Miracle-dz/UniFAR-FTUs huggingface dataset:
Inhibition of focal adhesion turnover prevents osteoblastic differentiation through β‐catenin mediated transduction of pro‐osteogenic substrate

Abstract The mechanism by which substrate surface characteristics are transduced by osteoblastic cells and their progenitors is not fully known. Data from previous studies by our group suggest the involvement of β‐catenin in the mechanism by which substrate surface characteristics are transduced. This focal adhesion and β‐catenin mediated mechanism functions through the liberation of β‐catenin from focal adhesion complexes in response to pro‐osteogenic substrate (POS) characteristics. After liberation, β‐catenin translocates and facilitates upregulation of genes associated with osteogenesis. It is not known whether the observed correlation between focal adhesion turnover and β‐catenin translocation directly results from focal adhesion turnover. In this study we inhibited focal adhesion turnover using a focal adhesion kinase inhibitor PF‐573228. We found that inhibition of focal adhesion turnover resulted in an abrogation of the more rapid translocation and increased transcriptional activity of β‐catenin induced by POS. In addition, inhibition of focal adhesion turnover mitigated the increase in osteoblastic differentiation induced by a POS as measured by alkaline phosphatase enzymatic activity and osteogenic gene and protein expression. Together, these data, coupled with previous findings, suggest that the observed β‐catenin translocation is a result of focal adhesion turnover, providing evidence for a focal adhesion initiated, β‐catenin mediated mechanism of substrate surface signal transduction.
Delivery of antisense oligonucleotides for splice‐correction of androgen receptor pre‐mRNA in castration‐resistant prostate cancer models using cell‐penetrating peptides

Cell‐penetrating peptides (CPPs) are a promising approach for delivering antisense oligonucleotides (AONs) as they form nanosized complexes through noncovalent interactions that show efficient cellular uptake. Previously, we have designed an AON system to correct splicing of the androgen receptor (AR) pre‐mRNA, thereby preventing the generation of the splice variant AR‐V7 mRNA. AON‐mediated knockdown of AR‐V7 resulted in inhibition of androgen‐independent cell proliferation. In this study, we evaluated the CPP‐mediated delivery of this AON into castration‐resistant prostate cancer cell line models 22Rv1, DuCaP (dura mater cancer of the prostate), and VCaP (vertebral cancer of the prostate).
Elevated microsatellite instability at selected tetranucleotide (EMAST) repeats in gastric cancer: a distinct microsatellite instability type with potential clinical impact?

We investigated the clinical impact of elevated microsatellite instability at selected tetranucleotide (EMAST) repeats in the context of neoadjuvant chemotherapy (CTx) in gastric/gastro‐oesophageal adenocarcinomas. We analysed 583 resected tumours (272 without and 311 after CTx) and 142 tumour biopsies before CTx. If at least two or three of the five tetranucleotide repeat markers tested showed instability, the tumours were defined as EMAST (2+) or EMAST (3+), respectively. Expression of mismatch repair proteins including MSH3 was analysed using immunohistochemistry. Microsatellite instability (MSI) and Epstein–Barr virus (EBV) positivity were determined using standard assays. EMAST (2+) and (3+) were detected in 17.8 and 11.5% of the tumours, respectively. The frequency of EMAST (2+) or (3+) in MSI‐high (MSI‐H) tumours was 96.2 or 92.5%, respectively, demonstrating a high overlap with this molecular subtype, and the association of EMAST and MSI status was significant (each overall p < 0.001). EMAST (2+ or 3+) alone in MSI‐H and EBV‐negative tumours demonstrated only a statistically significant association of EMAST (2+) positivity and negative lymph node status (42.3% in EMAST (2+) and 28.8% in EMAST negative, p = 0.045). EMAST alone by neither definition was significantly associated with overall survival (OS) of the patients. The median OS for EMAST (2+) patients was 40.0 months (95% confidence interval [CI] 16.4–63.6) compared with 38.7 months (95% CI 26.3–51.1) for the EMAST‐negative group (p = 0.880). The median OS for EMAST (3+) patients was 46.7 months (95% CI 18.2–75.2) and 38.7 months (95% CI 26.2–51.2) for the negative group (p = 0.879). No statistically significant association with response to neoadjuvant CTx was observed (p = 0.992 and p = 0.433 for EMAST (2+) and (3+), respectively). In conclusion, our results demonstrate a nearly complete intersection between MSI‐H and EMAST and they indicate that EMAST alone is not a distinct instability type associated with noticeable clinico‐pathological characteristics of gastric carcinoma patients.
Palyno‐morphological diversity of Asteraceous and Poaceous allergenic plant using microscopic techniques in lesser Himalaya‐Pakistan

In classification and identification of plant species, palyno morphological character has remain helpful for plant taxonomist. The aim to investigation this study was to identify the characteristic features of Asteraceae and Poaceae family member collected from lower Himalayas of Pakistan. Light microscope and Scanning electron microscope were used for feature study of allergenic pollen. Our study includes 10 species of Asteraceae and Poaceae family. The most dominant shape of pollen was Oblate‐spheroidal, Prolate‐Spheroidal, Prolate and Suboblate shape of pollen. Quantitative character of pollen includes maximum pollen diameter found in Dichanthium annulatum (46.0 μm) and minimum polar axis pollen diameter found in Parthenium hysterophorous (16.0 μm). Similarly highest value of P/E ratio was noted in Cenchrus echinatus (1.05) and smallest value of P/E ratio was observed in Erigeron bonariensis (0.88). Poaceae family member were monoporate. Character feature of exine sculpturing include Microechinate, granulate, echinate, conical base, lacunae Nanogammate, Aerolate‐Scabratre, Verrucate, like variation found in exine of both family member. Highest value of pollen fertility was observed in P. hysterophorous 93%, Similarly maximum value of pollen sterility was noted in E. bonariensis and Brachiaria reptans 24%. This investigation provides the characteristic feature of allergenic pollen species and help to arrange them in define class.
The timing of gamma irradiation and its effect on cell‐free and microvesicle‐bound hemoglobin. The BEST collaborative study

Gamma irradiation of red cell concentrates (RCCs) is regularly used to prevent transfusion‐associated graft‐versus‐host disease (TA‐GvHD) in at‐risk patients. While studies have indicated that irradiated RCCs exhibit increased hemolysis, there have been no efforts to differentiate between free‐ and microvesicle (MV)‐bound hemoglobin (Hb). As an increase in the proportion of free‐Hb in irradiated RCCs could alter vascular function, we sought to characterize differences in the state of extracellular Hb based on the timing of irradiation.
Inhibitory Control, Conduct Problems, and Callous Unemotional Traits in Children with ADHD and Typically Developing Children

ABSTRACT Compared children with CP/ADHD, CPCU/ADHD, ADHD-only, and controls on two measures of inhibitory control: a Simon/flanker task that measured response selection and a stop signal task that measured response inhibition. Results showed: (a) ADHD was associated with both measures of inhibitory control; (b) control children had better overall performance and ADHD-only had worse response selection than the CP groups; and (c) children with CPCU/ADHD had better response inhibition than children with ADHD-only or CP/ADHD. Results suggest inhibitory control dysfunction is associated with ADHD rather than CP and that response inhibition dysfunction distinguishes children with CP/ADHD from children with CPCU/ADHD.
Cisplatin-induced alterations in the blood-nerve barrier: effects of combination of vitamin B1, B6 and B12.

Cisplatin is a chemotherapeutic agent against solid cancers. However, neuropathy is a major side effect and has no effective treatment so far. Emerging evidence suggests that cisplatin might damage nerve capillaries leading to impaired blood-nerve barrier (BNB). This study aimed to investigate the ultrastructural changes of the BNB in the sciatic nerves and dorsal root ganglia of rats with cisplatin neuropathy and the effects of B₁₋₆₋₁₂. The results showed that cisplatin 2 mg/kg injected intraperitoneally twice a week for 5 consecutive weeks caused thermal hypoalgesia and structural abnormalities of nerves and ganglia. Co-treatment with oral B₁₋₆₋₁₂ (100:100:1) 100, 300 and 600 mg/kg/day for 5 weeks reduced the sensory deficit and structural alterations. EM analysis demonstrated the higher frequencies and wider distances of pericyte detachment in the capillaries of cisplatin than control groups. B1-6-12, especially the medium dose, reversed these abnormalities. Culture of endothelial cells and pericytes with cisplatin demonstrated reduced cell viability, increased caspase-3 activity, lower transendothelial electrical resistance and decreased expression of tight junction proteins, occludin and zonula occluden-2 (ZO-2). B1-6-12 could correct these toxic effects of cisplatin. These data confirm that cisplatin causes pathological alterations in the components of BNB which correlate with the severity of neuropathy. Furthermore, B1-6-12 is effective against these abnormalities and deserves further investigations as potential treatment for cisplatin-induced neuropathy.
Decoupled responses of above‐ and below‐ground stability of productivity to nitrogen addition at the local and larger spatial scale

Temporal stability of net primary productivity (NPP) is important for predicting the reliable provisioning of ecosystem services under global changes. Although nitrogen (N) addition is known to affect the temporal stability of aboveground net primary productivity (ANPP), it is unclear how it impacts that of belowground net primary productivity (BNPP) and NPP, and whether such effects are scale dependent. Here, using experimental N addition in a grassland, we found different responses of ANPP and BNPP stability to N addition at the local scale and that these responses propagated to the larger spatial scale. That is, N addition significantly decreased the stability of ANPP but did not affect the stability of BNPP and NPP at the two scales investigated. Additionally, spatial asynchrony of both ANPP and BNPP among communities provided greater stability at the larger scale and was not affected by N addition. Our findings challenge the traditional view that N addition would reduce ecosystem stability based on results from aboveground dynamics, thus highlighting the importance of viewing ecosystem stability from a whole system perspective.
COVID-19 Prevention Measures Targeting Homeless People in Japan: A Cross-sectional Study

ABSTRACT Reports worldwide have shown that COVID-19 has impacted vulnerable populations, including homeless populations. The rate of the COVID-19 infection among the homeless populations is still unknown in most countries due to these individuals being scattered inconsistently throughout urban areas; however, surveys have been conducted in some shelters and in areas outside of Japan. Further, psychological impacts associated with COVID-19 infection, such as stress and anxiety or preventive procedures to protect yourself from infection, have also not been well studied among homeless populations. This study analyzes the demographic characteristics of the homeless population, their anxieties about COVID-19, and whether the author’s weekly announcements related to COVID-19 are beneficial to them. A cross-sectional mixed methods study was conducted in a Japanese city from October 2020 to February 2021. Data regarding socio-demographic characteristics, individuals’ experiences of homelessness, and perceptions of COVID-19 were gathered via interviews and examined using quantitative and qualitative methods. 71.1% and 44.2% of the respondents expressed no history of previous diseases and having anxiety due to COVID-19 respectively. Data indicated that they associated COVID-19 with death and serious physical harm. Additionally, 78.6% found the health announcements to be helpful and took preventive measures. Homeless people do not visit doctors, except when experiencing unbearable pain. Therefore, it is necessary to continuously provide comprehensive support for Japan’s homeless population.
Stereotyped B-cell responses are linked to IgG constant region polymorphisms in multiple sclerosis

Clonally related B cells infiltrate the brain, meninges and cerebrospinal fluid (CSF) of multiple sclerosis (MS) patients, but the mechanisms driving the B-cell response and shaping the immunoglobulin repertoires remain unclear. Here, we used single-cell full-length RNA-seq and B-cell receptor reconstruction to simultaneously assess the phenotypes, isotypes, constant region polymorphisms, and the paired heavy- and light-chain repertoires in intrathecal B-lineage cells. We detected extensive clonal connections between the memory B cell and antibody-secreting cell (ASC) compartments and observed clonally related cells of different isotypes, including IgM/IgG1, IgG1/IgA1, IgG1/IgG2, and IgM/IgA1. There was a strong dominance of the G1m1 allotype constant region polymorphisms in ASCs, but not in memory B cells. Tightly linked to the G1m1 allotype, we found a preferential pairing of the IGHV4 gene family with the κ variable (IGKV)1 gene family. These results link IgG constant region polymorphisms to stereotyped B-cell responses in MS, indicating that the intrathecal B-cell response in these patients could be directed against structurally similar epitopes. The data also suggest that the dominance of the G1m1 allotype in ASCs may occur as a result of biased differentiation of intrathecal memory B cells.
Effectiveness of mepolizumab in patients with severe eosinophilic asthma: results from real-world clinical practice in Finland

Abstract Objectives Mepolizumab treatment provides clinical benefits for patients with severe eosinophilic asthma in randomized controlled trials. However, real-world data for patients in Finland are lacking. Methods This retrospective, non-interventional, chart review study included patients with severe eosinophilic asthma ≥18 years of age initiating mepolizumab between January 1, 2016 and January 31, 2019 at three investigational sites in Finland. Patient characteristics during the 12 months prior to mepolizumab initiation (baseline) were recorded and primary and secondary endpoints included changes from baseline in disease outcomes during follow-up (up to 24 months following mepolizumab initiation). Exploratory endpoints included association between patient characteristics and exacerbation frequency/annual cumulative oral corticosteroid (OCS) dose. Results Overall, 51 patients were included (mean 17.8 months follow-up). At baseline, patients had a mean (standard deviation) blood eosinophil count of 550 (410) cells/µL; impaired lung function and health-related quality of life; poor symptom control; frequent exacerbations (2.78/year); and 90% were using OCS (mean: 9.80 mg/day). At the last follow-up visit, reductions from baseline in blood eosinophil count (84%) and fractional exhaled nitric oxide (26%) were observed, as were improvements in Asthma Quality of Life Questionnaire score (36%) and Asthma Control Test score (34%). Reductions in the mean number of annual exacerbations (82%) and mean daily OCS dose (39%) were also seen; reductions were observed even after adjustment for several patient baseline characteristics. Conclusions Results are consistent with previous randomized clinical trials, indicating that Finnish patients experience clinically relevant improvements when treated with mepolizumab in real-world clinical practice.
Predictors of sustained response and effects of the discontinuation of anti‐calcitonin gene related peptide antibodies and reinitiation in resistant chronic migraine

Guidelines for migraine prophylaxis suggest stopping medication after 6–12 months to reevaluate treatment appropriateness. The Italian Medicines Agency set a mandatory regulation to stop anti‐calcitonin gene related protein (CGRP) pathway monoclonal antibody (anti‐CGRP mAb) treatments for 3 months after 12 months of treatment. Herein, the effects of discontinuation and retreatment of anti‐CGRP mAbs in resistant chronic migraine patients are assessed, evaluating predictive factors of sustained response.
SPEDE‐sampler: An R Shiny application to assess how methodological choices and taxon sampling can affect Generalized Mixed Yule Coalescent output and interpretation

Species delimitation tools are vital to taxonomy and the discovery of new species. These tools can make use of genetic data to estimate species boundaries, where one of the most widely used methods is the Generalized Mixed Yule Coalescent (GMYC) model. Despite its popularity, a number of factors are known to influence the performance and resulting inferences of the GMYC. Moreover, the few studies that have assessed model performance to date have been predominantly based on simulated data sets, where model assumptions are not violated. Here, we present a user‐friendly R Shiny application, ‘SPEDE‐sampler’ (SPEcies DElimitation sampler), that assesses the effect of computational and methodological choices, in combination with sampling effects, on the GMYC model. Output phylogenies are used to test the effect that (1) sample size, (2) BEAST and GMYC parameters (e.g. prior settings, single vs multiple threshold, clock model), and (3) singletons have on GMYC output. Optional predefined grouping information (e.g. morphospecies/ecotypes) can be uploaded in order to compare it with GMYC species and estimate percentage match scores. Additionally, predefined groups that contribute to inflated species richness estimates are identified by SPEDE‐sampler, allowing for the further investigation of potential cryptic species or geographical substructuring in those groups. Merging by the GMYC is also recorded to identify where traditional taxonomy has overestimated species numbers. Four worked examples are provided to illustrate the functionality of the program's workflow, and the variation that can arise when applying the GMYC model to empirical data sets. The R Shiny program is available for download at https://github.com/clarkevansteenderen/spede_sampler_R.
Airway and Feeding Outcomes in Pierre Robin Sequence: A Comparison of Three Management Strategies

Background Controversy remains regarding optimal management of Pierre Robin sequence (PRS). The goal of this study was to compare airway and feeding outcomes in infants with PRS who underwent surgical intervention, specifically mandibular distraction osteogenesis (MDO) or tongue-lip adhesion (TLA), or who had conservative management (CM) without surgery. Methods All consecutive patients treated for PRS at a pediatric academic medical center, with at least one year follow-up, were included. Patients who underwent tracheostomy as an index procedure were excluded. Patients were divided into those who underwent MDO, TLA or CM. Feeding status and data from initial and follow-up polysomnograms were collected. Comparisons between groups were made using the Kruskal-Wallis test, followed by Mann-Whitney pairwise comparison with a Bonferroni correction, when appropriate. Results 67 neonates were included. 19 underwent TLA, 29 underwent MDO and 19 underwent CM. The proportions of syndromic patients were similar between groups. Patients undergoing CM had the lowest baseline AHI (9.1), but there were no significant differences between TLA (20.1) and MDO (25.4). At follow-up, the three groups had similar mean AHI (MDO 1.3, TLA 4.2, CM 4.5). A similar proportion of patients achieved AHI 5 or less (TLA 89.5%, MDO 96.6%, CM 84.2%). At one year, there were no significant differences in weight percentiles or in risk of failure-to-thrive between groups. One patient from the TLA group required a tracheostomy. Conclusion The three treatment modalities achieved high airway and feeding success rates. All three modalities should have a place in the armamentarium of the craniofacial surgeon.
Performance of ophthalmic artery Doppler velocimetry in the complementary diagnosis of preeclampsia

Abstract Objectives To calculate the accuracy (A) and establish the best cutoff value for ophthalmic artery (OA) Doppler velocimetry indexes in patients diagnosed with preeclampsia (PE), compared with healthy pregnant women. Methods This prospective experimental study enrolled 268 women: 133 with PE and 135 healthy pregnant women. All patients were evaluated by OA Doppler sonography, bilaterally, to assess their pulsatility index (PI), resistance index (RI), peak systolic velocity (PVS), second peak systolic velocity (P2), end-diastolic velocity (EDV), and peak ratio (PR). Means were compared using Student’s T-test. Receiver Operating Characteristics (ROC) curve was used to establish the cutoff value and estimate the sensitivity (S), specificity (Sp), accuracy (A) of all variables, and a significance of 95% was adopted. Results ROC curve analysis showed that P2 and PR were superior to the other parameters for PE diagnosis. We tested two cutoff values: (1) using PR ≥0.70, obtained A: 88.72%, S: 81.95%, and Sp: 95.48% and (2) using PR ≥0.75, and A: 86.24%, S: 74.43%, and Sp: 99.24%. By adopting P2 ≥ 21.5 cm/s, we obtained A: 87.59%, S: 84.96%, and Sp: 90.22% and when the cutoff point was P2 ≥ 22 cm/s, there was a slight decrease in A to 86.46% and S to 81.20%, with Sp: 91.89. 3%. Conclusion Ophthalmic artery Doppler demonstrated to be an effective and high-performance imaging method for the diagnosis of PE and the indexes P2 and PR demonstrated superior accuracy to the other Doppler parameters assessed. Higher performance occurred when the cutoff values with greater specificity were adopted, PR ≥ 0.75 and P2 ≥ 22 cm/s, considering that the proposed OA Doppler is to be a complementary method for preeclampsia.