Miracle-dz/UniFAR-FTUs huggingface dataset:
A Universal Probe Set for Targeted Sequencing of 353 Nuclear Genes from Any Flowering Plant Designed Using k-Medoids Clustering

Sequencing of target-enriched libraries is an efficient and cost-effective method for obtaining DNA sequence data from hundreds of nuclear loci for phylogeny reconstruction. Much of the cost associated with developing targeted sequencing approaches is preliminary data needed for identifying orthologous loci for probe design. In plants, identifying orthologous loci has proven difficult due to a large number of whole-genome duplication events, especially in the angiosperms (flowering plants). We used multiple sequence alignments from over 600 angiosperms for 353 putatively single-copy protein-coding genes to design a set of targeted sequencing probes for phylogenetic studies of any angiosperm lineage. To maximize the phylogenetic potential of the probes while minimizing the cost of production, we introduce a k-medoids clustering approach to identify the minimum number of sequences necessary to represent each coding sequence in the final probe set. Using this method, five to 15 representative sequences were selected per orthologous locus, representing the sequence diversity of angiosperms more efficiently than if probes were designed using available sequenced genomes alone. To test our approximately 80,000 probes, we hybridized libraries from 42 species spanning all higher-order lineages of angiosperms, with a focus on taxa not present in the sequence alignments used to design the probes. Out of a possible 353 coding sequences, we recovered an average of 283 per species and at least 100 in all species. Differences among taxa in sequence recovery could not be explained by relatedness to the representative taxa selected for probe design, suggesting that there is no phylogenetic bias in the probe set. Our probe set, which targeted 260 kbp of coding sequence, achieved a median recovery of 137 kbp per taxon in coding regions, a maximum recovery of 250 kbp, and an additional median of 212 kbp per taxon in flanking non-coding regions across all species. These results suggest that the Angiosperms353 probe set described here is effective for any group of flowering plants and would be useful for phylogenetic studies from the species level to higher-order lineages, including all angiosperms.
Performance of colorectal cancer screening in the European Union Member States: data from the second European screening report

Objective To present comparative data about the performance of colorectal cancer (CRC) screening programmes in the European Union Member States (EU MSs). Design Cross-sectional study. We analysed key performance indicators—participation rate, positivity rate (PR), detection rate (DR) and positive predictive value for adenomas and CRC—based on the aggregated quantitative data collected for the second EU screening report. We derived crude and pooled (through a random effects model) estimates to describe and compare trends across different MSs/regions and screening protocols. Results Participation rate was higher in countries adopting faecal immunochemical test (FIT) (range: 22.8%–71.3%) than in those using guaiac faecal occult blood test (gFOBT) (range 4.5%–66.6%), and it showed a positive correlation (ρ=0.842, p<0.001) with participation in breast cancer screening in the same areas. Screening performance showed a large variability. Compliance with referral for colonoscopy (total colonoscopy (TC)) assessment ranged between 64% and 92%; TC completion rate ranged between 92% and 99%. PR and DR of advanced adenomas and CRC were higher in FIT, as compared with gFOBT programmes, and independent of the protocol among men, older subjects and those performing their first screening. Conclusions The variability in the results of quality indicators across population-based screening programmes highlights the importance of continuous monitoring, as well as the need to promote quality improvement efforts, as recommended in the EU guidelines. The implementation of monitoring systems, ensuring availability of data for the entire process, together with initiatives aimed to enhance reproducibility of histology and quality of endoscopy, represent a priority in screening programmes management.
The Value of Unilateral CIs, CI-CROS and Bilateral CIs, with and without Beamformer Microphones, for Speech Understanding in a Simulation of a Restaurant Environment

Objective: Our primary aim was to determine, in a simulation of a crowded restaurant, the value to speech understanding of (i) a unilateral cochlear implant (CI), (ii) a CI plus CROS (contralateral routing of signals) aid system and (iii) bilateral CIs when tested with and without beamforming microphones. Design: The listeners were 7 CI listeners who had used bilateral CIs for an average of 9 years. The listeners were tested with three device configurations (bilateral CI, unilateral CI + CROS, and unilateral CI), two signal processing conditions (without and with beamformers) and with speech either from +90°, –90°, or from the front. Speech understanding scores for the TIMIT sentences were obtained in the 8-loudspeaker R-SPACETM test environment – an environment which simulates listening in a crowded restaurant. Results: In the unilateral condition, speech understanding, relative to speech directed to the CI ear, fell by 17% when speech was from the front and fell 28% when speech was to the side opposite the CI. These deficits were overcome with both CI-CROS and bilateral CIs, and scores for the two devices did not differ significantly for any location of speech input. Beamformer microphones improved speech understanding for speech from the front and depressed speech understanding for speech from the sides for all device configurations. Patients with bilateral CIs and beamformers achieved slightly, but significantly, higher scores for speech from the front than patients with CI-CROS and beamformers. Conclusions: CI-CROS is a valuable addition to the hardware options available to patients fit with a single CI. For patients fit with bilateral CIs, bilateral beamformers are a valuable addition in the condition of speech coming from in front of the listener. The small differences in performance in the CI-CROS and bilateral CI conditions suggest that patient preference for bilateral CIs is based largely on factors other than speech understanding in noise.
Optimizing respiratory management in resource-limited settings

Purpose of review This review focuses on the emerging body of literature regarding the management of acute respiratory failure in low- and middle-income countries (LMICs). The aim is to abstract management principles that are of relevance across a variety of settings where resources are severely limited. Recent findings Mechanical ventilation is an expensive intervention associated with considerable mortality and a high rate of iatrogenic complications in many LMICs. Recent case series report crude mortality rates for ventilated patients of between 36 and 72%. Measures to avert the need for invasive mechanical ventilation in LMICs are showing promise: bubble continuous positive airway pressure has been demonstrated to decrease mortality in children with acute respiratory failure and trials suggest that noninvasive ventilation can be conducted safely in settings where resources are low. Summary The management of patients with acute respiratory failure in LMICs should focus on avoiding intubation where possible, improving the safety of mechanical ventilation and expediting weaning. Future directions should involve the development and trialing of robust and context-appropriate respiratory support technology.
Ursane-type triterpenoids from the roots of Rosa multiflora with their anti-inflammatory activity

Abstract Nine ursane-type triterpenoids including three new ones 2α, 19α-dihydroxyurs-3-O-acetyltormentic acid (1), 1α, 2α, 3α, 20β-tetrahydroxyurs -13(18)-en-28-oic acid (2), and 2α, 3α, 20β, 24-tetrahydroxyurs-13(18)-en-28-oic acid (3) were isolated from the roots of Rosa multiflora. Their structures were elucidated by extensive spectroscopic methods, including NMR, MS, and IR spectroscopic analyses data. All the isolates were evaluated for their anti-inflammatory activity in vitro and the results showed that compounds 1–9 displayed moderate inhibitory activity with IC50 values ranging from 24.7 to 86.2 μM compared with the postitive control Amino guanidine (IC50 4.3 μM).
Clarifying the relationship between mindfulness and executive attention: a combined behavioral and neurophysiological study

Abstract Mindfulness is frequently associated with improved attention. However, the nature of the relationship between mindfulness and executive attention, a core function of the attentional system, is surprisingly unclear. Studies employing behavioral measures of executive attention have been equivocal. Although neuroscientific studies have yielded more consistent findings, reporting functional and structural changes in executive attention brain regions, the observed changes in brain activity have not been linked to behavioral performance. The current study aimed to fill these gaps in the literature by examining the extent to which trait mindfulness related to behavioral and neurophysiological (indexed by the stimulus‐locked P3) measures of executive attention. Results revealed that higher trait mindfulness was related to less flanker interference on accuracy and reaction time, consistent with enhanced executive attention. Critically, mediational analyses showed that the P3 accounted for the relationship between trait mindfulness and executive attention performance, elucidating a neural mechanism through which mindfulness enhances executive attention.
Homoeostatic maintenance of nonstructural carbohydrates during the 2015-2016 El Niño drought across a tropical forest precipitation gradient.

Nonstructural carbohydrates (NSCs) are essential for maintenance of plant metabolism and may be sensitive to short- and long-term climatic variation. NSC variation in moist tropical forests has rarely been studied, so regulation of NSCs in these systems is poorly understood. We measured foliar and branch NSC content in 23 tree species at three sites located across a large precipitation gradient in Panama during the 2015-2016 El Niño to examine how short- and long-term climatic variation impact carbohydrate dynamics. There was no significant difference in total NSCs as the drought progressed (leaf P = 0.32, branch P = 0.30) nor across the rainfall gradient (leaf P = 0.91, branch P = 0.96). Foliar soluble sugars decreased while starch increased over the duration of the dry period, suggesting greater partitioning of NSCs to storage than metabolism or transport as drought progressed. There was a large variation across species at all sites, but total foliar NSCs were positively correlated with leaf mass per area, whereas branch sugars were positively related to leaf temperature and negatively correlated with daily photosynthesis and wood density. The NSC homoeostasis across a wide range of conditions suggests that NSCs are an allocation priority in moist tropical forests.
Long noncoding RNA Breast cancer antiestrogen resistance 4 is associated with cancer progression and its significant prognostic value

Breast cancer antiestrogen resistance 4 (BCAR4) is a novel long noncoding RNA. It was originally identified in a screen for genes responsible for the development of resistance to antiestrogens in breast cancer cells and plays a major role in various tumors. However, the clinical diagnostic role of BCAR4 in tumors is not completely understood. This current meta‐analysis aimed to comprehensively explore the potential role of BCAR4 as a prognostic biomarker in a number of cancers. Five public databases PubMed, EMBASE, Web of Science, Wiley Online Library, and Medline were used to search for articles. Nine studies comprising 1,293 patients were included in this meta‐analysis. The results of analysis showed that BCAR4 expression in human cancer was significantly associated with poor overall survival (hazard ratio [HR] = 1.98, confidence interval [CI]: [1.71–2.29]), p < 0.00001, and high BCAR4 expression was associated with clinical stage (OR and its 95% CI was 3.30 [1.99–5.46], p < 0.00001), distant metastasis (OR = 3.83, 95% CI: 2.15–6.82, p < 0.00001), and lymph node metastasis (OR and its 95% CI was 2.91 [1.62–5.25], p = 0.0004) in patients with cancer. Furthermore, the results revealed the prognostic significance of BCAR4 in gastrointestinal malignancy, breast cancer, and osteosarcoma (HR and its 95% CI were 2.05 [1.56–2.68], p < 0.00001; 1.78 [1.46–2.16], p < 0.00001; and 2.47 [1.41–4.34], p < 0.00001, respectively). This meta‐analysis indicated the potential value of BCAR4 as a biomarker for predicting a poor prognosis in patients with cancer.
Assessment of the common carotid artery wall stiffness by Shear Wave Elastography in Behcet's disease.

AIM To evaluate endothelial dysfunction and subclinical atherosclerosis in Behcet's disease (BD) by measuring the common carotid artery (CCA) wall stiffness and carotid intima-media thickness (CIMT). MATERIALS AND METHODS We prospectively evaluated CIMT and the CCA wall stiffness of 34 BD patients and 28 age/sex-matched controls. CIMT measurements were performed from the posterior wall of the carotid artery approximately 10 mm proximal to the initiation of the carotid bulb using B-mode ultrasound. The stiffness of the CCA was measured from the superficial wall of the CCA using shear wave elastography (SWE). SWE measurements were recorded as shear wave velocity (SWV) using m/s as a unit. RESULTS The mean right (0.5±0.11 mm) and left (0.5±0.14 mm) CIMT of the patients were significantly higher compared to the mean right (0.41±0.07 mm) and left (0.41±0.11 mm) CIMT of the healthy controls (p=0.001 and p= 0.003 respectively). The mean right (3.72±0.94 m/s) and left (3.57±0.72 m/s) CCA wall stiffness of the patients were significantly higher compared to the mean right (2.42±0.49 m/s) and left (2.56±0.49 m/s) CCA wall stiffness of the controls (p<0.001 for both). CONCLUSIONS SWE seems to be a promising modality to evaluate endothelial dysfunction in BD by interpreting the arterial stiffness, and SWE might be an important adjunct to clinical and laboratory findings, and imaging modalities to assess cardiovascular risk in BD. Moreover, SWE evaluation of the arterial stiffness might assist us to understand pathophysiological aspects of BD.
Metabolic features and regulation in cell senescence

Organismal aging is accompanied by a host of progressive metabolic alterations and an accumulation of senescent cells, along with functional decline and the appearance of multiple diseases. This implies that the metabolic features of cell senescence may contribute to the organism’s metabolic changes and be closely linked to age-associated diseases, especially metabolic syndromes. However, there is no clear understanding of senescent metabolic characteristics. Here, we review key metabolic features and regulators of cellular senescence, focusing on mitochondrial dysfunction and anabolic deregulation, and their link to other senescence phenotypes and aging. We further discuss the mechanistic involvement of the metabolic regulators mTOR, AMPK, and GSK3, proposing them as key metabolic switches for modulating senescence.
Breakfast replacement with a liquid formula improves glycemic variability in patients with type 2 diabetes: a randomized clinical trial.

There is emerging evidence that glycaemic variability (GV) plays an important role in the development of diabetic complications. The current study aimed to compare the effects of lifestyle intervention (LI) with and without partial meal replacement (MR) on GV. A total of 123 patients with newly diagnosed and untreated type 2 diabetes (T2D) were randomised to receive either LI together with breakfast replacement with a liquid formula (LI+MR) (n 62) or LI alone (n 61) for 4 weeks and completed the study. Each participant was instructed to have three main meals per d and underwent 72-h continuous glucose monitoring (CGM) both before and after intervention. Measures of GV assessed by CGM included the incremental AUC of postprandial blood glucose (AUCpp), standard deviation of blood glucose (SDBG), glucose CV and mean amplitude of glycaemic excursions (MAGE). After a 4-week intervention, the improvements in systolic blood pressure (P=0·046) and time in range (P=0·033) were more pronounced in the LI+MR group than in the LI group. Furthermore, LI+MR caused significantly greater improvements in all GV metrics including SDBG (P=0·005), CV (P=0·002), MAGE (P=0·016) and AUCpp (P<0·001) than did LI. LI+MR (v. LI) was independently associated with improvements in GV after adjustment of covariates (all P<0·05). Our study showed that LI+MR led to significantly greater improvements in GV compared with LI, suggesting that LI+MR could be an effective treatment to alleviate glucose excursions.
The Role of Extracellular Vesicles and PIBF in Embryo-Maternal Immune-Interactions

Pregnancy represents a unique immunological situation. Though paternal antigens expressed by the conceptus are recognized by the immune system of the mother, the immune response does not harm the fetus. Progesterone and a progesterone induced protein; PIBF are important players in re-adjusting the functioning of the maternal immune system during pregnancy. PIBF expressed by peripheral pregnancy lymphocytes, and other cell types, participates in the feto-maternal communication, partly, by mediating the immunological actions of progesterone. Several splice variants of PIBF were identified with different physiological activity. The full length 90 kD PIBF protein plays a role in cell cycle regulation, while shorter splice variants are secreted and act as cytokines. Aberrant production of PIBF isoforms lead to the loss of immune-regulatory functions, resulting in and pregnancy failure. By up regulating Th2 type cytokine production and by down-regulating NK activity, PIBF contributes to the altered attitude of the maternal immune system. Normal pregnancy is characterized by a Th2-dominant cytokine balance, which is partly due to the action of the smaller PIBF isoforms. These bind to a novel form of the IL-4 receptor, and induce increased production of IL-3, IL-4, and IL-10. The communication between the conceptus and the mother is established via extracellular vesicles (EVs). Pre-implantation embryos produce EVs both in vitro, and in vivo. PIBF transported by the EVs from the embryo to maternal lymphocytes induces increased IL-10 production by the latter, this way contributing to the Th2 dominant immune responses described during pregnancy.
Frequencies in Perception and Production Differentially Affect Child Speech.

Purpose Frequent sounds and frequent words are both acquired at an earlier age and are produced by children more accurately. Recent research suggests that frequency is not always a facilitative concept, however. Interactions between input frequency in perception and practice frequency in production may limit or inhibit growth. In this study, we consider how a range of input frequencies affect production accuracy and referent identification. Method Thirty-three typically developing 3- and 4-year-olds participated in a novel word-learning task. In the initial test block, participants heard nonwords 1, 3, 6, or 10 times-produced either by a single talker or by multiple talkers-and then produced them immediately. In a posttest, participants heard all nonwords just once and then produced them. Referent identification was probed in between the test and posttest. Results Production accuracy was most clearly facilitated by an input frequency of 3 during the test block. Input frequency interacted with production practice, and the facilitative effect of input frequency did not carry over to the posttest. Talker variability did not affect accuracy, regardless of input frequency. The referent identification results did not favor talker variability or a particular input frequency value, but participants were able to learn the words at better than chance levels. Conclusions The results confirm that the input can be facilitative, but input frequency and production practice interact in ways that limit input-based learning, and more input is not always better. Future research on this interaction may allow clinicians to optimize various types of frequency commonly used during therapy.
Profiling proliferative cells and their progeny in damaged murine hearts

Significance The adult mammalian heart does not functionally repair itself after injury. Therefore, identification of cardiac stem cell (CSC) populations is of great interest for regenerative intervention. However, the significance of such CSC populations remains heavily debated. Using single-cell mRNA sequencing and genetic lineage tracing, we interrogate the existence of CSCs with unbiased mouse models of proliferation. Cycling cardiomyocytes were only robustly observed in the early postnatal growth phase, while cycling cells in homoeostatic and damaged adult myocardium consisted mainly of various noncardiomyocyte cell types. Injury-activated cardiac fibroblasts that acquire a gene expression profile similar to that of neonatal cardiac fibroblasts signal—in an autocrine fashion—to prevent cardiac rupture. We find no evidence for the existence of a quiescent CSC population. The significance of cardiac stem cell (CSC) populations for cardiac regeneration remains disputed. Here, we apply the most direct definition of stem cell function (the ability to replace lost tissue through cell division) to interrogate the existence of CSCs. By single-cell mRNA sequencing and genetic lineage tracing using two Ki67 knockin mouse models, we map all proliferating cells and their progeny in homoeostatic and regenerating murine hearts. Cycling cardiomyocytes were only robustly observed in the early postnatal growth phase, while cycling cells in homoeostatic and damaged adult myocardium represented various noncardiomyocyte cell types. Proliferative postdamage fibroblasts expressing follistatin-like protein 1 (FSTL1) closely resemble neonatal cardiac fibroblasts and form the fibrotic scar. Genetic deletion of Fstl1 in cardiac fibroblasts results in postdamage cardiac rupture. We find no evidence for the existence of a quiescent CSC population, for transdifferentiation of other cell types toward cardiomyocytes, or for proliferation of significant numbers of cardiomyocytes in response to cardiac injury.