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The cytosolic innate immune sensor cyclic GMP-AMP synthase-stimulator of interferon genes (cGAS-STING) pathway is crucial for priming adaptive antitumour immunity through antigen-presenting cells (APCs). Natural agonists, such as cyclic dinucleotides (CDNs), activate the cGAS-STING pathway, but their clinical translation is impeded by poor cytosolic entry and serum stability, low specificity and rapid tissue clearance. Here we developed an ultrasound (US)-guided cancer immunotherapy platform using nanocomplexes composed of 2'3'-cyclic guanosine monophosphate-adenosine monophosphate (cGAMP) electrostatically bound to biocompatible branched cationic biopolymers that are conjugated onto APC-targeting microbubbles (MBs). The nanocomplex-conjugated MBs engaged with APCs and efficiently delivered cGAMP into the cytosol via sonoporation, resulting in activation of cGAS-STING and downstream proinflammatory pathways that efficiently prime antigen-specific T cells. This bridging of innate and adaptive immunity inhibited tumour growth in both localized and metastatic murine cancer models. Our findings demonstrate that targeted local activation of STING in APCs under spatiotemporal US stimulation results in systemic antitumour immunity and improves the therapeutic efficacy of checkpoint blockade, thus paving the way towards novel image-guided strategies for targeted immunotherapy of cancer.

To assess the effectiveness and safety of combined pulsed-dye laser (PDL) and NAFL for treatment of surgical scars.PDL and NAFL have not been compared to healing by time alone.Randomized controlled, single-blinded clinical trial at an urban, university hospital. Healthy adults' status post skin surgery with primary closure were randomized to either 3 sessions of combination PDL and NAFL every 2 to 8 weeks, or control of no treatment. At baseline and 36-week follow-up, Patient and observer Scar Assessment Scale and Scar Cosmesis Assessment and Rating were completed by participants and blinded physicians. The primary outcome was scar improvement, as measured by the score difference over time.Of 76 participants, 52 completed the study (July 2017 to June 2019). No severe adverse events were reported. Patient and observer Scar Assessment Scale assessments demonstrated improvement in total score in the laser group compared to controls, as reported by patients [mean difference (standard deviation), laser: 12.86 (6.91) vs control: 7.25 (6.34); P = 0.004] and blinded physicians [18.32 (8.69) vs 13.08 (9.63); P = 0.044]. Patients observed a greater improvement in scar thickness [3.68 (2.04) vs 1.88 (1.85); P = 0.002] and stiffness [3.57 (2.78) vs 1.50 (2.11); P = 0.004] with lasers, and physicians reported greater improvement in vascularity [3.71 (1.98) vs 1.71 (1.52); P = 0.0002]. The live Scar Cosmesis Assessment and Rating subscore for erythema improved significantly with lasers [1.04 (0.79) vs 0.42 (0.50); P = 0.001].Combined PDL and NAFL resulted in scar improvement. Scar thickness, stiffness, and erythema were improved.ClinicalTrials.gov (NCT03057964).

Background Treatment options for patients with melanoma brain metastasis (MBM) have changed significantly in the last decade. Few studies have evaluated changes in outcomes and factors associated with survival in MBM patients over time. The aim of this study is to evaluate changes in clinical features and overall survival (OS) for MBM patients. Methods Patients diagnosed with MBMs from 1/1/2009 to 12/31/2013 (Prior Era; PE) and 1/1/2014 to 12/31/2018 (Current Era; CE) at The University of Texas MD Anderson Cancer Center were included in this retrospective analysis. The primary outcome measure was OS. Log-rank test assessed differences between groups; multivariable analyses were performed with Cox proportional hazards models and recursive partitioning analysis (RPA). Results A total of 791 MBM patients (PE, n = 332; CE, n = 459) were included in analysis. Median OS from MBM diagnosis was 10.3 months (95% CI, 8.9–12.4) and improved in the CE vs PE (14.4 vs 10.3 months, P Conclusions OS and factors associated with OS have changed for MBM patients. This information can inform contemporary patient management and clinical investigations.

Background A recent phase III trial (NCT01372774) comparing use of stereotactic radiosurgery [SRS] versus whole-brain radiation therapy [WBRT] after surgical resection of a single brain metastasis revealed that declines in cognitive function were more common with WBRT than with SRS. A secondary endpoint in that trial, and the primary objective in this secondary analysis, was to identify baseline biomarkers associated with cognitive impairment after either form of radiotherapy for brain metastasis. Here we report our findings on APOE genotype and serum levels of associated proteins and their association with radiation-induced neurocognitive decline. Methods In this retrospective analysis of prospectively collected samples from a completed randomized clinical trial, patients provided blood samples every 3 months that were tested by genotyping and enzyme-linked immunosorbent assay, and results were analyzed in association with cognitive impairment. Results The APOE genotype was not associated with neurocognitive impairment at 3 months. However, low serum levels of ApoJ, ApoE, or ApoA protein (all P < .01) and higher amyloid beta (Aβ 1–42) levels (P = .048) at baseline indicated a greater likelihood of neurocognitive decline at 3 months after SRS, whereas lower ApoJ levels were associated with decline after WBRT (P = .014). Conclusions Patients with these pretreatment serum markers should be counseled about radiation-related neurocognitive decline.

The incidence of liver cirrhosis is increasing worldwide. Patients with cirrhosis are generally at a higher risk of harbouring hepatic and non-hepatic malignancies, including bladder cancer, likely due to the presence of related risk factors such as smoking. Cirrhosis can complicate both the operative and non-surgical management of bladder cancer. For example, cirrhotic patients undergoing abdominal surgery generally demonstrate worse postoperative outcomes, and chemotherapy in patients with cirrhosis often requires dose reduction due to its direct hepatotoxic effects and reduced hepatic clearance. Multiple other considerations in the peri-operative management for cirrhosis patients with muscle-invasive bladder cancer must be taken into account to optimize outcomes in these patients. Unfortunately, the current literature specifically related to the treatment of cirrhotic bladder cancer patients remains sparse. We aim to review the literature on treatment considerations for this patient population with respect to perioperative, surgical, and adjuvant management.

Nodule formation after autologous fat grafting to the breast is the most common complication. In the reconstructive population, this generates significant patient anxiety and presents a diagnostic challenge. The authors characterized palpable nodule occurrence after autologous fat grafting in breast reconstruction and compared benign versus malignant nodule characteristics.Chart review of the senior author's experience with breast fat grafting was performed. Data extracted included demographics, intraoperative details, nodule data, radiographic characteristics, and biopsy results. Logistic regression identified risk factors for nodule formation. Unpaired t tests and Fisher exact tests compared characteristics of benign versus malignant nodules.In total, 775 breasts were identified that underwent 1158 fat grafting procedures, of which 67 (8.6 percent) developed palpable nodules. Sonographic characterization of nodules included presumed fat necrosis (38.2 percent), benign lesions (27.6 percent), presumed oil cysts (17.1 percent), indeterminate (8.9 percent), and concerning for malignancy (8.1 percent). Lesions concerning for malignancy were more often irregular (10.0 percent versus 0 to 2.9 percent of benign nodules) and more often larger than 0.8 cm in greatest dimension (80 percent versus 42.9 to 61.8 percent of benign nodules). Six patients developed a palpable local recurrence. Malignant nodules tended to be larger (1.45 cm versus 0.70 cm; p = 0.03), were more often vascular (50 percent versus 3.8 percent; p = 0.03), and tended to occur later (17.5 months versus 10.0 months; p = 0.60). Benign nodules occurred in the setting of larger fat graft volumes (64.2 cc versus 40.0 cc; p = 0.008).This study provides the first comparison of radiographic and clinical characteristics between benign and malignant palpable nodules after autologous fat grafting in breast reconstruction.Risk, III.

Quick and reliable mass testing of infected people is an effective tool for the contingency of SARS-CoV-2. During the COVID-19 pandemic, Point-of-Care (POC) tests using Loop-Mediated Isothermal Amplification (LAMP) arose as a useful diagnostic tool. LAMP tests are a robust and fast alternative to Polymerase Chain Reaction (PCR), and their isothermal property allows easy incorporation into POC platforms. The main drawback of using colorimetric LAMP is the reported short-term stability of the pre-mixed reagents, as well as the relatively high rate of false-positive results. Also, low-magnitude amplification can produce a subtle color change, making it difficult to discern a positive reaction. This paper presents Hilab Molecular, a portable device that uses the Internet of Things and Artificial Intelligence to pre-analyze colorimetric data. In addition, we established manufacturing procedures to increase the stability of colorimetric RT-LAMP tests. We show that ready-to-use reactions can be stored for up to 120 days at −20 °C. Furthermore, we validated both the Hilab Molecular device and the Hilab RT-LAMP test for SARS-CoV-2 using 581 patient samples without any purification steps. We achieved a sensitivity of 92.93% and specificity of 99.42% (samples with CT ≤ 30) when compared to RT-qPCR.

The present study describes evaluation of epigenetic regulation by a small molecule as the therapeutic potential for treatment of Huntington’s disease (HD). We identified 5-allyloxy-2-(pyrrolidin-1-yl)quinoline (APQ) as a novel SETDB1/ESET inhibitor using a combined in silico and in vitro cell based screening system. APQ reduced SETDB1 activity and H3K9me3 levels in a HD cell line model. In particular, not only APQ reduced H3K9me3 levels in the striatum but it also improved motor function and neuropathological symptoms such as neuronal size and activity in HD transgenic (YAC128) mice with minimal toxicity. Using H3K9me3-ChIP and genome-wide sequencing, we also confirmed that APQ modulates H3K9me3-landscaped epigenomes in YAC128 mice. These data provide that APQ, a novel small molecule SETDB1 inhibitor, coordinates H3K9me-dependent heterochromatin remodelling and can be an epigenetic drug for treating HD, leading with hope in clinical trials of HD., Graphical Abstract

1. Moulting is a natural physiological process in birds when they shed their old feathers and replace them with new ones, and it is followed by reproductive quiescence resulting in reduced egg production. Different birds undergo moulting at different points in their life. Some birds have seasonal moulting while some moult at the end of their breeding cycle. This review will mainly focus on moulting practices associated with commercial layer birds because, in all other bird types, this is not managed.2. Commercial farms commonly analyse the cost-benefit ratio to decide the time and method to adopt for moulting. Commercial layer farms adopt different practices to force birds out of moult and restart the production cycle. Animal welfare groups consider this as stressful and against animal welfare, raising questions about the ethics of this practice.3. Many studies have been conducted using complete or partial feed withdrawal and non-feed withdrawal programs to measure their effectiveness in maintaining animal welfare, economy, and post-moult performance in mind.4. Animal welfare should not be compromised during moulting. The United States Egg Producers and other such groups from the United Kingdom and Europe have decided to sell eggs produced only through a non-feed withdrawal moulting programs.

Although the pathological contributions of reactive astrocytes have been implicated in Alzheimer's disease (AD), their in vivo functions remain elusive due to the lack of appropriate experimental models and precise molecular mechanisms. Here, we show the importance of astrocytic reactivity on the pathogenesis of AD using GiD, a newly developed animal model of reactive astrocytes, where the reactivity of astrocytes can be manipulated as mild (GiDm) or severe (GiDs). Mechanistically, excessive hydrogen peroxide (H2O2) originated from monoamine oxidase B in severe reactive astrocytes causes glial activation, tauopathy, neuronal death, brain atrophy, cognitive impairment and eventual death, which are significantly prevented by AAD-2004, a potent H2O2 scavenger. These H2O2--induced pathological features of AD in GiDs are consistently recapitulated in a three-dimensional culture AD model, virus-infected APP/PS1 mice and the brains of patients with AD. Our study identifies H2O2 from severe but not mild reactive astrocytes as a key determinant of neurodegeneration in AD.

Dermatofibrosarcoma protuberans (DFSP) is a cutaneous sarcoma that has remained a challenge for oncologic and reconstructive surgeons due to a high rate of local recurrence. The objective of this study is to investigate the oncologic and reconstructive benefits of employing a multidisciplinary two-step approach to the treatment of DFSP. A retrospective review was conducted using a prospectively collected database of all patients who underwent resection and reconstruction of large DFSPs by a multidisciplinary team, including a Mohs micrographic surgeon, surgical oncologist, dermatopathologist, and plastic and reconstructive surgeon, at one academic institution from 1998–2018. Each patient underwent Mohs micrographic surgery for peripheral margin clearance (Step 1) followed by wide local excision (WLE) of the deep margin by surgical oncology and immediate reconstruction by plastic surgery (Step 2). 57 patients met inclusion criteria. Average defect size after WLE (Step 2): 87.3 cm2 (range 8.5–1073.5 cm2). Mean follow-up time was 37 months (range 0–138 months). There were no cases of recurrence. A two-step multidisciplinary surgical treatment approach for DFSP minimizes risk of recurrence, decreases patient discomfort, and allows immediate reconstruction after deep margin clearance.

Light Detection and Ranging (LiDAR) is a primary sensor for autonomous vehicles to recognize surroundings. It detects near-infrared (NIR) light pulses, typically at 905nm, which is emitted and reflected by surrounding objects. Here, the fact of the matter is that conventional black or dark-tone cars with extremely low NIR reflection are hard to be detected by LiDAR and endanger the future highway. In this work, we propose to use platelet-shaped effect pigments with visible absorption and NIR reflectivity. Copper(II) oxide and Silicon dioxide multilayer are theoretically investigated with different numbers of layers and thicknesses. The optimized structures appear various dark-tone colors with high NIR-reflectivity over 90%.

Recently, a shallow and conformal doping profile is required for promising 3D structured devices. In this study, we deposited the dopant phosphorus (P) using modified plasma assisted doping (PaD) followed by an annealing process to electrically activate the dopants. A rapid thermal annealing process (RTP) was the first approach tested for activation but it resulted in a deep junction (>35 nm). To reduce the junction depth, we tried the flash lamp annealing process (FLP) to shorten the annealing time. We also predicted the annealing temperature by numerical thermal analysis, which reached 1,020 °C. However, the FLP resulted in a deep junction (~ 30 nm), which was not shallow enough to suppress short channel effects. Since an even shorter annealing process was required to form a ultra-shallow junction, we tried the laser annealing process (LAP) as a promising alternative. The LAP, which had a power density of 0.3 J/cm2, increased the surface temperature up to 1,100 °C with a shallow isothermal layer. Using the LAP, we achieved a USJ with an activated surface dopant concentration of 3.86×10 19 cm-3 and a junction depth of 10 nm, which will allow further scaling-down of devices.

Triple-negative breast cancer (TNBC) is the most lethal subtypes of breast cancer. Although chemotherapy is considered the most effective strategy for TNBC, most chemotherapeutics in current use are cytotoxic, meaning they target antiproliferative activity but do not inhibit tumor cell metastasis. Here, a TNBC-specific targeted liposomal formulation of epalrestat (EPS) and doxorubicin (DOX) with synergistic effects on both tumor cell proliferation and metastasis is described. These liposomes are biocompatible and effectively target tumor cells owing to hyaluronic acid (HA) modification on their surface. This active targeting, mediated by CD44-HA interaction, allows DOX and EPS to be delivered simultaneously to tumor cells in vivo, where they suppress not only TNBC tumor growth and the epithelial-mesenchymal transition, but also cancer stem cells, which collectively suppress tumor growth and metastasis of TNBC and may also act to prevent relapse of TNBC.

The spatial and angular organization of biological macromolecules is a key determinant, as well as informative readout, of their function. Correlative imaging of the dynamic spatio-angular architecture of cells and organelles is valuable, but remains challenging with current methods. Correlative imaging of spatio-angular dynamics requires fast polarization-, depth-, and wavelength-diverse measurement of intrinsic optical properties and fluorescent labels. We report a multimodal instant polarization microscope (miPolScope) that combines a broadband polarization-resolved detector, automation, and reconstruction algorithms to enable label-free imaging of phase, retardance, and orientation, multiplexed with fluorescence imaging of concentration, anisotropy, and orientation of molecules at diffraction-limited resolution and high speed. miPolScope enabled multimodal imaging of myofibril architecture and contractile activity of beating cardiomyocytes, cell and organelle architecture of live HEK293T and U2OS cells, and density and anisotropy of white and grey matter of mouse brain tissue across the visible spectrum. We anticipate these developments in joint quantitative imaging of density and anisotropy to enable new studies in tissue pathology, mechanobiology, and imaging-based screens.

Extramammary Paget disease (EMPD) is a frequently recurring malignant neoplasm with metastatic potential that presents in older adults on the genital, perianal, and axillary skin. Extramammary Paget disease can precede or occur along with internal malignant neoplasms.To develop recommendations for the care of adults with EMPD.A systematic review of the literature on EMPD from January 1990 to September 18, 2019, was conducted using MEDLINE, Embase, Web of Science Core Collection, and Cochrane Libraries. Analysis included 483 studies. A multidisciplinary expert panel evaluation of the findings led to the development of clinical care recommendations for EMPD.The key findings were as follows: (1) Multiple skin biopsies, including those of any nodular areas, are critical for diagnosis. (2) Malignant neoplasm screening appropriate for age and anatomical site should be performed at baseline to distinguish between primary and secondary EMPD. (3) Routine use of sentinel lymph node biopsy or lymph node dissection is not recommended. (4) For intraepidermal EMPD, surgical and nonsurgical treatments may be used depending on patient and tumor characteristics, although cure rates may be superior with surgical approaches. For invasive EMPD, surgical resection with curative intent is preferred. (5) Patients with unresectable intraepidermal EMPD or patients who are medically unable to undergo surgery may receive nonsurgical treatments, including radiotherapy, imiquimod, photodynamic therapy, carbon dioxide laser therapy, or other modalities. (6) Distant metastatic disease may be treated with chemotherapy or individualized targeted approaches. (7) Close follow-up to monitor for recurrence is recommended for at least the first 5 years.Clinical practice guidelines for EMPD provide guidance regarding recommended diagnostic approaches, differentiation between invasive and noninvasive disease, and use of surgical vs nonsurgical treatments. Prospective registries may further improve our understanding of the natural history of the disease in primary vs secondary EMPD, clarify features of high-risk tumors, and identify superior management approaches.

Scarring negatively impacts patient mental health, causing worsened self-confidence, body image, and social interactions, as well as anxiety and depression. The objective of this study is to evaluate the scarring impact after facial surgery, breast surgery, and full abdominoplasty for symptoms, appearance, psychosocial health, career, and sexual well-being using validated patient-reported outcome measures.A total of 901 patients from five providers completed the SCAR-Q (covering symptoms, appearance, and psychosocial) and Career/Sexual Well-being assessments via phone or email where a higher score indicated a more positive scar perception.Of the 901 patients, 38.1% had abdominoplasty surgery, 38.1% breast reduction, 15.3% facial surgery, 4.7% breast lift, and 3.9% breast augmentation. The differences in SCAR-Q, appearance, and symptom scores between the five procedures were statistically significant. Breast augmentation SCAR-Q scores (median = 256) and facial surgery (median = 242) were significantly higher than those of abdominoplasty patients (median = 219;This study is the first to show that breast augmentation and facial surgery patients have a more positive perception of their scars in terms of appearance, symptoms, psychosocial, career, and sexual well-being impact than abdominoplasty patients. Furthermore, the data suggest that symptoms may improve over time for abdominoplasty, breast augmentation, and facial surgery patients. This study highlights the need for further follow-up, counseling, or other improvements to postoperative scar care.

In recent decades, the safety of ships at sea has become a major concern of the global maritime industries. Ships are rarely subject to severe accidents during their life cycle. Collision is one of the most hazardous accidents, with potentially serious consequences such as the loss of human life, structural damage and environmental damage, especially if large tankers, LNG and/or nuclear-powered vessels are involved. This study presents a Quantitative Risk Assessment (QRA) for double hull oil tankers that have collided with different types of ships. The methodology used to perform the QRA is based on the International Maritime Organization’s (IMO) definition of a Formal Safety Assessment (FSA). Using probabilistic approaches, ship-ship collision scenarios are randomly selected to create a representative sample of all possible scenarios. The collision frequency is then calculated for each scenario. As this is a virtual experiment, the LS-DYNA nonlinear finite element method (NLFEM) is used to predict the structural consequences of each scenario selected. In addition, the environmental consequences are estimated by calculating the size of each scenario’s oil spill. To assess the economic consequences, the property and environmental damages are calculated in terms of monetary units. The total risk is then calculated as the sum of the resultant structural and environmental damages. Exceedance curves are established that can be used to define the collision design loads in association with various design criteria.

Background Women with cosmetic breast implants have significantly lower rates of subsequent breast cancer than the general population (relative risk, 0.63; 95 percent CI, 0.56 to 0.71). The authors hypothesize that breast implant-induced local inflammation stimulates immunosurveillance recognition of breast tumor antigen. Methods Sera were collected from two cohorts of healthy women: women with long-term breast implants (i.e., breast implants for >6 months) and breast implant-naive women. Antibody responses to breast tumor antigens were tested by enzyme-linked immunosorbent assay and compared between cohorts by unpaired t test. Of the implant-naive cohort, nine women underwent breast augmentation, and antibody responses before and after implant placement were compared by paired t test. Results Sera were collected from 104 women: 36 (34.6 percent) long-term breast implants and 68 (65.4 percent) implant-naive women. Women with long-term breast implants had higher antibody responses than implant-naive women to mammaglobin-A (optical density at 450 nm, 0.33 versus 0.22; p = 0.003) and mucin-1 (optical density at 450 nm, 0.42 versus 0.34; p = 0.02). There was no difference in antibody responses to breast cancer susceptibility gene 2, carcinoembryonic antigen, human epidermal growth factor receptor-2, or tetanus. Nine women with longitudinal samples preoperatively and 1 month postoperatively demonstrated significantly elevated antibody responses following implant placement to mammaglobin-A (mean difference, 0.13; p = 0.0002) and mucin-1 (mean difference 0.08; p = 0.02). There was no difference in postimplant responses to other breast tumor antigens, or tetanus. Conclusions Women with long-term breast implants have higher antibody recognition of mammaglobin-A and mucin-1. This study provides the first evidence of implant-related immune responses to breast cancer antigens. Clinical question/level of evidence Therapeutic, V.

Major parts of an IR–visible two-color interferometer (TCI) on KSTAR have been upgraded for the multi-chord operation: (1) a diode-pumped-solid-state (DPSS) laser (660 nm) replacing the former HeNe laser (633 nm), (2) vacuum-compatible vibration isolator with titanium retro-reflectors, and (3) full digital phase comparator for multi-chord real-time density signals. The commercial compact DPSS laser suits the multiple chord configuration with its strong beam power (500 mW) and long coherent length (>100 m). Ti retro-reflectors are mounted on vacuum-compatible vibration isolators. The isolators are essential for the visible beams to avoid any fringe skips due to their short wavelength, considering the speed of the mechanical vibration (up to hundreds of μm). Field-programmable-gate-array (FPGA) modules count the entire fringes fast enough with a signal output rate up to 1.25 MHz, solving the fringe skip issues. The FPGA module enables the full digital processing of the phase comparator with a CORDIC algorithm after the sampling rate of 160 MS/s for the 40 MHz intermediate frequency of each beam. The full digital signals are transferred to the main plasma control system in real-time. Stable single-input-single-output operation of the KSTAR density control was demonstrated with the TCI. The real-time density profile control is also promising in the near future, with multiple actuators such as pellets and gas puffings.

Study question Is the prostaglandin D2 (PGD2) associated with growing follicles and ovarian reserve of poor ovarian responders? Summary answer PGD2 is correlated with ovarian stimulation activity and follicle growth. Especially, poor ovarian responders show a significant decrease in the level of follicular fluid. What is known already Prostaglandins (PGs) are involved in the female reproductive process, mainly ovulation, fertilization, and implantation. Study design, size, duration We investigated the PGD2 level in the follicular fluid of poor ovarian responders. The collection of human follicular fluid was approved by the Institutional Research and Ethical Committees of CHA University (approval number: 1044308–201611-BR–027–04) from January to December 2019. Follicular fluid was collected from patients with normal ovarian response and patients with POR. Participants/materials, setting, methods We studied whether prostaglandin has related to POR in the clinical key factor by measuring human follicular fluid. Follicular fluid was collected from patients with normal ovarian response and patients with POR. The concentration of PGD2 in follicular fluid was determined with ELISA kits following the manufacturer’s protocol. Main results and the role of chance We analyzed the level of PGD2 in the follicular fluid of patients with normal ovarian response and patients with POR using an ELISA. The PGD2 concentration was significantly lower in the follicular fluid of patients with POR than in the follicular fluid of young and old patients with normal ovarian response. Limitations, reasons for caution This study has an identification of biomarker of the clinical samples as POR criteria patients. Therefore, further investigations aimed at specific recovery of low PGD2 metabolic activity in the CCs during control ovarian stimulation. Wider implications of the findings: Until now there is no specific biomarker of POR. AMH is just an ovary reserve marker for an indication of ovary function. PGD2 is one of the metabolites in steroid metabolism in the ovary. Therefore, we can find some cure through further study for improved PGD2 production to POR patients. Trial registration number none

Study question What is primary factor of bioenergetics product activity between microtubule instability and the functional activity of mitochondria in embryo? Summary answer The actin cytoskeleton instability is presumably the primary cause for the bioenergenesis of mitochondrial function to the preimplantation embryo development. What is known already Mitochondria are cellular organelles dynamically moving and morphological changes. It provides for homeostatic energy to the cell. The dynamic property of the mitochondria is associated with the microtubule network in the cell. However, the stability of the microtubule was clearly identified for preimplantation embryo development. Study design, size, duration This study is designed to assess the ATP productivity of the mitochondria, and specifically to observe what its primary factor is in terms of providing microtubule stability in mammalian cells. Additionally, we investigated the relationship between blastocyst formation and actin cytoskeleton stabilization by EpD with 2-cell mice. Participants/materials, setting, methods We prepared the microtubule stability regulation model with the HEK293 cell line by using the microtubule stabilizer as an Epothilone D (EpD). Then we analyzed the metabolic activity of the cells through oxidative phosphorylation (OXP) ratios analysis. Also, we performed confocal live imaging to observe mitochondria morphology depending on the cells’ microtubule. Next, we treated EpD to 2-cell culture media for the analysis of blastocyst development ratios. Main results and the role of chance EpD significantly increased fusion form. Also, EpD enhance bioenergy ratios like OXP in the mitochondria and functional activity related marker, like mTOR compared with the control. These results suggest that microtubule stabilization enhances mitochondrial metabolism by increasing oxygen consumption. Also, EpD in 2-cell culture media led to a significant increase in the speed of development and 50% higher hatched out blastocyst formation ratios compared to the control group. Limitations, reasons for caution This study had limited animal experiments. For the next study, we are planning with an aim to improve the quality and development ratios of human embryos by EpD. Wider implications of the findings: Microtubule stabilizer has a possibility to recover the mitochondria’s functional activity in the preimplantation embryo development. Mitochondrial functional activity along the actin cytoskeleton may play a pivotal role in determining the embryo quality and development ratios for archive pregnancy. Trial registration number non-clinical trials

Study question Lovastatin enhanced E2 productive ratios in the cumulus cells through promoted expression of Low-density lipoprotein receptor (LDLR). Summary answer Lovastatin up-regulated gene expression of LDLR in the CCs. And the high expression of LDLR promoted E2 productive ratios from CCs. What is known already We already reported that the up-regulation of LDLR correlated with clinical pregnancy. Therefore, we found lovastatin as an up-regulator of LDLR expression of clinical pregnancy. Study design, size, duration This is an expended study of LDLR to enhance steroidogenesis regarding the effect of lovastatin in the CCs. The collection of human cumulus cells was approved by the Institutional Research and Ethical Committees of CHA University (approval number: 1044308–201611-BR–027–04) from January to December 2019. The CCs were collected from 12 patients with normal ovarian response after oocyte denudation for ICSI. Participants/materials, setting, methods We studied whether lovastatin has up-regulated LDLR expression in human CCs. Cumulus cells were collected from patients with young (∼ 36) and old aged patients (37 ∼). After culturing human CCs, they were treated lovastatin for one day. The concentration of E2 in culture medium was measured using Chemiluminescence immunoassay. The mRNA isolated from CCs was analyzed gene expression level through real time-PCR. Main results and the role of chance The concentration of E2 was significantly increased in the culture medium treated with lovastatin. The CCs treated with lovastatin increased the expression of LDLR and StAR which are components of the steroidogenesis pathway. Limitations, reasons for caution We have found that the role of lovastatin promotes the E2 production by increasing the ldlr gene of CCs. Therefore, further investigations aimed at lovastatin effect on human oocytes embryo whether enhanced quality of oocytes or not. Wider implications of the findings: Previous data show that high activation of LDLR and StAR was associated with embryo quality and clinical pregnancy in infertile women. Our data suggest that lovastatin is stimulated LDLR expression to enhanced pregnancy ratios of IVF patients. Trial registration number none

Background Deaths in gluteal autografting occur due to gluteal vein injuries, but data are lacking on the precise location and caliber of these veins. Objectives The authors sought to present the first in vivo study of gluteal vein anatomy utilizing magnetic resonance imaging. Methods Magnetic resonance imaging venography of 16 volunteer hemi-sections was conducted in the supine, prone, prone with a bump (jack-knife), and left and right decubitus positions in 1 session after a single contrast administration. Caliber and course of the superior and inferior gluteal veins (SGV/IGV) were analyzed vs bony landmarks and position changes. Results The SGV has a very short submuscular course before splitting into 2 smaller branches superolaterally. The IGV runs immediately deep to the gluteus maximus in the center of the buttock as a single large trunk, on average 56 mm deep (mean 27 mm of muscle belly and 30 mm subcutaneous fat). No intramuscular or subcutaneous branches greater than 2 mm were found. In the prone position, the IGV and SGV have an average caliber of 5.96 mm and 5.63 mm. Vessel caliber decreased by 21% and 27%, respectively, in the jack-knife position and by 14% and 15% in lateral decubitus. Conclusions The SGV and IGV are immediately deep to gluteus maximus approximately 6 cm deep with a caliber on the order of 6 mm in the prone position. The distribution of these vessels suggests there is no “safe zone” in the intramuscular or submuscular planes. The jackknife or lateral decubitus positions can decrease vein caliber by up to 27%, possibly reducing the risk of injury due to either traction or direct cannula impact.

To achieve a high concentration of dopants over 1 × 1020 cm-3 on germanium (Ge), co-doping with phosphorus (P) and antimony (Sb) by plasma assisted atomic layer deposition (PALD) and a subsequent annealing process [rapid thermal annealing process (RTP) or flash lamp annealing process (FLP)] are proposed and investigated. We found that the PALD stacked co-doping (POx /SiOy and Sb2O5 ) films were uniformly deposited. Using the conventional RTP method led to a low doping concentration (19 cm-3 ). However, FLP with a Xenon (Xe) lamp (lamp duration: 3 ms; energy density: 56 J/cm2 ) raised the surface temperature to nearly 800 °C. Furthermore, high concentrations of both P and Sb (>1 × 1020 cm-3 ) were achieved at the surface. Our findings suggest that the FLP with high energy in a short amount of time (~3 ms) can create the peak power effect and the co-doping effect. The evidence shows that these effects contribute to enhancing n-type doping levels in the Ge structure.

We investigate the influence of the ratio between carbon and boron on glass-forming ability, thermal stability and mechanical properties of the Co65Cr13Mo22 ternary eutectic alloy modified by carbon and boron addition. Besides, the correlation between the extension of the supercooled liquid region (SCLR) and three bonding parameters, i.e. electronegativity, atomic size, and valence electron is investigated. The results reveal that carbon is more effective than boron to form a glassy phase in this system, and fully glassy alloys or metallic glass composites can be obtained when the metalloid contents are in the range of 20–25 at.%. Fully glassy alloys are only obtained when the carbon-to-boron ratio is 2:1. The glassy alloys and the glass composites exhibit high strength and extraordinarily wide SCLRs of >120 K. The width of the SCLR of the Co-based BMGs can be articulated as a function of three bonding parameters, which is different to the relationship previously observed for Fe-, Mg- and Pd-based BMGs. Based on these findings we propose the optimum C/B ratio for glass phase formation and the new criterion for predicting the width of the SCLR of Co-based BMGs by the three bonding parameters.

To investigate the predictive value of integrated 2-[The PubMed, Cochrane, and EMBASE databases, from the earliest available date of indexing through 31 October 2020, were searched for studies evaluating the diagnostic performance ofAcross seven studies (473 patients), the pooled sensitivity forThe current meta-analysis showed a moderate sensitivity and specificity of

A major rate-limiting step in developing more effective immunotherapies for GBM is our inadequate understanding of the cellular complexity and the molecular heterogeneity of immune infiltrates in gliomas. Here, we report an integrated analysis of 201,986 human glioma, immune, and other stromal cells at the single cell level. In doing so, we discover extensive spatial and molecular heterogeneity in immune infiltrates. We identify molecular signatures for nine distinct myeloid cell subtypes, of which five are independent prognostic indicators of glioma patient survival. Furthermore, we identify S100A4 as a regulator of immune suppressive T and myeloid cells in GBM and demonstrate that deleting S100a4 in non-cancer cells is sufficient to reprogram the immune landscape and significantly improve survival. This study provides insights into spatial, molecular, and functional heterogeneity of glioma and glioma-associated immune cells and demonstrates the utility of this dataset for discovering therapeutic targets for this poorly immunogenic cancer.

To compare the impact of orchidopexy approach (scrotal vs inguinal) on analgesic requirements, postoperative pain scores and complication rates.A superiority randomized controlled trial including boys 10 to 95 months of age at surgery, diagnosed with palpable undescended testis, was conducted. Patients with nonpalpable or bilateral undescended testis, previous inguinal surgery on the ipsilateral side and concurrent procedures were excluded. Block randomization with 1:1 allocation ratio and a standardized anesthesia protocol were employed. The primary outcome was postoperative pain and analgesic use in-hospital and at home using the validated pain scales FLACC (Face, Legs, Activity, Cry, and Consolability Behavioural Scale), CHEOPS (Children's Hospital of Eastern Ontario Pain Scale), PPPM (Parents Postoperative Pain Measure) and TPPPS (Toddler-Preschooler Postoperative Pain Scale). Secondary outcomes included operative time, conversion and success rates, and complications. An intention to treat protocol was followed.We enrolled 173 patients, and 12 withdrew. Of the 161 patients who completed followup, 80 had scrotal orchidopexy and 81 inguinal orchidopexy. In-hospital use of ibuprofen (p=0.02) and acetaminophen (p0.01), as well as FLACC (p0.01) and CHEOPS (p=0.04) pain scores were slightly higher in patients who underwent orchidopexy. No difference in mean operative time and median at-home administration of analgesic was noted. The conversion rate was 24% (19/80). Of these, 13 (68%) were canalicular testes. The overall complication rate was 4% (6/161): 1 testicular atrophy, 3 re-ascents and 2 wound infections. Of these, 5 underwent scrotal orchidopexy and 1 had inguinal orchidopexy (wound infection).Even though in-hospital mean postoperative pain scores and analgesic consumption were slightly lower for scrotal orchidopexy cases, the pain levels were mild across all scales. Median at-home analgesic use and pain scores were similar for both groups, as well as operative time and complication rates. Scrotal orchidopexy is an effective alternative to inguinal orchidopexy for low-lying undescended testis, as 68% of cases that needed conversion were canalicular testes.

Introduction The coronavirus disease 2019 (COVID-19) pandemic has been unprecedented in recent history. The rapid global spread has demonstrated how the emergence of a novel pathogen necessitates new information to advise both healthcare systems and policy-makers. The directives for the management of COVID-19 have been limited to infection control measures and treatment of patients, which has left physicians and researchers alone to navigate the massive amount of research being published while searching for evidence-based strategies to care for patients. To tackle this barrier, we launched CovidReview.ca, an open-access, continually updated, online platform that screens available COVID-19 research to determine higher quality publications. This paper uses data from this review process to explore the activity and trends of COVID-19 research worldwide over time, while specifically looking at the types of studies being published. Materials and Methods The literature search was conducted on PubMed. Search terms included “COVID-19”, “severe acute respiratory syndrome coronavirus 2”, “coronavirus 19”, “SARS-COV-2”, and “2019-nCoV”. All articles captured by this strategy were reviewed by a minimum of two reviewers and categorized by type of research, relevant medical specialties, and type of publication. Criteria were developed to allow for inclusion or exclusion to the website. Due to the volume of research, only a level 1 (title and abstract) screen was performed. Results The time period for the analysis was January 17, 2020, to May 10, 2020. The total number of papers captured by the search criteria was 10,685, of which 2,742 were included on the website and 7,943 were excluded. The greatest increase in the types of studies over the 16 weeks was narrative review/expert opinion papers followed by case series/reports. Meta-analyses, systematic reviews, and randomized controlled trials remained the least published types of studies. Conclusions The surge of research that accompanied the COVID-19 pandemic is unparalleled in recent years. From our analysis, it is clear that case reports and narrative reviews were the most widely published, particularly in the earlier days of this pandemic. Continued research that falls higher on the evidence pyramid and is more applicable to clinical settings is warranted.

The nematic phase in iron based superconductors (IBSs) has attracted attention with a notion that it may provide important clue to the superconductivity. A series of angle-resolved photoemission spectroscopy (ARPES) studies were performed to understand the origin of the nematic phase. However, there is lack of ARPES study on LaFeAsO nematic phase. Here, we report the results of ARPES studies of the nematic phase in LaFeAsO. Degeneracy breaking between the \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$d_{xz}$$\end{document}dxz and \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$d_{yz}$$\end{document}dyz hole bands near the \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$\Gamma$$\end{document}Γ and M point is observed in the nematic phase. Different temperature dependent band splitting behaviors are observed at the \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$\Gamma$$\end{document}Γ and M points. The energy of the band splitting near the M point decreases as the temperature decreases while it has little temperature dependence near the \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$\Gamma$$\end{document}Γ point. The nematic nature of the band shift near the M point is confirmed through a detwin experiment using a piezo device. Since a momentum dependent splitting behavior has been observed in other iron based superconductors, our observation confirms that the behavior is a universal one among iron based superconductors.