Miracle-dz/UniFAR-FTUs huggingface dataset:
Lysyl hydroxylase 1 (LH1) deficiency promotes angiotensin II (Ang II)-induced dissecting abdominal aortic aneurysm

Rationale: The progressive disruption of extracellular matrix (ECM) proteins, particularly early elastin fragmentation followed by abnormalities in collagen fibril organization, are key pathological processes that contribute to dissecting abdominal aortic aneurysm (AAA) pathogenesis. Lysyl hydroxylase 1 (LH1) is essential for type I/III collagen intermolecular crosslinking and stabilization. However, its function in dissecting AAA has not been explored. Here, we investigated whether LH1 is significantly implicated in dissecting AAA progression and therapeutic intervention. Methods and Results: Sixteen-week-old male LH1-deficient and wild-type (WT) mice on the C57Bl/6NCrl background were infused with angiotensin II (Ang II, 1000 ng/kg per minute) via subcutaneously implanted osmotic pumps for 4 weeks. Ang II increased LH1 levels in the abdominal aortas of WT mice, whereas mice lacking LH1 developed dissecting AAA. To evaluate the related mechanism, we performed whole-transcriptomic analysis, which demonstrated that LH1 deficiency aggravated gene transcription alterations; in particular, the expression of thrombospondin-1 was markedly upregulated in the aortas of LH1-deficient mice. Furthermore, targeting thrombospondin-1 with TAX2 strongly inhibited the proinflammatory process, matrix metalloproteinase (MMP) activity and vascular smooth muscle cells (VSMCs) apoptosis, ultimately decreasing the incidence of dissecting AAA. Restoration of LH1 protein expression in LH1-deficient mice by intraperitoneal injection of an adeno-associated virus normalized thrombospondin-1 levels, subsequently alleviating dissecting AAA formation and preserving aortic structure and function. Consistently, in human AAA specimens, decreased LH1 expression was associated with increased thrombospondin-1 levels. Conclusions: LH1 deficiency contributes to dissecting AAA pathogenesis, at least in part, by upregulating thrombospondin-1 expression, which subsequently enables proinflammatory processes, MMP activation and VSMCs apoptosis. Our study provides evidence that LH1 is a potential critical therapeutic target for AAA.
Robotic Surgery for Non-Small Cell Lung Cancer Treatment in High-Risk Patients

Robotic-assisted pulmonary resection has greatly increased over the last few years, yet data on the application of robotic surgery in high-risk patients are still lacking. The objective of this study is to evaluate the perioperative outcomes in ASA III-IV patients who underwent robotic-assisted lung resection for NSCLC. Between January 2010 and December 2017, we retrospectively collected the data of 148 high-risk patients who underwent lung resection for NSCLC via a robotic approach at our institution. For this study, the prediction of operative risk was based on the ASA-PS score, considering patients in ASA III and IV classes as high-risk patients: of the 148 high-risk patients identified, 146 patients were classified as ASA III (44.8%) and two as ASA IV (0.2%). Possible prognostic factors were also analysed. The average hospital stay was 6 days (8–30). Post-operative complications were observed in 87 (58.8%) patients. Patients with moderate/severe COPD developed in 33 (80.5%) cases post-operative complications, while elderly patients in 25 (55%) cases, with a greater incidence of high-grade complications. No difference was observed when comparing the data of obese and non-obese patients. Robotic surgery appears to be associated with satisfying post-operative results in ASA III-IV patients. Both marginal respiratory function and advanced age represent negative prognostic factors. Due to its safety and efficacy, robotic surgery can be considered the treatment of choice in high-risk patients.
Bimodal activity of diurnal flower visitation at high elevation

Abstract Successful pollination in animal‐pollinated plants depends on the temporal overlap between flower presentation and pollinator foraging activity. Variation in the temporal dimension of plant–pollinator networks has been investigated intensely across flowering seasons. However, over the course of a day, the dynamics of plant–pollinator interactions may vary strongly due environmental fluctuations. It is usually assumed there is a unimodal, diurnal, activity pattern, while alternative multimodal types of activity patterns are often neglected and deserve greater investigation. Here, we quantified the daily activity pattern of flower visitors in two different habitats contrasting high elevation meadows versus forests in Southwest China to investigate the role of abiotic conditions in the temporal dynamics of plant–pollinator interactions. We examined diurnal activity patterns for the entire pollinator community. Pollinator groups may differ in their ability to adapt to habitats and abiotic conditions, which might be displayed in their patterns of activity. We hypothesized that (a) pollinator communities show multimodal activity patterns, (b) patterns differ between pollinator groups and habitat types, and (c) abiotic conditions explain observed activity patterns. In total, we collected 4,988 flower visitors belonging to six functional groups. There was a bimodal activity pattern when looking at the entire pollinator community and in five out of six flower visitor groups (exempting solitary bees) regardless of habitat types. Bumblebees, honeybees, dipterans, lepidopterans, and other insects showed activity peaks in the morning and afternoon, whereas solitary bees were most active at midday. Activity of all six pollinator groups increased as solar radiation increased and then decreased after reaching a certain threshold. Our findings suggest that in habitats at higher elevations, a bimodal activity pattern of flower visitation is commonly employed across most pollinator groups that are diurnal foragers. This pattern may be caused by insects avoiding overheating due to elevated temperatures when exposed to high solar radiation at midday.
MICAL2 Contributes to Gastric Cancer Cell Proliferation by Promoting YAP Dephosphorylation and Nuclear Translocation

Dynamic cytoskeletal rearrangements underlie the changes that occur during cell division in proliferating cells. MICAL2 has been reported to possess reactive oxygen species- (ROS-) generating properties and act as an important regulator of cytoskeletal dynamics. However, whether it plays a role in gastric cancer cell proliferation is not known. In the present study, we found that MICAL2 was highly expressed in gastric cancer tissues, and this high expression level was associated with carcinogenesis and poor overall survival in gastric cancer patients. The knockdown of MICAL2 led to cell cycle arrest in the S phase and attenuated cell proliferation. Concomitant with S-phase arrest, a decrease in CDK6 and cyclin D protein levels was observed. Furthermore, MICAL2 knockdown attenuated intracellular ROS generation, while MICAL2 overexpression led to a decrease in the p-YAP/YAP ratio and promoted YAP nuclear localization and cell proliferation, effects that were reversed by pretreatment with the ROS scavenger N-acetyl-L-cysteine (NAC) and SOD-mimetic drug tempol. We further found that MICAL2 induced Cdc42 activation, and activated Cdc42 mediated the effect of MICAL2 on YAP dephosphorylation and nuclear translocation. Collectively, our results showed that MICAL2 has a promotive effect on gastric cancer cell proliferation through ROS generation and Cdc42 activation, both of which independently contribute to YAP dephosphorylation and its nuclear translocation.
Monitoring of Enoxaparin during Hemodialysis Covered by Regional Citrate Anticoagulation in Acute Kidney Injury: A Prospective Cohort Study

Background: Current guidelines recommend the monitoring of anti-factor Xa (anti-Xa) levels to avoid an accumulation of low-molecular-weight heparins in patients with acute kidney injury, but there is no evidence on how to proceed with such monitoring during continuous renal replacement therapy. Against this background, we investigated the potential accumulation of enoxaparin administered subcutaneously for venous thromboembolism prophylaxis in critically ill patients during continuous renal replacement therapy covered by regional citrate anticoagulation. Methods: Anti-Xa levels were measured at baseline (≤12 h before renal replacement therapy) and on three consecutive days (A to C) when enoxaparin had reached trough levels. Supplementary testing included modified assays of rotational thromboelastometry known to be highly sensitive for low-molecular-weight heparins. Results: The 16 men and 13 women included were adults comparable in age, body mass index, thromboembolism risk assessment, and clinical severity of the disease. Throughout the four examinations, the median trough levels of anti-Xa remained below the detection limit of the test (<0.1 IU mL−1), with interquartile ranges of <0.1 to 0.14 IU mL−1 at baseline and <0.1 to 0.16 IU mL−1 on days A/B/C. All rotational thromboelastometry parameters of clot initiation and clot formation dynamics did not significantly change from baseline to day C. Conclusions: Neither anti-Xa levels nor modified assays of rotational thromboelastometry revealed any accumulation of enoxaparin administered for thromboprophylaxis during continuous renal replacement therapy covered by regional citrate anticoagulation. Although generally recommended in patients with acute kidney injury, monitoring of anti-Xa levels should be questioned in this defined setting.
Evidence-Based Practices and Use among Employees and Students at an Austrian Medical University

Developed in the pre-internet era in the early 1980s, empirical medical practice, i.e., evidence-based practice (EBP) has become crucial in critical thinking and statistical reasoning at the point-of-care. As little evidence is available so far on how EBP is perceived in the Austrian academic context, we conducted a cross-sectional online survey among a nonrandom purposive sample of employees and students at the Medical University Vienna, Austria (total n = 1247, 59.8% females). The German questionnaire assessed both EBP capability beliefs and EBP use, with the respective indices both yielding good internal consistency. We conducted subgroup comparisons between employees (n = 638) and students (n = 609). In line with Bandura’s self-efficacy theory, we found a correlation between EBP capability beliefs and EBP use, with higher scores reported in the employee group. The results indicated that the participants did not strictly follow the sequential EBP steps as grounded in the item-response theory. Since its emergence, EBP has struggled to overcome the dominating traditional way of conducting medicine, which is also known as eminence-based medicine, where ad hoc decisions are based upon expert opinions, and nowadays frequently supplemented by quick online searches. Medical staff and supervisors of medical students should be aware of the existing overlaps and synergies of these potentially equivalent factors in clinical care. There is a need for intensifying the public and scientific debate on how to deal with the divergence between EBP theory and EBP practice.
Post-Embryonic Lateral Organ Development and Adaxial—Abaxial Polarity Are Regulated by the Combined Effect of ENHANCER OF SHOOT REGENERATION 1 and WUSCHEL in Arabidopsis Shoots

The development of above-ground lateral organs is initiated at the peripheral zone of the shoot apical meristem (SAM). The coordination of cell fate determination and the maintenance of stem cells are achieved through a complex regulatory network comprised of transcription factors. Two AP2/ERF transcription factor family genes, ESR1/DRN and ESR2/DRNL/SOB/BOL, regulate cotyledon and flower formation and de novo organogenesis in tissue culture. However, their roles in post-embryonic lateral organ development remain elusive. In this study, we analyzed the genetic interactions among SAM-related genes, WUS and STM, two ESR genes, and one of the HD-ZIP III members, REV, whose protein product interacts with ESR1 in planta. We found that esr1 mutations substantially enhanced the wus and stm phenotypes, which bear a striking resemblance to those of the wus rev and stm rev double mutants, respectively. Aberrant adaxial–abaxial polarity is observed in wus esr1 at relatively low penetrance. On the contrary, the esr2 mutation partially suppressed stm phenotypes in the later vegetative phase. Such complex genetic interactions appear to be attributed to the distinct expression pattern of two ESR genes because the ESR1 promoter-driving ESR2 is capable of rescuing phenotypes caused by the esr1 mutation. Our results pose the unique genetic relevance of ESR1 and the SAM-related gene interactions in the development of rosette leaves.
Structural Analysis of Low Defect Ammonothermally Grown GaN Wafers by Borrmann Effect X-ray Topography

X-ray topography defect analysis of entire 1.8-inch GaN substrates, using the Borrmann effect, is presented in this paper. The GaN wafers were grown by the ammonothermal method. Borrmann effect topography of anomalous transmission could be applied due to the low defect density of the substrates. It was possible to trace the process and growth history of the GaN crystals in detail from their defect pattern imaged. Microscopic defects such as threading dislocations, but also macroscopic defects, for example dislocation clusters due to preparation insufficiency, traces of facet formation, growth bands, dislocation walls and dislocation bundles, were detected. Influences of seed crystal preparation and process parameters of crystal growth on the formation of the defects are discussed.
Using Breast Cancer Gene Expression Signatures in Clinical Practice: Unsolved Issues, Ongoing Trials and Future Perspectives

Simple Summary Gene expression signatures were initially developed to take into account tumor biology for adjuvant chemotherapy decision and have become a standard option in hormone receptors-positive/HER2-negative early breast cancer. While recent randomized phase III studies have provided high level evidence to support their use, much more remains to be explored. This prospective review highlights the unsolved issues regarding targeted populations, delineates the best clinical indications and addresses questions that ongoing and future trials will have to meet. Apart from adjuvant chemotherapy indications, we review their potential interest to tailor neoadjuvant systemic treatments, adjuvant radiation therapy, extended adjuvant hormone therapy and CDK4/6 inhibitor adjuvant treatment. Abstract The development of gene expression signatures since the early 2000′s has offered standardized assays to evaluate the prognosis of early breast cancer. Five signatures are currently commercially available and recommended by several international guidelines to individualize adjuvant chemotherapy decisions in hormone receptors-positive/HER2-negative early breast cancer. However, many questions remain unanswered about their predictive ability, reproducibility and external validity in specific populations. They also represent a new hope to tailor (neo)adjuvant systemic treatment, adjuvant radiation therapy, hormone therapy duration and to identify a subset of patients who might benefit from CDK4/6 inhibitor adjuvant treatment. This review will highlight these particular issues, address the remaining questions and discuss the ongoing and future trials.
A Review of the Molecular Mechanisms Underlying Cardiac Fibrosis and Atrial Fibrillation

The cellular and molecular mechanism involved in the pathogenesis of atrial fibrosis are highly complex. We have reviewed the literature that covers the effectors, signal transduction and physiopathogenesis concerning extracellular matrix (ECM) dysregulation and atrial fibrosis in atrial fibrillation (AF). At the molecular level: angiotensin II, transforming growth factor-β1, inflammation, and oxidative stress are particularly important for ECM dysregulation and atrial fibrotic remodelling in AF. We conclude that the Ang-II-MAPK and TGF-β1-Smad signalling pathways play a major, central role in regulating atrial fibrotic remodelling in AF. The above signalling pathways induce the expression of genes encoding profibrotic molecules (MMP, CTGF, TGF-β1). An important mechanism is also the generation of reactive oxygen species. This pathway induced by the interaction of Ang II with the AT2R receptor and the activation of NADPH oxidase. Additionally, the interplay between cardiac MMPs and their endogenous tissue inhibitors of MMPs, is thought to be critical in atrial ECM metabolism and fibrosis. We also review recent evidence about the role of changes in the miRNAs expression in AF pathophysiology and their potential as therapeutic targets. Furthermore, keeping the balance between miRNA molecules exerting anti-/profibrotic effects is of key importance for the control of atrial fibrosis in AF.
Inositols: From Established Knowledge to Novel Approaches

Myo-inositol (myo-Ins) and D-chiro-inositol (D-chiro-Ins) are natural compounds involved in many biological pathways. Since the discovery of their involvement in endocrine signal transduction, myo-Ins and D-chiro-Ins supplementation has contributed to clinical approaches in ameliorating many gynecological and endocrinological diseases. Currently both myo-Ins and D-chiro-Ins are well-tolerated, effective alternative candidates to the classical insulin sensitizers, and are useful treatments in preventing and treating metabolic and reproductive disorders such as polycystic ovary syndrome (PCOS), gestational diabetes mellitus (GDM), and male fertility disturbances, like sperm abnormalities. Moreover, besides metabolic activity, myo-Ins and D-chiro-Ins deeply influence steroidogenesis, regulating the pools of androgens and estrogens, likely in opposite ways. Given the complexity of inositol-related mechanisms of action, many of their beneficial effects are still under scrutiny. Therefore, continuing research aims to discover new emerging roles and mechanisms that can allow clinicians to tailor inositol therapy and to use it in other medical areas, hitherto unexplored. The present paper outlines the established evidence on inositols and updates on recent research, namely concerning D-chiro-Ins involvement into steroidogenesis. In particular, D-chiro-Ins mediates insulin-induced testosterone biosynthesis from ovarian thecal cells and directly affects synthesis of estrogens by modulating the expression of the aromatase enzyme. Ovaries, as well as other organs and tissues, are characterized by a specific ratio of myo-Ins to D-chiro-Ins, which ensures their healthy state and proper functionality. Altered inositol ratios may account for pathological conditions, causing an imbalance in sex hormones. Such situations usually occur in association with medical conditions, such as PCOS, or as a consequence of some pharmacological treatments. Based on the physiological role of inositols and the pathological implications of altered myo-Ins to D-chiro-Ins ratios, inositol therapy may be designed with two different aims: (1) restoring the inositol physiological ratio; (2) altering the ratio in a controlled way to achieve specific effects.
Study on the Influence of Proprioceptive Control versus Visual Control on Reaction Speed, Hand Coordination, and Lower Limb Balance in Young Students 14–15 Years Old

Currently, sports activities require a high reaction speed, coordination, and balance, highlighting the relationship between proprioceptive control, visual control, and hand–eye coordination in youth. The present research assessed the proprioceptive control, reaction speed, and lower limb balance of youth from five different schools to identify the level of physical preparation of children in this direction. This prospective study was conducted between 1 January 2020 and 29 February 2020. A total of 107 healthy children (33 females and 74 males) with appropriate medical conditions, aged between 14 and 15 years, from five Romanian schools were included in the experiment. All children were assessed for visual control and reaction speed with the ruler drop test, and for lower limb balance, the standing stork test was used. Statistical analysis included descriptive statistics, data series distribution, and comparison of means and medians using specific statistical programs. Comparison of medians highlighted significant statistical differences in the standing stork test with eyes closed and the dominant leg compared with the nondominant leg (p = 0.0057). Males were compared to females at the nondominant leg (p = 0.0179); closed eyes were compared with opened eyes for the nondominant leg (p = 0.0175 and 0.0006) for the ruler drop test comparing the dominant hand with the nondominant hand (p = 0.0212). Children who engage in sports activities better integrated sensory information in motor action execution based on reaction speed and coordination with the nondominant hand.
Repetition without Repetition or Differential Learning of Multiple Techniques in Volleyball?

A variety of approaches have been proposed for teaching several volleyball techniques to beginners, ranging from general ball familiarization to model-oriented repetition to highly variable learning. This study compared the effects of acquiring three volleyball techniques in parallel with three approaches. Female secondary school students (N = 42; 15.6 ± 0.54 years) participated in a pretest for three different volleyball techniques (underhand pass, overhand pass, and overhead serve) with an emphasis on accuracy. Based on their results, they were parallelized into three practice protocols, a repetitive learning group (RG), a differential learning group (DG), and a control group (CG). After a period of six weeks with 12 intervention sessions, all participants attended a posttest. An additional retention test after two weeks revealed a statistically significant difference between DG, RG, and CG for all single techniques as well as the combined multiple technique. In each technique—the overhand pass, the underhand pass, the overhand service, and the combination of the three techniques—DG performed best (each p < 0.001).
Lights, Camera, Interaction: Studying Protein–Protein Interactions of the ER Protein Translocase in Living Cells

Various landmark studies have revealed structures and functions of the Sec61/SecY complex in all domains of live demonstrating the conserved nature of this ancestral protein translocase. While the bacterial homolog of the Sec61 complex resides in the plasma membrane, the eukaryotic counterpart manages the transfer of precursor proteins into or across the membrane of the endoplasmic reticulum (ER). Sec61 complexes are accompanied by a set of dynamically recruited auxiliary proteins assisting the transport of certain precursor polypeptides. TRAP and Sec62/Sec63 are two auxiliary protein complexes in mammalian cells that have been characterized by structural and biochemical methods. Using these ER membrane protein complexes for our proof-of-concept study, we aimed to detect interactions of membrane proteins in living mammalian cells under physiological conditions. Bimolecular luminescence complementation and competition was used to demonstrate multiple protein–protein interactions of different topological layouts. In addition to the interaction of the soluble catalytic and regulatory subunits of the cytosolic protein kinase A, we detected interactions of ER membrane proteins that either belong to the same multimeric protein complex (intra-complex interactions: Sec61α–Sec61β, TRAPα–TRAPβ) or protein complexes in juxtaposition (inter-complex interactions: Sec61α–TRAPα, Sec61α–Sec63, and Sec61β–Sec63). In the process, we established further control elements like synthetic peptide complementation for expression profiling of fusion constructs and protease-mediated reporter degradation demonstrating the cytosolic localization of a reporter complementation. Ease of use and flexibility of the approach presented here will spur further research regarding the dynamics of protein–protein interactions in response to changing cellular conditions in living cells.