Miracle-dz/UniFAR-FTUs huggingface dataset:
Sclerostin Antibody Treatment Increases Bone Mass and Normalizes Circulating Phosphate Levels in Growing Hyp Mice

X‐linked hypophosphatemia (XLH), caused by a loss‐of‐function mutation in the phosphate regulating gene with homology to endopeptidase located on the X chromosome (PHEX), is the most common form of vitamin D‐resistant rickets. Loss of functional PHEX results in elevated fibroblast growth factor 23 (FGF23) levels, impaired phosphate reabsorption, and inhibited skeletal mineralization. Sclerostin, a protein produced primarily in osteocytes, suppresses bone formation by antagonizing Wnt signaling and is reported to be elevated in XLH patients. This study used the Hyp mouse model to investigate sclerostin's role in the pathophysiology of XLH by evaluating the use of a monoclonal antibody to sclerostin in a mouse model of XLH, the Hyp mouse. Male and female wild‐type and Hyp littermates were injected with 25 mg/kg of vehicle or sclerostin antibody (Scl‐Ab) twice weekly, beginning at 4 weeks of age and euthanized at 8 weeks of age. Scl‐Ab treatment increased serum phosphate levels and suppressed circulating levels of intact FGF23 in treated wild‐type and Hyp mice of both sexes. Cortical area, trabecular bone volume fraction (BV/TV), metaphyseal apparent density, and the peak load increased with Scl‐Ab treatment in both sexes. This short‐term treatment study suggests that Scl‐Ab treatment can effectively improve some of the pathologies associated with XLH, including normalization of phosphate, and that sclerostin may play a role in regulating FGF23 and phosphate metabolism in XLH. © 2019 American Society for Bone and Mineral Research.
Histological evaluation of peri-implant mucosal and gingival tissues in peri-implantitis, peri-implant mucositis and periodontitis patients: a cross-sectional clinical study

Abstract Objective: Aim of present study was to evaluate gingival tissue samples obtained from healthy and diseased sites of teeth and dental implants in terms of hypoxia and collagenase activity. Methods: Four study groups were created as Group-1; healthy individuals (H), Group-2; periodontitis patients with stage 3 grade B (P), Group-3; patients with peri-implant mucositis. Group-4; patients with peri-implantitis (P-IMP). Plaque index (PI), gingival index (GI) and probing pocket depth (PPD) were recorded. Gingival and peri-implant mucosal biopsies were obtained. Fibroblast and inflammatory cells were counted. Hypoxia-inducible factor (HIF)-1α, prolyl hydroxylase (PH), matrix metalloproteinase (MMP)-8, tissue inhibitor of MMPs (TIMP)-1, cyclooxygenase (COX)-2 and inducible nitric oxide synthase (iNOS) levels were determined via immunohistochemistry. Results: Healthy controls had highest fibroblast cell counts and lowest inflammatory cell counts compared to other groups. Peri-implantitis and periodontitis samples had similar fibroblast and inflammatory cell counts, while peri-implant mucositis had higher fibroblast cells and lowered inflammatory cells compared to periodontitis and peri-implantitis samples. HIF-1α, COX-2 and iNOS levels were lowest in healthy controls and increased in other groups. Peri-implant mucositis samples had significantly lower expressions of HIF-1α, COX-2 and iNOS compared to peri-implantitis and periodontitis groups. PH expressions were lower in periodontitis and peri-implantitis groups compared to healthy controls and peri-implant mucositis groups. MMP-8 levels were lower in healthy group compared to other groups while levels were similar in periodontitis, peri-implant mucositis and peri-implantitis groups. TIMP levels were similar in groups. Conclusion: Periodontitis, peri-implantitis, and peri-implant mucositis samples exhibited higher inflammation and lower fibroblast cell counts and tend to have increased tissue collagenase activity, hypoxia and inflammation compared to healthy samples.
ERK Inhibitor LY3214996 Targets ERK Pathway–Driven Cancers: A Therapeutic Approach Toward Precision Medicine

The ERK pathway is critical in oncogenesis; aberrations in components of this pathway are common in approximately 30% of human cancers. ERK1/2 (ERK) regulates cell proliferation, differentiation, and survival and is the terminal node of the pathway. BRAF- and MEK-targeted therapies are effective in BRAF V600E/K metastatic melanoma and lung cancers; however, responses are short-lived due to emergence of resistance. Reactivation of ERK signaling is central to the mechanisms of acquired resistance. Therefore, ERK inhibition provides an opportunity to overcome resistance and leads to improved efficacy. In addition, KRAS-mutant cancers remain an unmet medical need in which ERK inhibitors may provide treatment options alone or in combination with other agents. Here, we report identification and activity of LY3214996, a potent, selective, ATP-competitive ERK inhibitor. LY3214996 treatment inhibited the pharmacodynamic biomarker, phospho-p90RSK1, in cells and tumors, and correlated with LY3214996 exposures and antitumor activities. In in vitro cell proliferation assays, sensitivity to LY3214996 correlated with ERK pathway aberrations. LY3214996 showed dose-dependent tumor growth inhibition and regression in xenograft models harboring ERK pathway alterations. Importantly, more than 50% target inhibition for up to 8 to 16 hours was sufficient for significant tumor growth inhibition as single agent in BRAF- and KRAS-mutant models. LY3214996 also exhibited synergistic combination benefit with a pan-RAF inhibitor in a KRAS-mutant colorectal cancer xenograft model. Furthermore, LY3214996 demonstrated antitumor activity in BRAF-mutant models with acquired resistance in vitro and in vivo. Based on these preclinical data, LY3214996 has advanced to an ongoing phase I clinical trial (NCT02857270).
Tantra and Modern Neurosciences: Is there any Correlation?

Background and Aims: Many studies have conclusively proven that meditative techniques derived from the Indian systems of philosophy, meditation and ritual classified as “Tantra” can bring about sustained changes in the structure and function of the nervous system of practitioners. The aim of this study is to provide neuroscientists a framework through which to interpret Tantra, and thereby provide a foundation upon which future interdisciplinary study can be built. Methods: We juxtapose Tantric concepts such as the subtle body, nadis and mantras with relevant neuroscientific findings. Our premise is that through sustained internalization of attention, Tantric practitioners were able to identify and document subtle changes in their field of awareness, which usually do not cross the threshold to come into our perception. Results: The descriptions left by Tantric philosophers are often detailed and empirical, but they are about subjective phenomena, rather than external objects. They also focus on individual experiences, rather than the group-level analyses favored by modern medical science. Conclusion: Systematic exploration of Tantric texts can be of tremendous value in expanding our understanding of human beings' experiential reality, by enabling us to build bridges between first-person and third-person approaches to the nervous system. This may open up new avenues for cognitive enhancement and treating neurological diseases.
Serum Zinc, Selenium and Total Antioxidant Contents of Nigerian Children with Asthma: Association with Disease Severity and Symptoms Control.

BACKGROUND Micronutrients and antioxidants may ameliorate oxidative stress. This study aimed to determine the serum Zinc (Zn), Selenium (Se) and Total Antioxidant Contents (TAC) of Nigerian children with asthma and relate these to disease severity and symptoms control. METHODS Children aged 2-15 years with asthma and age and sex matched controls were consecutively recruited. The children's serum Zn, Se and TAC were assayed and compared. RESULTS Eighty children each with asthma and controls participated in the study. Serum Zn (71.0 ± 30.3 µg/dl vs. 84.2 ± 31.7 µg/dl; p = 0.008), Se (67.3 ± 29.8 µg/l vs. 80.0 ± 31.7 µg/l; p = 0.033) and TAC [median (interquartile range) 5.2 (3.8-6.8) ng/dl vs. 6.2 (4.3-8.0) ng/dl; p = 0.019] were lower in children with asthma. Serum Se (65.7 ± 29.1 µg/l vs. 92.4 ± 28.6 µg/l; p = 0.001) was lower in those with moderate/severe than mild disease, but no association with symptoms control (p > 0.05). CONCLUSION Micronutrient supplementation may be beneficial in Nigerian children with asthma as they have relatively lower antioxidant micronutrients than nonasthmatics.
An Interactive Mobile Phone App (SMART 5-A-DAY) for Increasing Knowledge of and Adherence to Fruit and Vegetable Recommendations: Development and Pilot Randomized Controlled Trial

Background Fruit and vegetable consumption is important for health, but many individuals fail to consume adequate amounts for health benefits. Although many individuals are aware of current fruit and vegetable consumption recommendations, research suggests that adherence to these is hampered by low knowledge of the details of these recommendations. Objective This paper reports the development and details of a pilot randomized controlled test of a novel interactive mobile phone app for addressing low knowledge of the UK 5-a-day fruit and vegetable recommendations. Methods Requirements for the app were first defined by researchers and potential end users and prioritized using the MoSCoW (Must have, Should have, Could have, Won’t have) method. Second, a prototype mobile phone app was developed using an agile approach. Third, the prototype app was tested in a randomized controlled pilot trial for impacts on knowledge and intake of fruit and vegetables. Volunteers were randomized to either receive (n=50) or not receive the app (n=44) for 2 or 4 weeks, and fruit and vegetable knowledge, intake, and behavior were assessed at the beginning of the study and after 1 and 2 weeks or after 2 and 4 weeks, respectively. App usage and qualitative feedback were also investigated. All findings then informed the development of a final app. Results Low knowledge of consumption recommendations centered around portion sizes and the need for variety, and an interactive mobile phone app was considered a suitable tool for improving this knowledge in a practical manner that would be available both at time of consumption and outside of these times. The pilot test revealed improved behavior after 2 weeks compared with baseline in volunteers who received the app, but improvements in knowledge on fruit and vegetable recommendations were found in both groups, and no improvements in fruit and vegetable intakes were found in formal measures. Patterns of app usage and qualitative feedback also suggested a number of modifications. The resultant final app incorporates several behavior change techniques (goal-setting, self-monitoring, and personalized feedback) as well as aiming to improve knowledge. Conclusions A novel interactive mobile phone app was successfully developed based on requirements, and when tested in a pilot randomized controlled trial, this app was found to have some impacts on fruit and vegetable outcomes. Although benefits from the app were small, impacts will likely increase as a result of recent modifications. The final SMART 5-A-DAY app is available in the Google Play Store and now needs testing in the target population. Trial Registration ClinicalTrials.gov NCT02779491; https://www.clinicaltrials. gov/ct2/show/NCT02779491
The Potential of Influenza HA-Specific Immunity in Mitigating Lethality of Postinfluenza Pneumococcal Infections

Influenza virus infections pre-dispose an individual to secondary pneumococcal infections, which represent a serious public health concern. Matching influenza vaccination was demonstrated helpful in preventing postinfluenza bacterial infections and associated illnesses in humans. Yet, the impact of influenza hemagglutinin (HA)-specific immunity alone in this dual-infection scenario remains elusive. In the present study, we assessed the protective effect of neutralizing and non-neutralizing anti-hemagglutinin immunity in a BALB/c influenza-pneumococcus superinfection model. Our immunogens were insect cell-expressed hemagglutinin-Gag virus-like particles that had been differentially-treated for the inactivation of bioprocess-related baculovirus impurities. We evaluated the potential of several formulations to restrain the primary infection with vaccine-matched or -mismatched influenza strains and secondary bacterial replication. In addition, we investigated the effect of anti-HA immunity on the interferon status in mouse lungs prior to bacterial challenge. In our experimental setup, neutralizing anti-HA immunity provided significant but incomplete protection from postinfluenza bacterial superinfection, despite effective control of viral replication. In view of this, it was surprising to observe a survival advantage with non-neutralizing adaptive immunity when using a heterologous viral challenge strain. Our findings suggest that both neutralizing and non-neutralizing anti-HA immunity can reduce disease and mortality caused by postinfluenza pneumococcal infections.
SNR-Dependent Environmental Model: Application in Real-Time GNSS Landslide Monitoring

The Global Navigation Satellite System (GNSS) is currently one of the important tools for landslide monitoring and early warning. However, the majority of GNSS devices are installed in mountainous areas and a variety of vegetation. These harsh environments lead to defective signals at high elevation angles, rendering real-time successive and reliable positioning results for monitoring difficult. In this study, an environmental model derived from signal-to-noise ratio (SNR) is proposed to enhance the precision and convergence time of positioning in harsh environments. A series of experiments are conducted on weighting and ambiguity-fixed models to evaluate performance. The results indicate that the proposed SNR-dependent environment model could lead to a significant improvement in precision and convergence time; with an obtained root mean squared result on the millimeter level, a convergence time of a few seconds, and utilization which could reach 100%, for continuous and reliable positioning results. These results indicate that the proposed SNR-dependent environment model enhances the performance of GNSS monitoring and early warning to provide continuous and reliable positioning results in real-time.
Synthesis of Alloyed ZnSeTe Quantum Dots as Bright, Color-Pure Blue Emitters.

Considering a strict global environmental regulation, fluorescent quantum dots (QDs) as key visible emitters in the next-generation display field should be compositionally non-Cd. When compared to green and red emitters obtainable from size-controlled InP QDs, development of non-Cd blue QDs remains stagnant. Herein, we explore synthesis of non-Cd, ZnSe-based QDs with binary and ternary compositions toward blue photoluminescence (PL). First, size increment of binary ZnSe QDs is attempted by a multiply repeated growth until blue PL is attained. Although this approach offers a relevant blue color, excessively large-sized ZnSe QDs inevitably entail a low PL quantum yield (QY). As an alternative strategy to the above size enlargement the alloying of high-band gap ZnSe with lower-band gap ZnTe in QD synthesis is carried out. These alloyed ternary ZnSeTe QDs after ZnS shelling exhibit systematically tunable PL of 422-500 nm as a function of Te/Se ratio. Analogous to state-of-the-art heterostructure of InP QDs with a double-shelling scheme, an inner shell of ZnSe is newly inserted with different thicknesses prior to an outer shell of ZnS, where the effects of the thickness of ZnSe inner shell on PL properties are examined. Double-shelled ZnSeTe/ZnSe/ZnS QDs with an optimal thickness of ZnSe inner shell are then employed for all-solution-processed fabrication of blue QD-light-emitting diode (QLED). The present blue QLED as the first ZnSeTe QD-based device yields a peak luminance of 1195 cd/m2, current efficiency of 2.4 cd/A, and external quantum efficiency of 4.2%, corresponding to the record values reported from non-Cd blue devices.
The prognostic significance of tumor-infiltrating lymphocytes assessment with hematoxylin and eosin sections in resected primary lung adenocarcinoma

The prognostic significance of tumor-infiltrating lymphocytes has been determined in cancers of the lung, colon and breast, though there is no standardized method for using this prognostic indicator for lung cancer. We applied a modified version of the method proposed by the International Immuno-Oncology Biomarkers Working Group to primary lung adenocarcinoma, which uses histologic findings of hematoxylin and eosin sections. The study included a total cohort of 146 lung adenocarcinoma patients who underwent lobectomy with lymph node dissection at two hospitals between 2008 and 2012. The full-face sections of hematoxylin and eosin-stained slides were reviewed, and we evaluated the level of tumor-infiltrating lymphocytes as a percentage of the area occupied out of the total intra-tumoral stromal area. Histopathologic factors include histologic grade, necrosis, extracellular mucin, lymphovascular invasion, lymph node metastasis, level of tumor infiltrating lymphocytes, tertiary lymphoid structures around the tumor, and the presence of a germinal center in tertiary lymphoid structures. The high level of tumor-infiltrating lymphocytes was found to be significantly correlated with the histologic grade (p = 0.023), necrosis (p = 0.042), abundance of tertiary lymphoid structures(p<0.001) and presence of a germinal center in tertiary lymphoid structures (p = 0.004). A high level of tumor-infiltrating lymphocytes was associated with better progression-free survival (p = 0.011) as well as overall survival (p = 0.049). On multivariable analysis, high tumor-infiltrating lymphocyte levels were a good independent prognostic factor for progression-free survival (Hazard ratio: 0.389, 95% confidence interval: 0.161–0.941, p = 0.036). Histologic evaluation of tumor-infiltrating lymphocytes level in lung adenocarcinoma with H&E sections therefore has prognostic value in routine surgical pathology.
Two new phenylpropanoids and a new dihydrostilbenoid from the flower buds of Magnolia biondii pamp and their acetylcholinesterase inhibitory activities

Abstract Two new phenylpropanoids, named (2'R*,3'R*)-2',3'-dihydroxy-4'-methoxy-caffeoyl butyrate (1), 9-acetoxy syringin (2), and a new dihydrostilbene, named (8'R)-4',5-dihydroxy-4,8'-dimethoxy-2-hydroxyethyl diphenylethane (3), together with five analogues (4–8), were isolated from the flower buds of Magnolia biondii Pamp. Their structures were elucidated by extensive spectroscopic analyses and comparison with literature data. The absolute configurations were deduced by comparison of experimental and calculated gauge-independent atomic orbital (GIAO) 1 D NMR data. Moreover, the isolated compounds (1–8) were evaluated in vitro for their acetylcholinesterase (AChE) inhibitory activities.
Surgical Offloading Techniques Should be Used More Often and Earlier in Treating Forefoot Diabetic Ulcers: An Evidence-Based Review

Conservative treatment is the basis for diabetic foot ulcer (DFU) management, whereas surgical treatment is usually reserved for patients with failed, recurrent, or nonresponsive infected wounds. However, many reports demonstrated good to excellent results following surgery. Evidence synthesis on surgical offloading techniques and clear guidelines regarding the timing of surgery are lacking. The present study aimed to investigate the evidence behind surgical offloading techniques and propose a cutoff time for surgical indication following failed conservative treatment of neuropathic diabetic forefoot ulcers. Electronic databases were searched from inception to identify the best evidence level articles related to non-vascular surgical treatment of DFUs, such as metatarsal head resection, resection arthroplasty, metatarsal osteotomy, Achilles tendon lengthening, gastrocnemius recession, and flexor tenotomy, that have been employed for managing DFUs. Based on the highest level of evidence available, surgery was found to generate better values than standard conservative care for all outcomes except for the transfer rate. In particular, surgical bony offloading procedures demonstrated significantly better outcomes than standard conservative nonsurgical care in terms of higher healing rates, shorter healing durations, and lower recurrence rates. Moreover, 96% of DFUs healed in <1 month following surgical bony offloading, whereas 68% of ulcers healed within 3 months after standard care. The findings could challenge the classical guidelines of DFU management. This evidence-based review indicates that surgical offloading could be used more often and be proposed earlier during the course of ulcer management. The results imply that a period of 12 weeks could be considered a reasonable cutoff value to consider surgical treatment for patients with nonhealing DFUs.
Oleuropein: A natural antioxidant molecule in the treatment of metabolic syndrome

Olive (Olea europaea Linn., Fam. Oleaceae) is commonly known as Zaytoon in Mediterranean region. Its fruits and oil are essential components of Mediterranean diets. Olive tree is a prevalent plant species and one of the important cultivated crops of Mediterranean region. Oleuropein is a phenolic constituents of olive, which, along with its related compounds, has been indicated to be majorly responsible for its beneficial effects. Oleuropein is a secoiridoid type of phenolic compound and consists of three structural subunits: hydroxytyrosol, elenolic acid, and a glucose molecule. It is also reported to be the chemotaxonomic marker of olive. The oleuropein is reported to possess a number of biological activities including action against dyslipidemia, antiobesity, antidiabetic, antioxidant, antiatherogenic, antihypertensive, antiinflammatory, and hepatoprotective actions. The scientific evidence supports the role of oleuropein as a potential agent against metabolic syndrome. The present review discusses chemistry of oleuropein along with potential role of oleuropein with reference to pathophysiology of metabolic syndrome.