bluuebunny/crossref_metadata_2025_split huggingface dataset:
Body mass index, C-reactive protein, and pancreatic cancer: A Mendelian randomization analysis to investigate causal pathways
Authors: Li Zhenqi , Jin Liquan , Xia Lu , Li Xiangzhi , Guan Yunfei , He Hongyang 
Published: February 2023

AimTo explore whether C-reactive protein (CRP) mediates the risk of body mass index (BMI) in pancreatic cancer (PC) and calculate the mediate proportion of CRP in this possible mechanism.MethodsBased on two-sample Mendelian randomization (TSMR), a two-step Mendelian randomization (TM) model was conducted to determine whether CRP was a mediator of the causal relationship between BMI and PC. The multivariable Mendelian randomization (MVMR) study was designed for mediating analysis and to calculate the mediating proportion mediated by CRP.ResultsBMI has a positive causal relationship with PC (n = 393 SNPs, OR = 1.484, 95% CI: 1.021–2.157, p&lt; 0.05). BMI has a positive causal relationship with CRP (n = 179 SNPs, OR = 1.393, 95% CI: 1.320–1.469, p&lt; 0.05). CRP has a positive causal relationship with PC (n = 54 SNPs, OR = 1.348, 95% CI: 1.004–1.809, p&lt; 0.05). After adjusting CRP, BMI has no causal relationship with PC (n = 334 SNPs, OR = 1.341, 95% CI: 0.884–2.037, p&lt; 0.05). After adjusting BMI, there was still a positive causal relationship between CRP and PC (n = 334 SNPs, OR = 1.441, 95% CI: 1.064–1.950, p&lt; 0.05). The mediating effect of CRP was 29%.ConclusionsIn clinical practice, while actively advocating for weight loss among obese patients, we should focus on chronic inflammation levels in obese patients as well. In addition, anti-inflammatory dietary patterns and appropriate physical activity are important in preventing PC.
Antibody-removal therapies for de novo DSA in pediatric intestinal recipients: Why, when, and how? A single-center experience
Authors: Lasa-Lázaro María , Ramos-Boluda Esther , Mancebo Esther , Castro-Panete María José , González-Sacristán Rocío , Serradilla Javier , Andrés-Moreno Ane Miren , Hernández-Oliveros Francisco , Paz-Artal Estela , Talayero Paloma 
Published: February 2023

BackgroundDonor-specific anti-HLA antibodies (DSA) impact negatively on the outcome of intestinal grafts. Although the use of antibody-removal therapies (ART) is becoming more frequent in the last few years, issues regarding their timing and effectiveness remain under discussion.MethodsIn the present study, we report our experience with eight ART procedures (based on plasmapheresis, intravenous immunoglobulin, and rituximab) in eight pediatric intestinal and multivisceral transplants with de novo DSA (dnDSA).ResultsART were performed when dnDSA appeared in two contexts: (1) concomitant with rejection (acute or chronic) or (2) without rejection or any other clinical symptom. Complete DSA removal was observed in seven out of eight patients, showing an effectiveness of 88%. In the group treated for dnDSA without clinical symptoms, the success rate was 100%, with complete DSA removal and without rejection afterward. A shorter time between DSA detection and ART performance appeared as a significant factor for the success of the therapy (p = 0.0002). DSA against HLA-A and DQ alleles were the most resistant to ART, whereas anti-DR DSA were the most sensitive. In addition, the 8-year allograft survival rate in recipients undergoing ART was similar to that in those without DSA, being significantly lower in non-treated DSA-positive recipients (p = 0.013).ConclusionThe results confirm the effectiveness of ART in terms of DSA removal and allograft survival and encourage its early use even in the absence of clinical symptoms.
MDCT-based longitudinal automated airway and air trapping analysis in school-age children with mild cystic fibrosis lung disease
Authors: Weinheimer Oliver , Konietzke Philip , Wagner Willi L. , Weber Dorothea , Newman Beverly , Galbán Craig J. , Kauczor Hans-Ulrich , Mall Marcus A. , Robinson Terry E. , Wielpütz Mark O. 
Published: February 2023

ObjectivesQuantitative computed tomography (QCT) offers some promising markers to quantify cystic fibrosis (CF)-lung disease. Air trapping may precede irreversible bronchiectasis; therefore, the temporal interdependencies of functional and structural lung disease need to be further investigated. We aim to quantify airway dimensions and air trapping on chest CT of school-age children with mild CF-lung disease over two years.MethodsFully-automatic software analyzed 144 serial spirometer-controlled chest CT scans of 36 children (median 12.1 (10.2–13.8) years) with mild CF-lung disease (median ppFEV1 98.5 (90.8–103.3) %) at baseline, 3, 12 and 24 months. The airway wall percentage (WP5–10), bronchiectasis index (BEI), as well as severe air trapping (A3) were calculated for the total lung and separately for all lobes. Mixed linear models were calculated, considering the lobar distribution of WP5–10, BEI and A3 cross-sectionally and longitudinally.ResultsWP5–10 remained stable (P = 0.248), and BEI changed from 0.41 (0.28–0.7) to 0.54 (0.36–0.88) (P = 0.156) and A3 from 2.26% to 4.35% (P = 0.086) showing variability over two years. ppFEV1 was also stable (P = 0.276). A robust mixed linear model showed a cross-sectional, regional association between WP5–10 and A3 at each timepoint (P &lt; 0.001). Further, BEI showed no cross-sectional, but another mixed model showed short-term longitudinal interdependencies with air trapping (P = 0.003).ConclusionsRobust linear/beta mixed models can still reveal interdependencies in medical data with high variability that remain hidden with simpler statistical methods. We could demonstrate cross-sectional, regional interdependencies between wall thickening and air trapping. Further, we show short-term regional interdependencies between air trapping and an increase in bronchiectasis. The data indicate that regional air trapping may precede the development of bronchiectasis. Quantitative CT may capture subtle disease progression and identify regional and temporal interdependencies of distinct manifestations of CF-lung disease.
Case report: Savolitinib induced severe adverse reactions resembling septic shock in an HIV-1–positive patient with advanced non-small cell lung cancer
Authors: Xiong Ye , Cao Qing , Guo Yongzheng , Liu Xiang , Zhu Xueling , Dai Bohao , Zhu Biao 
Published: February 2023

Savolitinib, a small-molecule inhibitor of the receptor tyrosine kinase mesenchymal-epithelial transition (MET) factor, was approved for the treatment of non-small cell lung cancer (NSCLC) by the China National Medical Products Administration in June 2021. Its safety for NSCLC treatment has been confirmed in several prospective cohort studies. Herein, we report a rare case of shock, a serious adverse event, after treatment with savolitinib in an HIV-1–positive patient with advanced NSCLC. A 38-year-old man with an 8-year history of HIV-1 positivity was diagnosed with NSCLC 5 years ago; the lung cancer recurred after surgical resection. Despite chemotherapy, immunotherapy, and targeted therapy, tumor progression continued. He received savolitinib because of MET amplification. In the first 2 weeks of savolitinib use, he developed a mild rash on his trunk. In the following month, he was hospitalized for fever and circulatory shock thrice after taking savolitinib 400 mg. He had no urticaria or eosinophilia. During the three hospitalizations, he was negative for pathogens. His condition gradually improved after treatment with antibiotics, steroids, and vasopressors. Attention should be paid to the occurrence of septic shock-like presentations when using savolitinib in HIV-1 patients with NSCLC.
Clofazimine for the treatment of tuberculosis
Authors: Stadler Jacob A. M. , Maartens Gary , Meintjes Graeme , Wasserman Sean 
Published: February 2023

Shorter (6–9 months), fully oral regimens containing new and repurposed drugs are now the first-choice option for the treatment of drug-resistant tuberculosis (DR-TB). Clofazimine, long used in the treatment of leprosy, is one such repurposed drug that has become a cornerstone of DR-TB treatment and ongoing trials are exploring novel, shorter clofazimine-containing regimens for drug-resistant as well as drug-susceptible tuberculosis. Clofazimine’s repurposing was informed by evidence of potent activity against DR-TB strains in vitro and in mice and a treatment-shortening effect in DR-TB patients as part of a multidrug regimen. Clofazimine entered clinical use in the 1950s without the rigorous safety and pharmacokinetic evaluation which is part of modern drug development and current dosing is not evidence-based. Recent studies have begun to characterize clofazimine’s exposure-response relationship for safety and efficacy in populations with TB. Despite being better tolerated than some other second-line TB drugs, the extent and impact of adverse effects including skin discolouration and cardiotoxicity are not well understood and together with emergent resistance, may undermine clofazimine use in DR-TB programmes. Furthermore, clofazimine’s precise mechanism of action is not well established, as is the genetic basis of clofazimine resistance. In this narrative review, we present an overview of the evidence base underpinning the use and limitations of clofazimine as an antituberculosis drug and discuss advances in the understanding of clofazimine pharmacokinetics, toxicity, and resistance. The unusual pharmacokinetic properties of clofazimine and how these relate to its putative mechanism of action, antituberculosis activity, dosing considerations and adverse effects are highlighted. Finally, we discuss the development of novel riminophenazine analogues as antituberculosis drugs.
Pharmacological screening of silibinin for antischizophrenic activity along with its acute toxicity evaluation in experimental animals
Authors: Ain Qurat Ul , Saleem Uzma , Ahmad Bashir , Khalid Iqra 
Published: February 2023

Silibinin (SIL), a flavolignan extracted from the medicinal plant “silybum marianum (milk thistle)”, has traditionally been used to treat liver disease. This phytochemical has displayed neuroprotective properties, its activity against schizophrenia is not elucidated. The present study was designed to evaluate the antipsychotic potential of silibinin and probe its toxic potential. The acute oral toxicity study was assessed as per OECD 425 guidelines. Animals were divided into two groups of female rats (n = 6): one group served as the normal control and the other group received a 2,000 mg/kg dose of SIL. We also evaluated the antipsychotic potential of SIL. To this end, animals were divided into six groups (n = 10) of mice for both the preventive and curative protocols. Group I (CMC 1 mL/kg) served as the normal control and received CMC 1 mL/kg; group II was the diseased group treated with ketamine (10 mg/kg) i.p; group III was the standard group treated with clozapine 1 mg/kg; groups IV, V, and VI served as the treatment groups, receiving SIL 50, 100, and 200 mg/kg, respectively, orally for both protocols. Improvement in positive symptoms of the disease was evaluated by stereotypy and hyperlocomotion, while negative symptoms (behavioral despair) were determined by a forced swim test and a tail suspension test in the mice models. The results suggested that the LD50 of SIL was greater than 2,000 mg/kg. Moreover, SIL prevented and reversed ketamine-induced increase in stereotypy (p &lt; 0.001) and behavioral despair in the forced swim and tail suspension tests (p &lt; 0.001). Taken together, the findings suggest that silibinin is a safe drug with low toxicity which demonstrates significant antipsychotic activity against the positive and negative symptoms of schizophrenia.
High-power Er:Y2O3 ceramic laser with an optical vortex beam output at ∼ 2.7 μm
Authors: Ding Manman , Wang Jun , Wang Fei , Shen Deyuan , Tang Dingyuan , Zhu Heyuan 
Published: February 2023

We report on the direct generation of the high-power optical vortices at ∼2.7 μm from an Er:Y2O3 ceramic laser end-pumped by an annular pump beam using a simple capillary fiber-based pump beam conditioning scheme. Taking advantage of the thermal gradient on the gain medium and mode matching between the pump and oscillating modes, vortex beams with a controllable topological charge order of l = 1 and l = 2 were successfully achieved. The laser yields 4.65 W of output power at an absorbed power of 19.8 W, corresponding to a slope efficiency of 25.9% with respect to the absorbed pump power. Adaptable beam profiles from a shallow crater-shape to quasi-top-hat intensity patterns were directly produced by actively defining the gain distribution in the ceramic, generating 4-W shallow crater-shape beams and 3.9-W quasi-top-hat beams, corresponding to a slope efficiency of 22.0% and 22.7%, respectively. Such optical vortices and tailored spatial intensity profiles in the 3-µm spectral region will enable novel applications, such as super-resolution molecular spectroscopy and material processing.
Effect of intimacy and dyadic coping on psychological distress in pancreatic cancer patients and spousal caregivers
Authors: Li Jiarong , Liu Linglong , Chen Mingxia , Su Wang , Yao Tianying , Li Xiaoxuan 
Published: February 2023

AimsThe aim of this study was to investigate the effect of intimacy and dyadic coping on anxiety and depression in patients with pancreatic cancer and their spousal caregivers.MethodsThis study conducted from October 2021 to June 2022, included 277 pancreatic cancer patients and their spousal caregivers. This research used actor-partner interdependence mediation model to explore the relationship of intimacy, dyadic coping, and psychological distress among pancreatic cancer patients and their spousal caregivers.ResultsThe results of this study showed that there were two actor effects: the satisfaction of intimate relationship between pancreatic cancer patients and their spouse caregivers had a positive predictive effect on their dyadic coping (β = 1.787, p &lt; 0.001) and (β = 1.587, p &lt; 0.001). The dyadic coping of pancreatic cancer patients and their spouse caregivers had a negative predictive effect on their own anxiety and depression (β = −0.253, p &lt; 0.001) and (β = −0.293, p &lt; 0.001). The results of this study showed that there was a partner effect: intimate relationship satisfaction of pancreatic cancer patients had a positive predictive effect on dyadic coping of their spousal caregivers (β = 0.574, p &lt; 0.05).ConclusionThis study demonstrates the interdependence of pancreatic cancer patients and their spousal caregivers in coping with the disease. The healthy intimate relationship and effective dyadic coping styles are essential to alleviating disease pressure and lowering the psychological burden on cancer families.
Modeling disease progression and treatment pathways for depression jointly using agent based modeling and system dynamics
Authors: Brice Syaribah N. , Harper Paul R. , Gartner Daniel , Behrens Doris A. 
Published: February 2023

IntroductionDepression is a common mental health condition that affects millions of people worldwide. Care pathways for depression are complex and the demand across different parts of the healthcare system is often uncertain and not entirely understood. Clinical progression with depression can be equally complex and relates to whether or not a patient is seeking care, the care pathway they are on, and the ability for timely access to healthcare services. Considering both pathways and progression for depression are however rarely studied together in the literature.MethodsThis paper presents a hybrid simulation modeling framework that is uniquely able to capture both disease progression, using Agent Based Modeling, and related care pathways, using a System Dynamics. The two simulation paradigms within the framework are connected to run synchronously to investigate the impact of depression progression on healthcare services and, conversely, how any limitations in access to services may impact clinical progression. The use of the developed framework is illustrated by parametrising it with published clinical data and local service level data from Wales, UK.Results and discussionThe framework is able to quantify demand, service capacities and costs across all care pathways for a range of different scenarios. These include those for varying service coverage and provision, such as the cost-effectiveness of treating patients more quickly in community settings to reduce patient progression to more severe states of depression, and thus reducing the costs and utilization of more expensive specialist settings.
Liver injury associated with the severity of COVID-19: A meta-analysis
Authors: Yang Ruiqi , Feng Jihua , Wan Huan , Zeng Xiaona , Ji Pan , Zhang Jianfeng 
Published: February 2023

BackgroundThe current 2019 novel coronavirus disease (COVID-19) pandemic is a major threat to global health. It is currently uncertain whether and how liver injury affects the severity of COVID-19. Therefore, we conducted a meta-analysis to determine the association between liver injury and the severity of COVID-19.MethodsA systematic search of the PubMed, Embase, and Cochrane Library databases from inception to August 12, 2022, was performed to analyse the reported liver chemistry data for patients diagnosed with COVID-19. The pooled odds ratio (OR), weighted mean difference (WMD) and 95% confidence interval (95% CI) were assessed using a random-effects model. Furthermore, publication bias and sensitivity were analyzed.ResultsForty-six studies with 28,663 patients were included. The pooled WMDs of alanine aminotransferase (WMD = 12.87 U/L, 95% CI: 10.52–15.23, I2 = 99.2%), aspartate aminotransferase (WMD = 13.98 U/L, 95% CI: 12.13–15.83, I2 = 98.2%), gamma-glutamyl transpeptidase (WMD = 20.67 U/L, 95% CI: 14.24–27.10, I2 = 98.8%), total bilirubin (WMD = 2.98 μmol/L, 95% CI: 1.98–3.99, I2 = 99.4%), and prothrombin time (WMD = 0.84 s, 95% CI: 0.46–1.23, I2 = 99.4%) were significantly higher and that of albumin was lower (WMD = −4.52 g/L, 95% CI: −6.28 to −2.75, I2 = 99.9%) in severe cases. Moreover, the pooled OR of mortality was higher in patients with liver injury (OR = 2.72, 95% CI: 1.18–6.27, I2 = 71.6%).ConclusionsHepatocellular injury, liver metabolic, and synthetic function abnormality were observed in severe COVID-19. From a clinical perspective, liver injury has potential as a prognostic biomarker for screening severely affected patients at early disease stages.Systematic review registrationhttps://www.crd.york.ac.uk/prospero/, Identifier: CRD42022325206.
Design and psychometric properties of the family support for older people questionnaire
Authors: Shamsikhani Soheila , Ahmadi Fazlollah , Kazemnejad Anoshirvan , Vaismoradi Mojtaba 
Published: February 2023

Background and objectivesThe population of older people is increasing across the world. Older people need care and support from their families to be able to live independently. This study aimed to design and evaluate the psychometric properties of the family support for older people (FSOP) questionnaire.MethodsIn this instrument development study using a mixed-methods design, the psychometric properties of the FSOP questionnaire in terms of validity and reliability were evaluated.ResultsThe FSOP questionnaire consisted of 50 items in six domains. It was shown to have appropriate qualitative and quantitative validities (score &gt; 1.5). The indicators of content validity (CVR &gt; 0.62, ICVI ≥ 0.80, and SCVI &gt; 0.94) and confirmatory factor analysis (indexes of χ2/df = 2.50, CFI = 0.96, GFI = 0.97, AGFI = 0.96, NNFI = 0.96, PNFI = 0.89, TLI = 0.96, and RMSEA = 0.06) were satisfactory. Cronbach's alpha coefficient for reliability was 0.94, indicating an optimal score.ConclusionsHealthcare providers and family caregivers are suggested to use the FSOP questionnaire for improving the quality of life of older people at home.
Analyzing the efficiency of Chinese primary healthcare institutions using the Malmquist-DEA approach: Evidence from urban and rural areas
Authors: Zhou Junxu , Peng Rong , Chang Yajun , Liu Zijun , Gao Songhui , Zhao Chuanjun , Li Yixin , Feng Qiming , Qin Xianjing 
Published: February 2023

BackgroundChina has been increasing the investment in Primary Health Care Institutions (PHCIs) since the launch of the New Health Care System Reform in 2009. It is a crucial concern whether the PHCIs can meet residents' need both in urban and rural with the limited government finance, especially encountering the challenge of the COVID-19. This study aimed to reveal the trend of the primary health service efficiency in the past decade, compare the urban-rural differences, and explore relevant factors.MethodsDEA and Malmquist models were applied to calculate the health service efficiency of PHCIs among 28 provinces in China, with the input variables including the number of institutions, number of beds, number of health technicians, and the outputs variables including the number of outpatients and emergency visits, number of discharged patients. And the Tobit model was used to analyze the factors on the efficiency in urban and rural. A sensitivity analysis for model validations was also carried out.ResultsThe average technical efficiency (TE) of urban PHCIs fluctuated from 63.3% to 67.1%, which was lower than that in rural (75.8–82.2%) from 2009 to 2019. In terms of dynamic efficiency, the urban PHCIs performed better than the rural, and the trends in the total factor productivity change were associated with favorable technology advancement. The population density and dependency ratio were the key factors on TE in both of the urban and rural PHCIs, and these two factors were positively correlated to TE. In terms of TE, it was negatively correlated with the proportion of total health expenditure as a percentage of GDP in urban PHCIs, while in rural it was positively correlated with the urbanization rate and negatively correlated with GDP per capita. Besides, the tests of Mann–Whitney U, and Kruskal–Wallis H indicated the internal validity and robustness of the chosen DEA and Malmquist models.ConclusionsIt needs to reduce the health resource wastes and increase service provision in urban PHCIs. Meanwhile, it is necessary to strengthen medical technology and gaining greater efficiency in rural PHCIs by technology renovation.
Hospital efficiency in the eastern mediterranean region: A systematic review and meta-analysis
Authors: Ravaghi Hamid , Afshari Mahnaz , Isfahani Parvaneh , Mahboub-Ahari Alireza , Bélorgeot Victoria D. 
Published: February 2023

BackgroundRecent rising costs and shortages of healthcare resources make it necessary to address the issue of hospital efficiency. Increasing the efficiency of hospitals can result in the better and more sustainable achievement of their organizational goals.ObjectiveThe purpose of this research is to examine hospital efficiency in the Eastern Mediterranean Region (EMR) using data envelopment analysis (DEA).MethodsThis study is a systematic review and meta-analysis of all articles published on hospital efficiency in Eastern Mediterranean countries between January 1999 and September 2020, identified by searching PubMed through MEDLINE, Web of Science, Scopus, Science Direct, and Google Scholar. The reference lists of these articles were checked for additional relevant studies. Finally, 37 articles were selected, and data were analyzed through Comprehensive Meta-Analysis Software (v.2.2.064).ResultsUsing the random-effects model, the mean hospital efficiency in Eastern Mediterranean hospitals was 0.882 ± 0.01 at 95% CI. Technical efficiency (TE) was higher in some countries such as Iraq (0.976 ± 0.035), Oman (0.926 ± 0.032), and Iran (0.921 ±0.012). A significant statistical correlation was observed between the hospital efficiency and the year of publication and sample size (p &lt; 0.05).ConclusionEfficiency plays a significant role in hospital growth and development. Therefore, it is important for healthcare managers and policymakers in the EMR to identify the causes of inefficiency, improve TE, and develop cost-effective strategies.