bluuebunny/crossref_metadata_2025_split huggingface dataset:
Molecular landscape and subtype-specific therapeutic response of nasopharyngeal carcinoma revealed by integrative pharmacogenomics
Authors: Ding Ren-Bo , Chen Ping , Rajendran Barani Kumar , Lyu Xueying , Wang Haitao , Bao Jiaolin , Zeng Jianming , Hao Wenhui , Sun Heng , Wong Ada Hang-Heng , Valecha Monica Vishnu , Yang Eun Ju , Su Sek Man , Choi Tak Kan , Liu Shuiming , Chan Kin Iong , Yang Ling-Lin , Wu Jingbo , Miao Kai , Chen Qiang , Shim Joong Sup , Xu Xiaoling , Deng Chu-Xia 
Published: May 2021

AbstractNasopharyngeal carcinoma (NPC) is a malignant head and neck cancer type with high morbidity in Southeast Asia, however the pathogenic mechanism of this disease is poorly understood. Using integrative pharmacogenomics, we find that NPC subtypes maintain distinct molecular features, drug responsiveness, and graded radiation sensitivity. The epithelial carcinoma (EC) subtype is characterized by activations of microtubule polymerization and defective mitotic spindle checkpoint related genes, whereas sarcomatoid carcinoma (SC) and mixed sarcomatoid-epithelial carcinoma (MSEC) subtypes exhibit enriched epithelial-mesenchymal transition (EMT) and invasion promoting genes, which are well correlated with their morphological features. Furthermore, patient-derived organoid (PDO)-based drug test identifies potential subtype-specific treatment regimens, in that SC and MSEC subtypes are sensitive to microtubule inhibitors, whereas EC subtype is more responsive to EGFR inhibitors, which is synergistically enhanced by combining with radiotherapy. Through combinational chemoradiotherapy (CRT) screening, effective CRT regimens are also suggested for patients showing less sensitivity to radiation. Altogether, our study provides an example of applying integrative pharmacogenomics to establish a personalized precision oncology for NPC subtype-guided therapies.
Sensitivity, specificity, and accuracy of a liquid biopsy approach utilizing molecular amplification pools
Authors: Garcia Jessica , Kamps-Hughes Nick , Geiguer Florence , Couraud Sébastien , Sarver Brice , Payen Léa , Ionescu-Zanetti Cristian 
Published: May 2021

AbstractCirculating cell-free DNA (cfDNA) has the potential to be a specific biomarker for the therapeutic management of lung cancer patients. Here, a new sequencing error-reduction method based on molecular amplification pools (MAPs) was utilized to analyze cfDNA in lung cancer patients. We determined the accuracy of MAPs plasma sequencing with respect to droplet digital polymerase chain reaction assays (ddPCR), and tested whether actionable mutation discovery is improved by next-generation sequencing (NGS) in a clinical setting. This study reports data from 356 lung cancer patients receiving plasma testing as part of routine clinical management. Sequencing of cfDNA via MAPs had a sensitivity of 98.5% and specificity 98.9%. The ddPCR assay was used as the reference, since it is an established, accurate assay that can be performed contemporaneously on the same plasma sample. MAPs sequencing detected somatic variants in 261 of 356 samples (73%). Non-actionable clonal hematopoiesis-associated variants were identified via sequencing in 21% of samples. The accuracy of this cfDNA sequencing approach was similar to that of ddPCR assays in a clinical setting, down to an allele frequency of 0.1%. Due to broader coverage and high sensitivity for insertions and deletions, sequencing via MAPs afforded important detection of additional actionable mutations.
Power determination in vitamin D randomised control trials and characterising factors affecting it through a novel simulation-based tool
Authors: Wyse Jason , Mangan Rebecca , Zgaga Lina 
Published: May 2021

AbstractThousands of observational studies have linked vitamin D deficiency with numerous diseases, but randomised controlled trials (RCTs) often fail to show benefit of supplementation. Population characteristics and trial design have long been suspected to undermine power but were not systematically investigated. We propose a flexible generative model to characterise benefit of vitamin D supplementation at the individual level, and use this to quantify power in RCTs. The model can account for seasonality and population heterogeneity. In a simulated 1-year trial with 1000 participants per arm and assuming a 25-hydroxyvitamin D (25OHD) increase of 20 nmol/L due to the intervention, with baseline 25OHD in the population of 15, 35, 50, 60 and 75 nmol/L, the power to detect intervention effect was 77%, 99%, 95%, 68% and 19%, respectively. The number of participants required per arm to achieve 80% power according to baseline 25OHD of 15–60 nmol/L was 1200, 400, 600 and 1400, respectively. As expected, larger increases in 25OHD due to supplementation improved power in certain scenarios. For a population baseline of 50 nmol/L, with 1500 participants in each arm, there was 100% power to detect a 20 nmol/L 25OHD increase while it was 76% for a 10 nmol/L increase. Population characteristics and trial design, including temporal considerations, have a dramatic impact on power and required sample size in vitamin D RCTs.
Abiraterone induces SLCO1B3 expression in prostate cancer via microRNA-579-3p
Authors: Barbier Roberto H. , McCrea Edel M. , Lee Kristi Y. , Strope Jonathan D. , Risdon Emily N. , Price Douglas K. , Chau Cindy H. , Figg William D. 
Published: May 2021

AbstractUnderstanding mechanisms of resistance to abiraterone, one of the primary drugs approved for the treatment of castration resistant prostate cancer, remains a priority. The organic anion polypeptide 1B3 (OATP1B3, encoded by SLCO1B3) transporter has been shown to transport androgens into prostate cancer cells. In this study we observed and investigated the mechanism of induction of SLCO1B3 by abiraterone. Prostate cancer cells (22Rv1, LNCaP, and VCAP) were treated with anti-androgens and assessed for SLCO1B3 expression by qPCR analysis. Abiraterone treatment increased SLCO1B3 expression in 22Rv1 cells in vitro and in the 22Rv1 xenograft model in vivo. MicroRNA profiling of abiraterone-treated 22Rv1 cells was performed using a NanoString nCounter miRNA panel followed by miRNA target prediction. TargetScan and miRanda prediction tools identified hsa-miR-579-3p as binding to the 3′-untranslated region (3′UTR) of the SLCO1B3. Using dual luciferase reporter assays, we verified that hsa-miR-579-3p indeed binds to the SLCO1B3 3′UTR and significantly inhibited SLCO1B3 reporter activity. Treatment with abiraterone significantly downregulated hsa-miR-579-3p, indicating its potential role in upregulating SLCO1B3 expression. In this study, we demonstrated a novel miRNA-mediated mechanism of abiraterone-induced SLCO1B3 expression, a transporter that is also responsible for driving androgen deprivation therapy resistance. Understanding mechanisms of abiraterone resistance mediated via differential miRNA expression will assist in the identification of potential miRNA biomarkers of treatment resistance and the development of future therapeutics.
An in-depth analysis of the mitochondrial phylogenetic landscape of Cambodia
Authors: Kloss-Brandstätter Anita , Summerer Monika , Horst David , Horst Basil , Streiter Gertraud , Raschenberger Julia , Kronenberg Florian , Sanguansermsri Torpong , Horst Jürgen , Weissensteiner Hansi 
Published: May 2021

AbstractCambodia harbours a variety of human aboriginal populations that have scarcely been studied in terms of genetic diversity of entire mitochondrial genomes. Here we present the matrilineal gene pool of 299 Cambodian refugees from three different ethnic groups (Cham, Khmer, and Khmer Loeu) deriving from 16 Cambodian districts. After establishing a DNA-saving high-throughput strategy for mitochondrial whole-genome Sanger sequencing, a HaploGrep based workflow was used for quality control, haplogroup classification and phylogenetic reconstruction. The application of diverse phylogenetic algorithms revealed an exciting picture of the genetic diversity of Cambodia, especially in relation to populations from Southeast Asia and from the whole world. A total of 224 unique haplotypes were identified, which were mostly classified under haplogroups B5a1, F1a1, or categorized as newly defined basal haplogroups or basal sub-branches of R, N and M clades. The presence of autochthonous maternal lineages could be confirmed as reported in previous studies. The exceptional homogeneity observed between and within the three investigated Cambodian ethnic groups indicates genetic isolation of the whole population. Between ethnicities, genetic barriers were not detected. The mtDNA data presented here increases the phylogenetic resolution in Cambodia significantly, thereby highlighting the need for an update of the current human mtDNA phylogeny.
Berezinskii–Kosterlitz–Thouless phase induced by dissipating quasisolitons
Authors: Gawryluk Krzysztof , Brewczyk Mirosław 
Published: May 2021

AbstractWe theoretically study the sound propagation in a two-dimensional weakly interacting uniform Bose gas. Using the classical fields approximation we analyze in detail the properties of density waves generated both in a weak and strong perturbation regimes. While in the former case density excitations can be described in terms of hydrodynamic or collisionless sound, the strong disturbance of the system results in a qualitatively different response. We identify observed structures as quasisolitons and uncover their internal complexity for strong perturbation case. For this regime quasisolitons break into vortex pairs as time progresses, eventually reaching an equilibrium state. We find this state, characterized by only fluctuating in time averaged number of pairs of opposite charge vortices and by appearance of a quasi-long-range order, as the Berezinskii–Kosterlitz–Thouless (BKT) phase.
Agreement between laboratory-based and non-laboratory-based Framingham risk score in Southern Iran
Authors: Rezaei Fatemeh , Seif Mozhgan , Gandomkar Abdullah , Fattahi Mohammad Reza , Hasanzadeh Jafar 
Published: May 2021

AbstractThe Framingham 10-year cardiovascular disease risk is measured by laboratory-based and non-laboratory-based models. This study aimed to determine the agreement between these two models in a large population in Southern Iran. In this study, the baseline data of 8138 individuals participated in the Pars cohort study were used. The participants had no history of cardiovascular disease or stroke. For the laboratory-based risk model, scores were determined based on age, sex, current smoking, diabetes, systolic blood pressure (SBP) and treatment status, total cholesterol, and High-Density Lipoprotein. For the non-laboratory-based risk model, scores were determined based on age, sex, current smoking, diabetes, SBP and treatment status, and Body Mass Index. The agreement between these two models was determined by Bland Altman plots for agreement between the scores and kappa statistic for agreement across the risk groups. Bland Altman plots showed that the limits of agreement were reasonable for females < 60 years old (95% CI: −2.27–4.61%), but of concern for those ≥ 60 years old (95% CI: −3.45–9.67%), males < 60 years old (95% CI: −2.05–8.91%), and males ≥ 60 years old (95% CI: −3.01–15.23%). The limits of agreement were wider for males ≥ 60 years old in comparison to other age groups. According to the risk groups, the agreement was better in females than in males, which was moderate for females < 60 years old (kappa = 0.57) and those ≥ 60 years old (kappa = 0.51). The agreement was fair for the males < 60 years old (kappa = 0.39) and slight for those ≥ 60 years old (Kappa = 0.14). The results showed that in overall participants, the agreement between the two risk scores was moderate according to risk grouping. Therefore, our results suggest that the non-laboratory-based risk model can be used in resource-limited settings where individuals cannot afford laboratory tests and extensive laboratories are not available.
Fetal movement counting is associated with the reduction of delayed maternal reaction after perceiving decreased fetal movements: a prospective study
Authors: Koshida Shigeki , Tokoro Shinsuke , Katsura Daisuke , Tsuji Shunichiro , Murakami Takashi , Takahashi Kentaro 
Published: May 2021

AbstractMaternal perception of decreased fetal movement is associated with adverse perinatal outcomes. Although there have been several studies on interventions related to the fetal movements count, most focused on adverse perinatal outcomes, and little is known about the impact of the fetal movement count on maternal behavior after the perception of decreased fetal movement. We investigated the impact of the daily fetal movement count on maternal behavior after the perception of decreased fetal movement and on the stillbirth rate in this prospective population-based study. Pregnant women in Shiga prefecture of Japan were asked to count the time of 10 fetal movements from 34 weeks of gestation. We analyzed 101 stillbirths after the intervention compared to 121 stillbirths before the intervention. In multivariable analysis, maternal delayed visit to a health care provider after the perception of decreased fetal movement significantly reduced after the intervention (aOR 0.31, 95% CI 0.11–0.83). Our regional stillbirth rates in the pre-intervention and post-intervention periods were 3.06 and 2.70 per 1000 births, respectively. Informing pregnant women about the fetal movement count was associated with a reduction in delayed maternal reaction after the perception of decreased fetal movement, which might reduce stillbirths.
COVID-19 diagnosis by routine blood tests using machine learning
Authors: Kukar Matjaž , Gunčar Gregor , Vovko Tomaž , Podnar Simon , Černelč Peter , Brvar Miran , Zalaznik Mateja , Notar Mateja , Moškon Sašo , Notar Marko 
Published: May 2021

AbstractPhysicians taking care of patients with COVID-19 have described different changes in routine blood parameters. However, these changes hinder them from performing COVID-19 diagnoses. We constructed a machine learning model for COVID-19 diagnosis that was based and cross-validated on the routine blood tests of 5333 patients with various bacterial and viral infections, and 160 COVID-19-positive patients. We selected the operational ROC point at a sensitivity of 81.9% and a specificity of 97.9%. The cross-validated AUC was 0.97. The five most useful routine blood parameters for COVID-19 diagnosis according to the feature importance scoring of the XGBoost algorithm were: MCHC, eosinophil count, albumin, INR, and prothrombin activity percentage. t-SNE visualization showed that the blood parameters of the patients with a severe COVID-19 course are more like the parameters of a bacterial than a viral infection. The reported diagnostic accuracy is at least comparable and probably complementary to RT-PCR and chest CT studies. Patients with fever, cough, myalgia, and other symptoms can now have initial routine blood tests assessed by our diagnostic tool. All patients with a positive COVID-19 prediction would then undergo standard RT-PCR studies to confirm the diagnosis. We believe that our results represent a significant contribution to improvements in COVID-19 diagnosis.
Novel assessment of the variation in cervical inter-vertebral motor control in a healthy pain-free population
Authors: Lindstrøm René , Breen Alexander , Qu Ning , du Rose Alister , Andersen Victoria Blogg , Breen Alan 
Published: May 2021

AbstractSpinal control at intervertebral levels is dependent on interactions between the active, passive and neural control elements. However, this has never been quantifiable, and has therefore been outside the reach of clinical assessments and research. This study used fluoroscopy during repeated unconstrained flexion and return neck movements to calculate intersegmental motor control (MC), defined as the difference and variation in repeated continuous angular motion from its average path. The study aimed to determine control values for MC at individual levels and its variability. Twenty male volunteers aged 19–29 received fluoroscopic screening of their cervical spines during 4 repetitions of neutral to full flexion and return motion. Moving vertebral images from C0–C1 to C6–C7 were tracked using cross-correlation codes written in Matlab. MC for each level was defined as the mean of the absolute differences between each repetition’s angular path and their mean and its variability as represented by the SD. 1-way ANOVA and Tukey multiple comparisons were used to identify significant contrasts between levels. The mean MC differences and SDs were highest at C1-2, suggesting that this level has the least control and the most variability. Results at this level alone were highly significant (F-ratio 10.88 and 9.79 P < 0.0001). Significant contrasts were only found between C1-C2 and all other levels. The mean MC difference for summed C1-6 levels was 3.4° (0.7–6.1). This study is the first to quantify intervertebral MC in the cervical spine in asymptomatic people. Studies of neck pain patients are now merited.
Genome-wide SNPs redefines species boundaries and conservation units in the freshwater mussel genus Cyprogenia of North America
Authors: Kim Kyung Seok , Roe Kevin J. 
Published: May 2021

AbstractDetailed information on species delineation and population genetic structure is a prerequisite for designing effective restoration and conservation strategies for imperiled organisms. Phylogenomic and population genomic analyses based on genome-wide double digest restriction-site associated DNA sequencing (ddRAD-Seq) data has identified three allopatric lineages in the North American freshwater mussel genusCyprogenia.Cyprogenia stegariais restricted to the Eastern Highlands and displays little genetic structuring within this region. However, two allopatric lineages ofC. abertiin the Ozark and Ouachita highlands exhibit substantial levels (mean uncorrectedFST = 0.368) of genetic differentiation and each warrants recognition as a distinct evolutionary lineage. Lineages ofCyprogeniain the Ouachita and Ozark highlands are further subdivided reflecting structuring at the level of river systems. Species tree inference and species delimitation in a Bayesian framework using single nucleotide polymorphisms (SNP) data supported results from phylogenetic analyses, and supports three species ofCyprogeniaover the currently recognized two species. A comparison of SNPs generated from both destructively and non-destructively collected samples revealed no significant difference in the SNP error rate, quality and amount of ddRAD sequence reads, indicating that nondestructive or trace samples can be effectively utilized to generate SNP data for organisms for which destructive sampling is not permitted.
Integrative nomogram of intratumoral, peritumoral, and lymph node radiomic features for prediction of lymph node metastasis in cT1N0M0 lung adenocarcinomas
Authors: Das Sushant Kumar , Fang Ke-Wei , Xu Long , Li Bing , Zhang Xin , Yang Han-Feng 
Published: May 2021

AbstractRadiomics studies to predict lymph node (LN) metastasis has only focused on either primary tumor or LN alone. However, combining radiomics features from multiple sources may reflect multiple characteristic of the lesion thereby increasing the discriminative performance of the radiomic model. Therefore, the present study intends to evaluate the efficiency of integrative nomogram, created by combining clinical parameters and radiomics features extracted from gross tumor volume (GTV), peritumoral volume (PTV) and LN, for the preoperative prediction of LN metastasis in clinical cT1N0M0 adenocarcinoma. A primary cohort of 163 patients (training cohort, 113; and internal validation cohort, 50) and an external validation cohort of 53 patients with clinical stage cT1N0M0 were retrospectively included. Features were extracted from three regions of interests (ROIs): GTV; PTV (5.0 mm around the tumor) and LN on pre-operative contrast enhanced computed tomography (CT). LASSO logistic regression method was used to build radiomic signatures. Multivariable regression analysis was used to build a nomogram. The performance of the nomogram was assessed with respect to its calibration, discrimination, and clinical usefulness. The discriminative performance of nomogram was validated both internally and externally. The radiomic signatures using the features of GTV, PTV and LN showed a good ability in predicting LN metastasis with an area under the curve (AUC) of 0.74 (95% CI 0.60–0.88), 0.72 (95% CI 0.57–0.87) and 0.64 (95% CI 0.48–0.80) respectively in external validation cohort. The integration of different signature together further increases the discriminatory ability: GTV + PTV (GPTV): AUC 0.75 (95% CI 0.61–0.89) and GPTV + LN: AUC 0.76 (95% CI 0.61–0.91) in external validation cohort. An integrative nomogram of clinical parameters and radiomic features demonstrated further increase in discriminatory ability with AUC of 0.79 (95% CI 0.66–0.93) in external validation cohort. The nomogram showed good calibration. Decision curve analysis demonstrated that the radiomic nomogram was clinically useful. The integration of information from clinical parameters along with CT radiomics information from GTV, PTV and LN was feasible and increases the predictive performance of the nomogram in predicting LN status in cT1N0M0 adenocarcinoma patients suggesting merit of information integration from multiple sources in building prediction model.
Remote ischemic preconditioning improves tissue oxygenation in a porcine model of controlled hemorrhage without fluid resuscitation
Authors: Yaniv Gal , Eisenkraft Arik , Gavish Lilach , Wagnert-Avraham Linn , Nachman Dean , Megreli Jacob , Shimon Gil , Rimbrot Daniel , Simon Ben , Berman Asaf , Cohen Matan , Kushnir David , Shaylor Ruth , Batzofin Baruch , Firman Shimon , Shlaifer Amir , Hartal Michael , Heled Yuval , Glassberg Elon , Kreiss Yitshak , Gertz S. David 
Published: May 2021

AbstractRemote ischemic preconditioning (RIPC) involves deliberate, brief interruptions of blood flow to increase the tolerance of distant critical organs to ischemia. This study tests the effects of limb RIPC in a porcine model of controlled hemorrhage without replacement therapy simulating an extreme field situation of delayed evacuation to definitive care. Twenty-eight pigs (47 ± 6 kg) were assigned to: (1) control, no procedure (n = 7); (2) HS = hemorrhagic shock (n = 13); and (3) RIPC + HS = remote ischemic preconditioning followed by hemorrhage (n = 8). The animals were observed for 7 h after bleeding without fluid replacement. Survival rate between animals of the RIPC + HS group and those of the HS group were similar (HS, 6 of 13[46%]-vs-RIPC + HS, 4 of 8[50%], p = 0.86 by Chi-square). Animals of the RIPC + HS group had faster recovery of mean arterial pressure and developed higher heart rates without complications. They also had less decrease in pH and bicarbonate, and the increase in lactate began later. Global oxygen delivery was higher, and tissue oxygen extraction ratio lower, in RIPC + HS animals. These improvements after RIPC in hemodynamic and metabolic status provide essential substrates for improved cellular response after hemorrhage and reduction of the likelihood of potentially catastrophic consequences of the accompanying ischemia.