bluuebunny/crossref_metadata_2025_split huggingface dataset:
Quantitative autofluorescence findings in patients undergoing hydroxychloroquine treatment
Authors: Parrulli Salvatore , Cozzi Mariano , Airaldi Matteo , Romano Francesco , Viola Francesco , Sarzi‐Puttini Piercarlo , Staurenghi Giovanni , Invernizzi Alessandro 
Published: May 2022

AbstractBackgroundTo measure quantitative autofluorescence (qAF) in patients under treatment with hydroxychloroquine (HCQ) and at risk of retinal toxicity but with no apparent signs of retinal toxicity and to compare it with that of untreated subjects.MethodsConsecutive patients at risk for the development of HCQ retinal toxicity (duration of treatment >5 years or daily HCQ dose >5 mg/kg of actual body weight [ABW]) but no alterations on spectral domain—optical coherence tomography, short‐wavelength autofluorescence and 10–2 visual field examination were recruited. Healthy subjects matched by age and sex were also enrolled in the study. All subjects underwent qAF measurements in one eye. Images were analysed using the conventional qAF grid by Delori calculating the qAF of eight sectors of the intermediate ring and the mean of those values (qAF8).ResultsThirty‐nine patients treated with HCQ (38 females, mean age 52.1 ± 8.6 years) and 39 untreated subjects (38 females, mean age 51.2 ± 8.6 years) were included. In both HCQ patients and untreated subjects, qAF8 was positively correlated with age (p = 0.004). Although HCQ patients showed a higher mean qAF8 compared with untreated subjects (294.7 ± 65.3 vs. 268.9 ± 57.5), the difference was not significant (p = 0.068). HCQ patients showed significantly higher mean qAF values in the inferior‐temporal, inferior and inferior‐nasal sectors of the intermediate ring of qAF grid compared with untreated subjects (all p < 0.05).ConclusionsThese results suggest a possible preclinical increase of qAF values in inferior parafoveal sectors probably induced by HCQ exposure.
‘We can play tag with a stick’. Children's knowledge, experiences, feelings and creative thinking during the COVID‐19 pandemic
Authors: Waboso Nwakerendu , Donison Laurel , Raby Rebecca , Harding Evan , Sheppard Lindsay C. , Grossman Keely , Myatt Haley , Black Sara 
Published: May 2022

AbstractUsing a relational approach, we draw on repeated interviews with a group of 30 diverse children from Ontario to share and reflect on their knowledge, experiences and feelings early in the COVID‐19 pandemic. Prioritising relational interdependence and relational agency, this paper illustrates our participants' embedded engagements with the pandemic and their contribution to the co‐production of knowledge. We emphasise their thoughtful responses to the pandemic; their creative, self‐reflexive strategies for managing a difficult time; and their advice to others. We thus prioritise children's viewpoints and emphasise their relational interconnections with others during a time that was marked by social isolation.
Programmed cell death ligand 1 expression on monocytes is inversely correlated with tumour response to preoperative chemoradiotherapy for locally advanced rectal cancer
Authors: Tojo Mineyuki , Horie Hisanaga , Koinuma Koji , Miyato Hideyo , Tsukui Hidenori , Kaneko Yuki , Futoh Yurie , Kimura Yuki , Takahashi Kazuya , Saito Akira , Ohzawa Hideyuki , Yamaguchi Hironori , Lefor Alan Kawarai , Sata Naohiro , Kitayama Joji 
Published: May 2022

AbstractAimThe clinical efficacy of chemoradiotherapy (CRT) is largely dependent on host immune status. The aim of this study was to identify possible markers expressed on circulating mononuclear cells to predict tumour response in patients with locally advanced rectal cancer (LARC).MethodsPeripheral blood samples were obtained from 47 patients diagnosed with LARC before and after CRT. The numbers of lymphocytes and monocyte subsets were analysed using flow cytometry. Based on clinical and pathological findings, patients were classified as high or low responders.ResultsLymphocyte counts were markedly decreased after CRT. Total numbers of lymphocytes (p = 0.030) and CD4(+) T cells (p = 0.041) in post‐CRT samples were significantly lower in low responders than in high responders. In contrast, monocyte counts were not reduced and the number of CD14dim(+) CD16(+) nonclassical (patrolling) monocytes were somewhat increased after CRT (p = 0.050). Moreover, the ratios of programmed cell death ligand 1 (PD‐L1) (+) cells on patrolling monocytes before and after CRT were significantly higher in low responders than in high responders (p = 0.0046, p = 0.0006). The same trend was observed for classical and intermediate monocytes. The expression of PD‐L1 on patrolling monocytes before CRT correlated inversely with the number of T cells and natural killer (NK) cells after CRT. PD‐L1(+) ratio in patrolling monocytes was an independent predictor for response to CRT.ConclusionProgrammed cell death ligand 1 (PD‐L1) expression on patrolling monocytes suppresses cell‐mediated immunity in patients receiving CRT which could be related to tumour response, and may be a useful biomarker for decision‐making in the management of patients with LARC.
Tubulin‐binding peptide RR‐171 derived from human umbilical cord serum displays antitumor activity against hepatocellular carcinoma via inducing apoptosis and activating the NF‐kappa B pathway
Authors: Zhu Donglie , Fang Cheng , Yang Zelong , Ren Yanjie , Yang Fengrui , Zheng Shi , Jiang Mingzuo , Miao Xiangxia , Liu Duoduo , Chen Biliang , Yao Xuebiao , Chen Yong 
Published: May 2022

AbstractObjectivesHepatocellular carcinoma (HCC) still presents a high incidence of malignant tumours with poor prognosis. There is an urgent need for new therapeutic agents with high specificity, low toxicity and favourable solubility for the clinical treatment of HCC.Materials and MethodsThe bioactivity of human umbilical cord serum was investigated by proteomics biotechnology and a primitive peptide with certain biological activity was identified. The antitumour effect of RR‐171 was detected by cell viability assay in vitro, and determined by subcutaneous xenograft models assay and miniPDX assay in vivo. Pull‐down experiments were conducted to identify the potential targeting proteins of RR‐171. Immunofluorescence assay and tubulin polymerization assay were conducted to explore the relationship between RR‐171 and α‐tubulin. Fluorescence imaging in xenograft models was used to explore the biodistribution of RR‐171 in vivo. A phosphospecific protein microarray was performed to uncover the underlying signalling pathway by which RR‐171 induces tumour cell death.ResultsThe results indicated that RR‐171 could be effective in the treatment of HCC in vivo and in vitro. RR‐171 could aggregate significantly in solid tumours and had no obvious systemic toxicity in vivo. RR‐171 could interact with α‐tubulin and activate the NF‐Kappa B pathway in HCC cells.ConclusionsTaken together, RR‐171 exhibited significant antitumour activity against HCC in vivo and in vitro and could potentially be used in the clinical application of HCC.
GFI1 regulates chromatin state essential in human endothelial‐to‐haematopoietic transition
Authors: Kang Baoqiang , Zhang Tian , Huang Ke , Wang Tianyu , Li Yuhang , Mai Yuchan , Li Jinbing , Dang Shiying , Zhang Zhishuai , Huang Wenhao , Wang Junwei , Gao Minghui , Wang Yi , Pan Guangjin 
Published: May 2022

AbstractObjectivesDuring embryonic haematopoiesis, haematopoietic stem/progenitor cells (HSPCs) develop from hemogenic endothelial cells (HECs) though endothelial to haematopoietic transition (EHT). However, little is known about how EHT is regulated in human. Here, we report that GFI1 plays an essential role in enabling normal EHT during haematopoietic differentiation of human embryonic stem cells (hESCs).ResultsGFI1 deletion in hESCs leads to a complete EHT defect due to a closed chromatin state of hematopoietic genes in HECs. Mechanically, directly regulates important signaling pathways essential for the EHT such as PI3K signaling.etc.ConclutionsTogether, our findings reveal an essential role of GFI1 mediated epigenetic mechanism underlying human EHT during hematopoiesis.
Ordering decisions under supply uncertainty and inventory record inaccuracy: An experimental investigation
Authors: Hofstra Nienke , Spiliotopoulou Eirini , de Leeuw Sander 
Published: May 2022

AbstractUncertainty on the supply side is a common issue planners face. How do decision‐makers incorporate inventory uncertainty when placing orders? We investigate ordering decisions under two forms of uncertainty regarding total inventory available to satisfy demand: supply uncertainty (SU; unreliability in incoming shipments) and inventory record inaccuracy (IRI; internal inefficiencies leading to a discrepancy between physical and recorded inventories). The experimental results reveal behavioral regularities in ordering decisions under both forms of total inventory uncertainty. We find that subjects overstock in settings with low profit margins, and overstocking is more pronounced under IRI than under SU. This overstocking under low profit margins is similar to observed ordering decisions under demand uncertainty. In these settings, subjects show a stronger shortage aversion under IRI (which is internal uncertainty) than under SU (which is external uncertainty). Furthermore, we find that subjects chase past realizations of supply/on‐hand inventory, although the effect depends on the uncertainty type. Although SU and IRI are, in practice, often simultaneously present, their causes are different. By providing insight into the relative effect of the types of uncertainty on the quality of inventory replenishment decisions, this study highlights the importance of reducing SU and IRI for products with low profit margins.
Entomopathogenic potential of Bacillus subtilis and Bacillus amyloliquefaciens strains against Musca domestica under controlled conditions
Authors: Torres María Julia , Rocha Voyko Flores , Petroselli Gabriela , Villena Reinaldo Rojas , Audisio Marcela Carina 
Published: May 2022

AbstractThe housefly, Musca domestica L. (Diptera: Muscidae), is a key pest in animal production areas; the resistance of this insect to chemical insecticides makes it necessary to develop new control alternatives. The aim of this work was to study the entomopathogenic activity of eight strains of Bacillus subtilis Ehrenberg ssp. subtilis and two strains of Bacillus amyloliquefaciens Priest et al., isolated from different ecological niches, against the housefly. Cell suspension (CS) of each Bacillus strain and cell‐free supernatant (CFS) and crude lipopeptide fraction (LF) of 7 mg ml−1 of B. amyloliquefaciens CBMDDrag3 and CBMDLO3 strains were evaluated. Various housefly cohorts, resulting from systematic crosses, were used for the bioassays. The eight strains of B. subtilis ssp. subtilis affected the survival of the larvae by 10–20%, whereas strains CBMDDrag3 and CBMDLO3 decreased the survival of these individuals by 30 and 50%, respectively. CBMDLO3 was the strain with the highest pupicidal activity, reducing the survival of these individuals by up to 50%. To evaluate the effect of CBMDLO3 on the fertility of housefly females and longevity of individuals, adults from larvae fed CS, CFS, and LF were used. Females from the CS and CFS diets reduced their oviposition capacity by approximately 50% compared to females from the DL and DMH control diets (i.e., DCS 144.3 eggs, DCFS 128 eggs, and DL 346.5 eggs, respectively). On the other hand, the life cycle of females and males was only affected by LF, i.e., 4 and 6 days shorter than the control, respectively. The UV MALDI TOF analysis of CBMDLO3 LF identified several surfactin homologues. Results show the ability of B. amyloliquefaciens CBMDLO3 strain to reduce the survival of larvae and pupae of M. domestica and the fecundity of female adults, thus allowing cycles of inhibition of housefly development in laying hen farms. Therefore, B. amyloliquefaciens CBMDLO3 strain can make an important contribution to the continuous search of new biocontrol alternatives.
Long‐term safety and efficacy of ravulizumab in patients with paroxysmal nocturnal hemoglobinuria: 2‐year results from two pivotal phase 3 studies
Authors: Kulasekararaj Austin G. , Griffin Morag , Langemeijer Saskia , Usuki Kensuke , Kulagin Alexander , Ogawa Masayo , Yu Ji , Mujeebuddin Arshad , Nishimura Jun‐ichi , Lee Jong Wook , Peffault de Latour Régis ,   301/302 Study Group
Published: May 2022

AbstractObjectivesThe complement component 5 (C5) inhibitor ravulizumab demonstrated non‐inferiority to eculizumab following 26 weeks of treatment in complement inhibitor‐naïve and complement inhibitor‐experienced patients with paroxysmal nocturnal hemoglobinuria (PNH; studies 301 and 302, respectively). This study aims to describe the results of both studies from 27 weeks to 2 years.MethodsPatients (N = 441) continued to receive ravulizumab throughout the extension period. Efficacy endpoints included lactate dehydrogenase (LDH) normalization, transfusion avoidance and fatigue score (FACIT‐F). Safety analyses were also performed.ResultsFrom 27 weeks to 2 years, improvements in LDH levels were maintained in both study populations. Transfusion avoidance was maintained in 81.9% (study 301) and 85.6% (study 302) of patients, and FACIT‐F scores remained stable. Ravulizumab was well tolerated, and the incidence of adverse events (AEs) were similar between patients of both studies. Incidence of serious AEs deemed related to ravulizumab treatment was low (<3%).ConclusionsThis study reports, to date, the longest period of follow‐up in over 400 patients with PNH treated with ravulizumab (662 patient‐years). Long‐term, ravulizumab demonstrated durable efficacy and was well tolerated, highlighting the importance of C5 inhibitors as the mainstay of PNH treatment.
Lung adenocarcinoma manifesting as subsolid nodule potentially represents tumour in the equilibrium phase of immunoediting
Authors: Xiao Rongxin , Ma Yi , Li Hao , Li Xiao , Sun Zewen , Qi Qingyi , Yin Ping , Yang Fan , Qiu Mantang 
Published: May 2022

AbstractLung adenocarcinomas manifesting as subsolid nodules (SSN‐LUADs) possess distinct dormant behaviour. This study was designed to compare the immune landscapes of normal lungs (nLungs), SSN‐LUADs and LUADs manifesting as solid nodules (SN‐LUADs) so as to better understand the status of anti‐tumour immunity in SSN‐LUADs. Mass cytometry by time‐of‐flight analysis was performed on 299, 570 single cells from nLung, SSN‐LUAD and SN‐LUAD tissues. The immune cells were identified by phenotype, and the percentages of different immune cell subclusters were compared between SSN‐LUADs, SN‐LUADs and nLungs. Elevated percentage of CD8+ T cells were identified in SSN‐LUADs compared with in nLungs and SN‐LUADs. Elevated CD56bright NK cells and decreased CD56dim NK cells were identified in both SSN‐LUADs and SN‐LUADs compared with in nLungs. The immune landscape of SSN‐LUAD fits the theory of equilibrium phase of immunoediting, thus functional adaptive anti‐tumour immunity but impaired innate anti‐tumour immunity potentially contributes to the maintaining of its dormant behaviour.
Ketoprofen, piroxicam and indomethacin-suppressed quorum sensing and virulence factors in Acinetobacter baumannii
Authors: Elshaer Soha Lotfy , Shaldam Moataz A. , Shaaban Mona I. 
Published: May 2022

AbstractAimQuorum sensing (QS) inhibition is a promising strategy to suppress bacterial virulence and control infection caused by Gram-negative and Gram-positive bacteria. This study explores the QS inhibiting activity of the non-steroidal anti-inflammatory drugs (NSAIDs) in Acinetobacter baumannii.Methods and ResultsKetoprofen, piroxicam and indomethacin revealed QS inhibition via elimination of violacein production of the reporter strain Chromobacterium violaceum ATCC 12472 without affecting bacterial growth. The minimal inhibitory concentration (MIC) of ketoprofen, piroxicam and indomethacin was determined against A. baumannii strains ATCC 17978, ATCC 19606, A1, A11 and A27 by the microbroth dilution method. The MICs of ketoprofen against tested isolates were 0.7–6.25 mg ml−1, piroxicam MICs were 1.25–2.5 mg ml−1, and indomethacin MICs were 3.12–12.5 mg ml−1. Those compounds significantly inhibited QS-associated virulence factors such as biofilm formation, and surface motility, as well as, significantly increased bacterial tolerance to oxidative stress without affecting bacterial growth. On the molecular level, the three compounds significantly inhibited the transcription of QS regulatory genes abaI/abaR and biofilm-regulated genes cusD and pgaB. Molecular docking analysis revealed the potent binding affinity of the three compounds with AbaI via hydrogen and/or hydrophobic bonds.ConclusionThese results indicate that NSAIDs, ketoprofen, piroxicam and indomethacin, could be potential inhibitors of the QS and could suppress the QS-related virulence factors of A. baumannii.Significance and ImpactKetoprofen, piroxicam and indomethacin could provide promising implications and strategies for combating the virulence and pathogenesis of A. baumannii.
Betelvine (Piper betleL.): A comprehensive insight into its ethnopharmacology, phytochemistry, and pharmacological, biomedical and therapeutic attributes
Authors: Biswas Protha , Anand Uttpal , Saha Suchismita Chatterjee , Kant Nishi , Mishra Tulika , Masih Harison , Bar Ananya , Pandey Devendra Kumar , Jha Niraj Kumar , Majumder Madhumita , Das Neela , Gadekar Vijaykumar Shivaji , Shekhawat Mahipal S. , Kumar Manoj , Radha  , Proćków Jarosław , Lastra José M. Pérez de la , Dey Abhijit 
Published: May 2022

AbstractPiper betleL. (synonym:Piper betelBlanco), or betel vine, an economically and medicinally important cash crop, belongs to the family Piperaceae, often known as the green gold. The plant can be found all over the world and is cultivatedprimarily in South East Asian countries for its beautiful glossy heart‐shaped leaves, which are chewed or consumed as betelquidand widely used in Chinese and Indian folk medicine, as carminative, stimulant,astringent, against parasitic worms, conjunctivitis, rheumatism, wound, etc., andis also used for religious purposes. Hydroxychavicol is the most important bioactive compound among the wide range of phytoconstituents found in essential oil and extracts. The pharmacological attributes ofP. betleare antiproliferation, anticancer, neuropharmacological, analgesic, antioxidant, antiulcerogenic, hepatoprotective, antifertility, antibacterial, antifungal and many more. Immense attention has been paid to nanoformulations and their applications. The application ofP. betledid not show cytotoxicity in preclinical experiments, suggesting that it could serve as a promising therapeutic candidate for different diseases. The present review comprehensively summarizes the botanical description, geographical distribution, economic value and cultivation, ethnobotanical uses, preclinical pharmacological properties with insights of toxicological, clinical efficacy, and safety ofP. betle. The findings suggest thatP. betlerepresents an orally active and safe natural agent that exhibits great therapeutic potential for managing various human medical conditions. However, further research is needed to elucidate its underlying molecular mechanisms of action, clinical aspects, structure–activity relationships, bioavailability and synergistic interactions with other drugs.
Long‐term proton pump inhibitor use and risk of osteoporosis and hip fractures: A nationwide population‐based and multicenter cohort study using a common data model
Authors: Park Da Hee , Seo Seung In , Lee Kyung Joo , Kim Jinseob , Kim Yerim , Seo Won‐Woo , Lee Hyung Seok , Shin Woon Geon , Yoo Jong Jin 
Published: May 2022

AbstractBackground and AimAssociation between protonpump inhibitors (PPIs) and osteoporosis, hip fractures has not been fully elucidated. We aimed to evaluate the relationship between PPIs use and the risk of osteoporosis and hip fractures in the databases converted to a common data model (CDM) and to compare the results across the databases.MethodsThis was a population‐based, propensity‐matched, retrospective cohort study that included patients aged ≥ 50 years who were prescribed with PPIs for over 180 days. We compared the incidence of osteoporosis and hip fractures between new PPI user and new user of other drugs using the Cox proportional hazards model and performed meta‐analysis in the electronic health record (EHR) databases.ResultsIn the Korean National Health Insurance Service (NHIS)–CDM database, long‐term PPI users had greater risk of osteoporosis [PPIs vs non‐PPIs groups, 28.42/1000 person‐years vs 19.29/1000 person‐years; hazard ratio (HR), 1.62; 95% confidence interval (CI), 1.22–2.15; P = 0.001]. The meta‐analytic results of six EHR databases also showed similar result (pooled HR, 1.57; 95% CI, 1.28–1.92). In the analysis of hip fracture, PPI use was not significantly associated with a hip fracture in the NHIS–CDM database (PPI vs non‐PPI groups, 3.09/1000 person‐years vs 2.26/1000 person‐years; HR, 1.45; 95% CI, 0.74–2.80; P = 0.27). However, in the meta‐analysis of four EHR databases, the risk of hip fractures was higher in PPI users (pooled HR, 1.82; 95% CI, 1.04–3.19).ConclusionsLong‐term PPI was significantly associated with osteoporosis; however, the results of hip fractures were inconsistent. Further study based on better data quality may be needed.
Turning trash into treasure: An approach to the environmental assessment of waste prevention and its application to clothing and furniture in Switzerland
Authors: Wiprächtiger Maja , Rapp Martina , Hellweg Stefanie , Shinde Rhythima , Haupt Melanie 
Published: May 2022

AbstractAccording to the waste hierarchy, waste prevention is environmentally superior to recycling or recovery, hence its inclusion in government policy. The assessment and prioritization of waste prevention strategies are impeded, inter alia, by ambiguous definitions and the lack of a sound environmental assessment method. In this study, a systematic approach to the environmental assessment of waste prevention activities (WPAs), covering the whole life cycle of products, was developed. The approach combines material flow analysis and life cycle assessment with a sustainable circular system design framework whilst giving special consideration to pivotal factors such as diffusion factor (share of population engaging in WPA), substitutability (degree to which a new product is replaced), effects on use‐phase impacts, and rebound effects. The application of the approach to the case studies of clothing and household furniture in Switzerland revealed lower impact saving potential than assumed initially, due to lack of participation, low substitutability, or high rebounds. For example, reusing clothing locally, instead of exporting it to low‐income countries, as currently done, displayed no or even negative impact savings since secondhand clothing in high‐income countries is often consumed in addition to new clothing. Drastic scenarios for clothes led to only moderate impact reductions of less than 15%, whereas a take‐back scheme for furniture reduced impacts by 70%. Concluding, the four factors (diffusion rate, substitutability, effects on use‐phase impacts, and rebounds) proved crucial in the assessment of waste prevention strategies and the approach presented was able to pinpoint improvement potentials of the waste prevention scenarios investigated.