bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pharmacogenetic interventions to improve outcomes in patients with multimorbidity or prescribed polypharmacy: a systematic review
Authors: O’Shea Joseph , Ledwidge Mark , Gallagher Joseph , Keenan Catherine , Ryan Cristín 
Published: February 2022

AbstractConventional medicines optimisation interventions in people with multimorbidity and polypharmacy are complex and yet limited; a more holistic and integrated approach to healthcare delivery is required. Pharmacogenetics has potential as a component of medicines optimisation. Studies involving multi-medicine pharmacogenetics in adults with multimorbidity or polypharmacy, reporting on outcomes derived from relevant core outcome sets, were included in this systematic review. Narrative synthesis was undertaken to summarise the data; meta-analysis was inappropriate due to study heterogeneity. Fifteen studies of diverse design and variable quality were included. A small, randomised study involving pharmacist-led medicines optimisation, including pharmacogenetics, suggests this approach could have significant benefits for patients and health systems. However, due to study design heterogeneity and the quality of the included studies, it is difficult to draw generalisable conclusions. Further pragmatic, robust pharmacogenetics studies in diverse, real-world patient populations, are required to establish the benefit of multi-medicine pharmacogenetic screening on patient outcomes.
The impact of anthracyclines in intermediate and high-risk HER2-negative early breast cancer—a pooled analysis of the randomised clinical trials PlanB and SUCCESS C
Authors: de Gregorio Amelie , Janni Wolfgang , Friedl Thomas W. P. , Nitz Ulrike , Rack Brigitte , Schneeweiss Andreas , Kates Ronald , Fehm Tanja , Kreipe Hans , Christgen Matthias , Kümmel Sherko , Trapp Elisabeth , Wuerstlein Rachel , Hartkopf Andreas , Clemens Michael , Reimer Toralf , Häberle Lothar , Fasching Peter A. , Gluz Oleg , Harbeck Nadia 
Published: February 2022

Abstract
Background
Anthracycline/cyclophosphamide-taxane-containing chemotherapy (AC-T) is the standard of care in the adjuvant treatment of HER2-negative early breast cancer (EBC), but recent studies suggest omission of anthracyclines for reduced toxicity without compromising efficacy.

Methods
Based on individual patient data (n = 5924) pooled from the randomised Phase III trials PlanB and SUCCESS C, we compared disease-free survival (DFS) and overall survival (OS) between intermediate to high-risk HER2-negative EBC-patients treated with either six cycles of docetaxel/cyclophosphamide (TC6) or an AC-T regime using univariable and adjusted multivariable Cox regression models.

Results
AC-T conferred no significant DFS or OS advantage in univariable (DFS: hazard ratio (HR) for TC vs. AT 1.05, 95% confidence interval (CI): 0.89–1.24, P = 0.57; OS: HR 1.00, 95% CI: 0.80–1.26, P = 1.00) and adjusted multivariable analysis (DFS: HR 1.01, 95% CI: 0.86–1.19, P = 0.91; OS: HR 0.97, 95% CI: 0.77–1.22, P = 0.79). Patients receiving TC6 had significantly fewer grade 3–4 adverse events. Exploratory subgroup analysis showed that AC-T was associated with significantly better DFS and OS in pN2/3 patients, specifically in those with lobular histology.

Conclusion
For most patients with HER2-negative EBC, AC-T is not associated with a survival benefit compared to TC6. However, patients with lobular pN2/pN3 tumours seem to benefit from anthracycline-containing chemotherapy.
Association of smoking and polygenic risk with the incidence of lung cancer: a prospective cohort study
Authors: Zhang Peidong , Chen Pei-Liang , Li Zhi-Hao , Zhang Ao , Zhang Xi-Ru , Zhang Yu-Jie , Liu Dan , Mao Chen 
Published: February 2022

Abstract
Background
Genetic variation increases the risk of lung cancer, but the extent to which smoking amplifies this effect remains unknown. Therefore, we aimed to investigate the risk of lung cancer in people with different genetic risks and smoking habits.

Methods
This prospective cohort study included 345,794 European ancestry participants from the UK Biobank and followed up for 7.2 [6.5–7.8] years.

Results
Overall, 26.2% of the participants were former smokers, and 9.8% were current smokers. During follow-up, 1687 (0.49%) participants developed lung cancer. High genetic risk and smoking were independently associated with an increased risk of incident lung cancer. Compared with never-smokers, HR per standard deviation of the PRS increase was 1.16 (95% CI, 1.11–1.22), and HR of heavy smokers (≥40 pack-years) was 17.89 (95% CI, 15.31–20.91). There were no significant interactions between the PRS and the smoking status or pack-years. Population-attributable fraction analysis showed that smoking cessation might prevent 76.4% of new lung cancers.

Conclusions
Both high genetic risk and smoking were independently associated with higher lung cancer risk, but the increased risk of smoking was much more significant than heredity. The combination of traditional risk factors and additional PRS provides realistic application prospects for precise prevention.
Peritoneal metastases from colorectal cancer belong to Consensus Molecular Subtype 4 and are sensitised to oxaliplatin by inhibiting reducing capacity
Authors: Laoukili Jamila , Constantinides Alexander , Wassenaar Emma C. E. , Elias Sjoerd G. , Raats Danielle A. E. , van Schelven Susanne J. , van Wettum Jonathan , Volckmann Richard , Koster Jan , Huitema Alwin D. R. , Nienhuijs Simon W. , de Hingh Ignace H. J. T. , Wiezer René J. , van Grevenstein Helma M. U. , Rinkes Inne H. M. Borel , Boerma Djamila , Kranenburg Onno 
Published: February 2022

Abstract
Background
Peritoneal metastases (PM) in colorectal cancer (CRC) are associated with therapy resistance and poor survival. Oxaliplatin monotherapy is widely applied in the intraperitoneal treatment of PM, but fails to yield clinical benefit. We aimed to identify the mechanism(s) underlying PM resistance to oxaliplatin and to develop strategies overcoming such resistance.

Experimental design
We generated a biobank consisting of 35 primary tumour regions and 59 paired PM from 12 patients. All samples were analysed by RNA sequencing. We also generated a series of PM-derived organoid (PMDO) cultures and used these to design and test strategies to overcome resistance to oxaliplatin.

Results
PM displayed various hallmarks of aggressive CRC biology. The vast majority of PM and paired primary tumours belonged to the Consensus Molecular Subtype 4 (CMS4). PMDO cultures were resistant to oxaliplatin and expressed high levels of glutamate-cysteine ligase (GCLC) causing detoxification of oxaliplatin through glutathione synthesis. Genetic or pharmacological targeting of GCLC sensitised PMDOs to a 1-h exposure to oxaliplatin, through increased platinum-DNA adduct formation.

Conclusions
These results link oxaliplatin resistance of colorectal PM to their CMS4 status and high reducing capacity. Inhibiting the reducing capacity of PM may be an effective strategy to overcome PM resistance to oxaliplatin.
Next generation self-replicating RNA vectors for vaccines and immunotherapies
Authors: Aliahmad Parinaz , Miyake-Stoner Shigeki J. , Geall Andrew J. , Wang Nathaniel S. 
Published: February 2022

AbstractRNA technology has recently come to the forefront of innovative medicines and is being explored for a wide range of therapies, including prophylactic and therapeutic vaccines, biotherapeutic protein expression and gene therapy. In addition to conventional mRNA platforms now approved for prophylactic SARS-CoV2 vaccines, synthetic self-replicating RNA vaccines are currently being evaluated in the clinic for infectious disease and oncology. The prototypical srRNA vectors in clinical development are derived from alphaviruses, specifically Venezuelan Equine Encephalitis Virus (VEEV). While non-VEEV alphaviral strains have been explored as single cycle viral particles, their use as synthetic vectors largely remains under-utilized in clinical applications. Here we describe the potential commonalities and differences in synthetic alphaviral srRNA vectors in host cell interactions, immunogenicity, cellular delivery, and cargo expression. Thus, unlike the current thinking that VEEV-based srRNA is a one-size-fits-all platform, we argue that a new drug development approach leveraging panels of customizable, synthetic srRNA vectors will be required for clinical success.
Degradation of DRAK1 by CUL3/SPOP E3 Ubiquitin ligase promotes tumor growth of paclitaxel-resistant cervical cancer cells
Authors: Pang Kyoungwha , Lee Jihee , Kim Junil , Park Jinah , Park Yuna , Hong Eunji , An Haein , Ooshima Akira , Son Minjung , Park Kyung-Soon , Cho Jae-Hyun , Lee Cheol , Song Yong Sang , Yang Kyung-Min , Kim Seong-Jin 
Published: February 2022

AbstractDespite favorable responses to initial chemotherapy, drug resistance is a major cause limiting chemotherapeutic efficacy in many advanced cancers. However, mechanisms that drive drug-specific resistance in chemotherapy for patients with advanced cancers are still unclear. Here, we report a unique role of death-associated protein kinase-related apoptosis-inducing kinase 1 (DRAK1) associated with paclitaxel resistance in cervical cancer cells. Interestingly, DRAK1 protein level was markedly decreased in paclitaxel-resistant cervical cancer cells without affecting its mRNA expression, which resulted in an increase in tumor necrosis factor receptor-associated factor 6 (TRAF6) expression, as well as an activation of TRAF6-mediated nuclear factor-kappa B (NF-κB) signaling cascade, thereby promoting tumor progression. DRAK1 depletion markedly increased the chemotherapeutic IC50 values of paclitaxel in cervical cancer cells. Ectopic expression of DRAK1 inhibited growth of paclitaxel-resistant cervical cancer cells in vitro and in vivo. Furthermore, DRAK1 was markedly underexpressed in chemoresistant cervical cancer patient tissues compared with chemosensitive samples. We found that DRAK1 protein was destabilized through K48-linked polyubiquitination promoted by the Cullin scaffold protein 3 (CUL3) / speckle-type POZ (poxvirus and zinc finger protein) protein (SPOP) E3 ubiquitin ligase in paclitaxel-resistant cells. Collectively, these findings suggest that DRAK1 may serve as a potential predictive biomarker for overcoming paclitaxel resistance in cervical cancer.
Parental folate deficiency induces birth defects in mice accompanied with increased de novo mutations
Authors: Zhao Ying , Chen Duoyuan , Tang Jianping , Zheng Yufang , Qi Ji , Wang Hongyan 
Published: February 2022

AbstractDietary folate deficiency (FD) is associated with the occurrence of birth defects. However, the mechanisms underlying this association remain elusive. In particular, how FD affects genome stability is unknown. To examine whether a folate-deficient diet can affect genome stability, C57BL/6 mice were maintained on a synthetic diet lacking of folic acid (FA) for two generations. F0 mice received the FD diet beginning at 3 weeks of age, and their offspring (F1) began the FD diet after weaning. Both male and female F1 mice fed the FD diet were intentionally crossed with F1 mice fed the normal diet to produce F2 mice. F2 embryos were dissected and collected at E14.5 and E18.5. The malformation ratio was significantly increased in F2 embryos fed the FD diet for two generations compared to those fed the normal diet. Whole-genome sequencing of multiple sibship with F1 males on the FD diet showed that the de novo mutation (DNM) rate in F2 embryos was three times of the reported spontaneous rate in mice. Furthermore, many DNMs observed in the F2 mice exhibited an allele ratio of 1:3 instead of 2:2, suggesting that these mutations are likely to accumulate in gamete cells as a form of mismatch in the DNA duplex. Our study indicated that FD for two generations significantly enhances DNM accumulation during meiosis, which might contribute to the increased negative birth outcomes among F2 mice. Not only maternal but also paternal FA supplementation is probably also necessary and beneficial to prevent birth defects.
Interrater reliability of routine screening for risk of malnutrition with the Mini Nutritional Assessment Short-Form in hospital
Authors: Trampisch Ulrike Sonja , Pourhassan Maryam , Daubert Diana , Volkert Dorothee , Wirth Rainer 
Published: February 2022

Abstract
Background/objectives
The Mini Nutritional Assessment Short-Form (MNA-SF) is the recommended screening tool for older persons. Data on interrater reliability in clinical routine are rare. Thus, we wanted to quantify the interrater reliability of the MNA-SF in hospital.

Subjects/methods
This observational cross-sectional study was undertaken retrospectively. The study population comprised 105 participants. Risk of malnutrition was measured twice with the routine MNA-SF performed by nurses (within 24 h after admission) and a dedicated dietician (one to three days after the first MNA-SF). The MNA-SF score was analyzed for interrater reliability between nurse and dietician.

Results
Participants’ mean age was 82.4 (±7.1) years and 71 (68%) were women. The mean total MNA-SF score was 7.4 (±2.4) assessed by dietician and 7.8 (±2.3) assessed by nurse. The intra-class correlation coefficient between the total MNA-SF scores was 0.74 (0.61; 0.82), indicating moderate reliability. For the MNA-SF nutritional status, Cohens Kappa was 0.37 (p < 0.05) showing a fair agreement.

Conclusion
Multiple misclassifications were observed between malnutrition and risk of malnutrition. Because mean scores were near the border between malnutrition and risk of malnutrition, we recommend to consider the total MNA-SF score in addition to the three risk groups to assess nutritional risk in geriatric hospital patients.
Fine-scale heterogeneity in population density predicts wave dynamics in dengue epidemics
Authors: Romeo-Aznar Victoria , Picinini Freitas Laís , Gonçalves Cruz Oswaldo , King Aaron A. , Pascual Mercedes 
Published: February 2022

AbstractThe spread of dengue and other arboviruses constitutes an expanding global health threat. The extensive heterogeneity in population distribution and potential complexity of movement in megacities of low and middle-income countries challenges predictive modeling, even as its importance to disease spread is clearer than ever. Using surveillance data at fine resolution following the emergence of the DENV4 dengue serotype in Rio de Janeiro, we document a pattern in the size of successive epidemics that is invariant to the scale of spatial aggregation. This pattern emerges from the combined effect of herd immunity and seasonal transmission, and is strongly driven by variation in population density at sub-kilometer scales. It is apparent only when the landscape is stratified by population density and not by spatial proximity as has been common practice. Models that exploit this emergent simplicity should afford improved predictions of the local size of successive epidemic waves.
Organic electrochemical neurons and synapses with ion mediated spiking
Authors: Harikesh Padinhare Cholakkal , Yang Chi-Yuan , Tu Deyu , Gerasimov Jennifer Y. , Dar Abdul Manan , Armada-Moreira Adam , Massetti Matteo , Kroon Renee , Bliman David , Olsson Roger , Stavrinidou Eleni , Berggren Magnus , Fabiano Simone 
Published: February 2022

AbstractFuture brain-machine interfaces, prosthetics, and intelligent soft robotics will require integrating artificial neuromorphic devices with biological systems. Due to their poor biocompatibility, circuit complexity, low energy efficiency, and operating principles fundamentally different from the ion signal modulation of biology, traditional Silicon-based neuromorphic implementations have limited bio-integration potential. Here, we report the first organic electrochemical neurons (OECNs) with ion-modulated spiking, based on all-printed complementary organic electrochemical transistors. We demonstrate facile bio-integration of OECNs with Venus Flytrap (Dionaea muscipula) to induce lobe closure upon input stimuli. The OECNs can also be integrated with all-printed organic electrochemical synapses (OECSs), exhibiting short-term plasticity with paired-pulse facilitation and long-term plasticity with retention >1000 s, facilitating Hebbian learning. These soft and flexible OECNs operate below 0.6 V and respond to multiple stimuli, defining a new vista for localized artificial neuronal systems possible to integrate with bio-signaling systems of plants, invertebrates, and vertebrates.
Acetylcholine deficiency disrupts extratelencephalic projection neurons in the prefrontal cortex in a mouse model of Alzheimer’s disease
Authors: Sun Qingtao , Zhang Jianping , Li Anan , Yao Mei , Liu Guangcai , Chen Siqi , Luo Yue , Wang Zhi , Gong Hui , Li Xiangning , Luo Qingming 
Published: February 2022

AbstractShort-term memory deficits have been associated with prefrontal cortex (PFC) dysfunction in Alzheimer’s disease (AD) and AD mouse models. Extratelencephalic projection (ET) neurons in the PFC play a key role in short-term working memory, but the mechanism between ET neuronal dysfunction in the PFC and short-term memory impairment in AD is not well understood. Here, using fiber photometry and optogenetics, we found reduced neural activity in the ET neurons in the medial prefrontal cortex (mPFC) of the 5×FAD mouse model led to object recognition memory (ORM) deficits. Activation of ET neurons in the mPFC of 5×FAD mice rescued ORM impairment, and inhibition of ET neurons in the mPFC of wild type mice impaired ORM expression. ET neurons in the mPFC that project to supramammillary nucleus were necessary for ORM expression. Viral tracing and in vivo recording revealed that mPFC ET neurons received fewer cholinergic inputs from the basal forebrain in 5×FAD mice. Furthermore, activation of cholinergic fibers in the mPFC rescued ORM deficits in 5×FAD mice, while acetylcholine deficiency reduced the response of ET neurons in the mPFC to familiar objects. Taken together, our results revealed a neural mechanism behind ORM impairment in 5×FAD mice.
Identification and establishment of type IV interferon and the characterization of interferon-υ including its class II cytokine receptors IFN-υR1 and IL-10R2
Authors: Chen Shan Nan , Gan Zhen , Hou Jing , Yang Yue Cong , Huang Lin , Huang Bei , Wang Su , Nie Pin 
Published: February 2022

AbstractInterferons (IFNs) are critical soluble factors in the immune system and are composed of three types, (I, II and III) that utilize different receptor complexes IFN-αR1/IFN-αR2, IFN-γR1/IFN-γR2, and IFN-λR1/IL-10R2, respectively. Here we identify IFN-υ from the genomic sequences of vertebrates. The members of class II cytokine receptors, IFN-υR1 and IL-10R2, are identified as the receptor complex of IFN-υ, and are associated with IFN-υ stimulated gene expression and antiviral activity in zebrafish (Danio rerio) and African clawed frog (Xenopus laevis). IFN-υ and IFN-υR1 are separately located at unique and highly conserved loci, being distinct from all other three-type IFNs. IFN-υ and IFN-υR1 are phylogenetically clustered with class II cytokines and class II cytokine receptors, respectively. Therefore, the finding of this IFN ligand-receptor system may be considered as a type IV IFN, in addition to the currently recognized three types of IFNs in vertebrates.
Residential environment in relation to self-report of respiratory and asthma symptoms among primary school children in a high-polluted urban area
Authors: Apichainan Nawarat , Norkaew Saowanee , Taneepanichskul Nutta 
Published: February 2022

AbstractRespiratory disease and its complication are the cause of children deaths worldwide every year. Several epidemiological studies pointed out an association between quality of residential in inner city and risk of children health. However, few studies had been focused in high-polluted urban area in low to middle income countries. A cross-sectional study was conducted to investigate the association between residential environments and respiratory symptoms including asthma among 658 primary school children living in urban area of Bangkok Thailand. The International Study of Asthma and Allergies in Childhood (ISAAC) questionnaire was modified to access symptoms during the past 12 months. Binary logistic regression model was performed. Living near garment and clothing shop is associated with shortness of breath (AOR = 1.846; 95% CI 1.034, 3.297). Vectors in home is related to dry cough at night (AOR = 1.505; 95% CI 1.052, 2.153) and phlegm (AOR = 1.414; 95% CI 1.014, 1.973). Wall dampness is increased odd of having wheezing or whistling (asthma) in the chest (AOR = 1.921; 95% CI 1.141, 3.235). Children age, gender, and a family history of asthma were modified the associations. Our finding may provide strategies focusing on living environment improvement with a specific group of children to address respiratory disease prevention.
Weighted correlation network analysis revealed novel long non-coding RNAs for colorectal cancer
Authors: Chodary Khameneh Sepideh , Razi Sara , Shamdani Sara , Uzan Georges , Naserian Sina 
Published: February 2022

AbstractColorectal cancer (CRC) is one of the most prevalent cancers worldwide, which after breast, lung and, prostate cancers, is the fourth prevalent cancer in the United States. Long non-coding RNAs (lncRNAs) have an essential role in the pathogenesis of CRC. Therefore, bioinformatics studies on lncRNAs and their target genes have potential importance as novel biomarkers. In the current study, publicly available microarray gene expression data of colorectal cancer (GSE106582) was analyzed with the Limma, Geoquery, Biobase package. Afterward, identified differentially expressed lncRNAs and their target genes were inserted into Weighted correlation network analysis (WGCNA) to obtain modules and hub genes. A total of nine differentially expressed lncRNAs (LINC01018, ITCH-IT, ITPK1-AS1, FOXP1-IT1, FAM238B, PAXIP1-AS1, ATP2B1-AS1, MIR29B2CHG, and SNHG32) were identified using microarray data analysis. The WGCNA has identified several hub genes for black (LMOD3, CDKN2AIPNL, EXO5, ZNF69, BMS1P5, METTL21A, IL17RD, MIGA1, CEP19, FKBP14), blue (CLCA1, GUCA2A, UGT2B17, DSC2, CA1, AQP8, ITLN1, BEST4, KLF4, IQCF6) and turquoise (PAFAH1B1, LMNB1, CACYBP, GLO1, PUM3, POC1A, ASF1B, SDCCAG3, ASNS, PDCD2L) modules. The findings of the current study will help to improve our understanding of CRC. Moreover, the hub genes that we have identified could be considered as possible prognostic/diagnostic biomarkers. This study led to the determination of nine lncRNAs with no previous association with CRC development.