Miracle-dz/UniFAR-FTUs huggingface dataset:
Inhibition of Glutaminase 1 Attenuates Experimental Pulmonary Fibrosis.

It has been increasingly recognized lately that aberrant cellular metabolism plays an important role in the pathogenesis of pulmonary fibrosis. In our previous systemic studies, we found that human lung myofibroblasts undergo glutaminolytic reprogramming, which is mediated by an increased expression of glutaminase 1 (Gls1). We showed that augmented glutaminolysis critically regulates collagen production by promoting its stabilization in human lung myofibroblasts. Our study indicates that lung fibroblast Gls1 is a promising therapeutic target for this disease. In this ensuing investigation, we primarily focused on delineating the in vivo role of fibroblast Gls1 in mouse models of pulmonary fibrosis and determining the efficacy of Gls1 inhibition in treating this pathology. We now show that fibroblast Gls1 is upregulated in fibrotic mouse lungs. We present evidence that mice with ablation of fibroblast Gls1 are protected from bleomycin induced lung fibrosis. We show that the Gls1 inhibitor CB-839 is therapeutically efficacious in treating both bleomycin and TGF-β1 induced pulmonary fibrosis. Our study has thus established a solid rationale for advancing Gls1 inhibitors, particularly CB-839, to the next stage of testing in the treatment of this disease.
Specific Leisure Activities and Cognitive Functions Among the Oldest-Old: the Chinese Longitudinal Healthy Longevity Survey.

Little is known about the role of specific leisure activities in affecting cognitive functions. We aim to examine the associations of specific leisure activities with the risk of cognitive impairment among oldest-old people in China. This community-based prospective cohort study included 10,741 cognitively normal Chinese individuals aged 80 years or older (median age 88 years) from the Chinese Longitudinal Healthy Longevity Survey. Cognitive function was assessed using the Mini-mental State Examination (MMSE). Cox proportional hazards models were utilized to estimate the effects of specific leisure activities on cognitive impairment outcome. During a median follow-up time of 3.4 years (41,760 person-years), 2,894 participants developed cognitive impairment. Compared to those who 'never' engaged in watching TV or listening to radio, reading books or newspapers, and playing cards or mah-jong, those who engaged in such activities 'almost every day' reduced their risk of cognitive impairment, the fully adjusted HRs were 0.56 (0.51-0.61), 0.64 (0.53-0.78), and 0.70 (0.56-0.86), respectively. The association between the risk of cognitive impairment and watching TV and listening to the radio, playing cards or mah-jong, and reading books or newspapers were stronger among those who had 2 or more years of education. Moreover, the association between risk of cognitive impairment and watching TV and listening to radio was stronger in men than in women. In conclusion, a greater frequency of TV watching or radio listening, reading books or newspapers and playing cards or mah-jong may decrease the risk of cognitive impairment among the oldest-old.
MusicBERT - learning multi-modal representations for music and text

Recent advances in deep learning have led to signiﬁcant advances in both text and music representations. However, the representations and tasks remain largely separate. Most Music Information Retrieval models focus on either music or text representations but not both. In this work we propose unifying these two modalities in a shared latent space. We propose building on a common framework of Transformer-based encoders for both text and music modalities using supervised and unsupervised methods for pre-training and ﬁne-tuning. We present initial results and key challenges that need to be overcome to make this possible. The result will be a new class of models that are able to perform advanced tasks that span both NLP and music.
Cross-sectional analysis of tubular polymer semi-finished products using ultrasound in comparison with other measuring methods

Abstract In the sector of biomedical engineering and implant technology, high-precision geometry is often decisive for successful end product functionalization. Especially in the production of tubular polymer semi-finished products, e.g. for stent fabrication, it is important to assure the desired parameters, such as inner and outer diameter and wall thickness. Within the current study we analyzed semifinished products for manufacturing of polymeric stents using three different methods. Biodegradable poly-L-lactide (PLLA) tubes were examined by means of micro computed tomography, ultrasonic scanning and scanning electron microscopy. The final evaluation presents clear advantages of the ultrasonic measuring method for the measurement of outer and inner diameter and wall thickness.
The Regulatory Role of Histone Modification on Gene Expression in the Early Stage of Myocardial Infarction

Myocardial infarction (MI) is a fatal heart disease with high morbidity and mortality. Various studies have demonstrated that a series of relatively specific biological events occur within 24 h of MI. However, the roles of histone modifications in this pathological process are still poorly understood. To investigate the regulation of histone modifications on gene expression in early MI, we performed RNA sequencing (RNA-seq) and chromatin immunoprecipitation sequencing (ChIP-seq) on myocardial tissues 24 h after the onset of MI. The genome-wide profiles of five histone marks (H3K27ac, H3K9ac, H3K4me3, H3K9me3, and H3K27me3) were explored through ChIP-seq. RNA-seq identified 1,032 differentially expressed genes (DEGs) between the MI and sham groups. ChIP-seq analysis found that 195 upregulated DEGs were modified by change of at least one of the three active histone marks (H3K27ac, H3K9ac, and H3K4me3), and the biological processes and pathways analysis showed that these DEGs were significantly enriched in cardiomyocyte differentiation and development, inflammation, angiogenesis, and metabolism. In the transcriptional regulatory network, Ets1, Etv1, and Etv2 were predicted to be involved in gene expression regulation. In addition, by integrating super-enhancers (SEs) with RNA-seq data, 76 DEGs were associated with H3K27ac-enriched SEs in the MI group, and the functions of these SE-associated DEGs were mainly related to angiogenesis. Our results suggest that histone modifications may play important roles in the regulation of gene expression in the early stage of MI, and the early angiogenesis response may be initiated by SEs.
Huidouba Improved Podocyte Injury by Down-Regulating Nox4 Expression in Rats With Diabetic Nephropathy

Diabetic nephropathy (DN), as the most common microvascular complication of diabetes mellitus (DM), has become one of the leading causes of end-stage renal disease (ESRD). Numerous studies have indicated that podocyte loss plays an important role in the development of DN and can even cause proteinuria in the early stage of DN. In the study, we found that Huidouba (HDB) significantly decreased the level of fasting blood glucose (FBG), the ratio of microalbumin to urine creatine (mAlb/Ucr), serum creatine (Scr), serum urea nitrogen (BUN), and malondialdehyde (MDA) in the kidney and downregulated the expression of Nox4 predominantly located in glomerular tissue while upregulating nephrin and WT1 expression in DN rats. In addition, HDB could also reduce podocyte damage and glomerular basement membrane (GBM) pathologic changes, as shown by transmission electron microscopy (TEM). In vitro study showed that HDB could inhibit high glucose (HG)-induced Reactive Oxygen Species (ROS) production and protect against podocyte apoptosis by downregulated Nox4 expression in podocytes. These results may provide a scientific basis for developing HDB as a potential folk medicine for the treatment of DN.
HLA*LA—HLA typing from linearly projected graph alignments

Abstract Summary HLA*LA implements a new graph alignment model for human leukocyte antigen (HLA) type inference, based on the projection of linear alignments onto a variation graph. It enables accurate HLA type inference from whole-genome (99% accuracy) and whole-exome (93% accuracy) Illumina data; from long-read Oxford Nanopore and Pacific Biosciences data (98% accuracy for whole-genome and targeted data) and from genome assemblies. Computational requirements for a typical sample vary between 0.7 and 14 CPU hours per sample. Availability and implementation HLA*LA is implemented in C++ and Perl and freely available as a bioconda package or from https://github.com/DiltheyLab/HLA-LA (GPL v3). Supplementary information Supplementary data are available at Bioinformatics online.
The newly introduced SARS-CoV-2 variant A222V is rapidly spreading in Lazio region, Italy

A new SARS-CoV-2 clade (GV) characterized by S substitution A222V, first reported from Spain in March, is rapidly spreading across Europe. To establish the A222V variant involvement in the infection rise in Italy, all GISAID sequences from Italy and those from our Laboratory (Lazio) in the period June-October were analysed. A222V, first recognized in August, represents 11.2% of sequences in this period, reaching 100% of autochthonous sequences in October, supporting increased GV circulation in Italy.
Intravenous Paracetamol in Adjunct to Intravenous Ketoprofen for Postoperative Pain in Children Undergoing General Surgery: A Double-Blinded Randomized Study

Background and objectives: The combination of non-steroidal anti-inflammatory drugs and paracetamol is widely used for pediatric postoperative pain management, although the evidence of superiority of a combination over either drug alone is insufficient. We aimed to find out if intravenous (i.v.) paracetamol in a dose of 60 mg kg−1 24 h−1, given in addition to i.v. ketoprofen (4.5 mg kg−1 24 h−1), improves analgesia, physical recovery, and satisfaction with postoperative well-being in children and adolescents following moderate and major general surgery. Materials and Methods: Fifty-four patients were randomized to receive either i.v. paracetamol or normal saline as a placebo in adjunct to i.v. ketoprofen. For rescue analgesia in patients after moderate surgery, i.v. tramadol (2 mg kg−1 up two doses in 24 h), and for children after major surgery, i.v. morphine-patient-controlled analgesia (PCA) were available. The main outcome measure was the amount of opioid consumed during the first 24 h after surgery. Pain level at 1 and over 24 h, time until the resumption of normal oral fluid intake, spontaneous urination after surgery, and satisfaction with postoperative well-being were also assessed. Results: Fifty-one patients (26 in the placebo group and 25 in the paracetamol group) were studied. There was no difference in required rescue tramadol doses (n = 11 in each group) or 24-h morphine consumption (mean difference (95% CI): 0.06 (–0.17; 0.29) or pain scores between placebo and paracetamol groups. In patients given morphine-PCA, time to normal fluid intake was faster in the paracetamol than the placebo subgroup: median difference (95% CI): 7.5 (1.3; 13.7) h, p = 0.02. Parental satisfaction score was higher in the paracetamol than the placebo group (mean difference: –1.3 (–2.5; –0.06), p = 0.04). Conclusions: There were no obvious benefits to opioid requirement or analgesia of adding regular intravenous paracetamol to intravenous ketoprofen in used doses. However, intravenous paracetamol may contribute to faster recovery of normal functions and higher satisfaction with postoperative well-being.
3D compositional hierarchies for object categorization

Deep learning methods have become the default tool for image classification. However, application of deep learning to surface shape classification is burdened by the limitations of existing methods, in particular, by lack of invariance to geometric transformations of input data. This thesis proposes two novel frameworks for learning a multi-layer representation of surface shape features, namely the view-based and the surface-based compositional hierarchical frameworks. The proposed representation is a hierarchical vocabulary of shape features, termed parts. Parts of the first layer are pre-defined, while parts of the subsequent layers, describing spatial relations of subparts, are learned. The view-based framework describes spatial relations between subparts using a camera-based reference frame. The key stage of the learning algorithm is part selection which forms the vocabulary based on multi-objective optimization, considering different importance measures of parts. Our experiments show that this framework enables efficient category recognition on a large-scale dataset. The surface-based framework exploits part-based intrinsic reference frames, which are computed for lower layers parts and inherited by parts of the subsequent layers. During learning spatial relations between subparts are described in these reference frames. During inference, a part is detected in input data when its subparts are detected at certain positions and orientations in each other’s reference frames. Since rigid body transformations don’t change positions and orientations of parts in intrinsic reference frames, this approach enables efficient recognition from unseen poses. Experiments show that this framework exhibits a large discriminative power and greater robustness to rigid body transformations than advanced CNN-based methods.
Prognostic impact of telomeric repeat-containing RNA expression on long-term oncologic outcomes in colorectal cancer

Abstract Telomeres are transcribed into long, noncoding telomeric repeat-containing RNAs (TERRA) that have been implicated in the regulation of telomerase, the enzyme that lengthens telomeres, in heterochromatin formation at telomeres, and in telomere stability. This study aimed to evaluate the correlation between TERRA expression and long-term oncologic outcomes in colorectal cancer (CRC). We evaluated 18p TERRA expression and telomere length using quantitative real-time PCR in 60 patients who underwent surgical resection for CRC between June 2008 and November 2010. Patients were grouped according to 18p TERRA expression, with 29 (48.3%) and 31 (51.7%) patients in the low and high TERRA expression groups, respectively. The median follow-up period was 80 months (range 2–103). The 18p TERRA expression was marginally significantly associated with preoperative carcinoembryonic antigen (CEA; P = .082) and was significantly associated with telomere length (P < .05). Multivariate analysis revealed that preoperative CEA (hazard ratio [HR], 2.728; 95% confidence interval [CI], 0.832–8.944, P = .098) and 18p TERRA expression (HR, 0.113; 95% CI, 0.011–1.126, P = .071) were marginally significant independent prognostic factors for overall survival (OS), whereas preoperative CEA (HR, 4.254; 95% CI, 1.394–12.985, P = .011) and 18p TERRA expression (HR, 0.108; 95% CI, 0.011–1.037, P = .054) were significant independent prognostic factors for disease-free survival (DFS). According to our prognostic model with 2 prognostic factors, the OS and DFS rate increased to 76.2% and 80.63%, respectively, in patients with high 18p TERRA expression and CEA levels ≤5 (P = .178, P = .057, respectively). 18p TERRA expression was marginally significantly associated with preoperative CEA and significantly associated with telomere length, rendering it a potential prognostic factor for long-term oncologic outcomes in CRC.
The future of skin tightening: Mechanical or biological?

Not too long ago, the concept of nonexcisional skin tightening was a field of dreams. Currently, the field of nonexcisional skin tightening is heavily device dependent. Though great strides have been made in both minimally invasive skin tightening and totally noninvasive devices, will these be in use for decades? Advances in biological research and development have been rapid. Consumer demand for regenerative solutions is high, despite the warnings from the Food and Drug Administration (FDA) noting that benefits are unproven and that instances of charlatan practice are high. While genetic modification of food is frowned upon, the use of biomarkers in medicine has become a standard of care.
Swipe up to smoke less cigarettes! Introducing a mobile Approach-Avoidance Task Application to fight Smoking

Abstract Automatic tendencies to approach addictionrelated stimuli have been linked to the development and maintenance of harmful drug use behavior. Recent studies have shown that these automatic approaches can be directly addressed and modified by cognitive bias modification (CBM). However, the training and treatment effects are rather small and compliance could be impaired by time-consuming, multiple laboratory training sessions. Here we present a mobile variant of the Approach-Avoidance Task (app-AAT), which is evaluated by a feasibility study. The app-AAT is designed to improve the efficiency of CBM training by allowing smokers to access the training at any time, and by offering the option to track consumed cigarettes. Our first run with eight participants showed that the app was rated very positively with 4.2 out of 5 points (engagement: 3.7, functionality: 4.5, aesthetics: 4.4) by using the german Mobile App Rating Scale (MARS-G).
The combination of whole‐exome sequencing and copy number variation sequencing enables the diagnosis of rare neurological disorders

This retrospective study aims to investigate the diagnostic yields of multiple strategies of next‐generation sequencing (NGS) for children with rare neurological disorders (NDs). A total of 220 pediatric patients with NDs who visited our hospital between Jan 2017 and Dec 2018 and had undergone NGS were included. Most patients were 5 years old or younger, and the number of patients visiting the hospital decreased with age. Seizures were the most common symptom in this cohort. The positive rates for targeted NGS panels (Panel), whole‐exome sequencing (WES), and copy number variation sequencing (CNVseq) were 26.5% (9/34), 36.6% (63/172), and 16.7% (22/132), respectively. The positive rate for patients undergoing a combination of WES and CNVseq (WES + CNVseq) was 47.8% (54/113), which was significantly better than the positive rate for patients who underwent WES alone (32.7%, 37/113). A total of 83 variants were found in 42 genes, and SCN1A was the most frequently mutanted gene. Twenty‐four CNVs were identified in 22 patients: two CNVs were inherited from the mother; 12 CNVs were de novo; and the CNV origins could not be determined in 10 patients. WES + CNVseq may potentially be the mostly effective NGS approach for diagnosis of rare NDs in pediatric patients.
Measuring lunchtime consumption in school cafeterias: a validation study of the use of digital photography

Abstract Objective The present study tested the validity of a digital image-capture measure of food consumption suitable for use in busy school cafeterias. Design Lunches were photographed pre- and post-consumption, and food items were weighed pre- and post-consumption for comparison. Setting A small research team recorded children’s lunchtime consumption in one primary and one secondary school over seven working days. Participants A primary-school sample of 121 children from North Wales and a secondary-school sample of 124 children from the West Midlands, UK, were utilised. Nineteen children were excluded because of incomplete data, leaving a final sample of 239 participants. Results Results indicated that (i) consumption estimates based on images were accurate, yielding only small differences between the weight- and image-based judgements (median bias=0·15–1·64 g, equating to 0·45–3·42 % of consumed weight) and (ii) good levels of inter-rater agreement were achieved, ranging from moderate to near perfect (Cohen’s κ=0·535–0·819). This confirmed that consumption estimates derived from digital images were accurate and could be used in lieu of objective weighed measures. Conclusions Our protocol minimised disruption to daily lunchtime routine, kept the attrition low, and enabled better agreement between measures and raters than was the case in the existing literature. Accurate measurements are a necessary tool for all those engaged in nutrition research, intervention evaluation, prevention and public health work. We conclude that our simple and practical method of assessment could be used with children across a range of settings, ages and lunch types.
Extended Memory Reuse: An Optimisation for Reducing Memory Allocations

In this paper we present an optimisation for reference counting based garbage collection. The optimisation aims at reducing the total number of calls to the heap manager while preserving the key benefits of reference counting, i.e. the opportunities for in-place updates as well as memory deallocation without global garbage collection. The key idea is to carefully extend the lifetime of variables so that memory deallocations followed by memory allocations of the same size can be replaced by a direct memory reuse. Such memory reuse turns out particularly useful in the context of innermost loops of compute-intensive applications. It leads to a runtime behaviour that performs pointer swaps between buffers in the same way it would be implemented manually in languages that require explicit memory management, e.g. C. We have implemented the proposed optimisation in the context of the Single-Assignment C compiler tool chain. The paper provides an algorithmic description of our optimisation and an evaluation of its effectiveness over a collection of benchmarks including a subset of the Rodinia benchmarks and the NAS Parallel Benchmarks. We show that for several benchmarks with allocations within loops our optimisation reduces the amount of allocations by a few orders of magnitude. We also observe no negative impact on the overall memory footprint nor on the overall runtime. Instead, for some sequential executions we find mild improvement, and on GPU devices we observe speedups of up to a factor of 4x.
The Effect of the Work-Life Interface on Insomnia: A Longitudinal Analysis of Male and Female Employees in Switzerland

Abstract This study draws on the Swiss Household Panel and employs specific panel data methods to investigate whether work-life conflict – decomposed into time-, and strain-based conflicts – and lack of recovery during off-job time (i. e. psychological detachment from work) cause insomnia. The findings indicate that, when adequately accounting for individual hetero geneity and the relative importance of multiple causal factors, recovery and recuperation processes appear crucial to the experience of insomnia, while the significance of perceived work-life conflict recede, for both men and women.
A multispectral 3D-Endoscope for Cholesteatoma Removal

Abstract We present a stereo-multispectral endoscopic prototype using a filter-wheel to guide the removal of cholesteatoma tissue in the middle ear. An image-based method is used that combines multispectral tissue classification for the detection of tissue to be removed and 3Dreconstruction to determine its metric dimensions. The multispectral illumination used for tissue classification ranges from λ = 400 nm to λ = 500 nm with step-size of 20 nm, which results in six different narrow-band illumination modes. For classical RGB imaging and metric calculations, a broadband illumination mode is applied before and after the narrow-band illumination. The spectral information is augmented into the broadband mode using an overlay technique. The combination of multispectral imaging with stereoscopic 3D-reconstruction results in new valuable visualization of intraoperative data. This allows to generate a 3D-model of the patients anatomy highlighting the identified malicious tissue and compare the anatomical dimensions with pre-operative CT data.