Miracle-dz/UniFAR-FTUs huggingface dataset:
Efficacy and safety of antiangiogenic agents or chemotherapy plus EGFR‐TKIs in advanced non‐small cell lung cancer: A systematic review and network meta‐analysis

The combination of antiangiogenic agents with epidermal growth factor receptor inhibitors (EGFR‐TKIs) and chemotherapy with EGFR‐TKIs are the most common combination treatment options in epidermal growth factor receptor (EGFR) positive non‐small cell lung cancer (NSCLC). This network meta‐analysis was performed to evaluate the differences between them.
On van den Bergh's Method for Measuring the Hubble Constant from Type Ia Supernovae

In a recent Letter, van den Bergh used the explosion-model light-curve calculations of Höflich & Khokhlov to calibrate the Hamuy et al. sample of remote Type Ia supernovae (SNe Ia) and obtained low values of H0 in the range 55-60 km s-1 Mpc-1. Citing a higher value of H0 obtained from Cepheid-based distance determinations to a few galaxies in the Virgo Cluster complex, van den Bergh concluded that unless the Cepheid distance scale is wrong, the models of Höflich & Khokhlov must be much too bright or much too red. Here we calibrate the same sample of remote SNe Ia in the same way as was suggested by van den Bergh, but now relying on Cepheid-based determinations of the distances to SN Ia parent galaxies instead of the explosion-model light-curve calculations. No corrections for extinction of the SNe Ia are required, and no SNe Ia need be excluded on grounds of peculiarity. We obtain H0 = 57 ± 5 km s-1 Mpc-1. Various subsamples of the data give H0 in the range 54-60 km s-1 Mpc-1. This shows that the fault lies not with the SN Ia models, nor with Cepheids, but with the hazardous route through the Virgo complex.
A chromosome‐level genome assembly enables the identification of the follicule stimulating hormone receptor as the master sex‐determining gene in the flatfish Solea senegalensis

Sex determination (SD) shows huge variation among fish and a high evolutionary rate, as illustrated by the Pleuronectiformes (flatfishes). This order is characterized by its adaptation to demersal life, compact genomes and diversity of SD mechanisms. Here, we assembled the Solea senegalensis genome, a flatfish of great commercial value, into 82 contigs (614 Mb) combining long‐ and short‐read sequencing, which were next scaffolded using a highly dense genetic map (28,838 markers, 21 linkage groups), representing 98.9% of the assembly. Further, we established the correspondence between the assembly and the 21 chromosomes by using BAC‐FISH. Whole genome resequencing of six males and six females enabled the identification of 41 single nucleotide polymorphism variants in the follicle stimulating hormone receptor (fshr) consistent with an XX/XY SD system. The observed sex association was validated in a broader independent sample, providing a novel molecular sexing tool. The fshr gene displayed differential expression between male and female gonads from 86 days post‐fertilization, when the gonad is still an undifferentiated primordium, concomitant with the activation of amh and cyp19a1a, testis and ovary marker genes, respectively, in males and females. The Y‐linked fshr allele, which included 24 nonsynonymous variants and showed a highly divergent 3D protein structure, was overexpressed in males compared to the X‐linked allele at all stages of gonadal differentiation. We hypothesize a mechanism hampering the action of the follicle stimulating hormone driving the undifferentiated gonad toward testis.
The Use of Box-Cox Transformations in the Development of Multivariate Tolerance Regions with Applications to Clinical Chemistry

Abstract Attempts often have been made to transform clinical and laboratory data to approximate normality for the purpose of developing either univariate “normal” ranges or multivariate reference ranges in the “supposedly healthy” population. For many of these transformations to be successful, it has been necessary to arbitrarily delete outlier values with no scientific justification for doing so. In this article, construction principles used in the determination of these ranges are reviewed. In addition, the Box–Cox family of power transformations is proposed as a means of obtaining an approximate multivariate normal distribution without an arbitrary deletion of outlier values. This method will allow for the construction of reference ranges for the clinical and laboratory variables of interest.
The central role of peripheral inflammation in ischemic stroke

Stroke pathology and its treatments conventionally focus on the brain. Probing inflammation, a critical secondary cell death mechanism in stroke, has been largely relegated to the brain. To this end, peripheral inflammation has emerged as an equally potent contributor to the onset and progression of stroke secondary cell death. Here, we review novel concepts on peripheral organs displaying robust inflammatory response to stroke. These inflammation-plagued organs include the spleen, cervical lymph nodes, thymus, bone marrow, gastrointestinal system, and adrenal glands, likely converging their inflammatory effects through B and T-cells. Recognizing the significant impact of this systemic inflammation, we also discuss innovative stroke therapeutics directed at sequestration of peripheral inflammation. This review paper challenges the paradigm of a brain-centered disease pathology and treatment and offers a peripheral approach to our stroke understanding.
Exercise preserves physical fitness during aging through AMPK and mitochondrial dynamics

Significance Exercise is a powerful anti-aging intervention. In muscle, exercise remodels mitochondrial metabolism and connectiveness, but the role of dynamic mitochondrial remodeling in exercise remains unknown. Using Caenorhabditis elegans, we find that the dynamic cycle of mitochondrial fission–fusion is critical for physical fitness. Exercise induces remodeling of the proteome that depends upon mitochondrial dynamics and delays an aging-associated decline in mitochondrial connectiveness and physical fitness. AMPK, a metabolic regulator that senses low energy availability and controls mitochondrial dynamics, is needed for exercise to maintain physical fitness with age and can recapitulate this exercise benefit. Our data identify the mitochondrial dynamics cycle as an essential mediator of exercise responsiveness and an entry point for interventions to maintain muscle function during aging.
A Qualitative Exploration of Desired mHealth App Mechanisms Related to Daily Life Influences for College Nursing Students

Introduction: Mobile health (mHealth) apps are digital health tools that allow for the delivery and access to vital health information, support, and encouragement needed to foster positive behavior change. Designing and developing mHealth solutions based on daily life influences for nursing students is imperative to establishing healthier physical and mental health habits. Methods: Multiple focus groups (n=10) were conducted, and a questionnaire (n=11) was administered to undergraduate students in the professional nursing component. Themed analysis of focus-group data was conducted along with descriptive analysis of the questionnaire. Results: All participants stated it has been more difficult to maintain a healthy lifestyle since beginning the nursing program. This deterioration can be attributed to three key areas: mental health needs/support, rigor of nursing school, and decline in positive health choices. Participants stated they would use an mHealth app designed specifically for nursing students to combat deterioration of their health. Conclusions: The results of this study (100% positive response rate) reveal mHealth applications might be a powerful tool in helping nursing students transform their physical and mental health. It appears that if an mHealth application is created with the specific “must-haves” of nursing students then we might experience a positive shift in health behaviors for nursing students, which will hopefully transcend into their careers as nurses.
Synthesising frontal face image using elastic net penalty and neighbourhood consistency prior

Traditional frontal face image synthesis based on the l 1-penalty has achieved remarkable success. However, the l 1-penalty on reconstruction coefficients has the drawback of instability when processing high-dimensional data (e.g. a facial image including hundreds of pixels). Moreover, the traditional l 1-penalty-based method requires consistency between the corresponding patches in frontal and profile faces, which is hard to guarantee due to self-occlusion. To overcome the instability problem of the traditional method, an extension of the l 1-penalty-based frontal face synthesis method, which benefits from the nature of the elastic net, is presented. 3 addition, to enhance the aforementioned consistency, a neighbourhood consistency penalty is imposed onto the reconstruction coefficients using the connected neighbour patches of the current patch. Furthermore, to ensure the synthesised result faithfully approximates the ground truth, a sparse neighbour selection strategy is introduced for finding related neighbours adaptively. Experimental results demonstrate the superiority of the proposed method over some state-of-the-art methods in both visual and quantitative comparisons.
Multi-wavelength access gate for WDM-formatted words in optical RAM row architectures

Optical RAM has emerged as a promising solution for overcoming the “Memory Wall” of electronics, indicating the use of light in RAM architectures as the approach towards enabling ps-regime memory access times. Taking a step further towards exploiting the unique wavelength properties of optical signals, we reveal new architectural perspectives in optical RAM structures by introducing WDM principles in the storage area. To this end, we demonstrate a novel SOAbased multi-wavelength Access Gate for utilization in a 4x4 WDM optical RAM bank architecture. The proposed multiwavelength Access Gate can simultaneously control random access to a 4-bit optical word, exploiting Cross-Gain-Modulation (XGM) to process 8 Bit and Bit channels encoded in 8 different wavelengths. It also suggests simpler optical RAM row architectures, allowing for the effective sharing of one multi-wavelength Access Gate for each row, substituting the eight AGs in the case of conventional optical RAM architectures. The scheme is shown to support 10Gbit/s operation for the incoming 4-bit data streams, with a power consumption of 15mW/Gbit/s. All 8 wavelength channels demonstrate error-free operation with a power penalty lower than 3 dB for all channels, compared to Back-to-Back measurements. The proposed optical RAM architecture reveals that exploiting the WDM capabilities of optical components can lead to RAM bank implementations with smarter column/row encoders/decoders, increased circuit simplicity, reduced number of active elements and associated power consumption. Moreover, exploitation of the wavelength entity can release significant potential towards reconfigurable optical cache mapping schemes when using the wavelength dimension for memory addressing.
The response of polyether ether ketone to one-dimensional shock loading

The behaviour of the polymer polyether ether ketone (PEEK) has been investigated under conditions of one-dimensional shock loading. This has involved measurement of the Hugoniot in terms of stress, shock velocity and particle velocity, and measurements of the lateral stress, which have been used to determine the shear strength, and its variation with shock stress. Analysis of the relationship between shock velocity and particle velocity shows a simple linear response, in common with many other materials. Shear strength has also been shown to increase with shock stress, with a break in slope at ca 1.0 GPa. Below this stress, the material appears to behave in a simple elastic manner, which suggests a Hugoniot elastic limit of 1 GPa. Shear strength has also been observed to increase significantly behind the shock front both above and below 1 GPa. This behaviour has been observed in other polymeric materials, where it was suggested that these materials were responding by a viscoplastic mechanism.
Effects of supplemental Zn concentration and trace mineral source on immune function and associated biomarkers of immune status in weaned beef calves received into a feedlot

Abstract Low-risk, weaned Angus-crossbred steers (n = 72; 284 ± 25 kg) were used in a 42-d receiving study. Steers were housed in pens (n = 6 steers per pen) equipped with GrowSafe bunks for determination of individual animal feed disappearance. Dietary treatments (n = 24 steers per treatment) included: 1) trace minerals (TM) from an organic source (Availa4; Zinpro Corp., Eden Prairie, MN) at 7 g·steer−1·d−1; for 42 d (ORG); 2) ORG for entire 42-d plus AvailaZn (Zn amino acid complex, Zinpro Corp., Eden Prairie, MN) to provide 1,000 mg Zn·steer−1·d−1 for first 14 d (ORG+Z); 3) inorganic TM sources to supplemented at equivalent concentration as in ORG for 42-d (ING). Cattle were weighed on day −1, 0, 14, 41, and 42. Whole blood was collected (n = 72 steers) on day 0, 14, and 42. Liver biopsies were conducted (n = 36 steers; 3 steers per pen) on day 0, 14, and 42. Flow cytometry measures were conducted using whole blood on day 1, 14, and 42 for determination of circulating frequencies of immune cell populations. There was a tendency for improved overall average daily gain (P = 0.07) where both ORG and ORG+Z were greater than ING. Final body weight did not differ (P = 0.21) and overall dry matter intake was unaffected by dietary treatment (P ≥ 0.18). However, overall gain-to-feed ratio was improved (P = 0.01) in steers supplemented organic TM (ORG and ORG+Z) compared to ING. Plasma Zn concentration did not differ at any time point during the study (P ≥ 0.20). Liver Zn concentration did not differ between treatments on day 0 or 42; however, on day 14 ING tended (P = 0.09) to be greater than ORG+Z with ORG being intermediate. Plasma Cu was unaffected by dietary treatment (P ≥ 0.34) on day 0, 14, and 42. Plasma Fe did not differ on day 0 or 42 but tended to be greater in ORG and ORG+Z compared to ING (P = 0.08) on day 14. Dietary treatment did not alter (P ≥ 0.22) liver Fe or Mn concentration at any time point. Frequency of total circulating natural killer (NK) and CD8 T cells measured on day 0, 14, and 42 did not differ (P ≥ 0.07). However, cell surface markers of activation (CD16, CD44, and CD8) on NK cells measured on day 14 did differ because of treatment (P ≤ 0.05). Results presented herein indicate TM from an organic source supplemented to steers during receiving can positively influence growth rate and feed efficiency. Regardless of source, TM supplementation affected markers of immune function but did not influence the prevalence of circulating NK and CD8 T-cell populations.
Product theorem of the fundamental group of a reducible curve

1. In this note, we study the fundamental groups of the complement of reducible curves and we prove the following generalization of the result of [2]. THEOREM. Let $C_{1}$ and $C_{2}$ be plane algebraic curves in $C^{2}$ . Assume that the intersection $C_{1}\cap C_{2}$ consists of distinct $d_{1}d_{2}$ Points where $d_{i}(i=1,2)$ are resPective degrees of $C_{1}$ and $C_{2}$ . Then the fundamental group $\pi_{1}(C^{2}-C_{1}\cup C_{2})$ is isomorPhic to the product of $\pi_{1}(C^{2}-C_{1})$ and $\pi_{1}(C^{2}-C_{2})$ . 2. PROOF. Let $(x, y)$ be a coordinate of $C^{2}$ , and let $f(x, y)$ and $g(x, y)$ be defining polynomials of $C_{1}$ and $C_{2}$ respectively. We can assume that the x-axis and y-axis are in general position with respect to $C_{1}$ and $C_{2}$ . Consider the deformations
Brachytherapy and osteoradionecrosis in patients with base of tongue cancer

Abstract Background Base of tongue cancer incidence and patient survival is increasing why treatment sequelae becomes exceedingly important. Osteoradionecrosis (ORN) is a late adverse effect of radiotherapy and brachytherapy (BT) could be a risk factor. Brachytherapy is used in three out of six health care regions in Sweden. Aims Investigate if patients treated in regions using BT show an increased risk for ORN and whether brachytherapy has any impact on overall survival. Material and Methods We used data from the Swedish Head and Neck Cancer Register between 2008–2014. Due to the nonrandomized nature of the study and possible selection bias we compared the risk for ORN in brachy vs non-brachy regions. Results Fifty out of 505 patients (9.9%) developed ORN; eight of these were treated in nonbrachy regions (16%), while 42 (84%) were treated in brachy regions. Neither age, sex, TNM-classification/stage, p16, smoking, neck dissection, or chemotherapy differed between ORN and no-ORN patients. The risk for ORN was significantly higher for patients treated in brachy regions compared to non-brachy regions (HR = 2,63, p = .012), whereas overall survival did not differ (HR = 0.95, p = .782). Conclusions and Significance Brachytherapy ought to be used cautiously for selected patients or within prospective randomized studies.
Exercise Volume Versus Intensity and the Progression of Coronary Atherosclerosis in Middle-Aged and Older Athletes: Findings From the MARC-2 Study

Background: Physical activity and exercise training are associated with a lower risk for coronary events. However, cross-sectional studies in middle-aged and older male athletes revealed increased coronary artery calcification (CAC) and atherosclerotic plaques, which were related to the amount and intensity of lifelong exercise. We examined the longitudinal relationship between exercise training characteristics and coronary atherosclerosis. Methods: Middle-aged and older men from the MARC-1 (Measuring Athlete’s Risk of Cardiovascular Events 1) study were invited for follow-up in MARC-2 (Measuring Athlete’s Risk of Cardiovascular Events 2) study. The prevalence and severity of CAC and plaques were determined by coronary computed tomography angiography. The volume (metabolic equivalent of task [MET] hours/week) and intensity (moderate [3 to 6 MET hours/week]; vigorous [6 to 9 MET hours/week]; and very vigorous [≥9 MET hours/week]) of exercise training were quantified during follow-up. Linear and logistic regression analyses were performed to determine the association between exercise volume/intensity and markers of coronary atherosclerosis. Results: We included 289 (age, 54 [50 to 60] years [median (Q1 to Q3)]) of the original 318 MARC-1 participants with a follow-up of 6.3±0.5 years (mean±SD). Participants exercised for 41 (25 to 57) MET hours/week during follow-up, of which 0% (0 to 19%) was at moderate intensity, 44% (0 to 84%) was at vigorous intensity, and 34% (0 to 80%) was at very vigorous intensity. Prevalence of CAC and the median CAC score increased from 52% to 71% and 1 (0 to 32) to 31 (0 to 132), respectively. Exercise volume during follow-up was not associated with changes in CAC or plaque. Vigorous intensity exercise (per 10% increase) was associated with a lesser increase in CAC score (β, −0.05 [−0.09 to −0.01]; P=0.02), whereas very vigorous intensity exercise was associated with a greater increase in CAC score (β, 0.05 [0.01 to 0.09] per 10%; P=0.01). Very vigorous exercise was also associated with increased odds of dichotomized plaque progression (adjusted odds ratio [aOR], 1.09 [1.01 to 1.18] per 10%; aOR, 2.04 [0.93 to 4.15] for highest versus lowest very vigorous intensity tertiles, respectively), and specifically with increased calcified plaques (aOR, 1.07 [1.00 to 1.15] per 10%; aOR, 2.09 [1.09 to 4.00] for highest versus lowest tertile, respectively). Conclusions: Exercise intensity but not volume was associated with progression of coronary atherosclerosis during 6-year follow-up. It is intriguing that very vigorous intensity exercise was associated with greater CAC and calcified plaque progression, whereas vigorous intensity exercise was associated with less CAC progression.
KPNA3 promotes epithelial-mesenchymal transition by regulating TGF-β and AKT signaling pathways in MDA-MB-231, a triple-negative breast cancer cell line

Karyopherin-α3 (KPNA3), a karyopherin-α isoform, is intimately associated with metastatic progression via epithelial-mesenchymal transition (EMT). However, the molecular mechanism underlying how KPNA3 acts as an EMT inducer remains to be elucidated. In this report, we identified that KPNA3 was significantly upregulated in cancer cells, particularly in triple-negative breast cancer, and its knockdown resulted in the suppression of cell proliferation and metastasis. The comprehensive transcriptome analysis from KPNA3 knockdown cells indicated that KPNA3 is involved in the regulation of numerous EMT-related genes, including the downregulation of GATA3 and E-cadherin and the up-regulation of HAS2. Moreover, it was found that KPNA3 EMT-mediated metastasis can be achieved by TGF-β or AKT signaling pathways; this suggests that the novel independent signaling pathways KPNA3-TGF-β-GATA3-HAS2/E-cadherin and KPNA3-AKT-HAS2/E-cadherin are involved in the EMT-mediated progress of TNBC MDA-MB-231 cells. These findings provide new insights into the divergent EMT inducibility of KPNA3 according to cell and cancer type.
Vitamin D and lactoferrin attenuate stress‐induced colitis in Wistar rats via enhancing AMPK expression with inhibiting mTOR–STAT3 signaling and modulating autophagy

Irritable bowel syndrome (IBS) is a global gastrointestinal disorder closely related to psychological stress exposure and local colonic inflammation. Herein, we investigated the effect of wrap‐restraint stress (WRS) on rat behavior, on adenosine monophosphate‐activated protein kinase–mammalian/mechanistic target of rapamycin–signal transducer and activator of transcription 3 (AMPK–mTOR–STAT3) signaling, and autophagy in colonic mucosa. The impact of chronic administration of vitamin D3 and lactoferrin was compared. Twenty‐four male Wistar rats were randomly divided into four groups. Chronic WRS protocol was applied as a rodent model of IBS. Group I: naïve animals, Group II: WRS animals, Group III: WRS‐exposed and treated with vitamin D3 (500 IU/kg/day), and Group IV: WRS‐exposed and treated with lactoferrin (300 mg/kg/day). In this study, we found that chronic administration of each of vitamin D3 and lactoferrin resulted in a significant increase in social interaction test, interleukin‐10, AMPK, optical density of LC3B, goblet cell count and marked decrease in serum cortisol level, STAT3, inflammatory cell count, and optical density of mTOR in comparison to the WRS rats. Our findings suggest that both vitamin D3 and Lactoferrin could augment colonic autophagy through enhanced AMPK expression and inhibition of mTOR–STAT3 signaling, which offers practical insights into their clinical use in the prevention and therapy of IBS. However, lactoferrin intake as a nutritional supplement could be more helpful for stress‐induced colitis treatment than vitamin D3.