bluuebunny/crossref_metadata_2025_split huggingface dataset:
An interrupted time series analysis of trends in opioid-related emergency department visits from pre-COVID-19 pandemic to pandemic, from the Canadian Hospitals Injury Reporting and Prevention Program
Authors: Yao Xiaoquan , McFaull Steven R. , Champagne André S. , Thompson Wendy 
Published: August 2023

Abstract
Background
Opioid-related emergency department (ED) visits in Canada increased during the COVID-19 pandemic, but how trends in volume and case severity changed from pre-pandemic times through the pandemic is not known. Trends in ED visits related to specific types of opioids also remain unclear. Our objective was to describe pre-pandemic trends and how they changed with the onset of COVID-19 and thereafter.

Methods
Based on data from the Canadian Hospitals Injury Reporting and Prevention Program, we identified opioid-related ED visits and constructed a time series from March 12, 2018 through March 7, 2021—two pre-COVID periods and one COVID period. We used an interrupted time series (ITS) analysis to examine trends in volume and case severity. We compared medians and means of monthly counts and percentages of severe cases between the periods, by sex, age, and opioid type.

Results
Before the pandemic, there was an increasing trend in fentanyl-related visits for males, females and 25- to 64-year-olds, and a decreasing trend in heroin-related visits for males and 18- to 64-year-olds. Fentanyl-related visits for 18- to 24-year-olds showed an immediate increase at the start of the pandemic and a decreasing trend during the pandemic. Heroin-related visits for 12- to 17-year-olds had an immediate increase at the start of the pandemic; for 18- to 24-year-olds and 45- to 64-year-olds, the prior decreasing pre-pandemic trend ceased. For pooled opioid-related visits, no significant trend in the percentage of severe cases was observed throughout the entire study period.

Conclusion
This study shows that an ITS approach in trend analysis is a valuable supplement to comparisons of before and after measures (with or without controlling seasonal effects). The findings provide evidence on how ED presentations for opioid use evolved in Canada from 2018 to 2021. The results can inform policies designed to reduce opioid-related harm in the context of a public health emergency.
Metabolic syndrome and the likelihood of knee pain and functional disability: evidence from a large middle eastern population-based study
Authors: Ibrahim Talal , Ahmed Abdulaziz F , Nofal Mariam , Hegazy Abdelsalam , Ghomrawi Hassan M. K. 
Published: August 2023

Abstract
Objectives
Metabolic Syndrome (MetS) has been associated with knee osteoarthritis (KOA) in animal studies, but epidemiologic evidence of the association remains controversial. We investigated the association between MetS and knee pain and functional disability, the hallmarks of KOA, in a Middle Eastern population with high reported MetS rates.

Methods
A population-based study of adult individuals was conducted between 01/2016 and 03/2019. Data collected included age, sex, blood pressure, body mass index (BMI), waist circumference (WC), and comprehensive metabolic panel blood tests. Knee symptoms were assessed using The Western Ontario and McMaster Arthritis index (WOMAC) The Adult Treatment Panel III criteria was applied to determine if participants had MetS. Multivariable regression was used to determine the association of MetS, and its components, with the WOMAC total and subscale scores.

Results
Of 6,000 participants enrolled, 15.5% had MetS. The multivariate regression demonstrated that participants with MetS had significantly higher WOMAC total and subscale scores after adjusting for demographic variables; however, these associations were not significant after adjusting for BMI. Multivariate regression examining the association between MetS components and the WOMAC scores showed sex-based significant differences with WOMAC scores; however, the differences were not larger than the minimally clinical important differences.

Conclusions
This study demonstrated that after adjustment for BMI, neither MetS nor its individual parameters were associated with worse knee symptoms. As such, the association between MetS and worse knee symptoms requires further study.
Risk factors analysis for clinical symptoms of prenatally diagnosed choledochal cysts: a retrospective study
Authors: Yang Dan , Li Long , Diao Mei , Xie Xianghui , Ming Anxiao , Gao Ruyue , Tian Yu 
Published: August 2023

Abstract
Background
This study aimed to screen the impact factors for clinical symptoms of prenatally diagnosed choledochal cysts (CDCs), to warn about the occurrence of clinical symptoms and the timing of surgery.

Methods
Medical records of patients with prenatally diagnosed CDCs admitted to our hospital from April 2013 to April 2018 were retrospectively reviewed. Fetal hilar or abdominal cysts were found by prenatal ultrasonogram. All patients underwent laparoscopic cyst excision and hepaticojejunostomy in our center. Univariate analysis and multivariate logistic regression analysis were performed to screen the factors related to clinical symptoms intimately.

Results
Two hundred eighteen cases were included. One hundred thirty-four patients (134/218, 61.5%) presented clinical symptoms before surgery. The results of univariate analysis showed that patients with clinical symptoms had earlier time of prenatal diagnosis (P = 0.002), higher values of GGT, TBIL, DBIL (P < 0.001, P < 0.001, P < 0.001, respectively) and larger maximum diameter of cyst before surgery (P = 0.012). Multivariate logistic regression analysis suggested that the time of prenatal diagnosis (P = 0.001, OR = 0.898, 95% CI: 0.845 ~ 0.955) and the GGT value within one week of life (P = 0.028, OR = 1.002, 95% CI: 1.000 ~ 1.003) were independent influencing factors for symptoms.

Conclusions
For children with prenatally diagnosed CDCs, approximately 2/3 patients presented noticeable clinical symptoms before surgery. The time of prenatal diagnosis and the GGT value within 1 week of life were independent impact factors for the occurrence of clinical symptoms.
An ontology-based approach for harmonization and cross-cohort query of Alzheimer’s disease data resources
Authors: Hao Xubing , Li Xiaojin , Zhang Guo-Qiang , Tao Cui , Schulz Paul E. ,   The Alzheimer’s Disease Neuroimaging Initiative, Cui Licong 
Published: August 2023

Abstract
Background
In the United States, the National Alzheimer’s Coordinating Center (NACC) and the Alzheimer’s Disease Neuroimaging Initiative (ADNI) are two major data sharing resources for Alzheimer’s Disease (AD) research. NACC and ADNI strive to make their data more FAIR (findable, interoperable, accessible and reusable) for the broader research community. However, there is limited work harmonizing and supporting cross-cohort interoperability of the two resources.

Method
In this paper, we leverage an ontology-based approach to harmonize data elements in the two resources and develop a web-based query system to search patient cohorts across the two resources. We first mapped data elements across NACC and ADNI, and performed value harmonization for the mapped data elements with inconsistent permissible values. Then we built an Alzheimer’s Disease Data Element Ontology (ADEO) to model the mapped data elements in NACC and ADNI. We further developed a prototype cross-cohort query system to search patient cohorts across NACC and ADNI.

Results
After manual review, we found 172 mappings between NACC and ADNI. These 172 mappings were further used to construct common concepts in ADEO. Our data element mapping and harmonization resulted in five files storing common concepts, variables in NACC and ADNI, mappings between variables and common concepts, permissible values of categorical type data elements, and coding inconsistency harmonization, respectively. Our cross-cohort query system consists of three core architectural elements: a web-based interface, an advanced query engine, and a backend MongoDB database.

Conclusions
In this work, ADEO has been specifically designed to facilitate data harmonization and cross-cohort query of NACC and ADNI data resources. Although our prototype cross-cohort query system was developed for exploring NACC and ADNI, its backend and frontend framework has been designed and implemented to be generally applicable to other domains for querying patient cohorts from multiple heterogeneous data sources.
Suspected clinical toxoplasmosis in a 12-week-old puppy in Singapore
Authors: Chen Audrey , Boulay Max , Chong Stacy , Ho Kelvin , Chan Amy , Ong Jasmine , Fernandez Charlene Judith , Chang Siow Foong , Yap Him Hoo 
Published: August 2023

AbstractBackgroundToxoplasma gondiiis traditionally known as a parasite of felids, with possible infection in intermediate hosts such as dogs and humans, and thus a disease of public health significance. Published data on the prevalence of toxoplasmosis in dogs and cats in Singapore is scanty, and this paper documents a suspect clinical case of toxoplasmosis in a free-roaming puppy trapped from an offshore island of Singapore.Case presentationA 12-week-old puppy presented with hindlimb weakness and sarcopenia, with rapidly progressing ascending paralysis and respiratory distress, one week after trapping. Toxoplasmosis was suspected after indirect fluorescence antibody testing (IFAT) revealed anti-T. gondiiantibodies. The puppy responded quickly to clindamycin treatment and was discharged from hospital after 10 days.ConclusionWhile rare and undocumented, veterinary clinicians in Singapore are advised to also include toxoplasmosis infection as a differential diagnosis in dogs presenting with similar clinical signs. This is especially so for dogs which have access to the outdoors.
Association of insulin use with LV remodeling and clinical outcomes in diabetic patients with heart failure and reduced ejection fraction: assessed by cardiac MRI
Authors: Shi Ke , Zhang Ge , Fu Hang , Huang Shan , Xu Hua-Yan , Gao Yue , Shi Rui , Yan Wei-Feng , Qian Wen-Lei , Li Yuan , Guo Ying-Kun , Yang Zhi-Gang 
Published: August 2023

Abstract
Background
Insulin is commonly used in type 2 diabetes mellitus (T2DM) to achieve glycemic control. However, recent evidence showed that insulin use is associated with poor outcomes in the context of heart failure (HF). Since heart failure with reduced ejection fraction (HFrEF) accounts for approximately 50% of cases in the general HF population, we aimed to evaluate the effect of insulin treatment on left ventricular (LV) remodeling and contractility abnormalities in a HFrEF cohort and assess whether insulin was a predictor of adverse outcomes in this entity.

Methods
A total of 377 HFrEF patients who underwent cardiac MRI were included and divided according to diabetes status and the need for insulin treatment. LV structural and functional indices, as well as systolic strains, were measured. The determinants of impaired myocardial strains were assessed using linear regression analysis. The associated endpoints were determined using a multivariable Cox proportional hazards model.

Results
T2DM patients on insulin displayed a higher indexed LV end-diastolic volume and LV mass than those with T2DM not on insulin or those without T2DM, despite similar LV ejection fractions, accompanied by a higher three-dimensional spherical index (P < 0.01). Worse longitudinal and circumferential peak systolic strain was shown to occur in T2DM patients on insulin (P < 0.01). Insulin treatment was independently associated with impaired magnitudes of systolic strain. The median follow-up duration was 32.4 months (IQR, 15.6–43.2 months). Insulin treatment remained consistently associated with poor outcomes after adjustment for established confounders, with an adjusted hazard ratio of 3.11; (95% CI, 1.45–6.87; P = 0.009) in the overall cohort and 2.16 (95% CI, 1.08–4.59; P = 0.030) in the diabetes cohort.

Conclusions
Insulin may further lead to adverse LV remodeling and contractile dysfunction in the context of HFrEF with T2DM. Considerable care should be taken when treating HFrEF patients with insulin.
Effect of tumor-associated macrophages on the pyroptosis of breast cancer tumor cells
Authors: Ji XuLing , Huang Xiaoxia , Li Chao , Guan Ningning , Pan Tingting , Dong Jing , Li Lin 
Published: August 2023

AbstractMacrophages are immune cells with high plasticity that are widely distributed in all tissues and organs of the body. Under the influence of the immune microenvironment of breast tumors, macrophages differentiate into various germline lineages. They exert pro-tumor or tumor-suppressive effects by secreting various cytokines. Pyroptosis is mediated by Gasdermin family proteins, which form holes in cell membranes and cause a violent inflammatory response and cell death. This is an important way for the body to fight off infections. Tumor cell pyroptosis can activate anti-tumor immunity and inhibit tumor growth. At the same time, it releases inflammatory mediators and recruits tumor-associated macrophages (TAMs) for accumulation. Macrophages act as “mediators” of cytokine interactions and indirectly influence the pyroptosis pathway. This paper describes the mechanism of action on the part of TAM in affecting the pyroptosis process of breast tumor cells, as well as its key role in the tumor microenvironment. Additionally, it provides the basis for in-depth research on how to use immune cells to affect breast tumors and guide anti-tumor trends, with important implications for the prevention and treatment of breast tumors.
Mendelian randomization and transcriptomic analysis reveal an inverse causal relationship between Alzheimer’s disease and cancer
Authors: Dong Zehua , Xu Mengli , Sun Xu , Wang Xiaosheng 
Published: August 2023

AbstractBackgroundAlzheimer’s disease (AD) and cancer are common age-related diseases, and epidemiological evidence suggests an inverse relationship between them. However, investigating the potential mechanism underlying their relationship remains insufficient.MethodsBased on genome-wide association summary statistics for 42,034 AD patients and 609,951 cancer patients from the GWAS Catalog using the two-sample Mendelian randomization (MR) method. Moreover, we utilized two-step MR to identify metabolites mediating between AD and cancer. Furthermore, we employed colocalization analysis to identify genes whose upregulation is a risk factor for AD and demonstrated the genes’ upregulation to be a favorable prognostic factor for cancer by analyzing transcriptomic data for 33 TCGA cancer types.ResultsTwo-sample MR analysis revealed a significant causal influence for increased AD risk on reduced cancer risk. Two-step MR analysis identified very low-density lipoprotein (VLDL) as a key mediator of the negative cause-effect relationship between AD and cancer. Colocalization analysis uncoveredPVRIGupregulation to be a risk factor for AD. Transcriptomic analysis showed thatPVRIGexpression had significant negative correlations with stemness scores, and positive correlations with antitumor immune responses and overall survival in pan-cancer and multiple cancer types.ConclusionAD may result in lower cancer risk. VLDL is a significant intermediate variable linking AD with cancer.PVRIGabundance is a risk factor for AD but a protective factor for cancer. This study demonstrates a causal influence for AD on cancer and provides potential molecular connections between both diseases.
Switching carbon metabolic flux for enhancing the production of sesquiterpene-based high-density biofuel precursor in Saccharomyces cerevisiae
Authors: Liang Bo , Yang Qun , Zhang Xinping , Zhao Yukun , Liu Yunhui , Yang Jianming , Wang Zhaobao 
Published: August 2023

Abstract
Background
Sesquiterpenes are designated as a large class of plant-derived natural active compounds, which have wide applications in industries of energy, food, cosmetics, medicine and agriculture. Neither plant extraction nor chemical synthesis can meet the massive market demands and sustainable development goals. Biosynthesis in microbial cell factories represents an eco-friendly and high-efficient way. Among several microorganisms, Saccharomyces cerevisiae exhibited the potential as a chassis for bioproduction of various sesquiterpenes due to its native mevalonate pathway. However, its inefficient nature limits biosynthesis of diverse sesquiterpenes at industrial grade.

Results
Herein, we exploited an artificial synthetic malonic acid-acetoacetyl-CoA (MAAC) metabolic pathway to switch central carbon metabolic flux for stable and efficient biosynthesis of sesquiterpene-based high-density biofuel precursor in S. cerevisiae. Through investigations at transcription and metabolism levels, we revealed that strains with rewired central metabolism can devote more sugars to β-caryophyllene production. By optimizing the MVA pathway, the yield of β-caryophyllene from YQ-4 was 25.8 mg/L, which was 3 times higher than that of the initial strain YQ-1. Strain YQ-7 was obtained by introducing malonic acid metabolic pathway. Combing the optimized flask fermentation process, the target production boosted by about 13-fold, to 328 mg/L compared to that in the strain YQ-4 without malonic acid metabolic pathway.

Conclusion
This designed MAAC pathway for sesquiterpene-based high-density biofuel precursor synthesis can provide an impressive cornerstone for achieving a sustainable production of renewable fuels.
Mesenchymal stem cells alleviate dexamethasone-induced muscle atrophy in mice and the involvement of ERK1/2 signalling pathway
Authors: Wang Belle Yu-Hsuan , Hsiao Allen Wei-Ting , Shiu Hoi Ting , Wong Nicodemus , Wang Amanda Yu-Fan , Lee Chien-Wei , Lee Oscar Kuang-Sheng , Lee Wayne Yuk-Wai 
Published: August 2023

Abstract
Background
High dosage of dexamethasone (Dex) is an effective treatment for multiple diseases; however, it is often associated with severe side effects including muscle atrophy, resulting in higher risk of falls and poorer life quality of patients. Cell therapy with mesenchymal stem cells (MSCs) holds promise for regenerative medicine. In this study, we aimed to investigate the therapeutic efficacy of systemic administration of adipose-derived mesenchymal stem cells (ADSCs) in mitigating the loss of muscle mass and strength in mouse model of DEX-induced muscle atrophy.

Methods
3-month-old female C57BL/6 mice were treated with Dex (20 mg/kg body weight, i.p.) for 10 days to induce muscle atrophy, then subjected to intravenous injection of a single dose of ADSCs ($$1\times {10}^{6}$$

1
×

10

6

cells/kg body weight) or vehicle control. The mice were killed 7 days after ADSCs treatment. Body compositions were measured by animal DXA, gastrocnemius muscle was isolated for ex vivo muscle functional test, histological assessment and Western blot, while tibialis anterior muscles were isolated for RNA-sequencing and qPCR. For in vitro study, C2C12 myoblast cells were cultured under myogenic differentiation medium for 5 days following 100 $$\mu$$
μ
M Dex treatment with or without ADSC-conditioned medium for another 4 days. Samples were collected for qPCR analysis and Western blot analysis. Myotube morphology was measured by myosin heavy chain immunofluorescence staining.

Results
ADSC treatment significantly increased body lean mass (10–20%), muscle wet weight (15–30%) and cross-sectional area (CSA) (~ 33%) in DEX-induced muscle atrophy mice model and down-regulated muscle atrophy-associated genes expression (45–65%). Hindlimb grip strength (~ 37%) and forelimb ex vivo muscle contraction property were significantly improved (~ 57%) in the treatment group. Significant increase in type I fibres (~ 77%) was found after ADSC injection. RNA-sequencing results suggested that ERK1/2 signalling pathway might be playing important role underlying the beneficial effect of ADSC treatment, which was confirmed by ERK1/2 inhibitor both in vitro and in vivo.

Conclusions
ADSCs restore the pathogenesis of Dex-induced muscle atrophy with an increased number of type I fibres, stronger muscle strength, faster recovery rate and more anti-fatigue ability via ERK1/2 signalling pathway. The inhibition of muscle atrophy-associated genes by ADSCs offered this treatment as an intervention option for muscle-associated diseases. Taken together, our findings suggested that adipose-derived mesenchymal stem cell therapy could be a new treatment option for patient with Dex-induced muscle atrophy.
Dehydrocostus lactone inhibits Candida albicans growth and biofilm formation
Authors: Zhang Jingxiao , Sun Jian , Zhang Yu , Zhang Min , Liu Xin , Yang Longfei , Yin Yongjie 
Published: August 2023

AbstractCandida albicans infections are threatening public health but there are only several antifungal drugs available. This study was to assess the effects of dehydrocostus lactone (DL) on the Candida albicans growth and biofilms Microdilution assays revealed that DL inhibits a panel of standard Candida species, including C. albicans, as well as 9 C. albicans clinical isolates. The morphological transition of C. albicans in RPMI-1640 medium and the adhesion to polystyrene surfaces can also be decreased by DL treatment, as evidenced by microscopic, metabolic activity and colony forming unit (CFU) counting assays. The XTT assay and microscopy inspection demonstrated that DL can inhibit the biofilms of C. albicans. Confocal microscopy following propidium iodide (PI) staining and DCFH-DA staining after DL treatment revealed that DL can increase the membrane permeability and intracellular reactive oxygen species (ROS) production. N-acetyl-cysteine could mitigate the inhibitory effects of DL on growth, morphological transition and biofilm formation, further confirming that ROS production induced by DL contributes to its antifungal and antibiofilm effects. This study showed that DL demonstrated antifungal and antibiofilm activity against C. albicans. The antifungal mechanisms may involve membrane damage and ROS overproduction. This study shows the potential of DL to fight Candida infections.
The impact of age-related syndromes on ICU process and outcomes in very old patients
Authors: Vallet Hélène , Guidet Bertrand , Boumendil Ariane , De Lange Dylan W. , Leaver Susannah , Szczeklik Wojciech , Jung Christian , Sviri Sigal , Beil Michael , Flaatten Hans 
Published: August 2023

AbstractIn this narrative review, we describe the most important age-related “syndromes” found in the old ICU patients. The syndromes are frailty, comorbidity, cognitive decline, malnutrition, sarcopenia, loss of functional autonomy, immunosenescence and inflam-ageing. The underlying geriatric condition, together with the admission diagnosis and the acute severity contribute to the short-term, but also to the long-term prognosis. Besides mortality, functional status and quality of life are major outcome variables. The geriatric assessment is a key tool for long-term qualitative outcome, while immediate severity accounts for acute mortality. A poor functional baseline reduces the chances of a successful outcome following ICU. This review emphasises the importance of using a geriatric assessment and considering the older patient as a whole, rather than the acute illness in isolation, when making decisions regarding intensive care treatment.