bluuebunny/crossref_metadata_2025_split huggingface dataset:
Tools and guidelines to assess the appropriateness of medication and aid deprescribing: An umbrella review
Authors: Anlay Degefaye Zelalem , Paque Kristel , Van Leeuwen Ellen , Cohen Joachim , Dilles Tinne 
Published: September 2023

AimsThe aim of this umbrella review was to identify tools and guidelines to aid the deprescribing process of potentially inappropriate medications (PIMs), evaluate development and validation methods, and describe evidence levels for medication inclusion.MethodsSearches were conducted on MEDLINE (Ovid), Embase.com, Cochrane CDSR, CINAHL (EBSCO), Web of Science Core Collection and guideline databases from the date of inception to 7 July 2022. Following the initial search, an additional search was conducted to identify an updated versions of tools on 17 July 2023. We analysed the contents of tools and guidelines.ResultsFrom 23 systematic reviews and guidelines, we identified 95 tools (72 explicit, 12 mixed and 11 implicit) and nine guidelines. Most tools (83.2%) were developed to use for older persons, including 14 for those with limited life expectancy. Seven tools were for children <18 years (7.37%). Most explicit/mixed tools (78.57%) and all guidelines were validated. We found 484 PIMs and 202 medications with different appropriateness independent of disease for older persons with normal and limited life expectancy, respectively. Only two tools and eight guidelines reported the evidence level, and a quarter of medications had high‐quality evidence.ConclusionsTools are available for a diversity of populations. There were discrepancies, with the same medication being classified as inappropriate in some tools and appropriate in others, possibly due to low‐quality evidence. In particular, tools for patients with limited life expectancy were developed based on very limited evidence, and research to generate this evidence is urgently needed. Our medication lists, along with the level of evidence, could facilitate efforts to strengthen the evidence.
Myeloperoxidase creates a permissive microenvironmental niche for the progression of multiple myeloma
Authors: Williams Connor M. D. , Noll Jacqueline E. , Bradey Alanah L. , Duggan Jvaughn , Wilczek Vicki J. , Masavuli Makutiro G. , Grubor‐Bauk Branka , Panagopoulos Romana A. , Hewett Duncan R. , Mrozik Krzysztof M. , Zannettino Andrew C. W. , Vandyke Kate , Panagopoulos Vasilios 
Published: September 2023

SummaryExpression of myeloperoxidase (MPO), a key inflammatory enzyme restricted to myeloid cells, is negatively associated with the development of solid tumours. Activated myeloid cell populations are increased in multiple myeloma (MM); however, the functional consequences of myeloid‐derived MPO within the myeloma microenvironment are unknown. Here, the role of MPO in MM pathogenesis was investigated, and the capacity for pharmacological inhibition of MPO to impede MM progression was evaluated. In the 5TGM1‐KaLwRij mouse model of myeloma, the early stages of tumour development were associated with an increase in CD11b+ myeloid cell populations and an increase in Mpo expression within the bone marrow (BM). Interestingly, MM tumour cell homing was increased towards sites of elevated myeloid cell numbers and MPO activity within the BM. Mechanistically, MPO induced the expression of key MM growth factors, resulting in tumour cell proliferation and suppressed cytotoxic T‐cell activity. Notably, tumour growth studies in mice treated with a small‐molecule irreversible inhibitor of MPO (4‐ABAH) demonstrated a significant reduction in overall MM tumour burden. Taken together, our data demonstrate that MPO contributes to MM tumour growth, and that MPO‐specific inhibitors may provide a new therapeutic strategy to limit MM disease progression.
Prevalence of urolithiasis in China: a systematic review and meta‐analysis
Authors: Tan Songsong , Yuan Dongbo , Su Hao , Chen Weihong , Zhu Siqi , Yan Bo , Sun Fa , Jiang Kehua , Zhu Jianguo 
Published: September 2023

ObjectiveTo estimate the pooled prevalence, as well as the spatial and temporal distribution, of urolithiasis among subjects in China.Materials and MethodsWe conducted a comprehensive search of both Chinese and English databases to retrieve literature pertaining to the prevalence of urolithiasis in the indigenous Chinese population. A random‐effects meta‐analysis model was employed to calculate the pooled prevalence of urolithiasis. Subgroup analyses were conducted based on factors such as time, region, gender, and sample size. Prevalence and spatial distribution maps were created based on provinces and latitude/longitude coordinates.ResultsA total of 46 studies conducted in 22 provinces across China were included in this meta‐analysis and the pooled prevalence of urolithiasis, kidney stones, ureteric calculi, urethral and bladder stones were 8.1% (95% confidence interval [CI] 5.6–11.1%), 7.8% (95% CI 5.8–10.0%), 3.2% (95% CI 0.6–5.7%), 0.5% (95% CI 0.1–0.9%). Most of the urolithiasis prevalence screening in China was concentrated between 100° E and 120° E, with higher rates observed in low latitude areas. Subgroup analysis of kidney stones revealed that Guangdong (12.7%) and Guangxi (10.3%) had the highest prevalence, with the eastern developed area exhibiting higher rates compared to the west. The prevalence in males was higher than in females (odds ratio 1.67, 95% CI 1.46–1.92), although the gender gap has significantly reduced since 2006. Moreover, a greater sample size is associated with a decreased prevalence of urolithiasis.ConclusionsThe prevalence of urolithiasis is increasing in China, and there are noteworthy regional or provincial disparities in occurrence. It is worth noting that the current number of screening studies in some areas is insufficient. Additional investigations with appropriate sample sizes should be supplemented in time.
Outsource to India: The impact of service outsourcing to India on the labor market in the United States
Authors: Park Jiwon 
Published: September 2023

AbstractService offshoring raises the fear of job loss for high‐skilled workers, unlike goods offshoring, because workers at home compete with highly educated workers in low‐income countries. This paper examines whether the increase in the United States's service offshoring to India has reduced the domestic employment of the occupations with greater exposure to Indian service imports. To account for endogeneity, I instrument for the growth of the United States's service imports from India by exploiting the change in Indian exports to European countries. Service offshoring reduces total employment from 2000 to 2006; however, this effect disappears overall and becomes positive for college‐educated workers in the later period from 2006 to 2016. Unlike goods offshoring, the employment effect is largely driven by college‐educated workers, and the employment growth in the later period is larger.
Flucloxacillin worsens while imipenem–cilastatin protects against vancomycin‐induced kidney injury in a translational rat model
Authors: Pais Gwendolyn M. , Marianski Sylwia , Valdez Kimberly , Melicor Renz Paulo , Liu Jiajun , Rohani Roxane , Chang Jack , Tong Steven Y. C. , Davis Joshua S. , Scheetz Marc H. 
Published: September 2023

Background and PurposeVancomycin is one of the most common clinical antibiotics, yet acute kidney injury is a major limiting factor. Common combinations of antibiotics with vancomycin have been reported to worsen and improve vancomycin‐induced kidney injury. We aimed to study the impact of flucloxacillin and imipenem–cilastatin on kidney injury when combined with vancomycin in our translational rat model.Experimental ApproachMale Sprague–Dawley rats received allometrically scaled (1) vancomycin, (2) flucloxacillin, (3) vancomycin + flucloxacillin, (4) vancomycin + imipenem–cilastatin or (5) saline for 4 days. Kidney injury was evaluated via drug accumulation and urinary biomarkers including urinary output, kidney injury molecule‐1 (KIM‐1), clusterin and osteopontin. Relationships between vancomycin accumulation in the kidney and urinary kidney injury biomarkers were explored.Key ResultsUrinary output increased every study day for vancomycin + flucloxacillin, but after the first dose only in the vancomycin group. In the vancomycin + flucloxacillin group, urinary KIM‐1 increased on all days compared with vancomycin. In the vancomycin + imipenem–cilastatin group, urinary KIM‐1 was decreased on Days 1 and 2 compared with vancomycin. Similar trends were observed for clusterin. More vancomycin accumulated in the kidney with vancomycin + flucloxacillin compared with vancomycin and vancomycin + imipenem–cilastatin. The accumulation of vancomycin in the kidney tissue correlated with increasing urinary KIM‐1.Conclusions and ImplicationsVancomycin + flucloxacillin caused more kidney injury compared with vancomycin alone and vancomycin + imipenem–cilastatin in a translational rat model. The combination of vancomycin + imipenem–cilastatin was nephroprotective.
The roles of apolipoprotein E ε4 on neuropathology and neuroinflammation in patients with Alzheimer's disease
Authors: He Mingyue , Lian Tenghong , Guo Peng , Zhang Weijiao , Zhang Yanan , Huang Yue , Liu Gaifen , Guan Huiying , Li Jinghui , Luo Dongmei , Zhang Weijia , Zhang Wenjing , Qi Jing , Yue Hao , Wang Xiaomin , Zhang Wei 
Published: September 2023

AbstractAimsTo explore the roles of apolipoprotein E (APOE) ε4 on the neuropathology and neuroinflammation in Alzheimer's disease (AD) patients.MethodsAD patients were divided into the APOE ε4 carrier and the APOE ε4 non‐carrier groups according to APOE genotype. Demographic information, cognitive function, the levels of neuropathological proteins and neuroinflammatory factors in cerebrospinal fluid (CSF) were compared between the two groups, and their correlations were subsequently analyzed.Resultsβ amyloid protein (Aβ)1–42 level from the APOE ε4 carrier group was significantly lower than that from the non‐carrier group (p = 0.023), which was associated with worse cognitive function. The nitric oxide (NO) level was significantly elevated in the APOE ε4 carrier group compared to the non‐carrier group (p = 0.016), which was significantly and positively correlated with the Trail Making Test (TMT)‐A‐time (r = 0.21, p = 0.026) and TMT‐B‐time (r = 0.38, p < 0.01).ConclusionAPOE ε4 is associated with poorer cognition, particularly the early symptoms of memory, language, and attention. APOE ε4 is associated with lower Aβ1–42 level, and the more numbers of APOE ε4 are carried, the lower level of Aβ1–42 is measured. APOE ε4 is associated with elevated NO level, which is linked to the impaired attention and executive function.
Human umbilical cord mesenchymal stem cell‐derived exosomes attenuate neuroinflammation and oxidative stress through the NRF2/NF‐κB/NLRP3 pathway
Authors: Che Ji , Wang Hui , Dong Jing , Wu Yuanyuan , Zhang Haichao , Fu Lei , Zhang Jun 
Published: September 2023

AbstractAimsWe investigated whether human umbilical cord mesenchymal stem cell (hUC‐MSC)‐derived exosomes bear therapeutic potential against lipopolysaccharide (LPS)‐induced neuroinflammation.MethodsExosomes were isolated from hUC‐MSC supernatant by ultra‐high‐speed centrifugation and characterized by transmission electron microscopy and western blotting. Inflammatory responses were induced by LPS in BV‐2 cells, primary microglial cultures, and C57BL/6J mice. H2O2 was also used to induce inflammation and oxidative stress in BV‐2 cells. The effects of hUC‐MSC‐derived exosomes on inflammatory cytokine expression, oxidative stress, and microglia polarization were studied by immunofluorescence and western blotting.ResultsTreatment with hUC‐MSC‐derived exosomes significantly decreased the LPS‐ or H2O2‐induced oxidative stress and expression of pro‐inflammatory cytokines (IL‐6 and TNF‐α) in vitro, while promoting an anti‐inflammatory (classical M2) phenotype in an LPS‐treated mouse model. Mechanistically, the exosomes increased the NRF2 levels and inhibited the LPS‐induced NF‐κB p65 phosphorylation and NLRP3 inflammasome activation. In contrast, the reactive oxygen species scavenger NAC and NF‐κB inhibitor BAY 11–7082 also inhibited the LPS‐induced NLRP3 inflammasome activation and switched to the classical M2 phenotype. Treatment with the NRF2 inhibitor ML385 abolished the anti‐inflammatory and anti‐oxidative effects of the exosomes.ConclusionhUC‐MSC‐derived exosomes ameliorated LPS/H2O2‐induced neuroinflammation and oxidative stress by inhibiting the microglial NRF2/NF‐κB/NLRP3 signaling pathway.
GRECCAR 14 – a multicentric, randomized, phase II–III study evaluating the tailored management of locally advanced rectal carcinoma after a favourable response to induction chemotherapy: Study protocol
Authors: Rouanet Philippe , Castan Florence , Mazard Thibault , Lemanski Claire , Nougaret Stephanie , Deshayes Emmanuel , Chalbos Patrick , Gourgou Sophie , Taoum Christophe ,   the GRECCAR, PRODIGE study group
Published: September 2023

AbstractAimTotal neoadjuvant treatment (TNT) is becoming standard in patients with locally advanced rectal carcinoma (LARC). Preoperative chemoradiotherapy (CRT) has proven side effects on bowel and genitourinary function. An early tumoral response to induction chemotherapy demonstrates its high prognostic value. Tailored management could be used as an alternative to systematic CRT. The GRECCAR 14 trial will attempt to personalize treatment strategy according to the patient's early tumour response to intensive chemotherapy with the aim of achieving the best toxicity–efficiency ratio.MethodGRECCAR 14 is a multicentric, randomized, two‐arm, phase II–III noninferiority trial. Patients with mid or low LARC with a predictive circumferential resection margin ≤2 mm or T3c‐d stage with extramural venous invasion will be included. Evaluation of the tumoral response will be performed after six courses of high‐dose FOLFIRINOX chemotherapy. Good responders (GRs) will be defined by a 60% decrease in tumoral volume on magnetic resonance imaging. Patients will be randomized to CRT before surgery. The primary endpoints will be R0 resection for phase II and the 3‐year disease‐free survival (DFS) for phase III.ResultsTailored management of LARC is becoming an exciting challenge for the modality of neoadjuvant treatment and for the type of surgery or its omission. Neoadjuvant FOLFIRINOX has established efficacy, with a significant increase in the 3‐year DFS. Better control of systemic disease must be accompanied by the same locoregional control, with the lowest morbidity. Our previous GRECCAR 4 trial demonstrated the high value of the early tumoral response after induction chemotherapy and the long‐term safety of tailored management for GRs.ConclusionIf GRECCAR 14 demonstrates the ability to tailor TNT for LARC, this could lead to changes in clinical practice.
Methylthio‐substituted coumarin‐based fluorescent probe for highly specific and fast detection of hypochlorite and bioimaging application
Authors: Zhao Baijun , Wang Wenwen , Song Yanxi , Li Hongqi , Jiang Lin , Chu Lingling 
Published: September 2023

AbstractHypochlorite is a kind of endogenously produced reactive oxygen species (ROS) in the human immune system and plays a crucial role in many pathophysiological processes. In this work a novel fluorescent probe derived from 6‐methylthio coumarin was designed and synthesised for detection of hypochlorite in acetonitrile/phosphate‐buffered saline (MeCN/PBS) (1:1, v/v, pH 7.4) medium. The probe displayed high specificity toward hypochlorite over other ROS analytes, rapid response to hypochlorite within 30 s, and a broad applicable range of pH 3–8. The detection limit was calculated to be 1.48 μM. Application of this probe for in vitro Hecat cell imaging to detect hypochlorite ions was confirmed. A sensing mechanism based on thioether to sulfoxide oxidation by hypochlorite was proposed and demonstrated. The study presented an effective approach for construction of highly efficient hypochlorite chemosensors from hydrophilic methylthio‐substituted coumarins considering their facile access.
Notochordal cells: A potential therapeutic option for intervertebral disc degeneration
Authors: Li Yanhu , Zhang Haijun , Zhu Daxue , Yang Fengguang , Wang Zhaoheng , Wei Ziyan , Yang Zhili , Jia Jingwen , Kang Xuewen 
Published: September 2023

AbstractIntervertebral disc degeneration (IDD) is a prevalent musculoskeletal degenerative disorder worldwide, and ~40% of chronic low back pain cases are associated with IDD. Although the pathogenesis of IDD remains unclear, the reduction in nucleus pulposus cells (NPCs) and degradation of the extracellular matrix (ECM) are critical factors contributing to IDD. Notochordal cells (NCs), derived from the notochord, which rapidly degrades after birth and is eventually replaced by NPCs, play a crucial role in maintaining ECM homeostasis and preventing NPCs apoptosis. Current treatments for IDD only provide symptomatic relief, while lacking the ability to inhibit or reverse its progression. However, NCs and their secretions possess anti‐inflammatory properties and promote NPCs proliferation, leading to ECM formation. Therefore, in recent years, NCs therapy targeting the underlying cause of IDD has emerged as a novel treatment strategy. This article provides a comprehensive review of the latest research progress on NCs for IDD, covering their biological characteristics, specific markers, possible mechanisms involved in IDD and therapeutic effects. It also highlights significant future directions in this field to facilitate further exploration of the pathogenesis of IDD and the development of new therapies based on NCs strategies.
Polarity reversal of canine intestinal organoids reduces proliferation and increases cell death
Authors: Csukovich Georg , Wagner Maximilian , Walter Ingrid , Burger Stefanie , Tschulenk Waltraud , Steinborn Ralf , Pratscher Barbara , Burgener Iwan Anton 
Published: September 2023

AbstractApical‐out intestinal organoids are a relatively simple method of gaining access to the apical cell surface and have faced increasing scientific interest over the last few years. Apical‐out organoids can thus be used for disease modelling to compare differing effects on the basolateral versus the apical cell surface. However, these ‘inside‐out’ organoids die relatively quickly and cannot be propagated as long as their basal‐out counterparts. Here, we show that apical‐out organoids have drastically reduced proliferative potential, as evidenced by immunohistochemical staining and the incorporation of the thymidine analogue EdU. At the same time, cell death levels are increased. Nevertheless, these phenomena cannot be explained by an induction of differentiation, as the gene expression of key marker genes for various cell types does not change over time.
Apoptotic vesicles derived from human red blood cells promote bone regeneration via carbonic anhydrase 1
Authors: Shao Yuzi , Jiang Yuhe , Yang Kunkun , Zhu Yuan , Liu Yunsong , Zhang Ping , Lv Longwei , Zhang Xiao , Zhou Yongsheng 
Published: September 2023

AbstractApoptotic vesicles (apoVs) are nanoscale vesicles derived from billions of apoptotic cells involved in the maintenance of the human body's homeostasis. Previous researches have shown that some apoVs, such as those derived from mesenchymal stem cells, contribute to bone formation. However, those apoVs cannot be extracted from patients in large quantities, and cell expansion is needed before apoV isolation, which limits their clinical translation. Mature RBCs, which have no nuclei or genetic material, are easy to obtain, showing high biological safety as a source of extracellular vesicles (EVs). Previous studies have demonstrated that RBC‐derived EVs have multiple biological functions, but it is unknown whether RBCs produce apoVs and what effect these apoVs have on bone regeneration. In this study, we isolated and characterized RBC‐derived apoVs (RBC‐apoVs) from human venous blood and investigated their role in the osteogenesis of human bone mesenchymal stem cells (hBMSCs). We showed that RBCs could produce RBC‐apoVs that expressed both general apoVs markers and RBC markers. RBC‐apoVs significantly promoted osteogenesis of hBMSCs and enhanced bone regeneration in rat calvarial defects. Mechanistically, RBC‐apoVs regulated osteogenesis by transferring carbonic anhydrase 1 (CA1) into hBMSCs and activating the P38 MAPK pathway. Our results indicated that RBC‐apoVs could deliver functional molecules from RBCs to hBMSCs and promote bone regeneration, pointing to possible therapeutic use in bone tissue engineering.
Adam Smith's moral foundations of self‐interest and ethical social order
Authors: Arevuo Mikko 
Published: September 2023

AbstractThis article draws on textual evidence from The Theory of Moral Sentiments and The Wealth of Nations to address mistaken interpretations of Adam Smith's fundamental concept of self‐interest as greed that has been said to have had a corrosive influence on markets, commercial behaviour, and widening inequality. To the contrary, Smith's complex set of human motivations, including self‐interest, his economic system that is based on free markets, and institutional frameworks governing productive property rights and the rule of law are argued to increase aggregate wealth, improve the position of those least well off, and maintain ethical social order.
Health human capital formation in the OECD: Exploring the role of welfare state composition
Authors: Santos Marcelo , Simões Marta , Sousa Sílvia 
Published: September 2023

AbstractThis study examines the relationship between welfare state or social expenditure composition and health human capital in 37 OECD countries spanning 1980–2018. Our findings confirm that public health spending has a positive effect on health capital formation. Dissecting social expenditure according to other nine social spending categories reveals a positive influence for old age pensions and unemployment benefits. The results for the remaining social programs vary with the health capital proxy and estimation method used. It thus appears that more comprehensive and universal social programs, possibly by guaranteeing the necessary income, do a better job in improving health human capital.