bluuebunny/crossref_metadata_2025_split huggingface dataset:
Microtubule disruption reduces metastasis more effectively than primary tumor growth
Authors: Thompson Keyata N. , Ju Julia A. , Ory Eleanor C. , Pratt Stephen J. P. , Lee Rachel M. , Mathias Trevor J. , Chang Katarina T. , Lee Cornell J. , Goloubeva Olga G. , Bailey Patrick C. , Chakrabarti Kristi R. , Jewell Christopher M. , Vitolo Michele I. , Martin Stuart S. 
Published: February 2022

AbstractClinical cancer imaging focuses on tumor growth rather than metastatic phenotypes. The microtubule-depolymerizing drug, Vinorelbine, reduced the metastatic phenotypes of microtentacles, reattachment and tumor cell clustering more than tumor cell viability. Treating mice with Vinorelbine for only 24 h had no significant effect on primary tumor survival, but median metastatic tumor survival was extended from 8 to 30 weeks. Microtentacle inhibition by Vinorelbine was also detectable within 1 h, using tumor cells isolated from blood samples. As few as 11 tumor cells were sufficient to yield 90% power to detect this 1 h Vinorelbine drug response, demonstrating feasibility with the small number of tumor cells available from patient biopsies. This study establishes a proof-of-concept that targeted microtubule disruption can selectively inhibit metastasis and reveals that existing FDA-approved therapies could have anti-metastatic actions that are currently overlooked when focusing exclusively on tumor growth.
Pericardiocentesis: ultrasound guidance is essential
Authors: Blanco Pablo , Figueroa Liliana , Menéndez María Fernanda , Berrueta Belén 
Published: February 2022

Abstract
Background
Pericardial effusion is a common entity which may have important implications in patient’s prognosis. In several cases, pericardiocentesis is indicated for diagnostic and/or therapeutic purposes.

Case presentation
A blind pericardiocentesis failed in a 95-year-old woman admitted to the emergency department with a large pericardial effusion incidentally diagnosed in the ambulatory setting. Ultrasound-guided pericardiocentesis aided in easily accessing to the pericardial cavity, without periprocedural complications.

Conclusions
Ultrasound-guided pericardiocentesis is simple, safe and effective, and should replace the blind technique. This procedure should be part of the armamentarium of ultrasound-guided practices of emergency or critical care physicians.
Association between hypoglycemia and dementia in patients with diabetes: a systematic review and meta-analysis of 1.4 million patients
Authors: Huang Lifen , Zhu Manlian , Ji Jie 
Published: February 2022

Abstract
Background
Diabetes mellitus (DM) is known to be a risk factor for dementia. However, it is unclear if hypoglycemic events play a role in the risk of dementia. We aimed to systematically review evidence on the risk of dementia in DM patients based on prior hypoglycemic events.

Methods
PubMed, Embase, ScienceDirect, CENTRAL, and Google Scholar databases were searched till 15th November 2021 for cohort studies assessing the risk of dementia based on prior hypoglycemic events in DM patients. Adjusted data were pooled in a random-effects model.

Results
Ten studies with a total of 1,407,643 patients were included. Pooled analysis of all ten studies indicated that hypoglycemic episodes were associated with a statistically significant increase in the risk of dementia in DM patients as compared to those not experiencing hypoglycemic episodes (HR: 1.44 95% CI: 1.26, 1.65 I2 = 89% p < 0.00001). The results did not change on the exclusion of any study. Sub-group analysis based on the study population, type of study, adjustment for glycated hemoglobin, gender, and the number of hypoglycemic episodes also presented similar results.

Conclusions
Evidence from observational studies with a large sample size indicates that DM patients with hypoglycemic episodes are at increased risk of dementia. Anti-hyperglycemic drugs should be adequately tailored in these patients to avoid the risk of dementia.
A cancer graph: a lung cancer property graph database in Neo4j
Authors: Tuck David 
Published: February 2022

Abstract
Objectives
A novel graph data model of non-small cell lung cancer clinical and genomic data has been constructed with two aims: (1) provide a suitable model for facilitating graph analytics within the Neo4j framework or through tools which can interact through existing Neo4j APIs; and (2) provide a base model extensible to other cancer types and additional datasets such as those derived from electronic health records and other real world sources.

Data description
Clinical and genomic data integrated with a novel property graph database schema from publicly available datasets and analyses based on The Cancer Genome Atlas lung cancer datasets augmented by with subgraphs patient-patient social network from similarity and correlation as well as individual based biological networks.
A simple adaptive difference algorithm with CO2 measurements for evaluating plant growth under environmental fluctuations
Authors: Gonome Hiroki , Yamada Jun , Nishimura Norito , Arai Yuta , Hirai Minoru , Kumagai Naoki , Rajagopalan Uma Maheswari , Kono Takahiro 
Published: February 2022

Abstract
Objective
The aim of this study is to demonstrate an adaptive method that is robust toward environmental fluctuations and provides a real-time measure of plant growth by measuring CO2 consumption. To verify the validity of the proposed method, the relation between the plant growth and variation in light conditions with a closed experimental system was investigated.

Results
The proposed method was used to measure the photosynthetic rate induced by photosynthetic photon flux density (PPFD) and to evaluate plant growth under continuous and pulsed light in arugula plants. The PPFD-dependent change in photosynthetic rate was measured. And in the condition range of 200–10,000 μs pulse period and 50% duty ratio of pulsed light, there was no change in the growth rate of plants assuming the same PPFD as continuous light. These experiments showed the validity of the adaptive method in removing environmental fluctuations without precise control of temperature and humidity.
Systemic problems require systemic solutions: the need for coordination and cooperation to improve research quality
Authors: Ganley Emma , Coriat Anne-Marie , Shenow Sarah , Prosser David 
Published: February 2022

AbstractVarious factors contribute to low reproducibility and replicability of scientific findings. Whilst not all of these are necessarily problematic, there is growing acceptance that there is room for improvement. Many sectoral organisations have a role to play in this, by refining incentives and rewards, promoting specific behaviours such as open research practices, and exploring innovations in grant funding and scientific publishing. However, given the systems nature of the challenge, real change will require the coordination of these efforts, and partnerships that ensure alignment of activity and interoperability of training. Efforts to improve research quality will require investment, in infrastructure, training, and research on research to ensure that innovative solutions are evidence-based, and potential unintended consequences are explored (and avoided). National structures (e.g., the planned UK Committee on Research Integrity) should focus on understanding the research system, identifying areas for improvement, and promoting research to understand the impact of novel approaches and innovations, in order to advise on how to maximise benefit and avoid harm.
The type of anticoagulant used for plasma collection affects in vitro Rhodococcus equi assays
Authors: Rivolta Alejandra A. , Pittman Dana C. , Kappes Amanda J. , Stancil Robert K. , Kogan Clark , Sanz Macarena G. 
Published: February 2022

Abstract
Objective
The efficacy of Rhodococcus equi-specific hyperimmune plasma (HIP) is usually evaluated in vitro. Anticoagulants (AC) used for plasma collection can negatively impact bacterial replication but their effect on R. equi growth has not been evaluated. The aim of this study was to establish the effect that AC routinely used in veterinary medicine (ACD, K2EDTA, Li Heparin, and Na Citrate) have on in vitro R. equi growth. To assess this, in vitro assays commonly used to test HIP efficacy (direct effect on microorganism and macrophage infection), were performed using each AC and non-treated bacteria.

Results
There was no direct effect of ACD, Li Heparin or Na Citrate on R. equi growth. These AC significantly (p < 0.05) delayed growth for 12 h following opsonization. The number of R. equi colonies after macrophage infection was significantly (p < 0.05) lower 72 h post-opsonization with Na Citrate. K2EDTA inhibited the formation of R. equi colonies by 12 h in all the assays. In conclusion, AC should be taken into consideration when interpreting in vitro results as their negative effect on bacterial growth may be mistakenly interpreted as HIP efficacy. ACD and Li Heparin appear more appropriate for the selected assays.
Primary hypothyroidism and chronotypes in adult women
Authors: Arosemena Marilyn A. , Ramos Alberto R. , Marcus Erin N. , Slota Katarzyna A. , Cheung Joseph , Castillo Pablo R. 
Published: February 2022

Abstract
Objective
Abnormal thyroid function may disrupt sleep architecture. We aimed to determine the frequency of various chronotypes in women with hypothyroidism. We performed a single-center retrospective study at an ambulatory clinic from January 2013-December 2015. Participants were women with hypothyroidism. Chronotype was determined from the Munich ChronoType Questionnaire. The χ2 test was used to compare differences in clinical characteristics and sleep patterns in early and intermediate/late chronotypes. The t test was used to compare differences between means.

Results
We evaluated 99 patients (mean [SD], 56 [7] years): calculated chronotype revealed: 56% early, 38% intermediate and 6% late. Analysis with the χ2 test showed significant differences between early and intermediate/late calculated chronotypes for sleep latency (P = 0.01), light exposure (P = 0.009), and no alcohol intake (P = 0.001). t test showed the following differences in mean (SD) between chronotypes: sleep duration, 7.30 (1.39) hours (early chronotype) and 7.04 (2.06) hours (intermediate/late); body mass index (BMI), 29.4 (7.3) (early) and 31.1 (6.8) (intermediate/late); and TSH level, 2.89 (3.69) mIU/L (early) and 1.69 (1.41) mIU/L (intermediate/late). Early chronotypes were frequent in women with hypothyroidism. Light exposure and BMI may influence chronotypes in patients with hypothyroidism; findings are consistent with healthier behaviors in patients who tend toward morningness.
Novel epigenetic network biomarkers for early detection of esophageal cancer
Authors: Maity Alok K. , Stone Timothy C. , Ward Vanessa , Webster Amy P. , Yang Zhen , Hogan Aine , McBain Hazel , Duku Margaraet , Ho Kai Man Alexander , Wolfson Paul , Graham David G. ,   SPIT Study Group, Beck Stephan , Teschendorff Andrew E. , Lovat Laurence B. 
Published: February 2022

AbstractBackgroundEarly detection of esophageal cancer is critical to improve survival. Whilst studies have identified biomarkers, their interpretation and validity is often confounded by cell-type heterogeneity.ResultsHere we applied systems-epigenomic and cell-type deconvolution algorithms to a discovery set encompassing RNA-Seq and DNA methylation data from esophageal adenocarcinoma (EAC) patients and matched normal-adjacent tissue, in order to identify robust biomarkers, free from the confounding effect posed by cell-type heterogeneity. We identify 12 gene-modules that are epigenetically deregulated in EAC, and are able to validate all 12 modules in 4 independent EAC cohorts. We demonstrate that the epigenetic deregulation is present in the epithelial compartment of EAC-tissue. Using single-cell RNA-Seq data we show that one of these modules, a proto-cadherin module centered around CTNND2, is inactivated in Barrett’s Esophagus, a precursor lesion to EAC. By measuring DNA methylation in saliva from EAC cases and controls, we identify a chemokine module centered around CCL20, whose methylation patterns in saliva correlate with EAC status.ConclusionsGiven our observations that a CCL20 chemokine network is overactivated in EAC tissue and saliva from EAC patients, and that in independent studies CCL20 has been found to be overactivated in EAC tissue infected with the bacteriumF. nucleatum, a bacterium that normally inhabits the oral cavity, our results highlight the possibility of using DNAm measurements in saliva as a proxy for changes occurring in the esophageal epithelium. Both the CTNND2/CCL20 modules represent novel promising network biomarkers for EAC that merit further investigation.
Combination of gut microbiota and plasma amyloid-β as a potential index for identifying preclinical Alzheimer’s disease: a cross-sectional analysis from the SILCODE study
Authors: Sheng Can , Yang Kun , He Beiqi , Du Wenying , Cai Yanning , Han Ying 
Published: February 2022

Abstract
Background
Plasma amyloid-β (Aβ) may facilitate identification of individuals with brain amyloidosis. Gut microbial dysbiosis in Alzheimer’s disease (AD) is increasingly being recognized. However, knowledge about alterations of gut microbiota in preclinical AD, as well as whether the combination of plasma Aβ and gut microbiota could identify preclinical AD, remains largely unknown.

Methods
This study recruited 34 Aβ-negative cognitively normal (CN−) participants, 32 Aβ-positive cognitively normal (CN+) participants, and 22 patients with cognitive impairment (CI), including 11 patients with mild cognitive impairment (MCI) and 11 AD dementia patients. All participants underwent neuropsychological assessments and fecal microbiota analysis through 16S ribosomal RNA (rRNA) Illumina Miseq sequencing technique. Meso Scale Discovery (MSD) kits were used to quantify the plasma Aβ40, Aβ42, and Aβ42/Aβ40 in CN− and CN+ participants. Using Spearman’s correlation analysis, the associations of global standard uptake value rate (SUVR) with altered gut microbiota and plasma Aβ markers were separately evaluated. Furthermore, the discriminative power of the combination of gut microbiota and plasma Aβ markers for identifying CN+ individuals was investigated.

Results
Compared with the CN− group, the CN+ group showed significantly reduced plasma Aβ42 (p = 0.011) and Aβ42/Aβ40 (p = 0.003). The relative abundance of phylum Bacteroidetes was significantly enriched, whereas phylum Firmicutes and class Deltaproteobacteria were significantly decreased in CN+ individuals in comparison with that in CN− individuals. Particularly, the relative abundance of phylum Firmicutes and its corresponding SCFA-producing bacteria exhibited a progressive decline tendency from CN− to CN+ and CI. Besides, the global brain Aβ burden was negatively associated with the plasma Aβ42/Aβ40 (r = −0.298, p = 0.015), family Desulfovibrionaceae (r = −0.331, p = 0.007), genus Bilophila (r = −0.247, p = 0.046), and genus Faecalibacterium (r = −0.291, p = 0.018) for all CN participants. Finally, the combination of plasma Aβ markers, altered gut microbiota, and cognitive performance reached a relatively good discriminative power in identifying individuals with CN+ from CN− (AUC = 0.869, 95% CI 0.782 ~ 0.955).

Conclusions
This study provided the evidence that the gut microbial composition was altered in preclinical AD. The combination of plasma Aβ and gut microbiota may serve as a non-invasive, cost-effective diagnostic tool for early AD screening. Targeting the gut microbiota may be a novel therapeutic strategy for AD.

Trial registration
This study has been registered in ClinicalTrials.gov (NCT03370744, https://www.clinicaltrials.gov) in November 15, 2017.
The economic cost of implementing antigen-based rapid diagnostic tests for COVID-19 screening in high-risk transmission settings: evidence from Germany
Authors: Hurtado Alfonso Valenzuela , Nguyen Hoa Thi , Schenkel Viktoria , Wachinger Jonas , Seybold Joachim , Denkinger Claudia M. , De Allegri Manuela 
Published: February 2022

Abstract
Background
Antigen-based rapid diagnostic tests (Ag-RDT) have been implemented in hospitals and nursing homes to screen for infectious individuals without symptoms suggestive of SARS-CoV-2 infections and to prevent entry into these high-risk settings. Despite their benefits for screening, the cost of large-scale implementation is largely understudied. Our study presents evidence on their implementation costs in high-risk settings.
This study aimed to estimate the economic costs of implementing Ag-RDT-based screening for SARS-CoV-2 in two tertiary care hospitals (University Hospital Heidelberg - UKHD, and Charité – Universitätsmedizin Berlin) and one nursing home in Germany.

Methods
We adopted a health system perspective and followed the three sequential steps to costing: identification of resources, measurement of resource consumption, and valuation of costs. Data on resource consumption were collected between October 2020 and April 2021 through various techniques and data sources. The cost estimation considered all costs along the screening algorithm including PCR confirmation tests for positive cases. We estimated the costs for the two implementation modalities observed: staff dedicated exclusively to screening and staff not dedicated exclusively to screening. Furthermore, cost estimations were performed under both observed capacity use and hypothetical capacity use assumptions (60, 80 and 100%).

Results
Our study indicates that the average cost per Ag-RDT is highly dependent on the capacity use and implementation mode. Staff time and test kits are the two main cost drivers of implementing the large-scale screening programs for SARS-CoV-2 using Ag-RDTs. For hospitals, the average cost per test in UKHD was €30.12 (capacity observed); €14.56 (non-dedicated mode); €19.47, €16.37, €14.53 at 60, 80, 100% capacity respectively (dedicated mode); and at Charité €13.10 (non-dedicated mode). For the nursing home the estimated average cost per test was €15.03 (non-dedicated mode).

Conclusions
The information on the estimated costs by mode of implementation and capacity use may support the planning of Ag-RDT-based covid-19 screening programs suitable for each institution. Further research is needed to cost this screening strategy for COVID-19 in other high-risk, high-income settings to reach generalizability.
Autophagy-mediated degradation of NOTCH1 intracellular domain controls the epithelial to mesenchymal transition and cancer metastasis
Authors: Zada Sahib , Hwang Jin Seok , Lai Trang Huyen , Pham Trang Minh , Ahmed Mahmoud , Elashkar Omar , Kim Wanil , Kim Deok Ryong 
Published: February 2022

AbstractBackgoundAutophagy controls levels of cellular components during normal and stress conditions; thus, it is a pivotal process for the maintenance of cell homeostasis. In cancer, autophagy protects cells from cancerous transformations that can result from genomic instability induced by reactive oxygen species or other damaged components, but it can also promote cancer survival by providing essential nutrients during the metabolic stress condition of cancer progression. However, the molecular mechanism underlying autophagy-dependent regulation of the epithelial to mesenchymal transition (EMT) and metastasis is still elusive.MethodsThe intracellular level of NOTCH1 intracellular domain (NICD) in several cancer cells was studied under starvation, treatment with chloroquine or ATG7-knockdown. The autophagy activity in these cells was assessed by immunocytochemistry and molecular analyses. Cancer cell migration and invasion under modulation of autophagy were determined by in vitro scratch and Matrigel assays.ResultsIn the study, autophagy activation stimulated degradation of NICD, a key transcriptional regulator of the EMT and cancer metastasis. We also found that NICD binds directly to LC3 and that the NICD/LC3 complex associates with SNAI1 and sequestosome 1 (SQSTM1)/p62 proteins. Furthermore, theATG7knockdown significantly inhibited degradation of NICD under starvation independent of SQSTM1-associated proteasomal degradation. In addition, NICD degradation by autophagy associated with the cellular level of SNAI1. Indeed, autophagy inhibited nuclear translocation of NICD protein and consequently decreased the transcriptional activity of its target genes. Autophagy activation substantially suppressed in vitro cancer cell migration and invasion. We also observed that NICD and SNAI1 levels in tissues from human cervical and lung cancer patients correlated inversely with expression of autophagy-related proteins.ConclusionsThese findings suggest that the cellular level of NICD is regulated by autophagy during cancer progression and that targeting autophagy-dependent NICD/SNAI1 degradation could be a strategy for the development of cancer therapeutics.
History-dependent operators and prox-regular sweeping processes
Authors: Nacry Florent , Sofonea Mircea 
Published: February 2022

AbstractWe consider an abstract inclusion in a real Hilbert space, governed by an almost history-dependent operator and a time-dependent multimapping with prox-regular values. We establish the unique solvability of the inclusion under appropriate assumptions on the data. The proof is based on the arguments of monotonicity, fixed point, and prox-regularity. We then use our result in order to deduce some direct consequences, including an existence and uniqueness result for a class of sweeping processes associated with prox-regular sets. Finally, we provide an example in a finite dimensional case inspired by a rheological model in solid mechanics.
LRRK2 mutant knock-in mouse models: therapeutic relevance in Parkinson's disease
Authors: Chang Eunice Eun Seo , Ho Philip Wing-Lok , Liu Hui-Fang , Pang Shirley Yin-Yu , Leung Chi-Ting , Malki Yasine , Choi Zoe Yuen-Kiu , Ramsden David Boyer , Ho Shu-Leong 
Published: February 2022

AbstractMutations in the leucine-rich repeat kinase 2 gene (LRRK2) are one of the most frequent genetic causes of both familial and sporadic Parkinson’s disease (PD). Mounting evidence has demonstrated pathological similarities betweenLRRK2-associated PD (LRRK2-PD) and sporadic PD, suggesting that LRRK2 is a potential disease modulator and a therapeutic target in PD.LRRK2mutant knock-in (KI) mouse models display subtle alterations in pathological aspects that mirror early-stage PD, including increased susceptibility of nigrostriatal neurotransmission, development of motor and non-motor symptoms, mitochondrial and autophagy-lysosomal defects and synucleinopathies. This review provides a rationale for the use ofLRRK2KI mice to investigate the LRRK2-mediated pathogenesis of PD and implications from current findings from differentLRRK2KI mouse models, and ultimately discusses the therapeutic potentials against LRRK2-associated pathologies in PD.