Miracle-dz/UniFAR-FTUs huggingface dataset:
Surrogate Markers of Neutrophil Extracellular Trap Formation are Associated with Ischemic Outcomes and Platelet Activation after Peripheral Angioplasty and Stenting

Neutrophil extracellular traps (NETs) are supposed to play a central role in atherothrombosis. We measured circulating citrullinated histone H3 (H3Cit) and cell-free DNA (cfDNA), which serve as surrogate markers of NET formation, in 79 patients with peripheral artery disease (PAD) following infrainguinal angioplasty with stent implantation. Analysis of cfDNA and H3Cit was performed using Quant-iT™ PicoGreen® dsDNA Assay Kit or an ELISA, respectively. Within two years of follow-up, the primary endpoint defined as nonfatal myocardial infarction, stroke or transient ischemic attack, cardiovascular death, and >80% target vessel restenosis occurred in 34 patients (43%). Both H3Cit (HR per 1-SD: 2.72; 95% CI: 1.2–6.3; p = 0.019) and cfDNA (HR per 1-SD: 2.15; 95% CI: 1.1–4.2; p = 0.028) were associated with the primary endpoint in a univariate Cox regression analysis. Multivariate linear regression analyses showed associations between cfDNA and platelet surface expression of P-selectin (p = 0.006) and activated glycoprotein IIb/IIIa (p < 0.001) in response to arachidonic acid (AA) after adjustment for age, sex, clinical risk factors, and inflammatory markers. H3Cit was also associated with P-selectin expression in response to thrombin-receptor activating peptide (p = 0.048) and AA (p = 0.032). Circulating H3Cit and cfDNA predict ischemic outcomes after peripheral angioplasty with stent implantation, and are associated with on-treatment platelet activation in stable PAD.
Adjuvant chemotherapy for locally advanced rectal cancer in elderly patients after neoadjuvant chemoradiotherapy and surgery

Abstract The treatment strategy for elderly patients with locally advanced rectal cancer (LARC) remains controversial. The aim of this study was to identify the significance of adjuvant chemotherapy (AC) for elderly patients with LARC after neoadjuvant chemoradiotherapy (nCRT) and surgical resection. Between February 2002 and December 2012, a total of 43 patients aged ≥70 years with LARC following nCRT and surgery were retrospectively reviewed. The median follow-up time was 51 months (range 15–161 months). All patients completed the programmed chemoradiotherapy, of which 20 patients (46.5%) received 5-fluorouracil-based AC, and other 23 patients (53.5%) received no adjuvant chemotherapy. The 5-year overall survival and disease-free survival rates for AC group and non-adjuvant chemotherapy (NAC) group were 74.7% vs 63.4% (P = .562) and 73.4% vs 66.3% (P = .445), respectively. More patients in AC group suffered from severe leucopenia than that in NAC group (60% vs 17.4%, P = .004). For elderly patients with LARC following nCRT and surgery, AC may not benefit for survival, but increase treatment related leucopenia.
Regulation of NMDA glutamate receptor functions by the GluN2 subunits

The N‐methyl‐D‐aspartate receptors (NMDARs) are ionotropic glutamate receptors that mediate the flux of calcium (Ca2+) into the post‐synaptic compartment. Ca2+ influx subsequently triggers the activation of various intracellular signalling cascades that underpin multiple forms of synaptic plasticity. Functional NMDARs are assembled as heterotetramers composed of two obligatory GluN1 subunits and two GluN2 or GluN3 subunits. Four different GluN2 subunits (GluN2A‐D) are present throughout the central nervous system; however, they are differentially expressed, both developmentally and spatially, in a cell‐ and synapse‐specific manner. Each GluN2 subunit confers NMDARs with distinct ion channel properties and intracellular trafficking pathways. Regulated membrane trafficking of NMDARs is a dynamic process that ultimately determines the number of NMDARs at synapses, and is controlled by subunit‐specific interactions with various intracellular regulatory proteins. Here we review recent progress made towards understanding the molecular mechanisms that regulate the trafficking of GluN2‐containing NMDARs, focusing on the roles of several key synaptic proteins that interact with NMDARs via their carboxyl termini.
Enhanced osteogenic differentiation of human mesenchymal stromal cells as response to periodical microstructured Ti6Al4V surfaces.

Titanium-based alloys, for example, Ti6Al4V, are frequently employed for load-bearing orthopedic and dental implants. Growth of new bone tissue and therefore osseointegration can be promoted by the implant's microtopography, which can lead to improved long-term stability of the implant. This study investigates the effect that an organized, periodical microstructure produced by an electron beam (EB) technique has on the viability, morphology, and osteogenic differentiation capacity of human mesenchymal stromal cells (hMSC) in vitro. The technique generates topographical features of 20 μm in height with varying distances of 80-240 μm. Applied alterations of the surface roughness and local alloy composition do not impair hMSC viability (>94%) or proliferation. A favorable growth of hMSC onto the structure peaks and well-defined focal adhesions of the analyzed cells to the electron beam microstructured surfaces is verified. The morphological adaptation of hMSC to the underlying topography is detected using a three-dimensional (3D) visualization. In addition to the morphological changes, an increase in the expression of osteogenic markers such as osteocalcin (up to 17-fold) and osteoprotegerin (up to sixfold) is observed. Taken together, these results imply that the proposed periodical microstucturing method could potentially accelerate and enhance osseointegration of titanium-based bone implants.
Suppression of Notch Signaling Stimulates Progesterone Synthesis by Enhancing the Expression of NR5A2 and NR2F2 in Porcine Granulosa Cells

The conserved Notch pathway is reported to be involved in progesterone synthesis and secretion; however, the exact effects remain controversial. To determine the role and potential mechanisms of the Notch signaling pathway in progesterone biosynthesis in porcine granulosa cells (pGCs), we first used a pharmacological γ-secretase inhibitor, N-(N-(3,5-difluorophenacetyl-l-alanyl))-S-phenylglycine t-butyl ester (DAPT), to block the Notch pathway in cultured pGCs and then evaluated the expression of genes in the progesterone biosynthesis pathway and key transcription factors (TFs) regulating steroidogenesis. We found that DAPT dose- and time-dependently increased progesterone secretion. The expression of steroidogenic proteins NPC1 and StAR and two TFs, NR5A2 and NR2F2, was significantly upregulated, while the expression of HSD3B was significantly downregulated. Furthermore, knockdown of both NR5A2 and NR2F2 with specific siRNAs blocked the upregulatory effects of DAPT on progesterone secretion and reversed the effects of DAPT on the expression of NPC1, StAR, and HSD3B. Moreover, knockdown of NR5A2 and NR2F2 stimulated the expression of Notch3. In conclusion, the inhibition of Notch signaling stimulated progesterone secretion by enhancing the expression of NPC1 and StAR, and the two TFs NR5A2 and NR2F2 acted as downstream TFs of Notch signaling in regulating progesterone synthesis.
miRNAs as Biomarkers in Disease: Latest Findings Regarding Their Role in Diagnosis and Prognosis

MicroRNAs (miRNAs) represent a class of small, non-coding RNAs with the main roles of regulating mRNA through its degradation and adjusting protein levels. In recent years, extraordinary progress has been made in terms of identifying the origin and exact functions of miRNA, focusing on their potential use in both the research and the clinical field. This review aims at improving the current understanding of these molecules and their applicability in the medical field. A thorough analysis of the literature consulting resources available in online databases such as NCBI, PubMed, Medline, ScienceDirect, and UpToDate was performed. There is promising evidence that in spite of the lack of standardized protocols regarding the use of miRNAs in current clinical practice, they constitute a reliable tool for future use. These molecules meet most of the required criteria for being an ideal biomarker, such as accessibility, high specificity, and sensitivity. Despite present limitations, miRNAs as biomarkers for various conditions remain an impressive research field. As current techniques evolve, we anticipate that miRNAs will become a routine approach in the development of personalized patient profiles, thus permitting more specific therapeutic interventions.
Helical nanobots as mechanical probes of intra- and extracellular environments

A rheological probe that can measure mechanical properties of biological milieu at well-defined locations with high spatial resolution, on a time scale faster than most biological processes, can further improve our understanding of how living systems operate and behave. Here, we demonstrate nanorobots actively driven in realistic ex vivo biological systems for fast mechanical measurements with high spatial accuracy. In the various demonstrations of magnetic nanobots as mechanical probes, we report the first direct observation of the internalization of probes by a living cell, the accurate measurement of the ‘fluid phase’ cytoplasmic viscosity of ~200 cP for a HeLa cell, demonstration of intracellular measurements in cells derived from human patients; all of which establish the strength of this novel technique for measurements in both intra- and extracellular environments.
Regulatory T-cell therapy in Crohn’s disease: challenges and advances

The prevalence of IBD is rising in the Western world. Despite an increasing repertoire of therapeutic targets, a significant proportion of patients suffer chronic morbidity. Studies in mice and humans have highlighted the critical role of regulatory T cells in immune homeostasis, with defects in number and suppressive function of regulatory T cells seen in patients with Crohn’s disease. We review the function of regulatory T cells and the pathways by which they exert immune tolerance in the intestinal mucosa. We explore the principles and challenges of manufacturing a cell therapy, and discuss clinical trial evidence to date for their safety and efficacy in human disease, with particular focus on the development of a regulatory T-cell therapy for Crohn’s disease.
Autoimmune Complications in Chronic Lymphocytic Leukemia in the Era of Targeted Drugs

Autoimmune phenomena are frequently observed in patients with chronic lymphocytic leukemia (CLL) and are mainly attributable to underlying dysfunctions of the immune system. Autoimmune cytopenias (AIC) affect 4–7% of patients with CLL and mainly consist of autoimmune hemolytic anemia and immune thrombocytopenia. Although less common, non-hematological autoimmune manifestations have also been reported. Treatment of CLL associated AIC should be primarily directed against the autoimmune phenomenon, and CLL specific therapy should be reserved to refractory cases or patients with additional signs of disease progression. New targeted drugs (ibrutinib, idelalisib and venetoclax) recently entered the therapeutic armamentarium of CLL, showing excellent results in terms of efficacy and became an alternative option to standard chemo-immunotherapy for the management of CLL associated AIC. However, the possible role of these drugs in inducing or exacerbating autoimmune phenomena still needs to be elucidated. In this article, we review currently available data concerning autoimmune phenomena in patients with CLL, particularly focusing on patients treated with ibrutinib, idelalisib, or venetoclax, and we discuss the possible role of these agents in the management of AIC.
Visuoauditory Associative Memory Established with Cholecystokinin Under Anesthesia Is Retrieved in Behavioral Contexts

Plastic change in neuronal connectivity is the foundation of memory encoding. It is not clear whether the changes during anesthesia can alter subsequent behavior. Here, we demonstrated that in male rodents under anesthesia, a visual stimulus (VS) was associated with electrical stimulation of the auditory cortex or natural auditory stimulus in the presence of cholecystokinin (CCK), which guided the animals' behavior in a two-choice auditory task. Auditory neurons became responsive to the VS after the pairings. Moreover, high-frequency stimulation of axon terminals of entorhinal CCK neurons in the auditory cortex enabled LTP of the visual response in the auditory cortex. Such pairing during anesthesia also generated VS-induced freezing in an auditory fear conditioning task. Finally, we verified that direct inputs from the entorhinal CCK neurons and the visual cortex enabled the above neural plasticity in the auditory cortex. Our findings suggest that CCK-enabled visuoauditory association during anesthesia can be translated to the subsequent behavior action. SIGNIFICANCE STATEMENT Our study provides strong evidence for the hypothesis that cholecystokinin plays an essential role in the formation of cross-modal associative memory. Moreover, we demonstrated that an entorhinal–neocortical circuit underlies such neural plasticity, which will be helpful to understand the mechanisms of memory formation and retrieval in the brain.
A novel visual ranking system based on arterial spin labeling perfusion imaging for evaluating perfusion disturbance in patients with ischemic stroke

We developed a visual ranking system by combining the parenchymal perfusion deficits (PPD) and hyperintense vessel signals (HVS) on arterial spin labeling (ASL) imaging. This study aimed to assess the performance of this ranking system by correlating with subtypes classified based on dynamic susceptibility contrast (DSC) imaging for evaluating the perfusion disturbance observed in patients with ischemic stroke. 32 patients with acute or subacute infarcts detected by DSC imaging were reviewed. Each patient’s brain was divided into 12 areas. ASL ranks were defined by the presence (+) or absence (-) of PPD/HVS as follows; I:–/–, II:–/+, III: +/+, and IV: +/–. DSC imaging findings were categorized based on cerebral blood flow (CBF) and time to peak (TTP) as normal (normal CBF/TTP), mismatched (normal CBF/delayed TTP), and matched (decreased CBF/delayed TTP). Two reviewers rated perfusion abnormalities in the total of 384 areas. The four ASL ranks correlated well with the DSC subtypes (Spearman’s r = 0.82). The performance of ASL ranking system was excellent as indicated by the area under the curve value of 0.94 using either matched or mismatched DSC subtype as the gold standard and 0.97 using only the matched DSC subtype as the gold standard. The two methods were in good-to-excellent agreement (maximum κ-values, 0.86). Inter-observer agreement was excellent (κ-value, 0.98). Although the number of patients was small and the number of dropouts was high, our proposed, ASL-based visual ranking system represented by PPD and HVS provides good, graded estimates of perfusion disturbance that agree well with those obtained by DSC perfusion imaging.
Modification of the Expression of the Aquaporin ZmPIP2;5 Affects Water Relations and Plant Growth1[OPEN]

The maize plasma membrane PIP2;5 aquaporin plays a role in controlling root radial water movement, leaf hydraulic conductivity, and plant growth. The plasma membrane intrinsic protein PIP2;5 is the most highly expressed aquaporin in maize (Zea mays) roots. Here, we investigated how deregulation of PIP2;5 expression affects water relations and growth using maize overexpression (OE; B104 inbred) or knockout (KO; W22 inbred) lines. The hydraulic conductivity of the cortex cells of roots grown hydroponically was higher in PIP2;5 OE and lower in pip2;5 KO lines compared with the corresponding wild-type plants. While whole-root conductivity decreased in the KO lines compared to the wild type, no difference was observed in OE plants. This paradox was interpreted using the MECHA hydraulic model, which computes the radial flow of water within root sections. The model hints that the plasma membrane permeability of the cells is not radially uniform but that PIP2;5 may be saturated in cell layers with apoplastic barriers, i.e. the endodermis and exodermis, suggesting the presence of posttranslational mechanisms controlling the abundance of PIP in the plasma membrane in these cells. At the leaf level, where the PIP2;5 gene is weakly expressed in wild-type plants, the hydraulic conductance was higher in the PIP2;5 OE lines compared with the wild-type plants, whereas no difference was observed in the pip2;5 KO lines. The temporal trend of leaf elongation rate, used as a proxy for that of xylem water potential, was faster in PIP2;5 OE plants upon mild stress, but not in well-watered conditions, demonstrating that PIP2;5 may play a beneficial role in plant growth under specific conditions.
Love at First Taste: Induction of Larval Settlement by Marine Microbes

Marine biofilms are composed of many species of bacteria, unicellular algae, and protozoa. Biofilms can induce, inhibit, or have no effect on settlement of larvae and spores of algae. In this review, we focus on induction of larval settlement by marine bacteria and unicellular eukaryotes and review publications from 2010 to September 2019. This review provides insights from meta-analysis on what is known about the effect of marine biofilms on larval settlement. Of great interest is the impact of different components of marine biofilms, such as bacteria and diatoms, extracellular polymeric substances, quorum sensing signals, unique inductive compounds, exoenzymes, and structural protein degradation products on larval settlement and metamorphosis. Molecular aspects of larval settlement and impact of climate change are reviewed and, finally, potential areas of future investigations are provided.
Preoperative platelet-lymphocyte ratio is a superior prognostic biomarker to other systemic inflammatory response markers in non-small cell lung cancer

Abstract Systemic inflammatory response markers are associated with poor survival in many types of malignances. This study aimed to evaluate the prognostic value of preoperative neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR), lymphocyte-monocyte ratio (LMR), and C-reactive protein (CRP) in patients with non-small cell lung cancer (NSCLC). We retrospectively evaluated 254 NSCLC patients who underwent radical surgery between January 2012 and April 2014 in the Sichuan Provincial Cancer Hospital. The cut-off values of NLR, PLR, LMR, and CRP were determined according to the receiver operating characteristic curve, and the correlation of NLR, PLR, LMR, and CRP with prognosis was analyzed based on the cut-off value. The cut-off value for NLR, PLR, LMR, and CRP were 3.18, 122, 4.04, and 8.8, respectively. Univariate analysis showed that age (P = .022), tumor-node-metastasis (TNM) stage (P < .001), T stage (P = .001), and N stage (P < .001) were significantly correlated with disease-free survival (DFS), while age (P = .011), TNM stage (P < .001), T stage (P = .008), N stage (P < .001), and PLR (P = .001) were significantly correlated with overall survival (OS). In multivariate analysis, age (hazard ratio [HR]: 1.564, 95% confidence interval [CI]: 1.087–2.252, P = .016) and TNM stage (HR: 1.704, 95% CI: 1.061–2.735, P = .027) remained independent risk factors affecting DFS, while age (HR: 1.721, 95% CI: 1.153–2.567, P = .008), TNM stage (HR: 2.198, 95% CI: 1.263–3.824, P = .005), and PLR (HR: 1.850, 95% CI: 1.246–2.746, P = .002) were independent risk factors affecting OS. The preoperative PLR is superior to NLR, LMR, and CRP as a biomarker for evaluating the prognosis of patients undergoing curative surgery for NSCLC.
Predictors of the need for laminectomy after indirect decompression via initial anterior or lateral lumbar interbody fusion.

OBJECTIVE The goal of this study was to evaluate factors that are associated with the need for additional posterior direct decompressive surgery after anterior lumbar interbody fusion (ALIF) or lateral lumbar interbody fusion (LLIF). METHODS Eighty-six adult patients who underwent ALIF or LLIF for degenerative spondylolisthesis and foraminal stenosis were enrolled. Patient factors (age, sex, number of surgery levels, and visual analog scale [VAS] score for leg and back pain); procedure-related factors (cage height and lordosis); and radiographic measurements (disc height [DH]; foraminal height [FH], foraminal area [FA], central canal diameter [CCD], and facet joint degeneration [FD]) were analyzed. All patients underwent staged surgery on 2 different days, with the anterior portion first, followed by the posterior portion. RESULTS Of 86 patients, 62 underwent posterior decompression and 24 had no posterior decompression. There were no significant differences between groups with regard to age, sex, preoperative VAS score for back pain, cage height, cage angulation, preoperative DH, FH, FA, CCD, and FD (p > 0.05). The group that underwent posterior decompression showed statistically different numbers of treated segments (1.92 vs 1.21, p < 0.01), preoperative VAS leg score (7.9 vs 6.3), symptom duration (14.2 months vs 9.4 months), postoperative DH improvement (61.3% vs 96.2%), postoperative FH improvement (21.5% vs 32.1%), postoperative FA improvement (24.1% vs 36.9%), and cage height minus preoperative DH (5.3 mm vs 7.5 mm) compared with the nondecompression group. CONCLUSIONS There appears to be some correlation between the need for posterior decompression and the number of treated segments, VAS leg scores, symptom duration, FH, FA, and difference between the cage height and preoperative DH. In selected patients undergoing staged surgery, indirect decompression without direct decompression may be a reasonable option in treating degenerative spinal conditions.