bluuebunny/crossref_metadata_2025_split huggingface dataset:
Novel low‐avidity glypican‐3 specific CARTs resist exhaustion and mediate durable antitumor effects against HCC
Authors: Caraballo Galva Leidy D. , Jiang Xiaotao , Hussein Mohamed S. , Zhang Huajun , Mao Rui , Brody Pierce , Peng Yibing , He Aiwu Ruth , Kehinde‐Ige Mercy , Sadek Ramses , Qiu Xiangguo , Shi Huidong , He Yukai 
Published: December 2021

Abstract

Background and Aims
Chimeric antigen receptor engineered T cells (CARTs) for HCC and other solid tumors are not as effective as they are for blood cancers. CARTs may lose function inside tumors due to persistent antigen engagement. The aims of this study are to develop low‐affinity monoclonal antibodies (mAbs) and low‐avidity CARTs for HCC and to test the hypothesis that low‐avidity CARTs can resist exhaustion and maintain functions in solid tumors, generating durable antitumor effects.

Methods and Results
New human glypican‐3 (hGPC3) mAbs were developed from immunized mice. We obtained three hGPC3‐specific mAbs that stained HCC tumors, but not the adjacent normal liver tissues. One of them, 8F8, bound an epitope close to that of GC33, the frequently used high‐affinity mAb, but with approximately 17‐fold lower affinity. We then compared the 8F8 CARTs to GC33 CARTs for their in vitro function and in vivo antitumor effects. In vitro, low‐avidity 8F8 CARTs killed both hGPC3high and hGPC3low HCC tumor cells to the same extent as high‐avidity GC33 CARTs. 8F8 CARTs expanded and persisted to a greater extent than GC33 CARTs, resulting in durable responses against HCC xenografts. Importantly, compared with GC33 CARTs, there were 5‐fold more of 8F8‐BBz CARTs in the tumor mass for a longer period of time. Remarkably, the tumor‐infiltrating 8F8 CARTs were less exhausted and apoptotic, and more functional than GC33 CARTs.

Conclusion
The low‐avidity 8F8‐BBz CART resists exhaustion and apoptosis inside tumor lesions, demonstrating a greater therapeutic potential than high‐avidity CARTs.
Identifying factors affecting dentists retention in deprived areas in Iran
Authors: Amiresmaeili Mohammadreza , Jamebozorgi Majid Heidari , Jamebozorgi Azam Heidari 
Published: December 2021

AbstractBackgroundOne of the concerns of health managers in regard to improving the oral health of residents in deprived areas is to increase the tendency of dentists to stay in those areas. The purpose of this study was to explore factors affecting the intention of dentists to stay in deprived areas.MethodsThe present qualitative study was carried out using semi‐structured interviews. We interviewed 22 informants (4 oral health managers and 18 dentists) who were identified purposefully. Informants were asked what factors affecting retention in remote and deprived areas. Content analysis through the 7‐step Colaizzi approach was used for data analysis.ResultsFifteen subthemes under five themes of individual factors, the development level of the region, social and cultural factors, financial issues, and managerial and organizational factors were identified as factors affecting tendency of dentist to stay and work in deprived areas.ConclusionAccording to the results of our study, health policymakers and managers should focus on culture and attitudes of the residents, Provision of financial incentives, structural problems and underdevelopment of the region, and high workload to increase the tendency of dentists to stay in remote and deprived areas.
Global health workforce research: Comparative analyses of the scientific publication trends in PubMed
Authors: Jesus Tiago S. , Castellini Greta , Gianola Silvia 
Published: December 2021

AbstractAimTo analyse the amount of Human Resources for Health (HRH) research publication trends [1990–2019], compared to the broader health policy, systems, and services research (HPSSR).MethodsPubMed and its indexation system with Medical Subject Headings (MeSH) are used for this time‐trend study. Searches combine MeSH terms for research publications and HPSSR or HRH subjects, except education. Sub‐group searches are conducted on: funding support, and high‐ versus low‐ and middle‐income countries (HICs vs. LMICs). Linear regressions are used for the analysis.ResultsHRH research publications rose exponentially (r2 = 0.94; p < 0.001) from 129 yearly publications in 1990, to 867 in 2018. Yet, HRH research publications had a logarithmic decrease (p < 0.001) in percentage of broader HPSSR publications, from 2.5% to 1.5% [1990–2018]. Funding support increased significantly and linearly (p < 0.001 r2 = 0.88), up to 44% in 2018. The percentage of HRH research publications addressing LMICs grew linearly (p < 0.001; r2 = 0.75), up to 23% in 2018.ConclusionHRH research publications in the PubMed database increased especially in the more recent years but did not outpace (in earlier times was outpaced) by the growth of HPSSR publications overall. Yearly, HICs still accounted for more than three‐quarters of HRH research. These findings can inform global and health research policies.
Application and progress of three‐dimensional bioprinting in spinal cord injury
Authors: Xia Qiu‐Qiu , Yuan Hao , Wang Ting‐Hua , Xiong Liu‐Lin , Xin Zhi‐Jun 
Published: December 2021

AbstractSpinal cord injury (SCI) is a central nervous system disorder that can lead to sensory and motor dysfunction, which can seriously increase pressure and economic burden on families and societies. The current SCI treatment is mainly to stabilize the spine, prevent secondary damage, and control inflammation. Drug treatment is limited to early, large‐scale use of steroids to reduce the effects of edema after SCI. In short, there is no direct treatment for SCI. Recent 3D bioprinting development provides a new solution for SCI treatment: a series of spinal cord bionic scaffolds are being developed to improve spinal cord function after injury. This paper reviews the pathophysiological characteristics of SCI, current treatment methods, and the progress of 3D bioprinting in SCI. Finally, its challenges and prospects in SCI treatment are summarized.
Application value and challenge of traditional Chinese medicine carried by ZIF‐8 in the therapy of ischemic stroke
Authors: Zhu Xiao‐Xi , Guo Dong‐Fen , Chen Ming , An Xiao‐Qiong , Wang Bi , Yu Wen‐Feng 
Published: December 2021

AbstractStroke is a group of major diseases that cause death or disability in adults, with high incidence and lack of available therapeutic strategies. Although traditional Chinese medicine (TCM) has continuously achieved good effects in the therapy of stroke while there is still not convincing due to the limitation of blood–brain permeability, as well as the individual differences in usage and dosage. With the improvement of nanotechnology, TCM nanopreparation has gradually become a research hotspot in various fields due to its advantages in permeating the blood–brain barrier, targeting delivery, enhancing sustained‐release drug delivery, changing the distribution in the body, and improving bioavailability. Zeolitic imidazolate framework‐8 (ZIF‐8) is an ideal nano‐drug delivery system for adsorption, catalysis, and drug loading, which is a biocompatible metal–organic framework framed by 2‐methylimidazole and zinc ions. At present, ZIF‐8 was wildly used in the treatment of ischemic stroke. However, challenges remain persists for its clinical application, such as preparation technology, detection technology in vivo, targeting specificity, safety and stability, and so forth. Therefore, more efforts need to overcome the above problems to develop the application of TCM nanopreparations in the therapy of ischemia/reperfusion in the future.
Effect of topdressing of compost, compost tea, and various fertilizers on soil and lawn characteristics
Authors: Bero Nicholas J. , Soldat Douglas J. 
Published: December 2021

AbstractMany cities in the United States collect and compost yard waste but need more effective and efficient ways to utilize the finished product. Home lawns represent a sizeable area that could benefit from land application of yard waste compost, but little research has been conducted regarding topdressing lawns with compost. The objectives of this study were to compare the impact of topdressing yard waste compost relative to organic and inorganic fertilizers in a mature, predominantly Kentucky bluegrass (Poa pratensis L.) lawn in Wisconsin. Three different composts (two from yard waste and one from food waste), two organic fertilizers, and a compost–compost tea combination were compared against a traditional synthetic fertilization program and a nontreated control. Treatments receiving compost (1.3 cm depth per year, in two equally sized applications) maintained acceptable turf quality over the 3.5‐yr study period and resulted in significant improvements in several important physical properties of the soil. Fertilizers were also able to maintain acceptable turfgrass quality but had no impact on the physical properties of soil over the study period relative to the control. Organic and synthetic fertilizers reduced weed populations compared with the control, though the compost treatments did not. Compost and one of the organic fertilizers significantly increased the levels of soil test P but did not reach levels of environmental concern.
Evaluation of the Pharmacokinetics and Safety of a Single Dose of Acalabrutinib in Subjects With Hepatic Impairment
Authors: Xu Yan , Izumi Raquel , Nguyen Helen , Kwan Anna , Kuo Howard , Madere Jeannine , Slatter J. Greg , Podoll Terry , Vishwanathan Karthick , Marbury Thomas , Smith William , Preston Richard A. , Sharma Shringi , Ware Joseph A. 
Published: December 2021

AbstractAcalabrutinib received approval for the treatment of adult patients with mantle cell lymphoma who received at least 1 prior therapy and adult patients with chronic lymphocytic leukemia or small lymphocytic lymphoma. This study investigated the impact of hepatic impairment (HI) on acalabrutinib pharmacokinetics (PK) and safety at a single 50‐mg dose in fasted subjects. This study was divided into 2 parts: study 1, an open‐label, parallel‐group study in Child‐Pugh class A or B subjects and healthy subjects; and study 2, an open‐label, parallel‐group study in Child‐Pugh class C subjects and healthy subjects. Baseline characteristics and safety profiles were similar across groups. Acalabrutinib exposure (area under the plasma concentration–time curve) increased slightly (1.90‐ and 1.48‐fold) in subjects with mild (Child‐Pugh class A) and moderate (Child‐Pugh class B) hepatic impairment compared with healthy subjects. In severe hepatic impairment (Child‐Pugh class C), acalabrutinib exposure (area under the plasma concentration–time curve and maximum plasma concentration) increased ≈5.0‐ and 3.6‐fold, respectively. Results were consistent across total and unbound exposures. Severe hepatic impairment did not impact total/unbound metabolite (ACP‐5862) exposures; the metabolite‐to‐parent ratio decreased to 0.6 to 0.8 (vs 3.1‐3.6 in healthy subjects). In summary, single oral dose of 50‐mg acalabrutinib was safe and well tolerated in subjects with mild, moderate, and severe hepatic impairment and in healthy control subjects. In subjects with severe hepatic impairment, mean acalabrutinib exposure increased by up to 5‐fold and should be avoided. Acalabrutinib does not require dose adjustment in patients with mild or moderate hepatic impairment.
Normal values of angle and distance between the superior mesenteric artery and aorta in Iraqi population: A single centre study
Authors: Hadi Sawsan Salah , Kareem Tara Farooq , Kamal Areege Mustafa 
Published: December 2021

AbstractIntroductionThe diagnosis of the superior mesenteric syndrome depends on measuring the distance and angle between the superior mesenteric artery (SMA) and aorta on CT scan in the presence of duodenal compression. Studies examining the normal range of these measurements are scarce and none of them was conducted on the Iraqi population. The aim of this study was to assess the values of aorto‐SMA angle (AMA) and aorto‐SMA distance (AMD) in asymptomatic patients to define the normal range in the Iraqi population and to compare it with the normal published range and different demographical values and body mass index (BMI).MethodsA total of 333 patients referred to arterial phase CT examinations for reasons unrelated to gastrointestinal tract were recruited. On axial and reformatted sagittal–oblique images, the angle and the distance between SMA and aorta were measured at the location where the duodenum crosses.ResultsBoth AMA and AMD had a wider range 10–147° and 4–44 mm, respectively, compared to the literature reported range. There was a significant reduction in AMA and AMD values in underweight participants (AMA, P < 0.001; and AMD, P = 0.014) and in female patients (AMA and AMD, P < 0.0001) and those who were younger than 20 (AMA, P = 0.014; and AMD, P = 0.001). A moderate correlation (r = 0.507, P < 0.0001) was found between AMA and AMD values. The correlation of BMI with AMD values was moderate (r = 0.46), and with AMA was weak (r = 0.23) (P < 0.0001).ConclusionVery low values of AMA and AMD can occur in normal asymptomatic patients without compressing the duodenum, which warrants further follow‐up studies. Evaluating normal values of AMA and AMD in the Iraqi population can help in providing a reference for CT‐based diagnosis of SMA syndrome.
Intra‐articular pressure characteristics of the knee joint: An exploratory study
Authors: Lee Jae H. , Kim Keewon , Chung Sun G. 
Published: December 2021

AbstractInflammation‐predominant osteoarthritis is an important clinical type of osteoarthritis, with synovitis suggested as its distinct pathophysiology. We investigated whether the synovium's mechanical properties in knees differed by osteoarthritis and other clinical parameters through retrospectively analyzing intra‐articular pressure–volume characteristics. We analyzed 60 knees that were administered intra‐articular corticosteroids while undergoing pressure monitoring. McMurray's test, pain complaints at end‐range knee flexion, Kellgren–Lawrence classification from standing anteroposterior radiographs, and suprapatellar effusion from ultrasound constituted clinical parameters. Pressure–volume profiles—phasic changes in pressure by volume infusion, the volume of Phase 1—the potential volume of the synovial space, the pressure at 45 ml infusion—intra‐articular pressure at a standardized volume, and the slope of Phase 2—synovial stiffness were compared with clinical parameters. All graphs were biphasic. Knees with suprapatellar effusion or radiologically definite osteoarthritis (Kellgren–Lawrence grade ≥2), had a lower Phase 1 volume. Knees with definite radiographic osteoarthritis also showed higher pressures at 45 ml and Phase 2 slopes (171.11 ± 94.35 mmHg and 5.08 ± 3.07 mmHg/ml, respectively) than those without (101.88 ± 58.12 mmHg and 2.84 ± 1.27 mmHg/ml, respectively). The Phase 2 slope was higher for knees with positive provocative tests than in those with negative provocative tests, although not statistically significant. The synovium stretched earlier in knees with effusion or radiologically definite osteoarthritis. Intra‐articular pressure and synovial stiffness were significantly higher in patients with radiologically definite osteoarthritis. The synovium's mechanical characteristics are altered by osteoarthritis of the knee joint. Intra‐articular pressure characteristics could be utilized for synovial evaluation clinically.
A non‐parametric approach for jointly combining evidence on progression free and overall survival time in network meta‐analysis
Authors: Daly Caitlin H. , Maconachie Ross , Ades A. E. , Welton Nicky J. 
Published: December 2021

AbstractRandomised controlled trials of cancer treatments typically report progression free survival (PFS) and overall survival (OS) outcomes. Existing methods to synthesise evidence on PFS and OS either rely on the proportional hazards assumption or make parametric assumptions which may not capture the diverse survival curve shapes across studies and treatments. Furthermore, PFS and OS are not independent; OS is the sum of PFS and post‐progression survival (PPS). Our aim was to develop a non‐parametric approach for jointly synthesising evidence from published Kaplan–Meier survival curves of PFS and OS without assuming proportional hazards. Restricted mean survival times (RMST) are estimated by the area under the survival curves (AUCs) up to a restricted follow‐up time. The correlation between AUCs due to the constraint that OS > PFS is estimated using bootstrap re‐sampling. Network meta‐analysis models are given for RMST for PFS and PPS and ensure that OS = PFS + PPS. Both additive and multiplicative network meta‐analysis models are presented to obtain relative treatment effects as either differences or ratios of RMST. The methods are illustrated with a network meta‐analysis of treatments for stage IIIA‐N2 non‐small cell lung cancer. The approach has implications for health economic models of cancer treatments, which require estimates of the mean time spent in the PFS and PPS health‐states. The methods can be applied to a single time‐to‐event outcome, and so have wide applicability in any field where time‐to‐event outcomes are reported, the proportional hazards assumption is in doubt, and survival curve shapes differ across studies and interventions.
A strategy for the enrichment and characterization of disulfide bond‐contained proteins from Chinese cobra (Naja atra) venom
Authors: Wei Yuanqing , Liu Ting , Zheng Binru , Song Yilin , Wang Shengsong , Zheng Mojuan , Xu Yanling , Chi Yumei , Zhao Ming , Duan Jin‐ao , Han Shuying , Liu Rui 
Published: December 2021

AbstractA new strategy combined gold‐coated magnetic nanocomposites assisted enrichment with mass spectrometry was developed for the characterization of disulfide bond‐contained proteins from Chinese cobra (Naja atra) venom. In this work, core‐shell nanocomposites were synthesized by the seed‐mediated growth method and used for the enrichment of snake venom proteins containing disulfide bonds. A total of 3545 tryptic digested peptides derived from 96 venom proteins in Naja atra venom were identified. The venom proteins comprised 14 toxin families including three‐finger toxins, phospholipase A2, snake venom metalloproteinase, cobra venom factor, and so forth. Extra 16 venom proteins were detected exclusively in the nanocomposites set, among which 11 venom proteins were from the three‐finger toxins family. In the present study, the proposed simple and efficient protocol replaced the tedious and laborious technologies commonly used for pre‐separating crude snake venom, suggesting widely implementation in low‐abundance or trace disulfide bond‐contained proteins or peptides characterization.
Gas chromatography of essential oil: State‐of‐the‐art, recent advances, and perspectives
Authors: Cagliero Cecilia , Bicchi Carlo , Marengo Arianna , Rubiolo Patrizia , Sgorbini Barbara 
Published: December 2021

AbstractThis review is an overview of the recent advances of gas chromatography in essential oil analysis; in particular, it focuses on both the new stationary phases and the advanced analytical methods and instrumentations. A paragraph is dedicated to ionic liquids as gas chromatography stationary phases, showing that, thanks to their peculiar selectivity, they can offer a complementary contribution to conventional stationary phases for the analysis of complex essential oils and the separation of critical pairs of components. Strategies to speed‐up the analysis time, thus answering to the ever increasing request for routine essential oils quality control, are also discussed. Last but not least, a paragraph is dedicated to recent developments in column miniaturization in particular that based on microelectromechanical‐system technology in a perspective of developing micro‐gas chromatographic systems to optimize the energy consumption as well as the instrumentation dimensions. A number of applications in the essential oil field is also included.
Molecularly imprinted monoliths: Recent advances in the selective recognition of biomacromolecules related biomarkers
Authors: Song Qingmei , Wang Bingwu , Lv Yongqin 
Published: December 2021

AbstractBiomarkers are significant indicators to assist the early diagnosis of diseases and assess the therapeutic response. However, due to the low abundance of biomarkers in complex biological fluids, it is highly desirable to explore efficient techniques to attain their selective recognition and capture before the detection. Molecularly imprinted monoliths integrate the high selectivity of imprinted polymers and the rapid convective mass transport of monoliths, and as a result, are promising candidates to achieve the specific enrichment of biomarkers from complex samples. This review summarizes the various imprinting approaches for the preparation of molecularly imprinted monoliths. The state‐of‐art advances as an effective platform for applications in the selective capture of biomacromolecules related biomarkers were also outlined.
Phenylboronic acid‐functionalized cross‐linked chitosan magnetic adsorbents for the magnetic solid‐phase extraction of benzoylurea pesticides
Authors: Cui Xiaoyan , Wang Yujiao , Yan Yumei , Meng Zilin , Lu Runhua , Gao Haixiang , Pan Canping , Wei Xinlin , Zhou Wenfeng 
Published: December 2021

AbstractIn this study, a 4‐formylphenylboronic acid‐modified cross‐linked chitosan magnetic nanoparticle (FPBA@CCHS@Fe3O4) was fabricated. The synthesized material was utilized as the magnetic solid‐phase extraction adsorbent for the enrichment of six benzoylurea pesticides. In addition to B‐N coordination, FPBA@CCHS@Fe3O4 interacts with benzoylureas through hydrogen bonds and π‐π stacking interaction on account of rich active groups (amino and hydroxyl) and aromatic rings in structure. Compared to traditional extraction methods, less adsorbent (20 mg) and reduced extraction time (3 min) were achieved. The adsorbent also exhibited good reusability (no less than 10 times). Coupled with a high‐performance liquid chromatography–diode array detector, satisfactory recoveries (89.1–103.9%) and an acceptable limit of detection (0.2–0.7 μg/L) were obtained. Under optimized conditions, the established method was successfully applied to the tea infusion samples from six major tea categories with acceptable recoveries ranging from 76.8 to 110%, indicating its application potential for the quantitative detection of pesticides in complex matrices.
A Transient Initiator for Polypeptoids Postpolymerization α‐Functionalization via Activation of a Thioester Group
Authors: Borova Solomiia , Schlutt Christine , Nickel Joachim , Luxenhofer Robert 
Published: December 2021

AbstractHere, a postpolymerization modification method for an α‐terminal functionalized poly‐(N‐methyl‐glycine), also known as polysarcosine, is introduced. 4‐(Methylthio)phenyl piperidine‐4‐carboxylate as an initiator for the ring‐opening polymerization of N‐methyl‐glycine‐N‐carboxyanhydride followed by oxidation of the thioester group to yield an α‐terminal reactive 4‐(methylsulfonyl)phenyl piperidine‐4‐carboxylate polymer is utilized. This represents an activated carboxylic acid terminus, allowing straightforward modification with nucleophiles under mild reaction conditions and provides the possibility to introduce a wide variety of nucleophiles as exemplified using small molecules, fluorescent dyes, and model proteins. The new initiator yielded polymers with well‐defined molar mass, low dispersity, and high end‐group fidelity, as observed by gel permeation chromatography, nuclear magnetic resonance spectroscopy, and matrix‐assisted laser desorption/ionization time‐of‐flight mass spectroscopy. The introduced method can be of great interest for bioconjugation, but requires optimization, especially for protein conjugation.