Miracle-dz/UniFAR-FTUs huggingface dataset:
The Influence of KDR Genetic Variation on the Efficacy and Safety of Patients With Advanced NSCLC Receiving First-Line Bevacizumab Plus Chemotherapy Regimen

Objective: Angiogenesis plays an important role in the growth and metastasis of non-small cell lung cancer (NSCLC). Bevacizumab is a humanized monoclonal antibody that mainly acts on vascular endothelial growth factor A (VEGFA). Kinase insert domain receptor (KDR) is the most important target of VEGFA. The aim of present study was to investigate the influence of KDR genetic variation on the efficacy and safety of patients with advanced NSCLC receiving first-line bevacizumab plus chemotherapy regimen. Methods: A total of 169 patients with advanced NSCLC who received bevacizumab combined with chemotherapy were recruited in this study. Clinical outcome of the regimens was evaluated in the hospital. Peripheral blood and biopsy tissue specimens of patients were collected for the genotyping of KDR genetic variation and KDR mRNA expression, respectively. The association between KDR genotype status and other variables were analyzed. Univariate analysis of genotype status and prognosis was implemented using the Kaplan-Meier survival analysis method. Multivariate Cox regression analysis was performed to adjust the confounding factors. Results: Of the polymorphisms analyzed, only V297 L was of clinical significance. The prevalence of V297 L among the study population were as follows: CC genotype 123 cases (72.8%), CT genotype 41 cases (24.3%), TT genotype 5 cases (2.9%). The minimum allele frequency is 0.15. The distribution frequencies of the 3 genotypes corresponded with Hardy-Weinberg equilibrium (P = 0.489). Patients with TT and CT genotypes were merged in the subsequent comparison of clinical outcomes. The analysis of efficacy exhibited that the objective response rates (ORR) of patients with CC genotype and CT/TT genotypes were 52.8% and 47.8% (P = 0.561), respectively. Prognosis indicated that the median progression free survival (PFS) of patients with CC genotype and CT/TT genotype were 8.9 and 5.5 months, respectively (P = 0.006). The median OS of the 2 genotypes were 20.0 and 14.9 months, respectively (P = 0.021). Adjusted in multivariate Cox regression analysis of PFS, CT/TT genotypes were an independent factor for PFS [hazard ratio (HR) = 1.59, P = 0.011). Safety profile according to genotype status of V297 L failed to find significant difference. Interestingly, the expression of KDR mRNA of patients with CT/TT genotype was significantly higher than that of patients with CC genotype in the 58 cancer tissue specimens (P < 0.001). Conclusion: The clinical comes of patients with advanced NSCLC receiving first-line bevacizumab plus chemotherapy regimens might be impacted by polymorphism V297 L through mediating the mRNA expression of KDR.
Altering transcription factor binding reveals comprehensive transcriptional kinetics of a basic gene

Abstract Transcription is a vital process activated by transcription factor (TF) binding. The active gene releases a burst of transcripts before turning inactive again. While the basic course of transcription is well understood, it is unclear how binding of a TF affects the frequency, duration and size of a transcriptional burst. We systematically varied the residence time and concentration of a synthetic TF and characterized the transcription of a synthetic reporter gene by combining single molecule imaging, single molecule RNA-FISH, live transcript visualisation and analysis with a novel algorithm, Burst Inference from mRNA Distributions (BIRD). For this well-defined system, we found that TF binding solely affected burst frequency and variations in TF residence time had a stronger influence than variations in concentration. This enabled us to device a model of gene transcription, in which TF binding triggers multiple successive steps before the gene transits to the active state and actual mRNA synthesis is decoupled from TF presence. We quantified all transition times of the TF and the gene, including the TF search time and the delay between TF binding and the onset of transcription. Our quantitative measurements and analysis revealed detailed kinetic insight, which may serve as basis for a bottom-up understanding of gene regulation.
High flow nasal cannula oxygenation in COVID-19 related acute respiratory distress syndrome: a safe way to avoid endotracheal intubation?

Backgrounds: High flow nasal cannula (HFNC) is an alternative therapy for acute respiratory distress syndrome (ARDS) due to coronavirus disease 2019 (COVID-19). This study aimed first to describe outcomes of patients suffering from COVID-19-related ARDS treated with HFNC; secondly to evaluate safety of HFNC (patients and healthcare workers) and compare patients according to respiratory outcome. Methods: A retrospective cohort was conducted in French general hospital intensive care unit (ICU). Patients were included if receiving HFNC for hypoxemia (saturation pulse oxygen (SpO2) <92% under oxygen ⩾6 L/min) associated with ARDS and positive SARS-CoV-2 polymerase chain reaction (PCR). Main clinical characteristics and outcomes are described in patients: (a) with do not intubate order (HFNC-DNIO); (b) who did not need intubation (HFNC-only); and (c) eventually intubated (HFNC-intubation). Medians are presented with (1st–3rd) interquartile range. Results: From 26 February to 30 June 2020, 46 patients of median age 75 (70–79) years were included. In the HFNC-DNIO group (n = 11), partial arterial oxygen pressure (PaO2)/inhaled fraction of oxygen (FiO2) ratio median worst PaO2/FiO2 ratio was 109 (102–172) and hospital mortality was 54.5%. Except the HFNC-DNIO patients (n = 35), 20 patients (57%) were eventually intubated (HFNC-intubation group) and 15 were only treated by HFNC (HFNC-only). HFNC-intubation patients presented higher worst respiratory rates per minute in ICU [37 (34–41) versus 33 (24–34) min, p < 0.05] and worsened ICU admission PaO2/FiO2 ratios [121 (103–169) versus 191 (162–219), p < 0.001] compared with HFNC-only patients. Hospital mortality was 35% (n = 7/20) in HFNC-intubation group, 0% in HFNC-only group with a global mortality of these two groups of 20% (n = 7/35). Among tests performed in healthcare workers, 1/12 PCR in symptomatic healthcare workers and 1.8% serologies in asymptomatic healthcare workers were positive. After review of each case, COVID-19 was likely to be acquired outside hospital. Conclusions: HFNC seems to be useful for COVID-19-related ARDS and safe for healthcare workers. ARDS severity with PaO2/FiO2 <150 associated with respiratory rate >35/min could be regarded as a predictor of intubation. The reviews of this paper are available via the supplemental material section.
Neural Representation in mPFC Reveals Hidden Selfish Motivation in White Lies

Identifying true motivation for Pareto lies, which are mutually beneficial for both the liar and others, can be challenging because different covert motivations can lead to identical overt behavior. In this study, we adopted a brain-fingerprinting approach, combining both univariate and multivariate analyses to estimate individual measures of selfish motivation in Pareto lies by the degree of multivoxel neural representation in the mPFC for Pareto lies conforming with those for selfish versus altruistic lies in human participants of either sex. An increase in selfish motivation for Pareto lies was associated with higher mean-level activity in both ventral and rostral mPFC. The former showed an increased pattern similarity to selfish lies, and the latter showed a decreased pattern similarity to altruistic lies. Higher ventral mPFC pattern similarity predicted faster response time in Pareto lies. Our findings demonstrated that hidden selfish motivation in white lies can be revealed by neural representation in the mPFC. SIGNIFICANCE STATEMENT True motivation for dishonesty serving both self and others cannot be accurately discerned from observed behaviors. Here we showed that fMRI combining both univariate and multivariate analyses can be effectively used to reveal hidden selfish motivation of Pareto lies serving both self and others. The present study suggests that selfish motivation for prosocial dishonesty is encoded primarily by increased activity of the ventromedial and the rostromedial prefrontal cortex, representing intuitive self-serving valuation and strategic switching of motivation depending on beneficiary of dishonesty, respectively.
A systematic review of nonsynonymous single nucleotide polymorphisms in the renin–angiotensin–aldosterone system

In this recent publication review the authors aimed to collect evidence of impact of nonsynonymous single nucleotide polymorphisms (nsSNP) in the renin–angiotensin–aldosterone system on patients’ phenotype not only regarding arterial hypertension and its complications, but also the impact on other diseases of interest outside the field of cardiovascular medicine. PubMed database records published between 2017–2020 were searched and all positive case-control studies or positive studies with human DNA were selected. The search identified 104 articles, of which 22 were included on the basis of the inclusion criteria. This paper presents the impact of 44 nsSNPs in panels for genes of renin, angiotensinogen, angiotensin-converting enzyme, angiotensin receptor and aldosterone on the clinical picture of investigated cohorts or on the peptide-protein interactions as consequence of nsSNPs. Genetic variability in nsSNPs of the RAAS is involved in the pathogenesis of arterial hypertension and its complications, and surprisingly also in the pathogenesis of conditions not associated with elevated blood pressure, like neoplasms or inflammatory diseases
Efficacy of viable BCG vaccine paste in the treatment of common warts: a double-blind randomized control trial

Abstract Background Treatment of common warts may be painful or leaves scars, mainly using traditional destructive methods. This study aimed to evaluate the efficacy of the viable Bacillus Calmette‐Guérin (BCG) vaccine in paste formula as an immunotherapeutic modality for common warts treatment. Methods This double-blind and randomized, parallel-group, placebo-controlled trial was conducted at the Ahvaz Imam Hospital Dermatology Department from November 2014 to 2015. Overall 80 patients with common warts in two groups (case and control) received BCG vaccine paste once weekly for eight consecutive weeks. Follow-up was done every two weeks during treatment and six months after the treatment to evaluate recurrence in patients with complete resolution. Results In group A, eight patients (20%) had a complete response, 15 patients (37.5%) partial response, four patients (10%) low response, and 13 patients (32.5%) no response (p < .001). All patients in group B had no response to treatment (p < .001). After six months of follow-up, no recurrence was seen. Duration of disease less than 12 months (p = .001) and the number of lesions less than three (p = .01) were determining factors of response to treatment. Conclusion Topical BCG vaccine paste was an effective treatment for common warts, without recurrence and significant complications.
The trajectory of cortical GABA across the lifespan, an individual participant data meta-analysis of edited MRS studies

γ-Aminobutyric acid (GABA) is the principal inhibitory neurotransmitter in the human brain and can be measured with magnetic resonance spectroscopy (MRS). Conflicting accounts report decreases and increases in cortical GABA levels across the lifespan. This incompatibility may be an artifact of the size and age range of the samples utilized in these studies. No single study to date has included the entire lifespan. In this study, eight suitable datasets were integrated to generate a model of the trajectory of frontal GABA estimates (as reported through edited MRS; both expressed as ratios and in institutional units) across the lifespan. Data were fit using both a log-normal curve and a nonparametric spline as regression models using a multi-level Bayesian model utilizing the Stan language. Integrated data show that an asymmetric lifespan trajectory of frontal GABA measures involves an early period of increase, followed by a period of stability during early adulthood, with a gradual decrease during adulthood and aging that is described well by both spline and log-normal models. The information gained will provide a general framework to inform expectations of future studies based on the age of the population being studied.
A new method to visualize CEP peptide-CEP receptor interactions in vascular tissue in vivo.

C-TERMINALLY ENCODED PEPTIDEs (CEPs) control diverse responses in plants including root development, root system architecture, nitrogen demand signalling, and nutrient allocation influencing yield and there is evidence that different ligands impart different phenotypic responses. Thus, there is a need for a simple method that identifies bona fide CEP hormone-receptor pairings in vivo and examines if different CEP family peptides bind the same receptor. We used formaldehyde or photo-activation to cross-link fluorescently tagged group 1 or group 2 CEPs to receptors in semi-purified Medicago truncatula or Arabidopsis thaliana leaf vascular tissues to verify that COMPACT ROOT ARCHITECTURE 2 (CRA2) is the Medicago CEP receptor, and to investigate if sequence diversity within the CEP family influences receptor binding. Formaldehyde cross-linked the fluorescein isothiocyanate (FITC)-tagged Medicago group 1 CEP (MtCEP1) to wild-type Medicago or Arabidopsis vascular tissue cells, but not to the CEP receptor mutants, cra2 or cepr1. Binding competition showed that unlabelled MtCEP1 displaces FITC-MtCEP1 from CRA2. By contrast, the group 2 CEP, FITC-AtCEP14, bound to vascular tissue independently of CEPR1 or CRA2, and AtCEP14 did not complete with FITC-MtCEP1 to bind CEP receptors. The binding of a photo-activatable FITC-MtCEP1 to the periphery of Medicago vascular cells suggested that CRA2 localises to the plasma membrane. We extracted and visualised a fluorescent 105 kDa protein corresponding to photo-cross-linked FITC-MtCEP1-CRA2 complex using SDS-PAGE. Mass spectrometry identified CRA2-specific peptides in this protein band. These results indicate that FITC-MtCEP1 binds to CRA2, MtCRA2 and AtCEPR1 are functionally equivalent, and that the binding specificity of group1 and group 2 CEPs are distinct. Using formaldehyde or photo-activated crosslinking of biologically-active, fluorescently-tagged ligands may find wider utility by identifying CEP-CEP receptor pairings in diverse plants.
Emergence of Resistance to Novel Cephalosporin–β-Lactamase Inhibitor Combinations through the Modification of the Pseudomonas aeruginosa MexCD-OprJ Efflux Pump

A ceftolozane-tazobactam- and ceftazime-avibactam-resistant Pseudomonas aeruginosa isolate was recovered after treatment (including azithromycin, meropenem, and ceftolozane-tazobactam) from a patient that had developed ventilator-associated pneumonia after COVID-19 infection. Whole-genome sequencing revealed that the strain, belonging to ST274, had acquired a nonsense mutation leading to truncated carbapenem porin OprD (W277X), a 7-bp deletion (nt213Δ7) in NfxB (negative regulator of the efflux pump MexCD-OprJ), and two missense mutations (Q178R and S133G) located within the first large periplasmic loop of MexD. ABSTRACT A ceftolozane-tazobactam- and ceftazime-avibactam-resistant Pseudomonas aeruginosa isolate was recovered after treatment (including azithromycin, meropenem, and ceftolozane-tazobactam) from a patient that had developed ventilator-associated pneumonia after COVID-19 infection. Whole-genome sequencing revealed that the strain, belonging to ST274, had acquired a nonsense mutation leading to truncated carbapenem porin OprD (W277X), a 7-bp deletion (nt213Δ7) in NfxB (negative regulator of the efflux pump MexCD-OprJ), and two missense mutations (Q178R and S133G) located within the first large periplasmic loop of MexD. Through the construction of mexD mutants and complementation assays with wild-type nfxB, it was evidenced that resistance to the novel cephalosporin–β-lactamase inhibitor combinations was caused by the modification of MexD substrate specificity.
Physical and psychological sequelae at three months after acute illness in COVID-19 survivors.

BACKGROUND Coronavirus disease 2019 (COVID-19) may leave behind an altered health status early after recovery. We evaluated the clinical status of COVID-19 survivors at three months after hospital discharge. METHODS In this prospective observational cohort study, hospitalized patients aged ≥18 years, evaluated at one (M1) and three (M3) months post-discharge were enrolled. 251 patients (71.3% males, median [IQR] age 61.8 [53.5-70.7] years) were included. Median (IQR) time from discharge to M3 was 89 (79.5-101) days. Primary outcome was residual respiratory dysfunction (RRD), defined by tachypnea, moderate to very severe dyspnea, or peripheral oxygen saturation ≤95% on room air at M3. RESULTS RRD was found in 30.4% of patients, with no significant difference compared with M1. Chronic obstructive pulmonary disease and length of stay were independent predictors of RRD at multivariable logistic regression (odds ratio, OR, [95% confidence interval, CI] 4.13 [1.17-16.88], p 0.033; OR [95% CI] 1.02 [1.00-1.04], p 0.047, respectively). Obesity and C-reactive protein levels upon admission were additional predictors at regression tree analysis. Impaired quality of life (QoL) was reported by 53.2% of patients. Anxiety and insomnia were each present in 25.5% of patients, and PTSD in 22.4%. No difference was found between M1 and M3 in QoL, anxiety or PTSD. Insomnia decreased at M3. Current major psychiatric disorder as well as anxiety, insomnia and PSTD at M1 independently predicted PTSD at M3. CONCLUSIONS Clinical damage may persist at three months after discharge in COVID-19 survivors. Post-recovery follow-up is an essential component of patient management.
Social inequality in type 2 diabetes mellitus in the Faroe Islands: a cross-sectional study

Aims: The Faroe Islands is considered a homogeneous society and has a low Gini coefficient, but the knowledge about the social distribution of health and disease is sparse. In a large population-based sample we investigated: (a) the association between socioeconomic position defined by level of education and the prevalence of type 2 diabetes mellitus by self-report in the Faroe Islands; and (b) to what degree lifestyle factors mediate the association. Methods: We used cross-sectional data from the population-based Public Health Survey Faroes 2015 (n=1095). We present odds ratios for type 2 diabetes mellitus by socioeconomic position from logistic regression models. In our main model we adjusted for potential confounders and in a secondary model we additionally adjusted for potential mediating lifestyle factors. Results: Individuals with middle and low levels of education display higher odds ratios of type 2 diabetes mellitus of 2.80 (95% confidence interval 1.32–5.92) and 4.65 (95% confidence interval 1.93–11.17) in adjusted analysis, respectively, compared to their counterparts with high education. After adjustment for potentially mediating lifestyle factors the estimates were attenuated slightly, but a significant statistical association remained, with lifestyle-related mediating factors in total explaining 21% for middle education and 34% for low education participants. Conclusions: Our results demonstrate that there may be a social gradient in the distribution of type 2 diabetes mellitus in the Faroe Islands, and that the association is partly mediated by lifestyle factors.
Thermal lesions of the SCN do not abolish all gene expression rhythms in rat white adipose tissue, NAMPT remains rhythmic

ABSTRACT Obesity and type 2 diabetes mellitus are major health concerns worldwide. In obese-type 2 diabetic patients, the function of the central brain clock in the hypothalamus, as well as rhythmicity in white adipose tissue (WAT), are reduced. To better understand how peripheral clocks in white adipose tissue (WAT) are synchronized, we assessed the importance of the central brain clock for daily WAT rhythms. We compared gene expression rhythms of core clock genes (Bmal1, Per2, Cry1, Cry2, RevErbα, and DBP) and metabolic genes (SREBP1c, PPARα, PPARγ, FAS, LPL, HSL, CPT1b, Glut4, leptin, adiponectin, visfatin/NAMPT, and resistin) in epididymal and subcutaneous white adipose tissue (eWAT and sWAT) of SCN-lesioned and sham-lesioned rats housed in regular L/D conditions. Despite complete behavioral and hormonal arrhythmicity, SCN lesioning only abolished Cry2 and DBP rhythmicity in WAT, whereas the other clock gene rhythms were significantly reduced, but not completely abolished. We observed no major differences in the effect of SCN lesions between the two WAT depots. In contrast to clock genes, all metabolic genes lost their daily rhythmicity in WAT, with the exception of NAMPT. Interestingly, NAMPT rhythmicity was even less affected by SCN lesioning than the core clock genes, suggesting that it is either strongly coupled to the remaining rhythmicity in clock gene expression, or very sensitive to other external rhythmic factors. The L/D cycle could be such a rhythmic external factor that generates modulating signals by photic masking via the intrinsic photosensitive retinal ganglion cells in combination with the autonomic nervous system. Our findings indicate that in normal weight rats, gene expression rhythms in WAT can be maintained independent of the central brain clock.
Omega-3 Polyunsaturated Fatty Acids Can Reduce C-Reactive Protein in Patients with Cancer: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

ABSTRACTS Omega-3 polyunsaturated fatty acids (PUFAs) possess anti-inflammatory properties. There is a lack of consensus regarding the effects of omega-3 PUFAs on C-reactive protein (CRP), a marker of systemic inflammation, in cancer patients. Herein, a meta-analysis of randomized controlled trials was conducted to evaluate the effects of omega-3 PUFAs on CRP levels in patients with cancer. PubMed and EMBASE were searched until May 2020 to identify randomized controlled trials that examined the effects of omega-3 PUFA administration on CRP levels in cancer patients. Standardized mean differences (SMDs) with their 95% confidence intervals (CIs) were calculated to determine the differences in omega-3 PUFA administration and control conditions. Seventeen eligible studies involving 916 cancer patients were included in this meta-analysis. Significant heterogeneity was present among individual studies (Pheterogeneity = 0.000; I 2 = 74.5%). The overall SMDs of CRP levels between omega-3 PUFA administration and control conditions were 0.628 (95% CI: 0.342-0.914) and 0.456 (95% CI: 0.322-0.590) by the random-effect and fixed-effect models, respectively. Sources of heterogeneity were not found through subgroup and meta-regression analyses. Existing publication bias contributed slightly to the effect size. Omega-3 PUFAs can reduce systemic inflammation, as indicated by CRP levels in cancer patients. The use of omega-3 PUFAs is recommended for cancer patients due to their anti-inflammatory properties.