Miracle-dz/UniFAR-FTUs huggingface dataset:
Association mapping of ectomycorrhizal traits in loblolly pine (Pinus taeda L.)

To understand how diverse mutualisms coevolve and how species adapt to complex environments, a description of the underlying genetic basis of the traits involved must be provided. For example, in diverse coevolving mutualisms, such as the interaction of host plants with a suite of symbiotic mycorrhizal fungi, a key question is whether host plants can coevolve independently with multiple species of symbionts, which depends on whether those interactions are governed independently by separate genes or pleiotropically by shared genes. To provide insight into this question, we employed an association mapping approach in a clonally replicated field experiment of loblolly pine (Pinus taeda L.) to identify genetic components of host traits governing ectomycorrhizal (EM) symbioses (mycorrhizal traits). The relative abundances of different EM fungi as well as the total number of root tips per cm root colonized by EM fungi were analyzed as separate mycorrhizal traits of loblolly pine. Single‐nucleotide polymorphisms (SNPs) within candidate genes of loblolly pine were associated with loblolly pine mycorrhizal traits, mapped to the loblolly pine genome, and their putative protein function obtained when available. The results support the hypothesis that ectomycorrhiza formation is governed by host genes of large effect that apparently have independent influences on host interactions with different symbiont species.
An Open‐Label Phase II Trial of Bevacizumab plus Docetaxel and Gemcitabine in Advanced, Previously Untreated Nonsquamous Non‐Small Cell Lung Cancer

Abstract Lessons Learned. The combination of bevacizumab with docetaxel‐gemcitabine resulted in unacceptable toxicity, particularly a high rate of pulmonary toxicity (30%). Despite promising efficacy, excessive toxicity of this regimen does not support its use in patients with advanced nonsquamous non‐small cell lung cancer. Background. Prior to immunotherapy, standard treatment for advanced non‐small cell lung cancer (NSCLC) was platinum doublet chemotherapy. In a previous phase II study, docetaxel‐gemcitabine demonstrated comparable efficacy and tolerability to platinum doublets. In this phase II trial, we evaluated the efficacy and tolerability of adding bevacizumab to docetaxel‐ gemcitabine in patients with advanced nonsquamous NSCLC. Methods. Patients with untreated advanced nonsquamous NSCLC were treated with up to six cycles of docetaxel‐gemcitabine‐bevacizumab, followed by bevacizumab until progression. The primary endpoint for this study was 1‐year progression‐free survival (PFS); secondary endpoints were safety, overall response rate (ORR) and overall survival (OS). The planned sample size was 46 patients. Results. A total of 13 patients were enrolled and received a median of six cycles of chemotherapy and four cycles of bevacizumab. The treatment was poorly tolerated, with five patients requiring dose reduction and four discontinuing treatment for toxicity. Grade 3–5 nonhematologic toxicity was seen in 10 patients, and 4 (30%) were hospitalized with pulmonary toxicity possibly related to study drugs. At this point, enrollment was halted for safety concerns. The 12‐month PFS was 8%. In 11 evaluable patients, ORR was 72%, median PFS 6 months, and median OS was 11 months. Conclusion. Docetaxel, gemcitabine, and bevacizumab at this dose and schedule resulted in excessive toxicity. Despite promising efficacy, in light of efficacious and safe alternative therapies, this regimen should not be used to treat advanced NSCLC.
The LIM protein Ajuba recruits DBC1 and CBP/p300 to acetylate ERα and enhances ERα target gene expression in breast cancer cells

Abstract Estrogen/ERα signaling is critical for breast cancer progression and therapeutic treatments. Thus, identifying new regulators of this pathway will help to develop new therapeutics to overcome chemotherapy resistance of the breast cancer cells. Here, we report Ajuba directly interacts with ERα to potentiate ERα target gene expression, and biologically Ajuba promotes breast cancer cell growth and contributes to tamoxifen resistance of these cells. Ajuba constitutively binds the DBD and AF2 regions of ERα, and these interactions can be markedly enhanced by estrogen treatment. Mechanistically, Ajuba recruits DBC1 and CBP/p300 and forms a ternary complex to co-activate ERα transcriptional activity and concomitantly enhances ERα acetylation. Moreover, components of this complex can be found at endogenous promoters containing functional ERα responsive elements. Taken together, these data demonstrate that Ajuba functions as a novel co-activator of ERα and that Ajuba/DBC1/CBP/p300 ternary complex may be a new target for developing therapeutics to treat breast cancer.
A National Snapshot of Patient-Reported Outcomes Comparing Types of Abdominal Flaps for Breast Reconstruction

Background: This study aimed to identify differences in patient-reported abdominal well-being, satisfaction, and quality of life in women with muscle-preserving free abdominal versus pedicle transverse rectus abdominis musculocutaneous (TRAM) flap for breast reconstruction. Methods: Women with a history of breast cancer surgery were recruited from the Army of Women foundation to take the BREAST-Q and a background questionnaire. Descriptive statistics and regression analyses were used to compare abdominal physical well-being, breast satisfaction, chest physical, psychosocial well-being, and sexual well-being in women undergoing free versus pedicle TRAM flaps. Results: Of 657 women, 273 (41 percent) underwent free flap surgery and 384 (58 percent) underwent pedicle TRAM flap surgery. Compared with unilateral pedicle TRAM flaps, those with unilateral free flaps scored an average of 9.5 points higher (95 percent CI, 5.4 to 13.6; p < 0.0001) and those with bilateral free flaps reported no difference in physical well-being of the abdomen. Compared with bilateral pedicle TRAM flaps, the following groups scored higher in physical well-being of the abdomen: unilateral free flaps, an average of 17.4 (95 percent CI, 11.5 to 23.3; p < 0.0001); bilateral free flaps, an average of 6.8 (95 percent CI, 0.3 to 13.3; p = 0.04); and unilateral pedicle TRAM flaps, an average of 7.9 (95 percent CI, 2.4 to 13.4; p = 0.005) higher. Women with bilateral pedicle flaps reported sexual well-being scores 7.4 (95 percent CI, 0.6 to 14.3; p = 0.03) and 6.8 (95 percent CI, 0.3 to 13.2; p = 0.04) points lower than those with unilateral free and unilateral pedicle flaps. Conclusions: Muscle-preserving techniques result in improved abdominal wall function and decreased morbidity compared with pedicle TRAM flap reconstruction. These data highlight the importance of offering patients the option of microsurgical techniques.
The Effect of the Thermosensitive Biodegradable PLGA–PEG–PLGA Copolymer on the Rheological, Structural and Mechanical Properties of Thixotropic Self-Hardening Tricalcium Phosphate Cement

The current limitations of calcium phosphate cements (CPCs) used in the field of bone regeneration consist of their brittleness, low injectability, disintegration in body fluids and low biodegradability. Moreover, no method is currently available to measure the setting time of CPCs in correlation with the evolution of the setting reaction. The study proposes that it is possible to improve and tune the properties of CPCs via the addition of a thermosensitive, biodegradable, thixotropic copolymer based on poly(lactic acid), poly(glycolic acid) and poly(ethylene glycol) (PLGA–PEG–PLGA) which undergoes gelation under physiological conditions. The setting times of alpha-tricalcium phosphate (α-TCP) mixed with aqueous solutions of PLGA–PEG–PLGA determined by means of time-sweep curves revealed a lag phase during the dissolution of the α-TCP particles. The magnitude of the storage modulus at lag phase depends on the liquid to powder ratio, the copolymer concentration and temperature. A sharp increase in the storage modulus was observed at the time of the precipitation of calcium deficient hydroxyapatite (CDHA) crystals, representing the loss of paste workability. The PLGA–PEG–PLGA copolymer demonstrates the desired pseudoplastic rheological behaviour with a small decrease in shear stress and the rapid recovery of the viscous state once the shear is removed, thus preventing CPC phase separation and providing good cohesion. Preliminary cytocompatibility tests performed on human mesenchymal stem cells proved the suitability of the novel copolymer/α-TCP for the purposes of mini-invasive surgery.
Sleep–wake regulation and the hallmarks of the pathogenesis of Alzheimer’s disease

While efficient treatments for Alzheimer's disease (AD) remain elusive, a growing body of research has highlighted sleep-wake regulation as a potential modifiable factor to delay disease progression. Evidence accumulated in recent years is pointing toward a tight link between sleep-wake disruption and the three main hallmarks of the pathogenesis of AD, i.e. abnormal amyloid-beta (Aβ) and tau proteins accumulation, and neurodegeneration. However, all three hallmarks are rarely considered together in the same study. In this review, we gather and discuss findings in favor of an association between sleep-wake disruption and each AD hallmark in animal models and in humans, with a focus on the preclinical stages of the disease. We emphasize that these relationships are likely bidirectional for each of these hallmarks. Altogether, current findings provide strong support for considering sleep-wake disruption as a true risk factor in the early unfolding of AD, but more research integrating recent technical advances is needed, particularly with respect to tau protein and neurodegeneration. Interventional longitudinal studies among cognitively healthy older individuals should assess the practical use of improving sleep-wake regulation to slow down the progression of AD pathogenesis.
PENGARUH PERMAINAN ULAR TANGGA TERHADAP KEMAMPUAN MENGGOSOK GIGI PADA ANAK SEKOLAH DASAR KELAS III DI SDN BARANANGSIANG KABUPATEN CIANJUR TAHUN 2017

Anak usia sekolah merupakan masa dimana terjadinya pergantian gigi susu menjadi gigi permanen. Kurang pemahaman tentang perawatan gigi dan mulut akan beresiko terjadinya masalah kesehatan gigi dan mulut, sehingga perlu dilakukan pendidikan kesehatan sebagai upaya pencegahan dengan menanamkan perilaku yang baik sejak dini. Metode penelitian yang digunakan adalah penelitian quasi experiment dengan jenis pre and post testwithout control. Sampel dalam penelitian ini menggunakan total sampling dengan sampel sebanyak 20 responden dan data yang diperoleh dalam penelitian dianalisis melalui dua tahapan, yaitu univariat untuk mengetahui rata-rata dan bivariat untuk mengetahui pengaruh (t-dependent). Hasil penelitian didapatkan bahwa rerata nilai kemampuan sebelum 5,85 dan sesudah 10,05. Hasil penelitian didapatkan adanya pengaruh permainan ular tangga terhadap kemampuan menggosok gigi pada anak dengan nilai p value = 0,001. Berdasarkan hasil penelitian ini penulis menyarankan agar metode pendidikan kesehatan dengan ular tangga dilakukan secara rutin untuk memperbaharui wawasan terhadap anak di SD, mendukung dan memotivasi anak dalam menggosok gigi yang baik dan benar.
Automotive tyre fault detection

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Modifying Serum Plant Sterol Concentrations: Effects on Markers for Whole Body Cholesterol Metabolism in Children Receiving Parenteral Nutrition and Intravenous Lipids

Background: Non-cholesterol sterols are validated markers for fractional intestinal cholesterol absorption (cholestanol) and endogenous cholesterol synthesis (lathosterol). This study’s objective was to evaluate markers for cholesterol synthesis and absorption in children exposed to two different intravenous lipid emulsions that rapidly change serum plant sterol concentrations as part of their parenteral nutrition (PN). Methods: Serum samples from two different studies were used: (1) nine PN-dependent children with intestinal failure associated liver disease (IFALD) whose soy-based, plant sterol-rich lipid (SO) was replaced with a fish-based, plant sterol-poor (FO) lipid; and (2) five neonates prescribed SO after birth. In the first study, samples were collected at baseline (prior to FO initiation) and after 3 and 6 months of FO. In study 2, samples were collected at 1 and 3 weeks of age. Results: In study 1, a 7-fold reduction in campesterol, a 12-fold reduction in sitosterol, and a 15-fold reduction in stigmasterol was observed 6 months after switching to FO. Serum cholesterol concentrations did not change, but cholesterol-standardized lathosterol increased (3-fold) and cholesterol-standardized cholestanol decreased (2-fold). In study 2, after 3 weeks of SO, sitosterol and campesterol concentrations increased 4-5 fold. At the same time, cholesterol-standardized lathosterol increased 69% and cholesterol-standardized cholestanol decreased by 29%. Conclusion: Based on these finding we conclude that changes in serum plant sterol concentrations might have direct effects on endogenous cholesterol synthesis, although this needs to be confirmed in future studies. Moreover, we speculate that this changed synthesis subsequently affects intestinal cholesterol absorption.
Salidroside promotes rat spinal cord injury recovery by inhibiting inflammatory cytokine expression and NF‐κB and MAPK signaling pathways

Spinal cord injury (SCI) is a public health problem in the world. The SCI usually triggers an excessive inflammatory response that brings about a secondary tissue wreck leading to further cellular and organ dysfunction. Hence, there is great potential of reducing inflammation for therapeutic strategies of SCI. In this study, we aim to investigate if Salidroside (SAD) exerts an anti‐inflammatory effect and promotes recovery of motor function on SCI through suppressing nuclear factor‐κB (NF‐κB) and the mitogen‐activated protein kinase (MAPK) pathways. In vitro, real‐time polymerase chain reaction (PCR) and enzyme‐linked immunosorbent assay (ELISA) were used to examine the inhibitory effect of SAD on the expression and release of interleukin‐1β (IL‐1β), interleukin‐6 (IL‐6) and tumor necrosis factor‐α (TNF‐α) activated by lipopolysaccharide (LPS) in astrocytes. In addition, SAD was found to inhibit NF‐κB, p38 and extracellular‐regulated protein kinases (ERK) signaling pathways by western blot analysis. Further, in vivo study showed that SAD was able to improve hind limb motor function and reduce tissue damage accompanied by the suppressed expression of inflammatory cytokines IL‐1β, IL‐6, and TNF‐α. Overall, SAD could reduce the inflammatory response and promote motor function recovery in rats after SCI by inhibiting NF‐κB, p38, and ERK signaling pathways.
Genotype/phenotype correlations in 538 congenital adrenal hyperplasia patients from Germany and Austria: discordances in milder genotypes and in screened versus prescreening patients

Congenital adrenal hyperplasia (CAH) due to CYP21A2 gene mutations is associated with a variety of clinical phenotypes (salt wasting, SW; simple virilizing, SV; nonclassical, NC) depending on residual 21-hydroxylase activity. Phenotypes and genotypes correlate well in 80–90% of cases. We set out to test the predictive value of CAH phenotype assignment based on genotype classification in a large multicenter cohort. A retrospective evaluation of genetic data from 538 CAH patients (195 screened) collected from 28 tertiary centers as part of a German quality control program was performed. Genotypes were classified according to residual 21-hydroxylase activity (null, A, B, C) and assigned clinical phenotypes correlated with predicted phenotypes, including analysis of Prader stages. Ultimately, concordance of genotypes with clinical phenotypes was compared in patients diagnosed before or after the introduction of nationwide CAH-newborn screening. Severe genotypes (null and A) correlated well with the expected phenotype (SW in 97 and 91%, respectively), whereas less severe genotypes (B and C) correlated poorly (SV in 45% and NC in 57%, respectively). This was underlined by a high degree of virilization in girls with C genotypes (Prader stage >1 in 28%). SW was diagnosed in 90% of screening-positive babies with classical CAH compared with 74% of prescreening patients. In our CAH series, assigned phenotypes were more severe than expected in milder genotypes and in screened vs prescreening patients. Diagnostic discrimination between phenotypes based on genotypes may prove overcome due to the overlap in their clinical presentations.
Effects of UPF1 expression on EMT process by targeting E-cadherin, N-cadherin, Vimentin and Twist in a hepatocellular carcinoma cell line

Hepatocellular carcinoma (HCC) is one of the most common malignancies worldwide. It has been reported that HCC has a poor prognosis. In the majority of cases, once metastatic, HCC is incurable. To identify an effective treatment for HCC, it is important to understand the underlying molecular mechanisms of HCC‑associated occurrence, proliferation, metastasis and carcinogenesis. In the present study, the role of Up‑frameshift 1 (UPF1), a potential tumor suppressor, was investigated in the HCC cell lines. The expression levels of UPF1 in an HCC cell line were examined by reverse transcription‑quantitative polymerase chain reaction. The expression levels of 19 key proteins in numerous signaling pathways were detected via protein array analysis in the presence of UPF1 overexpression. The present study further investigated the effects of UPF1 expression levels on the epithelial‑mesenchymal transition (EMT) process by targeting E‑cadherin, N‑cadherin, Vimentin and Twist‑related protein 1 (Twist). The results of the present study revealed that UPF1 was significantly downregulated in an HCC cell line. The majority of the proteins exhibited upregulated expression levels in the presence of UPF1 overexpression in the HCC cell line, Huh‑7. Key proteins, including cluster of differentiation (CD)31 (platelet endothelial cell adhesion molecule‑1), Vimentin, CD44, PCNA, Ki‑67, N‑Cadherin, Survivin, P53, Met and retinoblastoma exhibited a significant association with UPF1. Furthermore, western blotting indicated that the expression levels of N‑cadherin, Vimentin and Twist were notably upregulated while UPF1 was overexpressed; however, E‑cadherin was downregulated and opposing observations were reported with protein array analysis. In summary, E‑cadherin expression levels were regulated by the manifold, and UPF1, a potential tumor suppressor, may promote the EMT process in Huh‑7 HCC cells. The findings of the present study suggested that UPF1 expression levels affected the EMT process by targeting E‑cadherin, N‑cadherin, Vimentin and Twist.
Anti-Cancer Effects of Green Tea Polyphenols Against Prostate Cancer

Prostate cancer is the most common cancer among men. Green tea consumption is reported to play an important role in the prevention of carcinogenesis in many types of malignancies, including prostate cancer; however, epidemiological studies show conflicting results regarding these anti-cancer effects. In recent years, in addition to prevention, many investigators have shown the efficacy and safety of green tea polyphenols and combination therapies with green tea extracts and anti-cancer agents in in vivo and in vitro studies. Furthermore, numerous studies have revealed the molecular mechanisms of the anti-cancer effects of green tea extracts. We believe that improved understanding of the detailed pathological roles at the molecular level is important to evaluate the prevention and treatment of prostate cancer. Therefore, in this review, we present current knowledge regarding the anti-cancer effects of green tea extracts in the prevention and treatment of prostate cancer, with a particular focus on the molecular mechanisms of action, such as influencing tumor growth, apoptosis, androgen receptor signaling, cell cycle, and various malignant behaviors. Finally, the future direction for the use of green tea extracts as treatment strategies in patients with prostate cancer is introduced.
Parametric subtracted post‐ictal diffusion tensor imaging for guiding direct neurostimulation therapy

Parametric subtracted post‐ictal diffusion tensor imaging (pspiDTI) is a novel imaging technique developed at our center to visualize transient, patient‐specific, ictal‐associated water diffusion abnormalities in hippocampal‐associated axonal tissue. PspiDTI can elucidate putative connectivity patterns, tracing ictal propagation following a partial‐onset seizure without generalization secondarily. PspiDTI compares two DTI volumes acquired during the early post‐ictal period (<4 hr), and baseline inter‐ictal interval (>24 hr post‐seizure). This technique performs a voxel‐wise parametric test to identify statistically significant transient ictal‐associated changes in water diffusivity involving white matter (WM). Our technique was applied to six patients with refractory partial‐onset epilepsy who were candidates for direct cortical responsive neurostimulation (RNS) therapy. Global and region‐specific fractional anisotropy decreases, relative to baseline, were detected in all patients with a 17.01% (p < .01) relative mean decrement, while trace increases were found in 6/6 (100%) patients with a 13.30% (p < .01) relative global mean increment. Changes in diffusivity were anatomically compared with transient hyper‐perfusion as detected by subtracted ictal SPECT co‐registered to MRI (SISCOM). In 5/6 (83.33%) patients, alterations in WM diffusivity were detected adjacent to the SISCOM signal localized predominantly in gray matter. In 4/6 patients, post‐implant RNS electrocorticography revealed early ictal propagation between implanted RNS depth leads guided by pspiDTI, hence validating concordant abnormal diffusivity regions detected by our technique. PspiDTI can complement the conventional pre‐surgical evaluation to provide additional crucial information regarding WM ictal‐propagation pathways between predominantly gray matter ictal‐onset zones. When incorporated into a multi‐modality pre‐surgical workflow, pspiDTI can aid in defining critical nodes between ictogenic regions. This information can be used to strategically implant a limited set of two RNS depth leads for maximizing the extent to which direct cortical RNS can modulate a potentially extensive epileptogenic network.