Miracle-dz/UniFAR-FTUs huggingface dataset:
Are NR5A1 Variations a Frequent Cause of 46,XX Ovotesticular Disorders of Sex Development? Analysis from a Single Center and Systematic Review

Introduction: Ovotesticular disorder of sex development (OT-DSD) is a rare condition defined by concomitance of testicular tissue and ovarian tissue (containing follicles) in the same individual. In SRY-negative 46,XX OT-DSD, the presence of testicular tissue may be due to variations in NR5A1. Our aims were to search for NR5A1 variants in SRY-negative 46,XX OT-DSD patients and to perform a systematic review on the contribution of NR5A1 variations to 46,XX OT-DSD. Methods: Sanger sequencing of NR5A1 was performed in seven SRY-negative 46,XX OT-DSD patients: five simplex cases and two with another sibling with a 46,XX DSD. Systematic review of original studies on NR5A1 sequencing of 46,XX OT-DSD patients was performed according to PRISMA-P guideline. Case reports were selected for analysis of clinical features. Individuals with NR5A1-associated testicular DSD were not included. Results: Sanger sequencing of NR5A1 did not reveal pathogenic variants among our patients. Our cohort was included in this systematic review with seven other articles, totalizing fifty-six 46,XX OT-DSD patients investigated by Sanger or whole-exome sequencing. From them, three NR5A1 pathogenic variants were identified (5% of the cases). Clinical analysis of these 3 cases and 5 case reports revealed: predominance of ovotestis (13/16 gonads) and bilateral OT-DSD (5/8 cases). Conclusion: The etiology of most 46,XX OT-DSD cases remains elusive, highlighting the importance of a deeper molecular investigation.
Efficacy and Toxicity of Combined Inhibition of EGFR and VEGF in Patients With Advanced Non–small Cell Lung Cancer Harboring Activating EGFR Mutations

Dual inhibition of epidermal growth factor receptor (EGFR) and vascular endothelial growth factor (VEGF) pathways have demonstrated promising results for treatment of advanced non–small cell lung cancer. We conducted a systematic review and meta-analysis to assess the efficacy and toxicity of the combined treatment with EGFR tyrosine kinase inhibitors (TKIs) and VEGF blockade for patients with advanced non–small cell lung cancer harboring activating EGFR mutations, in comparison to EGFR TKIs alone. The electronic databases were searched for relevant randomized trials between 2000 and 2022. The primary endpoints were overall survival (OS) and progression-free survival. Secondary endpoints included objective response rate (ORR), disease control rate, and grade ≥3 adverse events (AEs). The pooled hazard ratios (HR) and odds ratios were meta-analyzed using the generic inverse variance and the Mantel-Haenszel methods. A total of 1528 patients from 8 trials were evaluated for analyses. The combination treatment decreased the risk of disease progression by 37% (HR=0.63; 95% CI, 0.56 to 0.72) but had no added benefit on OS compared with EGFR inhibition alone (HR=0.90; 95% CI, 0.76 to 1.05). There was no significant difference in objective response rate or disease control rate between treatments. There was a significantly increased number of AEs reported in the dual treatment arm (odds ratio=3.02; 95% CI, 1.71 to 5.31), with proteinuria and hypertension being the most significantly increased AEs. This meta-analysis suggests combined inhibition of EGFR and VEGF pathways significantly improves progression-free survival, with no OS benefit, and increases AEs. Mature OS data are needed along with results from more trials exploring this strategy with third-generation EGFR TKIs to strengthen these results.
The Five-substitution Option Enhances Teams’ Running Performance at High Speed in Football

Abstract The aim of this investigation was to describe how the introduction of the five-substitution option affected football teams’ running performance. A comparative analysis was performed in 17 professional football teams for the 2019-2020 (up to three substitutions) vs 2020–2021 (five substitutions option) seasons in LaLiga . The five-substitution option increased the number of substitutions (from 2.9±0.1 to 4.2±1.0 substitutions/match, respectively; p<0.01, Effect Size (ES)=2.11) but it did not change the time selected for the first substitution (from 57.5±13.0 to 56.2±13.7 min; p=0.06, ES=0.1). Total running distance was similar between seasons but running distance at 21.0–23.9 km/h (from 3.0±0.4 to 3.2±0.4 km; p=0.01, ES=0.6) and at≥24.0 km/h (from 3.0±0.6 to 3.2±0.5 km; p=0.01, ES=0.3) were higher with the five-substitution option. These increases were associated with a higher distance covered by starting players (p<0.05) rather than an effect of substitute players . With the five-substitution option, team coaches increased the number of substitutions per match which enhanced the possibilities of the team’s staff to manage players’ physical load. The five-substitution option allowed also increased running performance at≥21.0 km/h during the matches.
Simple Riemann functions

Research of Cohn [1] and Daggit [2] guesses or deduces functions M and G such that some Riemann functions have the form R = Mf(G). The Riemann function is then found by solving an ordinary differential equation for ƒ. Roughly speaking, all the results of Riemann, Cohn and Daggit are simple Riemann functions because (i) the equation is almost selfadjoint, (ii) the ordinary differential equation for ƒ has coefficients depending on G9 and (iii) the characteristic conditions for the Riemann function become initial conditions for ƒ. These restrictions, formulated in Definition 2, seem mild because omitting any one of the three would allow every Riemann function to satisfy Definition 2. Surprisingly, these conditions lead directly to expressions for M and G (Theorems 1 and 2). With these, all of Daggit's results are derived (Theorems 3 to 7) from one of his hypotheses. For a selfadjoint equation to have a simple Riemann function, Daggit's hypothesis is sufficient as well as necessary (Theorem 8). This announcement therefore contains proof that all simple Riemann functions are known for selfadjoint equations. The proofs for the general case are given in another paper [4]. DEFINITION 1. The unique Riemann function R for the equation
Validation of an improved vision-based web page parsing pipeline

In this paper, we present a novel approach to quantitative evaluation of a model for parsing web pages as visual images, intended to provide improvements for users with assistive needs (cognitive or visual deficits, enabling decluttering or zooming and supporting more effective screen reader output). This segmentation-classification pipeline is tested in stages: We first discuss the validation of the segmentation algorithm, showing that our approach produces automated segmentations that are very similar to those produced by real users when making use of a drawing interface to designate edges and regions. We also examine the properties of these ground truth segmentations produced under different conditions. We then describe our Hidden-Markov tree approach for classification and present results which serve provide important validation for this model. The analysis is set against effective choices for dataset and pruning options, measured with respect to manual ground truth labelling of regions. In all, we offer a detailed quantitative validation (focused on complex news pages) of a fully pipelined approach for interpreting web pages as visual images, an approach which enables important advances for users with assistive needs.
Testing for Unit Roots in Seasonal Time Series

Abstract Regression estimators of coefficients in seasonal autoregressive models are described. The percentiles of the distributions for time series that have unit roots at the seasonal lag are computed by Monte Carlo integration for finite samples and by analytic techniques and Monte Carlo integration for the limit case. The tabled distributions may be used to test the hypothesis that a time series has a seasonal unit root.
Robust estimation with dynamic integral quadratic constraints: the discrete-time case

The authors consider the problem of robust output estimation in the discrete-time setting. The uncertainty in the system is characterised by integral quadratic constraints with dynamic multipliers. The main technical contribution of this study is to derive two different synthesis conditions in terms of linear matrix inequalities (LMI) by two different approaches. The LMI condition derived by the first approach allows one to find the robust estimator and the performance certificate simultaneously, whereas the condition by the second approach has a smaller size but requires an additional step for recovering the estimator. The synthesis conditions are validated by numerical examples. The results verify the equivalence of the two approaches and show that the two-step approach is in fact computationally favourable when the system has large number of state variables.
FlatLSM: Write-Optimized LSM-Tree for PM-Based KV Stores

The Log-Structured Merge Tree (LSM-Tree) is widely used in key-value (KV) stores because of its excwrite performance. But LSM-Tree-based KV stores still have the overhead of write-ahead log and write stall caused by slow L0 flush and L0-L1 compaction. New byte-addressable, persistent memory (PM) devices bring an opportunity to improve the write performance of LSM-Tree. Previous studies on PM-based LSM-Tree have not fully exploited PM’s “dual role” of main memory and external storage. In this article, we analyze two strategies of memtables based on PM and the reasons write stall problems occur in the first place. Inspired by the analysis result, we propose FlatLSM, a specially designed flat LSM-Tree for non-volatile memory based KV stores. First, we propose PMTable with separated index and data. The PM Log utilizes the Buffer Log to store KVs of size less than 256B. Second, to solve the write stall problem, FlatLSM merges the volatile memtables and the persistent L0 into large PMTables, which can reduce the depth of LSM-Tree and concentrate I/O bandwidth on L0-L1 compaction. To mitigate write stall caused by flushing large PMTables to SSD, we propose a parallel flush/compaction algorithm based on KV separation. We implemented FlatLSM based on RocksDB and evaluated its performance on Intel’s latest PM device, the Intel Optane DC PMM with the state-of-the-art PM-based LSM-Tree KV stores, FlatLSM improves the throughput 5.2× on random write workload and 2.55× on YCSB-A.
Localized Validation Accelerates Distributed Transactions on Disaggregated Persistent Memory

Persistent memory (PM) disaggregation significantly improves the resource utilization and failure isolation to build a scalable and cost-effective remote memory pool in modern data centers. However, due to offering limited computing power and overlooking the bandwidth and persistence properties of real PMs, existing distributed transaction schemes, which are designed for legacy DRAM-based monolithic servers, fail to efficiently work on the disaggregated PM. In this article, we propose FORD, a Fast One-sided RDMA-based Distributed transaction system for the new disaggregated PM architecture. FORD thoroughly leverages one-sided remote direct memory access to handle transactions for bypassing the remote CPU in the PM pool. To reduce the round trips, FORD batches the read and lock operations into one request to eliminate extra locking and validations for the read-write data. To accelerate the transaction commit, FORD updates all remote replicas in a single round trip with parallel undo logging and data visibility control. Moreover, considering the limited PM bandwidth, FORD enables the backup replicas to be read to alleviate the load on the primary replicas, thus improving the throughput. To efficiently guarantee the remote data persistency in the PM pool, FORD selectively flushes data to the backup replicas to mitigate the network overheads. Nevertheless, the original FORD wastes some validation round trips if the read-only data are not modified by other transactions. Hence, we further propose a localized validation scheme to transfer the validation operations for the read-only data from remote to local as much as possible to reduce the round trips. Experimental results demonstrate that FORD significantly improves the transaction throughput by up to 3× and decreases the latency by up to 87.4% compared with state-of-the-art systems.
THE USE OF CHAIN-BINOMIALS WITH A VARIABLE CHANCE OF INFECTION FOR THE ANALYSIS OF INTRA-HOUSEHOLD EPIDEMICS

An important characteristic of highly infectious diseases is that they tend to produce groups of cases occurring within households rather than separate cases scattered throughout the community. If all the cases in a household were due to some single source of infection such as typhoid-infected water, then we should expect the total number of cases to follow a binomial distribution. On the other hand, if the disease were introduced into the household by one of its members and then transmitted from person to person, a very different situation would arise. For a disease involving a short period of high infectivity and an approximately constant incubation period, we should expect to be able to distinguish different generations of the intra-household epidemic. There might be a binomial distribution of secondary cases resulting from contact with the primary case, to be followed later by another binomial distribution of tertiary cases amongst the susceptibles who had previously escaped, and so on. In his classic paper on this subject Greenwood (1931) introduced such a chainbinomial model for the investigation of measles epidemics, for which the assumptions made are thought to be approximately true. When the period of infectivity is more extended, as with scarlet fever or whooping cough for example, the stochastic model recently discussed by Bailey (1953) may be more appropriate. Greenwood examined data on the 1926 measles epidemic in St Pancras, and showed that, so far as the total number of cases in a household was concerned, the hypothesis of a simple binomial distribution was quite inadequate, while the distribution expected from the chain-binomial model gave a satisfactory fit to the observations. It is important to notice, however, that this material provided information only on the total size of the epidemic in a given household; no analysis of the individual links of the chain was possible. Now Wilson, Bennett, Allen & Worcester (1939), in their investigation of cases of measles occurring in Providence, Rhode Island, during 1929-34, were able to go a stage further and break down the data into its constituent parts. Of course it must be recognized that departures from a constant incubation period, or the possibility of multiple primary cases, give rise to certain difficulties in the so-called chaining of this kind of material. However, it seemed likely that in the present case this source of confusion would not be serious. Wilson et al. were able to show that in none of the groups of available data did the Greenwood model give an adequate description of the numbers of cases occurring in the separate generations through which the epidemic passed, though it did sometimes give a satisfactory fit to the distribution of the total number of cases in a household. In a later paper, Wilson (1947) considered a somewhat different approach. According
Effect of melamine cyanurate on thermal and flame-retardant behaviour of chopped glass fibre reinforced polyphenylene ether/polystyrene/nylon-6

This paper deals with the effect of melamine cyanurate on the thermal and fire retardant behaviour of chopped glass fibre (40 wt.%) reinforced polyphenylene ether/polystyrene/nylon-6 (40/40/20 wt. %) which are processed in a twin screw co-rotating extruder. The composite specimens were fabricated by injection moulding. Addition of melamine cyanurate decreased the amount of toxic gases and organic volatile compounds, crystallinity, crystalline temperature and melt temperature but the same fire-retardant increased glass transition temperature and heat distortion temperature of the ternary alloy. Flame retardancy with V0 and V2 rating along with Limiting Oxygen Index 35% was observed in UL94 test for 5 wt. % and 10 wt. % addition of melamine cyanurate, respectively. Addition of melamine cyanurate increased tensile modulus and elongation at break but decreased the melt flow rate and the moisture content of the ternary alloy.
Early root phenotyping in sweetpotato (Ipomoea batatas L.) uncovers insights into root system architecture variability

Background We developed a novel, non-destructive, expandable, ebb and flow soilless phenotyping system to deliver a capable way to study early root system architectural traits in stem derived adventitious roots of sweetpotato (Ipomoea batatas L.). The platform was designed to accommodate up to 12 stems in a relatively small area for root screening. This platform was designed with inexpensive materials and equipped with an automatic watering system. Methods To test this platform, we designed a screening experiment for root traits using two contrasting sweetpotato genotypes, ‘Covington’ and ‘NC10-275’. We monitored and imaged root growth, architecture, and branching patterns every five days up to 20 days. Results We observed significant differences in both architectural and morphological root traits for both genotypes tested. After 10 days, root length, surface root area, and root volume were higher in ‘NC10-275’ compared to ‘Covington’. However, average root diameter and root branching density were higher in ‘Covington’. Conclusion These results validated the effective and efficient use of this novel root phenotyping platforming for screening root traits in early stem-derived adventitious roots. This platform allowed for monitoring and 2D imaging root growth over time with minimal disturbance and no destructive root sampling. This platform can be easily tailored for abiotic stress experiments, permit root growth mapping and temporal and dynamic root measurements of primary and secondary adventitious roots. This phenotyping platform can be a suitable tool for examining root system architecture and traits of clonally propagated material for a large set of replicates in a relatively small space. Subjects Plant Science, Agricultural Science
COL7A1 Expression Improves Prognosis Prediction for Patients with Clear Cell Renal Cell Carcinoma Atop of Stage

Clear cell renal cell carcinoma (ccRCC) accounts for 75% of kidney cancers. Due to the high recurrence rate, and treatment options that come with high costs and potential side effects correct prognosis of patient survival is essential for the successful and effective treatment of patients. Novel biomarkers could play an important role in the assessment of the overall survival of patients. COL7A1 encodes for collagen type VII, a constituent of the basal membrane. COL7A1 is associated with survival in many cancers; however, the prognostic value of COL7A1 expression as a standalone biomarker in ccRCC has not been investigated. We used Kaplan-Meier curves and Cox proportional hazards model to investigate the prognostic value of COL7A1, as well as Gene Set Enrichment Analysis to investigate genes that are co-expressed with COL7A1. COL7A1 expression was used to stratify patients into four groups of expression, where the 5-year survival probability of each group was 72.4%, 59.1%, 34.15%, and 8.6% in order of increasing expression. Additionally, COL7A1 expression was successfully used to further divide patients of each stage and histological grade into groups of high and low risk. Similar results were obtained in independent cohorts. In-vitro knockdown of COL7A1 expression significantly impacted ccRCC cells’ ability to migrate and proliferate. To conclude, we identified COL7A1 as a new prognosis marker that can stratify ccRCC patients.
GEARBOCS: An Adeno Associated Virus Tool for In Vivo Gene Editing in Astrocytes

In the mammalian central nervous system (CNS), astrocytes are indispensable for brain development, function, and health. However, non-invasive tools to study astrocyte biology and function in vivo have been limited to genetically modified mice. CRISPR/Cas9-based genome engineering enables rapid and precise gene manipulations in the CNS. Here, we developed a non-invasive astrocyte-specific method utilizing a single AAV vector, GEARBOCS (Gene Editing in AstRocytes Based On CRISPR/Cas9 System). We verified GEARBOCS’ specificity to mouse cortical astrocytes and demonstrated its utility for three types of gene manipulations: knockout (KO); tagging (TagIN); and reporter gene knock-in (Gene-TRAP) strategies. We deployed GEARBOCS to determine whether cortical astrocytes express Vamp2 protein. The presence of Vamp2-positive vesicles in cultured astrocytes is well-established, however, Vamp2 protein expression in astrocytes in vivo has proven difficult to ascertain due to its overwhelming abundance in neurons. Using GEARBOCS, we delineated the in vivo astrocytic Vamp2 expression and found that it is required for maintaining excitatory and inhibitory synapse numbers in the visual cortex. GEARBOCS strategy provides fast and efficient means to study astrocyte biology in vivo. Graphical Abstract (Main Points) • GEARBOCS is a single AAV-based CRISPR tool to target mouse astrocytes in vivo. • GEARBOCS can be used to knockout, tag, or gene-trap genes of interest in astrocytes in vivo. • Using GEARBOCS, we confirmed astrocytes express Vamp2 and found that astrocytic Vamp2 is required for maintenance of excitatory and inhibitory synapse numbers in vivo.
INTERSTELLAR ABUNDANCES TOWARD X Per, REVISITED

The nearby X-ray binary X Per (HD 24534) provides a useful beacon with which to examine dust grain types and measure elemental abundances in the local interstellar medium (ISM). The absorption features of O, Fe, Mg, and Si along this line of sight were measured using spectra from the Chandra X-Ray Observatory's LETG/ACIS-S and XMM-Newton's RGS instruments, and the Spex software package. The spectra were fit with dust analogs measured in the laboratory. The O, Mg, and Si abundances were compared to those from standard references, and the O abundance was compared to that along lines of sight toward other X-ray binaries. The results are as follows. First, it was found that a combination of MgSiO3 (enstatite) and Mg1.6Fe0. 4SiO4 (olivine) provided the best fit to the O K edge, with = 3.4. Second, the Fe L edge could be fit with models that included metallic iron, but it was not well described by the laboratory spectra currently available. Third, the total abundances of O, Mg, and Si were in very good agreement with that of recently re-analyzed B stars, suggesting that they are good indicators of abundances in the local ISM, and the depletions were also in agreement with expected values for the diffuse ISM. Finally, the O abundances found from X-ray binary absorption spectra show a similar correlation with Galactocentric distances as seen in other objects.
Deciphering the phenotypic heterogeneity and drug response in cancer cells using genome-wide activity and interaction of chromatin domains.

Chromatin is organised in the form of domains known to be insulated from neighbouring regions in the genome. The colocalisation of genes sharing similar functions in the topologically associated domains (TAD) and the orchestration of their activity in cancer-cells and their drug-response have not been comprehensively explored. Here we analyzed patterns in the activity of TADs in cancer-cells along with chromatin interaction profiles to understand their modes of drug-response. Using our approach on the transcriptome of 819 cancer cell lines revealed that for multiple drugs, IC50 values were substantially more correlated with the activity of a few TADs than any of the genes. Such a result signifies the potential utility of TAD activity in highlighting common mechanisms of drug response in spite of heterogeneity in the association of genes with drug-resistance. Further we performed analysis of 9014 cancer sample transcriptomes from 20 cancer types to find the