: Svenson Drew W. , Davidson Cameron J. , Thakur Chitra , Bowen Scott E.
Published: January 2022

Toluene is an aromatic hydrocarbon commonly abused by young adolescents for its central nervous system depressant effects. Although toluene's pharmacological effects at high concentrations are relatively well‐known, few studies have assessed toluene's effects on lung and brain tissues. The present study characterized the pathological effects of acute inhaled toluene exposure in the lungs and brains of male Swiss‐Webster mice (N = 68). Using a static vapor exposure chamber, mice (PND 28) received a single 30‐min toluene administration (0, 1000, 2000, or 4000 ppm). Lung and brain tissues were extracted 24‐h post‐exposure. Histology results revealed significant changes in the morphology of lung tissue (e.g., irregular cellular architecture) with the 2000‐ and 4000‐ppm exposures expressing greater signs of pathology than control 0‐ppm exposure. Markers of immune system activity (F4/80 and Ly‐6G) and cellular proliferation (Ki‐67) in the lung revealed no significant differences. Additionally, brain tissues were analyzed for changes of astrogliosis (glial fibrillary acidic protein [GFAP]) and oxidative stress (glutathione peroxidase [GPx]). GFAP showed increased astrogliosis in the striatum with 2000‐ppm toluene showing significantly higher expression than control (p < 0.05) and a marginal effect in the hippocampus. No other markers showed significant changes. The increased signs of inflammation and cellular damage suggest that exposure to a single high concentration of toluene, typical of abuse, is capable of producing pathology in both lung and brain tissue.
Featuring few essential Raman spectroscopic signatures between heterogeneous cells
Authors: Dai Yixin , Wang Liu , Luo Chuan , Li Wenkang , Huang Qing , Li Wenxue , Pang Lin
Published: January 2022

Here we demonstrate it is instructive to quantify cell Raman spectroscopy by sparse regularization. To be able to extract the specific spectral differences in a heterogeneous cell system with great spectroscopic similarities derived from many common biomolecular components, the maximum information entropy probability was proposed and exemplified by identifying normal lymphocytes from leukemia cells. The essential spectroscopic features were observed to locate at three Raman peaks whose spectral signatures were commensurate. The applicability of the extracted features was acknowledged by that the predicted identification accuracy of up to 93% was still achieved when only two peaks were loaded into decision tree model, which may provide the possibility of a clinically rapid hematological malignancy detection.
Social justice outcomes and professional counseling: An 11‐year content analysis
Authors: Clark Madeline , Moe Jeffry , Chan Christian D. , Best Mihkaya D. , Mallow Laura M.
Published: January 2022

Articles that assessed the outcomes of interventions based on multicultural‐social justice principles, and that were published in a journal sponsored by the American Counseling Association or its divisions, Chi Sigma Iota, or the National Board for Certified Counselors, were analyzed using qualitative content analysis. A total ofN= 35 empirical studies were identified for inclusion. The year published, methodology, population studied, sample size, operationalized constructs, and whether the study espoused a systemic or community focus were coded. Principal findings indicated a slight increase in multicultural‐social justice outcome research over time, a need for more rigorous multicultural‐social justice outcome research, and a need for scholars and practitioners to enhance their systemic and community‐based conceptualizations of their clients’ presenting concerns. Other implications for counseling, limitations, and future directions are discussed.
Circulating metabolites serve as diagnostic biomarkers for HER2‐positive breast cancer and have predictive value for trastuzumab therapy outcomes
Authors: Mao Changfei , Wang Min , Li Li , Tang Jin‐Hai
Published: January 2022

Human epidermal growth factor receptor 2 (HER2)‐positive is a particularly aggressive type of the breast cancer. Trastuzumab‐based therapy is a standard treatment for HER2‐positive breast cancer, but some patients are resistance to the therapy. There are no known diagnostic biomarkers to improve the early diagnosis of HER2‐positive breast cancer and the clinical utility of trastuzumab therapy. Using ultrahigh‐performance liquid time of flight mass spectrometry (UPLC‐TOF‐MS)‐based serum metabolomics and multivariate statistical analysis, we investigated and identified the circulating metabolites L‐arginine and arachidonic acid were elevated in trastuzumab‐responsive and trastuzumab‐resistant HER2‐positive breast cancer patients, and increased until reaching their peaks in trastuzumab‐resistant HER2‐positive breast cancer patients. Moreover, an equation for assessing the risk scores based on linear logistic regression models involving L‐arginine and arachidonic acid was created, which was beneficial for revealing metabolic changes in HER2‐positive breast cancer and enhancing current trastuzumab‐based therapy. In summary, we develop serum‐based metabolic biomarkers for diagnosis of HER2‐positive breast cancers and predicts the therapeutic effects of trastuzumab therapy.