bluuebunny/crossref_metadata_2025_split huggingface dataset:
Identification of the pivotal role of SPP1 in kidney stone disease based on multiple bioinformatics analysis
Authors: Hong Sen-Yuan , Xia Qi-Dong , Xu Jin-Zhou , Liu Chen-Qian , Sun Jian-Xuan , Xun Yang , Wang Shao-Gang 
Published: January 2022

Abstract
Background
Kidney stone disease (KSD) is a multifactorial disease involving both environmental and genetic factors, whose pathogenesis remains unclear. This study aims to explore the hub genes related to stone formation that could serve as potential therapeutic targets.

Methods
Based on the GSE73680 dataset with 62 samples, differentially expressed genes (DEGs) between Randall’s plaque (RP) tissues and normal tissues were screened and weighted gene co-expression network analysis (WGCNA) was applied to identify key modules associated with KSD. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis were performed to explore the biological functions. The protein–protein interaction (PPI) network was constructed to identify hub genes. Meanwhile, CIBERSORT and ssGSEA analysis were used to estimate the infiltration level of the immune cells. The correlations between hub genes and immune infiltration levels were also investigated. Finally, the top hub gene was selected for further GSEA analysis.

Results
A total of 116 DEGs, including 73 up-regulated and 43 down-regulated genes, were screened in the dataset. The red module was identified as the key module correlated with KSD. 53 genes were obtained for functional enrichment analysis by taking the intersection of DEGs and genes in the red module. GO analysis showed that these genes were mainly involved in extracellular matrix organization (ECM) and extracellular structure organization, and others. KEGG analysis revealed that the pathways of aldosterone-regulated sodium reabsorption, cell adhesion molecules, arachidonic acid (AA) metabolism, and ECM-receptor interaction were enriched. Through PPI network construction, 30 hub genes were identified. CIBERSORT analysis revealed a significantly increased proportion of M0 macrophages, while ssGSEA revealed no significant differences. Among these hub genes, SPP1, LCN2, MMP7, MUC1, SCNN1A, CLU, SLP1, LAMC2, and CYSLTR2 were positively correlated with macrophages infiltration. GSEA analysis found that positive regulation of JNK activity was enriched in RP tissues with high SPP1 expression, while negative regulation of IL-1β production was enriched in the low-SPP1 subgroup.

Conclusions
There are 30 hub genes associated with KSD, among which SPP1 is the top hub gene with the most extensive links with other hub genes. SPP1 might play a pivotal role in the pathogenesis of KSD, which is expected to become a potential therapeutic target, while its interaction with macrophages in KSD needs further investigation.
Multiple neonicotinoids in children’s cerebro-spinal fluid, plasma, and urine
Authors: Laubscher Bernard , Diezi Manuel , Renella Raffaele , Mitchell Edward A. D. , Aebi Alexandre , Mulot Matthieu , Glauser Gaëtan 
Published: January 2022

Abstract
Background
Neonicotinoids (NN) are selective neurotoxic pesticides that bind to insect but also mammal nicotinic acetycholine receptors (nAChRs). As the most widely used class of insecticides worldwide, they are ubiquitously found in the environment, wildlife, and foods, and thus of special concern for their impacts on the environment and human health. nAChRs are vital to proper brain organization during the prenatal period and play important roles in various motor, emotional, and cognitive functions. Little is known on children’s contamination by NN. In a pilot study we tested the hypothesis that children’s cerebro-spinal fluid (CSF) can be contaminated by NN.

Methods
NN were analysed in leftover CSF, blood, and urine samples from children treated for leukaemias and lymphomas and undergoing therapeutic lumbar punctions. We monitored all neonicotinoids approved on the global market and some of their most common metabolites by ultra-high performance liquid chromatography-tandem mass spectrometry.

Results
From August to December 2020, 14 children were consecutively included in the study. Median age was 8 years (range 3–18). All CSF and plasma samples were positive for at least one NN. Nine (64%) CSF samples and 13 (93%) plasma samples contained more than one NN. Thirteen (93%) CSF samples had N-desmethyl-acetamiprid (median concentration 0.0123, range 0.0024–0.1068 ng/mL), the major metabolite of acetamiprid. All but one urine samples were positive for ≥ one NN. A statistically significant linear relationship was found between plasma/urine and CSF N-desmethyl-acetamiprid concentrations.

Conclusions
We have developed a reliable analytical method that revealed multiple NN and/or their metabolites in children’s CSF, plasma, and urine. Our data suggest that contamination by multiple NN is not only an environmental hazard for non-target insects such as bees but also potentially for children.
GOx-assisted synthesis of pillar[5]arene based supramolecular polymeric nanoparticles for targeted/synergistic chemo-chemodynamic cancer therapy
Authors: Wang Jin , Wang Di , Cen Moupan , Jing Danni , Bei Jiali , Huang Youyou , Zhang Jiannan , Lu Bing , Wang Yang , Yao Yong 
Published: January 2022

Abstract
Background
Cancer is the most serious world's health problems on the global level and various strategies have been developed for cancer therapy. Pillar[5]arene-based supramolecular therapeutic nano-platform (SP/GOx NPs) was constructed successfully via orthogonal dynamic covalent bonds and intermolecular H-bonds with the assistance of glucose oxidase (GOx) and exhibited efficient targeted/synergistic chemo-chemodynamic cancer therapy.

Methods
The morphology of SP/GOx NPs was characterized by DLS, TEM, SEM and EDS mapping. The cancer therapy efficinecy was investigated both in vivo and in vitro.

Results
SP/GOx NPs can load drug molecules (Dox) and modify target molecule (FA-Py) on its surface conveniently. When the resultant FA-Py/SP/GOx/Dox NPs enters blood circulation, FA-Py will target it to cancer cells efficiently, where GOx can catalyst the overexpressed glucose to generate H2O2. Subsequently, the generated H2O2 in cancer cells catalyzed by ferrocene unit to form •OH, which can kill cancer cells. Furthermore, the loaded Dox molecules released under acid microenvironment, which can further achieve chemo-therapy.

Conclusion
All the experiments showed that the excellent antitumor performance of FA-Py/SP/GOx/Dox NPs, which provided an new method for pillar[5]arene-based supramolecular polymer for biomedical applications.

Graphical Abstract
Diverse psychotropic substances detected in drug and drug administration equipment samples submitted to drug checking services in Toronto, Ontario, Canada, October 2019–April 2020
Authors: Scarfone Kristy M. , Maghsoudi Nazlee , McDonald Karen , Stefan Cristiana , Beriault Daniel R. , Wong Ernest , Evert Mark , Hopkins Shaun , Leslie Peter , Watson Tara Marie , Werb Dan ,   Toronto’s Drug Checking Service Working Group
Published: January 2022

Abstract
Background
The overdose crisis has generated innovative harm reduction and drug market monitoring strategies. In Toronto, Ontario, Canada, a multi-site drug checking service (DCS) pilot project was launched in October 2019. The project provides people who use drugs with information on the chemical composition of their substances, thereby increasing their capacity to make more informed decisions about their drug use and avoid overdose. DCS also provides real-time market monitoring to identify trends in the unregulated drug supply.

Methods
Sample data were obtained through analyses of drug and used drug administration equipment samples submitted anonymously and free of charge to DCS in downtown Toronto from October 10, 2019, to April 9, 2020, representing the first six months of DCS implementation. Analyses were conducted in clinical laboratories using liquid chromatography- and/or gas chromatography-mass spectrometry (LC–MS, GC–MS) techniques.

Results
Overall, 555 samples were submitted, with 49% (271) of samples that were found to contain high-potency opioids, of which 87% (235) also contained stimulants. Benzodiazepine-type drugs were found in 21% (116) of all samples, and synthetic cannabinoids in 1% (7) of all samples. Negative effects (including overdose, adverse health events, and extreme sedation) were reported for 11% (59) of samples submitted for analysis.

Conclusions
Toronto’s DCS identified a range of high-potency opioids with stimulants, benzodiazepine-type drugs, and a synthetic cannabinoid, AMB-FUBINACA. This information can inform a range of evidence-informed overdose prevention efforts.
A method for small-area estimation of population mortality in settings affected by crises
Authors: Checchi Francesco , Testa Adrienne , Gimma Amy , Koum-Besson Emilie , Warsame Abdihamid 
Published: January 2022

Abstract
Background
Populations affected by crises (armed conflict, food insecurity, natural disasters) are poorly covered by demographic surveillance. As such, crisis-wide estimation of population mortality is extremely challenging, resulting in a lack of evidence to inform humanitarian response and conflict resolution.

Methods
We describe here a ‘small-area estimation’ method to circumvent these data gaps and quantify both total and excess (i.e. crisis-attributable) death rates and tolls, both overall and for granular geographic (e.g. district) and time (e.g. month) strata. The method is based on analysis of data previously collected by national and humanitarian actors, including ground survey observations of mortality, displacement-adjusted population denominators and datasets of variables that may predict the death rate. We describe the six sequential steps required for the method’s implementation and illustrate its recent application in Somalia, South Sudan and northeast Nigeria, based on a generic set of analysis scripts.

Results
Descriptive analysis of ground survey data reveals informative patterns, e.g. concerning the contribution of injuries to overall mortality, or household net migration. Despite some data sparsity, for each crisis that we have applied the method to thus far, available predictor data allow the specification of reasonably predictive mixed effects models of crude and under 5 years death rate, validated using cross-validation. Assumptions about values of the predictors in the absence of a crisis provide counterfactual and excess mortality estimates.

Conclusions
The method enables retrospective estimation of crisis-attributable mortality with considerable geographic and period stratification, and can therefore contribute to better understanding and historical memorialisation of the public health effects of crises. We discuss key limitations and areas for further development.
Kuala Lumpur train collision during the COVID-19 pandemic
Authors: Idrose Alzamani M. , Abu-Zidan Fikri M. , Roslan Nurul Liana , Hashim Khairul Izwan M. , Mohd Adibi Saiyidi Mohd Azizi , Abd. Wahab Mahathar 
Published: January 2022

Abstract
Background
Two city trains collided in an underground tunnel on 24 May 2021 at the height of COVID-19 pandemic near the Petronas Towers, Kuala Lumpur, Malaysia, immediately after the evening rush hours. We aim to evaluate the management of this mass casualty incident highlighting the lessons learned to be used in preparedness for similar incidents that may occur in other major cities worldwide.

Methods
Information regarding incident site and hospital management response were analysed. Data on demography, triaging, injuries and hospital management of patients were collected according to a designed protocol. Challenges, difficulties and their solutions were reported.

Results
The train's emergency response team (ERT) has shut down train movements towards the incident site. Red zone (in the tunnel), yellow zone (the station platform) and green zone (outside the station entrance) were established. The fire and rescue team arrived and assisted the ERT in the red zone. Incident command system was established at the site. Medical base station was established at the yellow zone. Two hundred and fourteen passengers were in the trains. Sixty-four of them were injured. They had a median (range) ISS of 2 (1–43), and all were sent to Hospital Kuala Lumpur (HKL). Six (9.4%) patients were clinically triaged as red (critical), 19 (29.7%) as yellow (semi-critical) and 39 (60.9%) as green (non-critical). HKL's disaster plan was activated. All patients underwent temperature and epidemiology link assessment. Seven (10.9%) patients were admitted to the hospital (3 to the ICU, 3 to the ward and 1 to a private hospital as requested by the patient), while the rest 56 (87.5%) were discharged home. Six (9.4%) needed surgery. The COVID-19 tests were conducted on seven patients (10.9%) and were negative. There were no deaths.

Conclusions
The mass casualty incident was handled properly because of a clear standard operating procedure, smooth coordination between multi-agencies and the hospitals, presence of a 'binary' system for 'COVID-risk' and 'non-COVID-risk' areas, and the modifications of the existing disaster plan. Preparedness for MCIs is essential during pandemics.
Adult patients with ACL tears have greater tibial internal rotation in MRI compared to adolescent patients
Authors: Hong Chih-Kai , Lin Yu-Ju , Cheng Ting-An , Chang Chih-Hsun , Hsu Kai-Lan , Kuan Fa-Chuan , Su Wei-Ren 
Published: January 2022

Abstract
Purpose
To compare the anterior translation and internal rotation of tibia on magnetic resonance imaging (MRI) between adult and adolescent patients with anterior cruciate ligament (ACL) tears.

Methods
Patients who underwent isolated ACL reconstruction from January 2013 to May 2021 were retrospectively reviewed. The exclusion criteria included incomplete data, poor image quality, a prior ACL surgery, and concomitant fractures or other ligament injuries. The enrolled patients were divided into two groups based on their ages: an adult group (age > 19 years) and an adolescent group (15 to 19 years of age). Anterior tibial translation and femorotibial rotation were measured on MRI. A Student’s t-test was used for the statistical analysis comparing the adult and adolescent groups.

Results
A total of 365 patients (279 adults and 86 adolescents) were enrolled in the present study. The anterior tibial translation in the adult group (4.8 ± 4.4 mm) and the adolescent group (5.0 ± 4.2 mm) was not significantly different (p = 0.740). On the other hand, the tibial internal rotation in the adult group (5.6 ± 5.0 degree) was significantly greater compared to the adolescent group (4.2 ± 5.6 degree) (p = 0.030). The intraclass correlation coefficients (ICC) of the measured data from two independent observers showed excellent reliability (0.964 and 0.961 for anterior tibial translation and tibial internal rotation, respectively).

Conclusion
The adult patients with ACL tears exhibited significant greater tibial internal rotation compared to the adolescent patients, whereas the magnitude of the anterior tibial translation was similar in both groups. Care should be taken if clinicians plan to establish the cutoff point values for diagnosis of ACL tears using the femorotibial internal rotation angle.
Maternal and early life exposures and their potential to influence development of the microbiome
Authors: Bolte Erin E. , Moorshead David , Aagaard Kjersti M. 
Published: January 2022

AbstractAt the dawn of the twentieth century, the medical care of mothers and children was largely relegated to family members and informally trained birth attendants. As the industrial era progressed, early and key public health observations among women and children linked the persistence of adverse health outcomes to poverty and poor nutrition. In the time hence, numerous studies connecting genetics (“nature”) to public health and epidemiologic data on the role of the environment (“nurture”) have yielded insights into the importance of early life exposures in relation to the occurrence of common diseases, such as diabetes, allergic and atopic disease, cardiovascular disease, and obesity. As a result of these parallel efforts in science, medicine, and public health, the developing brain, immune system, and metabolic physiology are now recognized as being particularly vulnerable to poor nutrition and stressful environments from the start of pregnancy to 3 years of age. In particular, compelling evidence arising from a diverse array of studies across mammalian lineages suggest that modifications to our metagenome and/or microbiome occur following certain environmental exposures during pregnancy and lactation, which in turn render risk of childhood and adult diseases. In this review, we will consider the evidence suggesting that development of the offspring microbiome may be vulnerable to maternal exposures, including an analysis of the data regarding the presence or absence of a low-biomass intrauterine microbiome.
Low frequency of disease flare in patients with rheumatic musculoskeletal diseases who received SARS-CoV-2 mRNA vaccine
Authors: Spinelli Francesca Romana , Favalli Ennio Giulio , Garufi Cristina , Cornalba Martina , Colafrancesco Serena , Conti Fabrizio , Caporali Roberto 
Published: January 2022

Abstract
Background
Little is known about the safety of SARS-CoV-2 vaccination in patients with rheumatic musculoskeletal disease (RMD). We evaluated the occurrence of adverse events following immunization (AEFI) in RMD patients and heathy subjects who received anti-SARS-CoV-2 mRNA vaccine.

Methods
We performed a telephone interview collecting any adverse event (AE) following immunization (AEFI) that occurred in RMD patients and healthy controls after the two doses of mRNA vaccine including common local reactogenicity and systemic events (for example, fever, fatigue/malaise, joint and muscle pain). We also investigated the onset of new signs or symptoms of the RMD after the vaccination.

Results
We evaluated 126 patients with RMDs [105 females and 19 males, median age 51(IQR 17)] and 85 controls [62 females and 23 males, (median age 49 (20)]. Seventy patients (55.6%) were taking immunosuppressants, conventional synthetic (n=31, 43.3%) and/or biological [TNF inhibitors (n=49, 68.6%)], and 30 (23.8%) were taking hydroxychloroquine; treatment remained unchanged in 77% of patients. Eleven out of 126 patients and none of the 85 controls previously contracted COVID-19. The median follow-up from the completion of vaccination was 15 (3) weeks both in patients and controls. We reviewed 5 suspected cases confirming mild articular flares in 3 women (2.8) with inflammatory arthritis (2 psoriatic arthritis and 1 rheumatoid arthritis) while no disease reactivation was recorded in patients with connective tissue diseases; the incidence rate of RMD reactivation was 0.007 person/month. Multivariable logistic regression analysis showed similar frequencies of local and systemic AEFI in patients and controls with no effect of therapies or previous COVID-19. Local reaction—pain in the injection site—was the most frequently reported AEFI both in RMD and controls (71% and 75% of all the AEFI, respectively) after the first dose. Overall, up to 66% of patients experienced at least one AEFI at the second dose and up to 62% in the control group. Most of AEFI occurred within 2 days of vaccine administration. Two RMD patients developed pauci-symptomatic COVID-19 after the first dose of vaccine.

Conclusion
The low incidence rate of disease reactivation and the similar AEFI occurrence compared to controls should reassure on mRNA vaccine safety in RMD patients.
Vomiting, electrolyte disturbance, and medications; the perfect storm for acquired long QT syndrome and cardiac arrest: a case report
Authors: Tiver K. D. , Dharmaprani D. , Quah J. X. , Lahiri A. , Waddell-Smith K. E. , Ganesan A. N. 
Published: January 2022

Abstract
Background
Acquired long QT syndrome is an important and preventable cause of cardiac arrest. Certain medications and electrolyte disturbance are common contributors, and often coexist. In this case, we report five contributors to cardiac arrest.

Case presentation
This case is of a 51-year-old Caucasian female patient who presented with vomiting associated with hypokalemia and hypomagnesemia. She subsequently received ondansetron and metoclopramide, on the background of chronic treatment with fluoxetine. She then suffered an in-hospital monitored cardiac arrest, with features of long QT and torsades de pointes retrospectively noted on her prearrest electrocardiogram. She was diagnosed with acquired long QT syndrome, and her QT interval later normalized after removal of offending causes.

Conclusions
This case highlights the importance of proper consideration prior to prescribing QT prolonging medications, especially in patients who have other risk factors for prolonged QT, such as electrolyte disturbances and pretreatment with QT prolonging medications.
Quantitative washout in patients with hepatocellular carcinoma undergoing TACE: an imaging biomarker for predicting prognosis?
Authors: Müller Lukas , Hahn Felix , Jungmann Florian , Mähringer-Kunz Aline , Stoehr Fabian , Halfmann Moritz C. , Pinto dos Santos Daniel , Hinrichs Jan , Auer Timo A. , Düber Christoph , Kloeckner Roman 
Published: January 2022

Abstract
Background
The delayed percentage attenuation ratio (DPAR) was recently identified as a novel predictor of an early complete response in patients with hepatocellular carcinoma (HCC) undergoing transarterial chemoembolization (TACE). In this study, we aimed to validate the role of DPAR as a predictive biomarker for short-, mid-, and long-term outcomes after TACE.

Methods
We retrospectively reviewed laboratory and imaging data for 103 treatment-naïve patients undergoing initial TACE treatment at our tertiary care center between January 2016 and November 2020. DPAR and other washin and washout indices were quantified in the triphasic computed tomography performed before the initial TACE. The correlation of DPAR and radiologic response was investigated. Furthermore, the influence of DPAR on the 6-, 12-, 18-, and 24-month survival rates and the median overall survival (OS) was compared to other established washout indices and estimates of tumor burden and remnant liver function.

Results
The DPAR was significantly of the target lesions (TLs) with objective response to TACE after the initial TACE session was significantly higher compared to patients with stable disease (SD) or progressive disease (PD) (125 (IQR 118–134) vs 110 (IQR 103–116), p < 0.001). Furthermore, the DPAR was significantly higher in patients who survived the first 6 months after TACE (122 vs. 115, p = 0.04). In addition, the number of patients with a DPAR > 120 was significantly higher in this group (n = 38 vs. n = 8; p = 0.03). However, no significant differences were observed in the 12-, 18-, and 24-month survival rates after the initial TACE. Regarding the median OS, no significant difference was observed for patients with a high DPAR compared to those with a low DPAR (18.7 months vs. 12.7 months, p = 0.260).

Conclusions
Our results confirm DPAR as the most relevant washout index for predicting the short-term outcome of patients with HCC undergoing TACE. However, DPAR and the other washout indices were not predictive of mid- and long-term outcomes.