ABSTRACT
Of the ~25 directly imaged planets to date, all are younger than 500Myr and all but 6 are younger than 100Myr1. Eps Ind A (HD209100, HIP108870) is a K5V star of roughly solar age (recently derived as 3.7-5.7Gyr2 and 3.5 - 1.3 + 0.8 Gyr3). A long-term radial velocity trend 4,5 as well as an astrometric acceleration6,7 led to claims of a giant planet2,8,9 orbiting the nearby star (3.6384±0.0013pc10). Here we report JWST coronagraphic images that reveal a giant exoplanet which is consistent with these radial and astrometric measurements, but inconsistent with the previously claimed planet properties. The new planet has temperature ~275K, and is remarkably bright at 10.65µm and 15.50µm. Non-detections between 3.5-5µm indicate an unknown opacity source in the atmosphere, possibly suggesting a high metallicity, high carbon-to-oxygen ratio planet. The best-fit temperature of the planet is consistent with theoretical thermal evolution models, which are previously untested at this temperature range. The data indicates that this is likely the only giant planet in the system and we therefore refer to it as "b", despite it having significantly different orbital properties than the previously claimed planet "b".
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BACKGROUND: Triple-negative breast cancer (TNBC) subtyping by gene profiling has provided valuable clinical information. Here, we aimed to evaluate the relevance of TNBC subtyping using immunohistochemistry (IHC), which could be a more clinically practical approach, for prognostication and applications in patient management. METHODS: A total of 123 TNBC cases were classified using androgen receptor (AR), CD8, Forkhead box C1 protein (FOXC1), and doublecortin-like kinase 1 (DCLK1) into luminal androgen receptor (LAR), basal-like immunosuppressive (BLIS), mesenchymal-like (MES), and immunomodulatory (IM) subtypes. The IM cases were further divided into the IM-excluded and IM-inflamed categories by CD8 spatial distribution. Their clinicopathological and biomarker profiles and prognoses were evaluated. RESULTS: LAR (28.6%) and MES (11.2%) were the most and least frequent subtypes. The IHC-TNBC subtypes demonstrated distinct clinicopathological features and biomarker profiles, corresponding to the reported features in gene profiling studies. IM-inflamed subtype had the best outcome, while BLIS had a significantly poorer survival. Differential breast-specific marker expressions were found. Trichorhinophalangeal syndrome type 1 (TRPS1) was more sensitive for IM-inflamed and BLIS, GATA-binding protein 3 (GATA3) for IM-excluded and MES, and gross cystic disease fluid protein 15 (GCDFP15) for LAR subtypes. CONCLUSIONS: Our findings demonstrated the feasibility of IHC surrogates to stratify TNBC subtypes with distinct features and prognoses. The IM subtype can be refined by its CD8 spatial pattern. Breast-specific marker expression varied among the subtypes. Marker selection should be tailored accordingly.
Subject(s)
Biomarkers, Tumor , Triple Negative Breast Neoplasms , Humans , Triple Negative Breast Neoplasms/genetics , Triple Negative Breast Neoplasms/pathology , Triple Negative Breast Neoplasms/diagnosis , Triple Negative Breast Neoplasms/classification , Female , Middle Aged , Prognosis , Biomarkers, Tumor/metabolism , Adult , Immunohistochemistry , AgedSubject(s)
Lacrimal Apparatus Diseases , Lacrimal Apparatus , Nasolacrimal Duct , Solitary Fibrous Tumors , Humans , Nasolacrimal Duct/pathology , Solitary Fibrous Tumors/diagnostic imaging , Solitary Fibrous Tumors/surgery , Lacrimal Apparatus/diagnostic imaging , Lacrimal Apparatus/surgery , Lacrimal Apparatus/pathology , Lacrimal Apparatus Diseases/diagnosis , Lacrimal Apparatus Diseases/surgery , Lacrimal Apparatus Diseases/pathologyABSTRACT
Due to the high smoking rate in developing countries and the rising aging population in high-income countries, the global prevalence of chronic obstructive pulmonary disease (COPD), estimated to be 11.7%, is increasing and is the third-leading cause of mortality. COPD is likely to be present in elderly individuals with impaired gastro-enteric functions. Gastrointestinal congestion, dyspnea, and anxiety are pathophysiological characteristics of COPD, contributing to poor appetite, reduced dietary intake, and high-energy expenditure. These factors are implicated in the progression of malnutrition in COPD patients. Malnutrition is detrimental to lung functions and is associated with an increased risk of infection, exacerbation and mortality, and a longer duration of hospitalization. Therefore, nutritional support to treat malnutrition in COPD patients is very vital. Oral nutritional supplements (ONS) may hold the key to COPD treatment. To clarify this statement, we review current evidence for ONS in COPD patients to benefit from clinical outcomes.
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Malnutrition , Pulmonary Disease, Chronic Obstructive , Aged , Dietary Supplements , Hospitalization , Humans , Nutritional Status , Nutritional Support , Pulmonary Disease, Chronic Obstructive/complicationsABSTRACT
PURPOSE: To evaluate the association between hemifacial spasm (HFS) patients and glaucoma as a function of the Botox dosage required. METHODS: A retrospective review of clinical documents and procedure records. RESULTS: Information of 76 consecutive patients (58 females) with HFS who received Botox treatment were reviewed. The age at onset of HFS was 66±11 (32-85) years, and all manifested unilaterally. Ten (13%, 95% confidence interval: 6.5-22.9%) patients were diagnosed with glaucoma, including 8 primary open-angle glaucoma (POAG) (4 unilateral and ipsilateral to the HFS), and 2 bilateral chronic angle-closure glaucoma (CACG). Nine of the 10 patients developed glaucoma after the onset of the HFS. The Botox dosage was significantly higher among those diagnosed with glaucoma (31+/8 vs. 26+/7units, P<0.05). There was a positive relationship between the presenting intraocular pressure (IOP) and the Botox dosage required (R=0.31, P=0.0116). However, there was a weak relationship between the Botox dosage required and the vertical cup to disc ratio (R=0.076, P=0.525). The presenting IOP of the HFS-affected eyes in those diagnosed with glaucoma was higher than those without glaucoma (19±3.5 vs. 13±3.2mmHg, P=<0.05). The presenting IOP between the HFS-affected and unaffected eyes was similar (16±4.8 vs. 15+/4.6mmHg, P=0.430). Smoking status, history of diabetes mellitus, hypertension, hyperlipidemia and obstructive sleep apnea were not different between HFS patients with or without glaucoma. CONCLUSIONS: Hemifacial spasm patients with glaucoma were associated with a higher Botox dosage. We found a positive relationship between the Botox dosage required and the presenting IOP. Whether hemifacial spasm can result in fluctuation of IOP, eventually causing glaucomatous damage, remains to be studied further.
Subject(s)
Botulinum Toxins, Type A , Glaucoma, Open-Angle , Glaucoma , Hemifacial Spasm , Female , Glaucoma/drug therapy , Glaucoma, Open-Angle/complications , Glaucoma, Open-Angle/diagnosis , Glaucoma, Open-Angle/drug therapy , Hemifacial Spasm/complications , Hemifacial Spasm/diagnosis , Hemifacial Spasm/drug therapy , Humans , Tonometry, OcularSubject(s)
COVID-19 , Retinal Artery Occlusion , COVID-19/blood , COVID-19/complications , COVID-19/epidemiology , Humans , Patient Care/methods , Retinal Artery Occlusion/epidemiology , Retinal Artery Occlusion/etiology , Retinal Artery Occlusion/physiopathology , Retinal Artery Occlusion/therapy , Risk Factors , SARS-CoV-2ABSTRACT
INTRODUCTION: Sarawak has a population that is geographically and characteristically widely varied. This study aimed to determine the demographic profile of patients in Sarawak, Malaysia. Materials and Methods - A cross-sectional study was conducted in 2019 at four major haemophilia treatment centres in Kuching, Sibu, Bintulu and Miri Hospitals, Sarawak. Demographic and clinical data were collected with consents from patients. RESULTS AND DISCUSSION: Ninety-six haemophilia patients were identified - 79(82.3%) haemophilia A(HA) and 17(17.7%) haemophilia B(HB). Severe haemophilia patients were noted in 45.6% (36/79) of HA and 64.7% (11/17) of HB. In all 44.3% of the HA and 52.9% of the HB population had no identifiable family history of haemophilia. Two-thirds of the patients with severe HA were on prophylaxis [24/36 (66.7%)] and only onethird [4/11 (36.4%)] in severe HB. Inhibitors developed in 9/79 (11.4%) of the HA population [3/79 (3.8%) high responders]. The median inhibitor titre was not significantly different between the different treatment groups - on demand versus prophylaxis (1.0BU versus 2.0BU; z statistic -1.043, p-value 0.297, Mann-Whitney test). None of the patients developed inhibitory alloantibodies to factor IX. Four HA patients (5.1%) underwent immune tolerance induction where one case had a successful outcome. Three severe HA patients received emicizumab prophylaxis and showed remarkable reduction in bleeding events with no thromboembolic events being reported. One female moderate HA patient received PEGylated recombinant anti-haemophilic factor. Eleven patients underwent radiosynovectomy. One mild HB patient succumbed to traumatic intracranial bleeding. Our data reported a prevalence (per 100,000 males) of 5.40 cases for all severities of HA, 2.46 cases for severe HA; 1.16 cases for all severities of HB, and 0.75 cases for severe HB. The overall incidence of HA and HB was 1 in 11,500 and 1 in 46,000, respectively. CONCLUSION: This study outlines the Sarawakian haemophilia landscape and offers objective standards for forward planning. Shared responsibilities among all parties are of utmost importance to improve the care of our haemophilia population.
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Hemophilia A , Hemophilia B , Cross-Sectional Studies , Female , Hemophilia A/epidemiology , Hemophilia B/epidemiology , Humans , Malaysia/epidemiology , Male , PrevalenceSubject(s)
COVID-19 , Interferon-gamma , Angiotensin-Converting Enzyme 2 , Humans , Keratinocytes , SARS-CoV-2 , Tropism , Up-RegulationABSTRACT
BACKGROUND: Obstructive sleep apnea (OSA) is associated with cancer incidence and mortality. The underlying mechanism is unclear. This study aims to evaluate the influence of intermittent hypoxia (IH), a novel hallmark of OSA, on tumor and to access the anti-tumor effect of endostatin on a mouse model with OSA. METHODS: The C57BL/6 J mice were randomly classified into four groups: control (normoxia) (CTL), control plus endostatin (CTL + ED), IH, and IH plus endostatin (IH + ED). Mice in IH and IH + ED groups were subjected to IH 8 h per day in 5 weeks. Lewis lung cancer cells were injected into the flank of each mouse after 1 week of IH exposure. Endostatin was also intraperitoneally injected after tumor volume reached about 200 mm3. The maximum standard uptake values (SUVmax) were detected by micro-positron emission tomography-computed tomography (micro-PET-CT) imaging prior and post-endostatin administration. Microvessel density (MVD) and vascular endothelial growth factor (VEGF) were determined for evaluating the anti-tumor effect of endostatin among the normoxia and IH conditions. RESULTS: Mice had higher SUVmax in the IH group than the CTL group (p < 0.01). When compared with mice in the CTL group, those in the IH group had significantly greater MVD values (p < 0.001). The SUVmax can be attenuated by endostatin both in the CTL (p < 0.01) and IH conditions (p < 0.001). When compared with CTL group, mice in the IH group had increased MVD values (p < 0.001) and VEGF expression both at mRNA (p < 0.05) and protein levels (p < 0.001 in western blotting results). Treatment with endostatin attenuated serum and tissue VEGF levels, lowering the MVD values. As compared to normoxia condition, the endostatin-therapeutic effects were more significant under the IH condition (p < 0.05 in western blotting results). CONCLUSIONS: Micro-PET-CT imaging is a promising non-invasive technique to evaluate the tumor metabolic characteristics under IH condition in vivo. The anti-tumor effect of endostatin under IH condition is superior to that of the normoxia condition.
Subject(s)
Antineoplastic Agents/pharmacology , Carcinoma, Lewis Lung/drug therapy , Disease Models, Animal , Endostatins/pharmacology , Hypoxia/physiopathology , Sleep Apnea, Obstructive/complications , Animals , Carcinoma, Lewis Lung/etiology , Male , Mice , Mice, Inbred C57BL , Tumor Cells, CulturedABSTRACT
We present a patient with positive donor-specific antibodies (DSA) and crossmatch of ABO-incompatible (ABOi) combined liver and kidney transplantation (CLKT). Antibody-mediated rejection did not occur and the graft had survived for over one year at the time of writing without infectious complications. A 56-year-old man with positive DSA and positive crossmatch underwent living donor CLKT. The preoperative protocol for ABOi consisted of a single dose of rituximab and total plasma exchange (TPE). The result of anti-B antibody titer for IgG was 1:32. The evaluations of complement-dependent cytotoxicity and flow cytometry cross-match revealed a change from T+/B+ to T-/B+. The patient required adult living donor CLKT. Acute rejection episodes were treated using antithymocyte globulin, and the kidney required 7 days' treatment to recover. No further rejection and infectious episodes have been observed in past 13 months since the transplant. DSA and crossmatches are important for antibody detection and analysis. In the rituximab era, TPE can be used to achieve a successful decrease in antibody titer. In countries with a severe shortage of cadaveric organ donors, it may be possible to select ABOi candidate donors with positive DSA and crossmatch.
Subject(s)
Blood Group Incompatibility/immunology , Graft Rejection/prevention & control , Kidney Transplantation/methods , Liver Transplantation/methods , Antibodies/blood , Graft Rejection/immunology , Graft Survival/immunology , Histocompatibility Testing/methods , Humans , Immunosuppressive Agents/therapeutic use , Living Donors , Male , Middle Aged , Plasmapheresis/methods , Rituximab/therapeutic useABSTRACT
Previously we showed that urine trefoil factor 3 (TFF3) levels were higher in females with irritable bowel syndrome (IBS) compared to non-IBS females. To assess if TFF3 is associated with symptoms and/or reflect alterations in gastrointestinal permeability and gut microbiota in an IBS population, we correlated stool and urine TFF3 levels with IBS symptoms, intestinal permeability, stool microbial diversity and relative abundance of predominant bacterial families and genera. We also tested the relationship of stool TFF3 to urine TFF3, and compared results based on hormone contraception use. Samples were obtained from 93 females meeting Rome III IBS criteria and completing 4-week symptom diaries. TFF3 levels were measured by ELISA. Permeability was assessed with the urine lactulose/mannitol (L/M) ratio. Stool microbiota was assessed using 16S rRNA. Stool TFF3, but not urine TFF3, was associated positively with diarrhoea and loose stool consistency. Higher stool TFF3 was also associated with lower L/M ratio and microbial diversity. Of the 20 most abundant bacterial families Mogibacteriaceae and Christensenellaceae were inversely related to stool TFF3, with only Christensenellaceae remaining significant after multiple comparison adjustment. There were no significant relationships between stool or urine TFF3 levels and other symptoms, nor between stool and urine levels. In premenopausal females, urine TFF3 levels were higher in those reporting hormone contraception. Collectively these results suggest that higher stool TFF3 levels are associated with IBS symptoms (loose/diarrhoeal stools), lower gut permeability, and altered stool bacteria composition (decreased diversity and decreased Christensenellaceae), which further suggests that TFF3 may be an important marker of host-bacteria interaction.
Subject(s)
Feces/chemistry , Gastrointestinal Microbiome , Irritable Bowel Syndrome/pathology , Microbiota , Permeability , Trefoil Factor-3/analysis , Urine/chemistry , Adult , Aged , DNA, Bacterial/chemistry , DNA, Bacterial/genetics , DNA, Ribosomal/chemistry , DNA, Ribosomal/genetics , Enzyme-Linked Immunosorbent Assay , Female , Humans , Middle Aged , Phylogeny , RNA, Ribosomal, 16S/genetics , Sequence Analysis, DNA , Young AdultABSTRACT
PURPOSE: Several studies have evaluated the effects of growth hormone (GH) on auxological and biochemical parameters in children with non-GH-deficient, idiopathic short stature (ISS). This study evaluated the efficacy and safety of Growtropin®-II (recombinant human GH) in Korean patients with ISS. METHODS: This was a 1-year, open-label, multicenter, phase III randomized trial of Growtropin®-II in Korean patients with ISS. In total, 70 prepubertal subjects (39 males, 31 females) between 4 and 12 years of age were included in the study. All patients were naive to GH treatment. RESULTS: Annual height velocity was significantly higher in the treatment group (10.68 ± 1.95 cm/year) than the control group (5.72 ± 1.72, p < 0.001). Increases in height and weight standard deviation scores (SDSs) at 26 weeks were 0.63 ± 0.16 and 0.64 ± 0.46, respectively, for the treatment group, and 0.06 ± 0.15 and 0.06 ± 0.28, respectively, for the control group (p < 0.001). Serum insulin-like growth factor (IGF-1) and insulin-like growth factor binding protein-3 (IGFBP-3) increased significantly in the treatment group at week 26 compared to baseline. However, the SDS for body mass index (BMI) at 26 weeks did not change significantly in either group. Growtropin®-II was well tolerated and safe over 1 year of treatment. CONCLUSIONS: One-year GH treatment for prepubertal children with ISS demonstrated increased annualized velocity, height and weight SDSs, and IGF-1 and IGFBP-3 levels, with a favorable safety profile. Further evaluations are needed to determine the optimal dose, final adult height, and long-term effects of ISS treatment.
Subject(s)
Body Height/drug effects , Dwarfism/drug therapy , Growth Disorders/drug therapy , Growth Hormone/administration & dosage , Human Growth Hormone/deficiency , Puberty , Case-Control Studies , Child , Child, Preschool , Female , Humans , Male , Republic of KoreaABSTRACT
BACKGROUND: Liver regeneration is dependent on the proliferation of hepatocytes. Hepatic progenitor cells are intra-hepatic precursor cells capable of differentiating into hepatocytes or biliary cells. Although liver progenitor cell proliferation during the regenerative process has been observed in animal models of severe liver injury, it has never been observed in vivo in humans because it is unethical to take multiple biopsy specimens for the purpose of studying the proliferation of liver progenitor cells and the roles they play in liver regeneration. Associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) is a staged procedure for inducing remnant liver hypertrophy so that major hepatectomy can be performed safely. This staged procedure allows for liver biopsy specimens to be taken before and after the liver begins to regenerate. CASE PRESENTATION: The liver progenitor cell proliferation is observed in a patient undergoing ALPPS for a metastatic hepatic tumour. Liver biopsy is acquired before and after ALPPS for the calculation of average number of liver progenitor cell under high magnification examination by stain of immunomarkers. This is the first in vivo evidence of growing liver progenitor cells demonstrated in a regenerating human liver.
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Hepatocytes/cytology , Liver Regeneration/physiology , Liver/cytology , Stem Cells/cytology , Adult , Cell Proliferation , Hepatectomy/methods , Humans , Ligation , Liver Neoplasms/surgery , Male , Portal Vein/surgerySubject(s)
Quality Improvement/organization & administration , Surgery Department, Hospital/organization & administration , Surgical Procedures, Operative , General Surgery/organization & administration , Humans , Patient Safety , Societies, Medical/organization & administration , Surgical Procedures, Operative/adverse effects , Surgical Procedures, Operative/standards , United StatesABSTRACT
The ability to control a magnetic phase with an electric field is of great current interest for a variety of low power electronics in which the magnetic state is used either for information storage or logic operations. Over the past several years, there has been a considerable amount of research on pathways to control the direction of magnetization with an electric field. More recently, an alternative pathway involving the change of the magnetic state (ferromagnet to antiferromagnet) has been proposed. In this paper, we demonstrate electric field control of the Anomalous Hall Transport in a metamagnetic FeRh thin film, accompanying an antiferromagnet (AFM) to ferromagnet (FM) phase transition. This approach provides us with a pathway to "hide" or "reveal" a given ferromagnetic region at zero magnetic field. By converting the AFM phase into the FM phase, the stray field, and hence sensitivity to external fields, is decreased or eliminated. Using detailed structural analyses of FeRh films of varying crystalline quality and chemical order, we relate the direct nanoscale origins of this memory effect to site disorder as well as variations of the net magnetic anisotropy of FM nuclei. Our work opens pathways toward a new generation of antiferromagnetic - ferromagnetic interactions for spintronics.
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OBJECTIVES: To determine differences in arch forms derived from the root apices locations between individuals with <2 mm maxillary crowding and controls. SETTING AND SAMPLE POPULATION: The Department of Orthodontics, Pusan National University. Cone-beam computed tomography (CBCT) images of 102 patients in the control group and 95 patients in the crowding group. MATERIALS AND METHODS: X, Y and Z coordinates of the tip of the crowns and the apex of the root of the maxillary teeth (except second molars) were determined on the CBCT images. The acquired three-dimensional (3D) coordinates were converted into two-dimensional (2D) coordinates via projection on the palatal plane, and the Procrustes analysis was employed to process the converted 2D coordinates. The mean shape of the arch form derived from the location of the tip of the crowns and the apex of the root was compared between groups using the statistical shape analysis. RESULTS: There was a statistically significant difference (P = .046) between the groups for the mean shape of the root apex arch form, but the difference was small and clinically irrelevant as it is minor compared to the degree of crowding. CONCLUSIONS: Maxillary arch from at the level of the maxillary apices only shows minor differences between crowded and non-crowded dentitions.