bluuebunny/crossref_metadata_2025_split huggingface dataset:
Health effects of milk consumption: phenome-wide Mendelian randomization study
Authors: Yuan Shuai , Sun Jing , Lu Ying , Xu Fengzhe , Li Doudou , Jiang Fangyuan , Wan Zhongxiao , Li Xue , Qin Li-Qiang , Larsson Susanna C. 
Published: November 2022

AbstractBackgroundWe performed phenome-wide Mendelian randomization analysis (MR-PheWAS), two-sample MR analysis, and systemic review to comprehensively explore the health effects of milk consumption in the European population.MethodsRs4988235 located upstream of theLCTgene was used as the instrumental variable for milk consumption. MR-PheWAS analysis was conducted to map the association of genetically predicted milk consumption with 1081 phenotypes in the UK Biobank study (n=339,197). The associations identified in MR-PheWAS were examined by two-sample MR analysis using data from the FinnGen study (n=260,405) and international consortia. A systematic review of MR studies on milk consumption was further performed.ResultsPheWAS and two-sample MR analyses found robust evidence in support of inverse associations of genetically predicted milk consumption with risk of cataract (odds ratio (OR) per 50 g/day increase in milk consumption, 0.89, 95% confidence interval (CI), 0.84–0.94;p=3.81×10−5), hypercholesterolemia (OR, 0.91, 95% CI 0.86–0.96;p=2.97×10−4), and anal and rectal polyps (OR, 0.85, 95% CI, 0.77–0.94;p=0.001). An inverse association for type 2 diabetes risk (OR, 0.92, 95% CI, 0.86–0.97;p=0.003) was observed in MR analysis based on genetic data with body mass index adjustment but not in the corresponding data without body mass index adjustment. The systematic review additionally found evidence that genetically predicted milk consumption was inversely associated with asthma, hay fever, multiple sclerosis, colorectal cancer, and Alzheimer’s disease, and positively associated with Parkinson’s disease, renal cell carcinoma, metabolic syndrome, overweight, and obesity.ConclusionsThis study suggests several health effects of milk consumption in the European population.
Identifying and ranking causal biochemical biomarkers for breast cancer: a Mendelian randomisation study
Authors: Tang Sonja N. , Zuber Verena , Tsilidis Konstantinos K. 
Published: November 2022

Abstract

Background
Only a few of the 34 biochemical biomarkers measured in the UK Biobank (UKB) have been associated with breast cancer, with many associations suffering from possible confounding and reverse causation. This study aimed to screen and rank all UKB biochemical biomarkers for possible causal relationships with breast cancer.

Methods
We conducted two-sample Mendelian randomisation (MR) analyses on ~420,000 women by leveraging summary-level genetic exposure associations from the UKB study (n = 194,174) and summary-level genetic outcome associations from the Breast Cancer Association Consortium (n = 228,951). Our exposures included all 34 biochemical biomarkers in the UKB, and our outcomes were overall, oestrogen-positive, and oestrogen-negative breast cancer. We performed inverse-variance weighted MR, weighted median MR, MR-Egger, and MR-PRESSO for 30 biomarkers for which we found multiple instrumental variables. We additionally performed multivariable MR to adjust for known risk factors, bidirectional MR to investigate reverse causation, and MR Bayesian model averaging to rank the significant biomarkers by their genetic evidence.

Results
Increased genetic liability to overall breast cancer was robustly associated with the following biomarkers by decreasing importance: testosterone (odds ratio (OR): 1.12, 95% confidence interval (CI): 1.04–1.21), high-density lipoprotein (HDL) cholesterol (OR: 1.08, 95% CI: 1.04–1.13), insulin-like growth factor 1 (OR: 1.08, 95% CI: 1.02–1.13), and alkaline phosphatase (ALP) (OR: 0.93, 95% CI: 0.89–0.98).

Conclusions
Our findings support a likely causal role of genetically predicted levels of testosterone, HDL cholesterol, and IGF-1, as well as a novel potential role of ALP in breast cancer aetiology. Further studies are needed to understand full disease pathways that may inform breast cancer prevention.
Homogenizing effect of PEEP on tidal volume distribution during neurally adjusted ventilatory assist: study of an animal model of acute respiratory distress syndrome
Authors: Widing Hannes , Chiodaroli Elena , Liggieri Francesco , Mariotti Paola Sara , Hallén Katarina , Perchiazzi Gaetano 
Published: November 2022

Abstract
Background
The physiological response and the potentially beneficial effects of positive end-expiratory pressure (PEEP) for lung protection and optimization of ventilation during spontaneous breathing in patients with acute respiratory distress syndrome (ARDS) are not fully understood. The aim of the study was to compare the effect of different PEEP levels on tidal volume distribution and on the ventilation of dependent lung region during neurally adjusted ventilatory assist (NAVA).

Methods
ARDS-like lung injury was induced by using saline lavage in 10 anesthetized and spontaneously breathing farm-bred pigs. The animals were ventilated in NAVA modality and tidal volume distribution as well as dependent lung ventilation were assessed using electric impedance tomography during the application of PEEP levels from 0 to 15 cmH20, in steps of 3 cmH20. Tidal volume distribution and dependent fraction of ventilation were analysed using Wilcoxon signed rank test. Furthermore, airway, esophageal and transpulmonary pressure, as well as airway flow and delivered volume, were continuously measured during the assisted spontaneous breathing.

Results
Increasing PEEP improved oxygenation and re-distributed tidal volume. Specifically, ventilation distribution changed from a predominant non-dependent to a more even distribution between non-dependent and dependent areas of the lung. Dependent fraction of ventilation reached 47 ± 9% at PEEP 9 cmH20. Further increasing PEEP led to a predominant dependent ventilation.

Conclusion
During assisted spontaneous breathing in this model of induced ARDS, PEEP modifies the distribution of ventilation and can achieve a homogenizing effect on its spatial arrangement. The study indicates that PEEP is an important factor during assisted spontaneous breathing and that EIT can be of valuable interest when titrating PEEP level during spontaneous breathing, by indicating the most homogeneous distribution of gas volumes throughout the PEEP spectrum.
Derivation and external validation of a simple prediction rule for the development of respiratory failure in hospitalized patients with influenza
Authors: Ayuso Blanca , Lalueza Antonio , Arrieta Estibaliz , Romay Eva María , Marchán-López Álvaro , García-País María José , Folgueira Dolores , Gude María José , Cueto Cecilia , Serrano Antonio , Lumbreras Carlos 
Published: November 2022

Abstract
Background
Influenza viruses cause seasonal epidemics worldwide with a significant morbimortality burden. Clinical spectrum of Influenza is wide, being respiratory failure (RF) one of its most severe complications. This study aims to elaborate a clinical prediction rule of RF in hospitalized Influenza patients.

Methods
A prospective cohort study was conducted during two consecutive Influenza seasons (December 2016–March 2017 and December 2017–April 2018) including hospitalized adults with confirmed A or B Influenza infection. A prediction rule was derived using logistic regression and recursive partitioning, followed by internal cross-validation. External validation was performed on a retrospective cohort in a different hospital between December 2018 and May 2019.

Results
Overall, 707 patients were included in the derivation cohort and 285 in the validation cohort. RF rate was 6.8% and 11.6%, respectively. Chronic obstructive pulmonary disease, immunosuppression, radiological abnormalities, respiratory rate, lymphopenia, lactate dehydrogenase and C-reactive protein at admission were associated with RF. A four category-grouped seven point-score was derived including radiological abnormalities, lymphopenia, respiratory rate and lactate dehydrogenase. Final model area under the curve was 0.796 (0.714–0.877) in the derivation cohort and 0.773 (0.687–0.859) in the validation cohort (p < 0.001 in both cases). The predicted model showed an adequate fit with the observed results (Fisher’s test p > 0.43).

Conclusion
we present a simple, discriminating, well-calibrated rule for an early prediction of the development of RF in hospitalized Influenza patients, with proper performance in an external validation cohort. This tool can be helpful in patient’s stratification during seasonal Influenza epidemics.
Time trends of cardiovascular risk management in type 1 diabetes - nationwide analyses of real-life data
Authors: Amadid Hanan , Clemmensen Kim Katrine Bjerring , Vistisen Dorte , Persson Frederik , Jørgensen Marit Eika 
Published: November 2022

Abstract
Background
Individuals diagnosed with and treated for type 1 diabetes (T1D) have increased risk of micro- and macrovascular disease and excess mortality. Improving cardiovascular (CV) risk factors in individuals with T1D is known to reduce diabetes- related CV complications.

Aim
To examine time trends in CV risk factor levels and CV-protective treatment patterns. Additionally, examine incidence rates of diabetes-related CV complications in relation to exposure CV-protective treatment.

Methods
We analysed records from 41,630 individuals with T1D, registered anytime between 1996 and 2017 in a nationwide diabetes register. We obtained CV risk factor measurements (2010–2017), CV-protective drug profiles (1996–2017) and CV complication history (1977–2017) from additional nationwide health registers.

Results
From 2010 to 2017 there were decreasing levels of HbA1c, LDL-C, and blood pressure. Decreasing proportion of smokers, individuals with glycaemic dysregulation (HbA1c ≥ 58 mmol/mol), dyslipidaemia (LDL-C > 2.6 mmol/l), and hypertension (≥ 140/85 mmHg). Yet, one fifth of the T1D population by January 1st, 2017 was severely dysregulated (HbA1c > 75 mmol/mol). A slight increase in levels of BMI and urinary albumin creatinine ratio and a slight decrease in estimated glomerular filtration rate (eGFR) levels was observed. By January 1st, 2017, one fourth of the T1D population had an eGFR < 60 ml/min/1.73 m2. The proportion of the T1D population redeeming lipid-lowering drugs (LLDs) increased from 5% in 2000 to 30% in 2010 followed by a plateau and then a decline. The proportion of the T1D population redeeming antihypertensive drugs (AHDs) increased from 28% in 1996 to 42% in 2010 followed by a tendency to decline. Use of LLDs was associated with lower incidence of micro- and macrovascular complications, while use of AHDs had higher incidence of CVD and CKD, when compared to non-use and discontinued use, respectively.

Conclusion
Improvements were seen in CV risk factor control among individuals with T1D in Denmark between 2010 and 2017. However, there is clearly a gap between current clinical guidelines and clinical practice for CV risk management in T1D. Action is needed to push further improvements in CV risk control to reduce CVD and the related excess mortality.
The hero of American and Polish nations: a molecular look at Thaddeus Kosciuszko’s cause of death suggests a contribution of endocarditis caused by Cutibacterium acnes infection
Authors: Witt Michał , Tokarski Miron , Ziętkiewicz Ewa , Lebioda Arleta , Szczypek Maria , Falkowski Wojciech , Mrozowski Przemysław , Kulak Teresa , Sobieszczańska Małgorzata , Mrugalska-Banaszak Magdalena , Jurek Tomasz , Dobosz Tadeusz 
Published: November 2022

AbstractThe remains of the heart tissue of Thaddeus Kosciuszko have been investigated as the possible cause of disease and death of the hero of Polish and American nations. Three specimens, DNA isolated from scrappings of wax surface, from the surface of a wooden plate, and from the linen cloth that have had contact with the object were subjected to nanosequencing. From the first two, among all reads identified, only one classified as Propionibacterium acnes (synonymous current name Cutibacterium acnes), had a purported clinical significance. The observed identity between the P. acnes sequences and reference was 89–90% consistent with the hypothesis that the identified reads represent the ancient P. acnes DNA (aDNA), which underwent fragmentation and sequence changes caused by its long-time presence in the environmental conditions conducive to degradation. We present a reasonable and entirely new hypothesis that the analyzed samples could reflect the presence of the bacteria in the original Kosciuszko’s heart tissue and that the process of C. acnes infection was progressing inside the organ (endocarditis), not on its surface (pericarditis) leading to rapid deterioration of health and eventually death. We again point out that normal skin and mucosal membranes commensal, a causative agent of common skin acne, may be associated with various severe organ infections posing a threat to health and life.
Machine learning for data integration in human gut microbiome
Authors: Li Peishun , Luo Hao , Ji Boyang , Nielsen Jens 
Published: November 2022

AbstractRecent studies have demonstrated that gut microbiota plays critical roles in various human diseases. High-throughput technology has been widely applied to characterize the microbial ecosystems, which led to an explosion of different types of molecular profiling data, such as metagenomics, metatranscriptomics and metabolomics. For analysis of such data, machine learning algorithms have shown to be useful for identifying key molecular signatures, discovering potential patient stratifications, and particularly for generating models that can accurately predict phenotypes. In this review, we first discuss how dysbiosis of the intestinal microbiota is linked to human disease development and how potential modulation strategies of the gut microbial ecosystem can be used for disease treatment. In addition, we introduce categories and workflows of different machine learning approaches, and how they can be used to perform integrative analysis of multi-omics data. Finally, we review advances of machine learning in gut microbiome applications and discuss related challenges. Based on this we conclude that machine learning is very well suited for analysis of gut microbiome and that these approaches can be useful for development of gut microbe-targeted therapies, which ultimately can help in achieving personalized and precision medicine.
Tiliroside suppresses triple-negative breast cancer as a multifunctional CAXII inhibitor
Authors: Han Rui , Yang Hongxing , Ling Changquan , Lu Lingeng 
Published: November 2022

AbstractTriple negative breast cancer (TNBC) is an aggressive subtype of breast cancer characterized by poor prognosis, early recurrence, and the lack of durable chemotherapy responses and specific targeted treatments. In this preclinical study, we examines Tiliroside (TS, C30H26O13), as one of the major compounds of Tribulus terrestris L. which has been used as an alternative therapy in clinic practice of breast cancer treatment, for its therapeutic use in TNBC. The association between CAXII expression level and survival probability of TNBC patients, and the difference of CAXII expression level between TNBC and normal samples were evaluated by using publicly accessible databases. To determine the anticancer efficacy of TS on TNBC cells, cell proliferation, wound healing, cell invasion, and 3D spheroid formation assays were performed and excellent anticancer activities of TS were displayed. Mouse models further demonstrated that TS significantly reduced the tumor burden and improved survival rate. The properties of TS as a novel CAXII inhibitor have also been evaluated by CAXII activity assay, pHi, pHe and lactate level assay. Further RT-PCR and Caspase-3 activity analyses also revealed the positive regulating effects of TS on E2F1,3/Caspase-3 axis in TNBC cells cultured in 2D or 3D systems. The findings indicate that TS suppresses TNBC progression as a potential novel CAXII inhibitor in preclinical experiments, which warrants further investigation on its therapeutic implications.
Immune modulating nanoparticles for the treatment of ocular diseases
Authors: Fang Lianfei , Liu Jin , Liu Zeyang , Zhou Huifang 
Published: November 2022

AbstractOcular diseases are increasingly influencing people’s quality of life. Complicated inflammatory mechanisms involved in the pathogenic process of ocular diseases make inflammation-targeting treatment a potential therapeutic approach. The limited efficacy of conventional anti-inflammatory therapeutic strategies, caused by various objective factors, such as complex ocular biological barriers, and subjective factors, such as poor compliance, are promoting the development of new therapeutic methods. With the advantages of considerable tissue permeability, a controllable drug release rate, and selective tissue targeting ability, nanoparticles have successfully captured researchers’ attention and have become a research hotspot in treating ocular diseases. This review will focus on the advantages of nanosystems over traditional therapy, the anti-inflammation mechanisms of nanoparticles, and the anti-inflammatory applications of nanoparticles in different ocular diseases (ocular surface diseases, vitreoretinopathy, uveal diseases, glaucoma, and visual pathway diseases). Furthermore, by analyzing the current situation of nanotherapy and the challenges encountered, we hope to inspire new ideas and incentives for designing nanoparticles more consistent with human physiological characteristics to make progress based on conventional treatments. Overall, some progress has been made in nanoparticles for the treatment of ocular diseases, and nanoparticles have rather broad future clinical translation prospects.
A carbon monoxide releasing metal organic framework nanoplatform for synergistic treatment of triple-negative breast tumors
Authors: Cong Yiyang , Sun Bo , Hu Jianlun , Li Xiaoyang , Wang Yanan , Zhang Jingyi , Yang Dongzhi , Lu Weifei , Ding Zhi , Wang Xiaofeng , Hong Hao 
Published: November 2022

Abstract
Background
Carbon monoxide (CO) is an important signaling molecule participating in multiple biological functions. Previous studies have confirmed the valuable roles of CO in cancer therapies. If the CO concentration and distribution can be controlled in tumors, new cancer therapeutic strategy may be developed to benefit the patient survival.

Results
In this study, a UiO-67 type metal–organic framework (MOF) nanoplatform was produced with cobalt and ruthenium ions incorporated into its structure (Co/Ru-UiO-67). Co/Ru-UiO-67 had a size range of 70–90 nm and maintained the porous structure, with cobalt and ruthenium distributed uniformly inside. Co/Ru-UiO-67 was able to catalyze carbon dioxide into CO upon light irradiation in an efficient manner with a catalysis speed of 5.6 nmol/min per 1 mg Co/Ru-UiO-67. Due to abnormal metabolic properties of tumor cells, tumor microenvironment usually contains abundant amount of CO2. Co/Ru-UiO-67 can transform tumor CO2 into CO at both cellular level and living tissues, which consequently interacts with relevant signaling pathways (e.g. Notch-1, MMPs etc.) to adjust tumor microenvironment. With proper PEGylation (pyrene-polyacrylic acid-polyethylene glycol, Py-PAA-PEG) and attachment of a tumor-homing peptide (F3), functionalized Co/Ru-UiO-67 could accumulate strongly in triple-negative MDA-MB-231 breast tumors, witnessed by positron emission tomography (PET) imaging after the addition of radioactive zirconium-89 (89Zr) into Co-UiO-67. When applied in vivo, Co/Ru-UiO-67 could alter the local hypoxic condition of MDA-MB-231 tumors, and work synergistically with tirapazamine (TPZ).

Conclusion
This nanoscale UiO-67 MOF platform can further our understanding of CO functions while produce CO in a controllable manner during cancer therapeutic administration.

Graphical Abstract
Intensity-adjustable pain management with prolonged duration based on phase-transitional nanoparticles-assisted ultrasound imaging-guided nerve blockade
Authors: Qiao Bin , Song Xinye , Zhang Weiyi , Xu Ming , Zhuang Bowen , Li Wei , Guo Huanling , Wu Wenxin , Huang Guangliang , Zhang Minru , Xie Xiaoyan , Zhang Nan , Luan Yong , Zhang Chunyang 
Published: November 2022

Abstract
Background
The lack of a satisfactory strategy for postoperative pain management significantly impairs the quality of life for many patients. However, existing nanoplatforms cannot provide a longer duration of nerve blockage with intensity-adjustable characteristics under imaging guidance for clinical applications.

Results
To overcome this challenge, we proposed a biocompatible nanoplatform that enables high-definition ultrasound imaging-guided, intensity-adjustable, and long-lasting analgesia in a postoperative pain management model in awake mice. The nanoplatform was constructed by incorporating perfluoropentane and levobupivacaine with red blood cell membranes decorated liposomes. The fabricated nanoplatform can achieve gas-producing and can finely escape from immune surveillance in vivo to maximize the anesthetic effect. The analgesia effect was assessed from both motor reactions and pain-related histological markers. The findings demonstrated that the duration of intensity-adjustable analgesia in our platform is more than 20 times longer than free levobupivacaine injection with pain relief for around 3 days straight. Moreover, the pain relief was strengthened by repeatable ultrasound irradiation to effectively manage postoperative pain in an intensity-adjustable manner. No apparent systemic and local tissue injury was detected under different treatments.

Conclusion
Our results suggest that nanoplatform can provide an effective strategy for ultrasound imaging-guided intensity-adjustable pain management with prolonged analgesia duration and show considerable transformation prospects.