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1.
Nature ; 609(7926): 269-275, 2022 09.
Artigo em Inglês | MEDLINE | ID: mdl-36071190

RESUMO

Nuclear fusion is one of the most attractive alternatives to carbon-dependent energy sources1. Harnessing energy from nuclear fusion in a large reactor scale, however, still presents many scientific challenges despite the many years of research and steady advances in magnetic confinement approaches. State-of-the-art magnetic fusion devices cannot yet achieve a sustainable fusion performance, which requires a high temperature above 100 million kelvin and sufficient control of instabilities to ensure steady-state operation on the order of tens of seconds2,3. Here we report experiments at the Korea Superconducting Tokamak Advanced Research4 device producing a plasma fusion regime that satisfies most of the above requirements: thanks to abundant fast ions stabilizing the core plasma turbulence, we generate plasmas at a temperature of 100 million kelvin lasting up to 20 seconds without plasma edge instabilities or impurity accumulation. A low plasma density combined with a moderate input power for operation is key to establishing this regime by preserving a high fraction of fast ions. This regime is rarely subject to disruption and can be sustained reliably even without a sophisticated control, and thus represents a promising path towards commercial fusion reactors.

2.
Clin Radiol ; 79(3): 189-196, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38092644

RESUMO

AIM: To investigate the importance of additional cranial magnetic resonance imaging (cMRI) in non-traumatic headache patients with a prior negative head computed tomography (CT) examination within 1 month. MATERIALS AND METHODS: This retrospective study analysed 162 adult patients with non-traumatic headache who underwent cMRI within 1 month of a negative initial head CT at the emergency department (ED). The diagnostic yield and false-referral rate were analysed according to the revisit duration (early [≤1 week] versus late [>1-4 weeks] revisits), patient care settings (ED versus outpatient clinics [OPC]), and clinical variables. Subsequent patient management change (PMC), such as admission and treatment (AT) or outpatient clinic treatment (OT), were also investigated. RESULTS: The overall diagnostic yield of cMRI was 17.3% (28/162) and the false-referral rate was 1.2% (2/162). The diagnostic yield of cMRI was significantly different according to the patient care settings (ED, 24.7% [21/85] versus OPC, 9.1% [7/77]; p=0.02). The diagnostic yield was highest in the ED-early-revisit group (25.4% [18/71]), 45% (9/20) in those with systemic signs, and 46.7% (14/30) in those with symptom change. Among patients with positive cMRI findings, 90% (27/30) received AT and 3.3% (1/30) received OT. Among OPC-revisit-negative cMRI patients, PMC occurred in 0% (0/50). CONCLUSION: The diagnostic yield of cMRI was relatively high for headache patients who revisited the ED earlier, especially in those with systemic signs or symptom change. Most positive cMRI cases experienced PMC. Negative cMRI in OPC-revisit patients might help clarify the benign nature of a condition.


Assuntos
Cabeça , Cefaleia , Adulto , Humanos , Estudos Retrospectivos , Cefaleia/diagnóstico por imagem , Imageamento por Ressonância Magnética , Serviço Hospitalar de Emergência , Tomografia Computadorizada por Raios X
3.
Clin Radiol ; 79(7): e924-e932, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38622045

RESUMO

AIM: The aim of this study was to identify preoperative magnetic resonance imaging (MRI) findings that can predict the shunt responsiveness in idiopathic normal-pressure hydrocephalus (iNPH) patients and to investigate postoperative outcome and complications. MATERIALS AND METHODS: A total of 192 patients with iNPH who underwent shunt at our hospital between 2000 and 2021 were included to investigate complications. Of these, after exclusion, 127 (1-month postoperative follow-up) and 77 (1-year postoperative follow-up) patients were evaluated. The preoperative MRI features (the presence of tightness of the high-convexity subarachnoid space, Sylvian fissure enlargement, Evans' index, and callosal angle) of the shunt-response and nonresponse groups were compared, and a systematic review was conducted to evaluate whether preoperative MRI findings could predict shunt response. RESULTS: Postoperative complications within one month after surgery were observed in 6.8% (13/192), and the most common complication was hemorrhage. Changes in corpus callosum were observed in 4.2% (8/192). The shunt-response rates were 83.5% (106/127) in the 1-month follow-up group and 70.1% (54/77) in 1-year follow-up group. In the logistic regression analysis, only Evans' index measuring >0.4 had a significant negative relationship with shunt response at 1-month follow-up; however, no significant relationship was observed at 1-year follow-up. According to our systematic review, it is still controversial whether preoperative MRI findings could predict shunt response. CONCLUSION: Evans' index measure of >0.4 had a significant relationship with the shunt response in the 1-month follow-up group. In systematic reviews, there is ongoing debate about whether preoperative MRI findings can accurately predict responses to shunt surgery. Postoperative corpus callosal change was observed in 4.2% of iNPH patients.


Assuntos
Hidrocefalia de Pressão Normal , Imageamento por Ressonância Magnética , Complicações Pós-Operatórias , Humanos , Hidrocefalia de Pressão Normal/cirurgia , Hidrocefalia de Pressão Normal/diagnóstico por imagem , Feminino , Masculino , Imageamento por Ressonância Magnética/métodos , Idoso , Complicações Pós-Operatórias/diagnóstico por imagem , Resultado do Tratamento , Derivações do Líquido Cefalorraquidiano , Estudos Retrospectivos , Cuidados Pré-Operatórios/métodos , Idoso de 80 Anos ou mais , Pessoa de Meia-Idade
4.
J Dairy Sci ; 107(2): 1143-1150, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37709019

RESUMO

Dairy cattle are often restrained for veterinary procedures, but restraint can cause fear responses that can make the procedure challenging for both the animal and the human handler. Positive reinforcement training (PRT) is used in other species to reduce fear responses and there is now evidence that this can also facilitate handling in cattle. The objectives of this study were to test the effect of PRT on anticipatory and play behavior in dairy heifers. We predicted that heifers trained with PRT would show more anticipatory and play behaviors than control heifers in the period before gaining access to a chute. We used 20 heifers (5 ± 0.6 mo old) that had been habituated to the chute area and had previous experience with handling. Heifers were randomly assigned to 2 treatments: control (n = 10) and PRT (n = 10). Positive reinforcement training heifers were subjected to a training protocol that included standard farm handling techniques, as well as target training with food reinforcement. Control heifers were moved to the chute using standard farm handling techniques only. As predicted, PRT heifers performed more behavioral transitions (7.6 ± 0.77 vs. 4.4 ± 0.57 transitions for control heifers; F1,9 = 21.99, P < 0.01), and specifically performed more locomotory play such as jumping (2.1 ± 0.30 vs. 0.4 ± 0.19 jumps; F1,9 = 57.18, P < 0.01) and running (2.0 ± 0.40 s vs. 0.5 ± 0.16 s; F1,9 = 20.73, P < 0.01). These results indicate that PRT results in heifers having a more positive emotional state in anticipation of handling, and support the use of training to improve the welfare of dairy cattle.


Assuntos
Comportamento Animal , Corrida , Bovinos , Animais , Feminino , Humanos , Comportamento Animal/fisiologia , Estresse Fisiológico , Criação de Animais Domésticos/métodos
5.
J Intellect Disabil Res ; 68(3): 212-222, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37899501

RESUMO

BACKGROUND: Obesity in adults without Down syndrome is associated with an adverse metabolic profile including high prevalence of pre-diabetes and diabetes, high levels of insulin, non-high-density lipoprotein (HDL) cholesterol, leptin and high-sensitivity C-reactive protein (hsCRP) and low levels of HDL and adiponectin. We examined whether obesity in middle-aged adults with Down syndrome is also related to an adverse metabolic profile. METHODS: This cross-sectional study included 143 adults with Down syndrome, with a mean age of 55.7 ± 5.7 years and 52.5% women. Body mass index (BMI) was classified as underweight (BMI < 18.5 kg/m2 ), normal (BMI 18.5-24.9 kg/m2 ), overweight (BMI 25-29.9 kg/m2 ) and obese (BMI ≥ 30 kg/m2 ). Diabetes was ascertained by history or by haemoglobin A1c (HbA1c) as normal glucose tolerance (HbA1c < 5.7%), pre-diabetes (HbA1c 5.7-6.4%) and diabetes (HbA1c ≥ 6.5%). We measured non-fasting lipids, hsCRP, insulin, adiponectin and leptin. RESULTS: The majority of the sample had an overweight (46.9%) or obesity (27.3%) status. However, there was a relatively low prevalence of pre-diabetes (9.8%) and diabetes (6.9%). Overweight and obesity status were not associated with lower HDL and adiponectin and higher insulin, non-HDL cholesterol and hsCRP as expected in adults without Down syndrome. However, overweight and obesity were strongly associated with higher leptin (P < 0.001). CONCLUSIONS: The only metabolic correlate of obesity in middle-aged adults with Down syndrome was high leptin levels. Our findings are limited by non-fasting laboratory tests but suggest that middle-aged adults with Down syndrome do not have the adverse metabolic profile related to obesity found in adults without Down syndrome.


Assuntos
Diabetes Mellitus , Síndrome de Down , Síndrome Metabólica , Estado Pré-Diabético , Adulto , Pessoa de Meia-Idade , Feminino , Humanos , Masculino , Leptina , Sobrepeso/epidemiologia , Síndrome Metabólica/epidemiologia , Síndrome Metabólica/complicações , Proteína C-Reativa , Adiponectina , Estado Pré-Diabético/epidemiologia , Estado Pré-Diabético/complicações , Hemoglobinas Glicadas , Estudos Transversais , Síndrome de Down/epidemiologia , Síndrome de Down/complicações , Obesidade/epidemiologia , Obesidade/complicações , Insulina , Índice de Massa Corporal , Colesterol
6.
Niger J Clin Pract ; 27(4): 541-544, 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38679780

RESUMO

ABSTRACT: Myotonic dystrophy (DM) is an autosomal dominant genetic disorder characterized by progressively worsening loss of muscle mass and weakness. Anesthesiologists face challenges in managing these patients due to risks such as prolonged intubation and delayed recovery associated with anesthesia in such conditions. We report a case of a 40-year-old male patient undergoing open total gastrectomy under general anesthesia. After the surgery, we administered sugammadex to reverse neuromuscular blockade and confirmed the patient's spontaneous breathing. We then proceeded to extubate the patient. However, the patient experienced complications such as apnea, desaturation, and mental changes. The patient was re-intubated and transferred to the intensive care unit for ventilator support. He was diagnosed with DM by genetic test later. Poor preoperative assessment or undiagnosed DM in surgical patients can lead to severe complications. Thus, it is important to carefully check preoperative laboratory results, patient history, and physical findings.


Assuntos
Anestesia Geral , Distrofia Miotônica , Humanos , Distrofia Miotônica/diagnóstico , Distrofia Miotônica/complicações , Masculino , Adulto , Anestesia Geral/métodos , Gastrectomia/métodos , Sugammadex , Bloqueio Neuromuscular/métodos
7.
Clin Radiol ; 78(12): e1075-e1080, 2023 12.
Artigo em Inglês | MEDLINE | ID: mdl-37806818

RESUMO

AIM: To review the imaging characteristics of granular cell tumours in the head and neck and assess their associations with pathological findings. MATERIALS AND METHODS: Eleven patients (10 [91%] women, mean age 43 years) with histopathologically confirmed granular cell tumours were included in this study. Preoperative imaging studies were performed, including computed tomography (CT), magnetic resonance imaging (MRI), or ultrasound. The location of the tumours, their imaging features, and histopathological findings were analysed. RESULTS: Among the 11 granular cell tumours, four (36%), three (27%), and two (18%) tumours were found in the submucosal layer, subcutaneous layer, and intramuscular area, respectively. On CT, all tumours exhibited homogeneous iso-attenuating enhancement compared with adjacent muscle, and nine out of the 11 tumours (81%) demonstrated well-defined margins. On T2-weighted imaging (T2WI), four out of five tumours (80%) demonstrated iso-signal intensity compared with adjacent muscles, and four tumours (80%) exhibited homogeneous signal intensity. The apparent diffusion coefficient (ADC) values ranged from 0.68-0.81 × 10-3 mm2/s. Histopathological examination revealed densely packed tumour cells with variable amounts of fibrous stroma. CONCLUSION: Granular cell tumours were characterised by well-defined and iso-signals on T2WI and low mean ADC values, and were predominantly located in the submucosal, subcutaneous, or intramuscular areas in middle-aged women. The characteristic locations, demographic characteristics, and imaging findings can help to differentiate granular cell tumours from other soft-tissue tumours in the head and neck.


Assuntos
Tumor de Células Granulares , Neoplasias de Cabeça e Pescoço , Pessoa de Meia-Idade , Humanos , Feminino , Adulto , Masculino , Tumor de Células Granulares/diagnóstico por imagem , Imageamento por Ressonância Magnética/métodos , Imagem de Difusão por Ressonância Magnética/métodos , Tomografia Computadorizada por Raios X , Neoplasias de Cabeça e Pescoço/diagnóstico por imagem , Estudos Retrospectivos
8.
Clin Radiol ; 78(8): e568-e573, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-37164808

RESUMO

AIM: To investigate computed tomography (CT) and magnetic resonance imaging (MRI) features of skull bases involving anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitides (AAV). MATERIALS AND METHODS: A retrospective review was undertaken to identify an institutional historical cohort of 17 patients with confirmed AAV who underwent CT or MRI and had skull base involvement between 2002 and 2021. Two radiologists reviewed the extent and features of the lesions, bone changes, and other MRI findings. RESULTS: A total of 17 patients (12 men; mean age ± standard deviation, 46.5 ± 17.1 years) were selected. AAV presented as infiltrative lesions with involvement at various sites. Most cases involved the paranasal sinuses (PNS; 88%, 15/17), nasopharynx (88%, 15/17), pterygopalatine fossa (82%, 14/17), and parapharyngeal space (82%, 14/17), frequently accompanied by mucosal irregularity of the PNS and nasopharynx (71%, 12/17). Central skull base and temporal bone involvement were seen in 53% (9/17) and 38% (6/16) of cases, respectively. On T1-weighted imaging (WI) and T2WI MRI, all lesions (15/15) showed predominant signal iso-intensity to grey matter. CONCLUSIONS: Although radiological findings of AAV are non-specific and skull base involvement is less common, AAV may be considered if infiltrative lesions predominantly involving the PNS, nasopharynx, pterygopalatine fossa, and parapharyngeal space with combined bone changes of skull base are seen.


Assuntos
Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos , Seios Paranasais , Masculino , Humanos , Base do Crânio , Tomografia Computadorizada por Raios X/métodos , Seios Paranasais/patologia , Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/diagnóstico por imagem , Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/patologia , Imageamento por Ressonância Magnética/métodos , Estudos Retrospectivos
9.
Hong Kong Med J ; 29(6): 489-497, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38111367

RESUMO

INTRODUCTION: Healthcare workers in intensive care units often experience moral distress, depression, and stress-related symptoms. These conditions can lower staff retention and influence the quality of patient care. This study aimed to evaluate the prevalence of moral distress and psychological status among healthcare workers in a newly established paediatric intensive care unit (PICU) in Hong Kong. METHODS: A cross-sectional questionnaire survey was conducted in the PICU of the Hong Kong Children's Hospital; healthcare workers (doctors, nurses and allied health professionals) were invited to participate. The Revised Moral Distress Scale (MDS-R) Paediatric Version and Depression Anxiety and Stress Scale-21 items were used to assess moral distress and psychological status, respectively. Demographic characteristics were examined in relation to moral distress, depression, anxiety, and stress scores to identify risk factors for poor psychological outcomes. Correlations of moral distress with depression, anxiety, and stress were examined. RESULTS: Forty-six healthcare workers completed the survey. The overall median MDS-R moral distress score was 71. Nurses had a significantly higher median moral distress score, compared with doctors and allied health professionals (102 vs 47 vs 20). Nurses also had the highest median anxiety and stress scores (11 and 20, respectively). Moral distress scores were correlated with depression (r=0.445; P=0.002) and anxiety scores (r=0.417; P<0.05). Healthcare workers intending to quit their jobs had significantly higher moral distress scores (P<0.05). CONCLUSION: Among PICU healthcare workers, nurses had the highest level of moral distress. Moral distress was associated with greater depression, anxiety, and intention to quit. Healthcare workers need support and a sustainable working environment to cope with moral distress.


Assuntos
Pessoal de Saúde , Unidades de Terapia Intensiva Pediátrica , Humanos , Criança , Estudos Transversais , Unidades de Terapia Intensiva , Assistência ao Paciente , Inquéritos e Questionários , Princípios Morais , Estresse Psicológico/epidemiologia , Estresse Psicológico/etiologia
10.
BMC Oral Health ; 23(1): 553, 2023 08 11.
Artigo em Inglês | MEDLINE | ID: mdl-37563659

RESUMO

BACKGROUND: Introducing artificial intelligence (AI) into the medical field proved beneficial in automating tasks and streamlining the practitioners' lives. Hence, this study was conducted to design and evaluate an AI tool called Make Sure Caries Detector and Classifier (MSc) for detecting pathological exposure of pulp on digital periapical radiographs and to compare its performance with dentists. METHODS: This study was a diagnostic, multi-centric study, with 3461 digital periapical radiographs from three countries and seven centers. MSc was built using Yolov5-x model, and it was used for exposed and unexposed pulp detection. The dataset was split into a train, validate, and test dataset; the ratio was 8-1-1 to prevent overfitting. 345 images with 752 labels were randomly allocated to test MSc. The performance metrics used to test MSc performance included mean average precision (mAP), precision, F1 score, recall, and area under receiver operating characteristic curve (AUC). The metrics used to compare the performance with that of 10 certified dentists were: right diagnosis exposed (RDE), right diagnosis not exposed (RDNE), false diagnosis exposed (FDE), false diagnosis not exposed (FDNE), missed diagnosis (MD), and over diagnosis (OD). RESULTS: MSc achieved a performance of more than 90% in all metrics examined: an average precision of 0.928, recall of 0.918, F1-score of 0.922, and AUC of 0.956 (P<.05). The results showed a higher mean of 1.94 for all right (correct) diagnosis parameters in MSc group, while a higher mean of 0.64 for all wrong diagnosis parameters in the dentists group (P<.05). CONCLUSIONS: The designed MSc tool proved itself reliable in the detection and differentiating between exposed and unexposed pulp in the internally validated model. It also showed a better performance for the detection of exposed and unexposed pulp when compared to the 10 dentists' consensus.


Assuntos
Inteligência Artificial , Polpa Dentária , Humanos , Polpa Dentária/diagnóstico por imagem , Curva ROC , Radiografia
11.
Phys Rev Lett ; 128(13): 132501, 2022 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-35426696

RESUMO

We report the first measurement of the parity-violating elastic electron scattering asymmetry on ^{27}Al. The ^{27}Al elastic asymmetry is A_{PV}=2.16±0.11(stat)±0.16(syst) ppm, and was measured at ⟨Q^{2}⟩=0.02357±0.00010 GeV^{2}, ⟨θ_{lab}⟩=7.61°±0.02°, and ⟨E_{lab}⟩=1.157 GeV with the Q_{weak} apparatus at Jefferson Lab. Predictions using a simple Born approximation as well as more sophisticated distorted-wave calculations are in good agreement with this result. From this asymmetry the ^{27}Al neutron radius R_{n}=2.89±0.12 fm was determined using a many-models correlation technique. The corresponding neutron skin thickness R_{n}-R_{p}=-0.04±0.12 fm is small, as expected for a light nucleus with a neutron excess of only 1. This result thus serves as a successful benchmark for electroweak determinations of neutron radii on heavier nuclei. A tree-level approach was used to extract the ^{27}Al weak radius R_{w}=3.00±0.15 fm, and the weak skin thickness R_{wk}-R_{ch}=-0.04±0.15 fm. The weak form factor at this Q^{2} is F_{wk}=0.39±0.04.

12.
Br Poult Sci ; 63(2): 211-217, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-34309442

RESUMO

1. Mineral excretion is an issue in the poultry industry. The use of micro minerals in nano form can increase bioavailability and decrease excretion rate. However, information concerning the bioavailability of nano manganese (Mn) in broiler chicks is limited.2. This experiment studied the influences of hot-melt extrusion (HME)-processed manganese sulphate on body weight gain, Mn bioavailability, nutrient digestibility and meat quality in broiler chicks fed a corn-soybean meal-based diet as a starter and grower phase. A total of 700 birds (Ross 308, 1-day-old) were randomly placed in 35 cages (20 birds per cage). The broiler chicks were fed one of seven experimental diets, which consisted of a control (without supplemental Mn), different levels of MnSO4 (IN-Mn60; 60, 120, and 200 mg/kg), or HME MnSO4 (HME-Mn; 60, 120, and 200 mg/kg).3. There was an increased serum Mn content in broilers fed diet supplemented with HME-Mn. In the grower phase, increased dietary Mn levels elevated the concentrations in the serum, liver, and tibia. There were increases in the excreta Mn content of broilers fed increasing levels. The supplementation of HME-Mn showed a lower percentage of abdominal fat compared with the IN-Mn treatment diets. Supplementation with HME-Mn decreased intramuscular fat compared with the diets supplemented with IN-Mn. The supplementation of HME-Mn decreased the thiobarbituric acid reactive substances (TBARS) at d 6 of age. The HME-Mn source showed a greater decrease in TBARS compared with the IN-Mn treatment.4. In conclusion, HME processing increased bioavailability and could be used as an environmentally friendly method to facilitate lower levels of Mn in the diet of broiler chickens.


Assuntos
Galinhas , Manganês , Ração Animal/análise , Fenômenos Fisiológicos da Nutrição Animal , Animais , Disponibilidade Biológica , Dieta/veterinária , Suplementos Nutricionais , Carne
13.
Ann Oncol ; 32(3): 368-374, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33278599

RESUMO

BACKGROUND: Adjuvant chemotherapy and chemoradiotherapy are some of the standards of care for gastric cancer (GC). The Adjuvant chemoRadioTherapy In Stomach Tumors (ARTIST) 2 trial compares two adjuvant chemotherapy regimens and chemoradiotherapy in patients with D2-resected, stage II or III, node-positive GC. PATIENTS AND METHODS: The ARTIST 2 compared, in a 1:1:1 ratio, three adjuvant regimens: oral S-1 (40-60 mg twice daily 4 weeks on/2 weeks off) for 1 year, S-1 (2 weeks on/1 week off) plus oxaliplatin 130 mg/m2 every 3 weeks (SOX) for 6 months, and SOX plus chemoradiotherapy 45 Gy (SOXRT). Randomization was stratified according to surgery type (total or subtotal gastrectomy), pathologic stage (II or III), and Lauren histologic classification (diffuse or intestinal/mixed). The primary endpoint was disease-free survival (DFS) at 3 years; a reduction of 33% in the hazard ratio (HR) for DFS with SOX or SOXRT, when compared with S-1, was considered clinically meaningful. The trial is registered at clinicaltrials.gov (NCT0176146). RESULTS: A total of 546 patients were recruited between February 2013 and January 2018 with 182, 181, and 183 patients in the S-1, SOX, and SOXRT arms, respectively. Median follow-up period was 47 months, with 178 DFS events observed. Estimated 3-year DFS rates were 64.8%, 74.3%, and 72.8% in the S-1, SOX, and SOXRT arms, respectively. HR for DFS in the control arm (S-1) was shorter than that in the SOX and SOXRT arms: S-1 versus SOX, 0.692 (P = 0.042) and S-1 versus SOXRT, 0.724 (P = 0.074). No difference in DFS was found between SOX and SOXRT (HR 0.971; P = 0.879). Adverse events were as anticipated in each arm, and were generally well-tolerated and manageable. CONCLUSIONS: In patients with curatively D2-resected, stage II/III, node-positive GC, adjuvant SOX or SOXRT was effective in prolonging DFS, when compared with S-1 monotherapy. The addition of radiotherapy to SOX did not significantly reduce the rate of recurrence after D2 gastrectomy.


Assuntos
Neoplasias Gástricas , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Capecitabina/uso terapêutico , Quimioterapia Adjuvante , Intervalo Livre de Doença , Fluoruracila/uso terapêutico , Humanos , Recidiva Local de Neoplasia/patologia , Estadiamento de Neoplasias , Oxaliplatina/uso terapêutico , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/patologia
14.
Cancer Immunol Immunother ; 70(5): 1305-1321, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33140189

RESUMO

Allogeneic natural killer (NK) cell transfer is a potential immunotherapy to eliminate and control cancer. A promising source are CD34 + hematopoietic progenitor cells (HPCs), since large numbers of cytotoxic NK cells can be generated. Effective boosting of NK cell function can be achieved by interleukin (IL)-15. However, its in vivo half-life is short and potent trans-presentation by IL-15 receptor α (IL-15Rα) is absent. Therefore, ImmunityBio developed IL-15 superagonist N-803, which combines IL-15 with an activating mutation, an IL-15Rα sushi domain for trans-presentation, and IgG1-Fc for increased half-life. Here, we investigated whether and how N-803 improves HPC-NK cell functionality in leukemia and ovarian cancer (OC) models in vitro and in vivo in OC-bearing immunodeficient mice. We used flow cytometry-based assays, enzyme-linked immunosorbent assay, microscopy-based serial killing assays, and bioluminescence imaging, for in vitro and in vivo experiments. N-803 increased HPC-NK cell proliferation and interferon (IFN)γ production. On leukemia cells, co-culture with HPC-NK cells and N-803 increased ICAM-1 expression. Furthermore, N-803 improved HPC-NK cell-mediated (serial) leukemia killing. Treating OC spheroids with HPC-NK cells and N-803 increased IFNγ-induced CXCL10 secretion, and target killing after prolonged exposure. In immunodeficient mice bearing human OC, N-803 supported HPC-NK cell persistence in combination with total human immunoglobulins to prevent Fc-mediated HPC-NK cell depletion. Moreover, this combination treatment decreased tumor growth. In conclusion,  N-803 is a promising IL-15-based compound that boosts HPC-NK cell expansion and functionality in vitro and in vivo. Adding N-803 to HPC-NK cell therapy could improve cancer immunotherapy.


Assuntos
Antineoplásicos/uso terapêutico , Interleucina-15/agonistas , Células Matadoras Naturais/imunologia , Leucemia/terapia , Células Progenitoras Linfoides/imunologia , Neoplasias Ovarianas/terapia , Proteínas Recombinantes de Fusão/uso terapêutico , Animais , Antígenos CD34/metabolismo , Antineoplásicos/farmacologia , Diferenciação Celular , Linhagem Celular Tumoral , Testes Imunológicos de Citotoxicidade , Modelos Animais de Doenças , Feminino , Humanos , Interferon gama/metabolismo , Células Matadoras Naturais/transplante , Leucemia/imunologia , Células Progenitoras Linfoides/transplante , Camundongos , Camundongos SCID , Neoplasias Ovarianas/imunologia , Proteínas Recombinantes de Fusão/farmacologia
15.
Ultrasound Obstet Gynecol ; 57(3): 431-439, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-32959909

RESUMO

OBJECTIVE: To evaluate the long-term outcomes of children born to women with a short cervix and otherwise low risk for preterm birth, after antenatal exposure to vaginal progesterone vs placebo. METHODS: This was a follow-up study of the Triple P trial, which randomized 80 low-risk women with a short cervix (≤ 30 mm) at 18-22 weeks' gestation to progesterone (n = 41) or placebo (n = 39). At 2 years of corrected age, children were invited for a neurodevelopmental assessment, using the Bayley Scales of Infant and Toddler Development, third edition (BSID-III), and a neurological and physical examination by an assessor blinded to the allocated treatment. Parents filled out the Ages and Stages Questionnaire, the Child Behavior Checklist (CBCL) and a general-health questionnaire. The main outcome of interest was mean BSID-III cognitive and motor scores. Additionally, a composite score of mortality and abnormal developmental outcome, including BSID-III ≤-1 SD, CBCL score in the clinical range and/or parental reported physical problems (at least two operations or at least two hospital admissions in the previous 2 years), was evaluated. Our sample size, dictated by the original sample of the Triple P trial, provided 80% power to detect a mean difference (MD) of 15 points (1 SD) between groups for the BSID-III tests. RESULTS: Of the 80 children born to the randomized women, one in the progesterone group and two in the placebo group died in the neonatal period. Follow-up data were obtained for 59/77 (77%) children and BSID-III outcomes in 57 children (n = 28 in the progesterone group and n = 29 in the placebo group) born at a median gestational age of 38 + 6 weeks (interquartile range (IQR), 37 + 3 to 40 + 1 weeks) with a median birth weight of 3240 g (IQR, 2785-3620 g). In the progesterone vs placebo groups, mean BSID-III cognitive development scores were 101.6 vs 105.0 (MD, -3.4 (95% CI, -9.3 to 2.6); P = 0.29) while mean motor scores were 102.4 vs 107.3 (MD, -4.9 (95% CI, -11.2 to 1.4); P = 0.13). No differences were seen between the two groups in physical (including genital and neurological examination), behavioral and health-related outcomes. CONCLUSION: In this sample of children born to low-risk women with a short cervix at screening, no relevant differences in neurodevelopmental, behavioral, health-related and physical outcomes were found between offspring exposed to vaginal progesterone and those exposed to placebo. © 2020 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.


Assuntos
Transtornos do Neurodesenvolvimento/epidemiologia , Nascimento Prematuro/prevenção & controle , Efeitos Tardios da Exposição Pré-Natal/epidemiologia , Progesterona/efeitos adversos , Progestinas/efeitos adversos , Administração Intravaginal , Adulto , Medida do Comprimento Cervical , Colo do Útero/patologia , Desenvolvimento Infantil/efeitos dos fármacos , Pré-Escolar , Feminino , Seguimentos , Humanos , Lactente , Recém-Nascido , Masculino , Testes de Estado Mental e Demência , Transtornos do Neurodesenvolvimento/induzido quimicamente , Gravidez , Nascimento Prematuro/diagnóstico por imagem , Efeitos Tardios da Exposição Pré-Natal/induzido quimicamente , Progesterona/administração & dosagem , Progestinas/administração & dosagem , Resultado do Tratamento
16.
Anim Genet ; 52(6): 824-833, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34523150

RESUMO

In the present study, we investigated the major histocompatibility complex (MHC)-B haplotypes diversity of Sri Lankan indigenous chickens from three different geographical sites consisting of highly mixed populations using 90 SNPs in the MHC-B region. A total of 48 haplotypes were identified. Those included 37 novel haplotypes and 11 previously identified 'standard' haplotypes. The MHC-linked marker, LEI0258, had 23 alleles showing less diversity than defined by MHC-B SNP haplotypes. Among those identified haplotypes, five standard haplotypes-BSNP-O02, BSNP-M01, BSNP-A04, BSNP-K03, BSNP-T04-were most commonly observed, suggesting past introgression of imported breeds. Comparison of the MHC-B haplotypes of Sri Lankan and four other global populations with previously defined haplotypes indicated the sharing of 23 standard haplotypes with common origins. Novel haplotypes are population-specific and not shared among the geographical boundaries. Backyard indigenous chickens are unselected, highly crossbred, and generally thrive under dynamic environmental conditions. Hence free-range production systems may be responsible for maintaining high diversity in the MHC-B region with novel haplotypes.


Assuntos
Proteínas Aviárias/genética , Galinhas/genética , Variação Genética , Polimorfismo de Nucleotídeo Único , Animais , Complexo Principal de Histocompatibilidade , Sri Lanka
17.
J Eur Acad Dermatol Venereol ; 35(3): 669-676, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33037671

RESUMO

BACKGROUND: The Breslow depth is an important parameter to determine the excision margin and prognosis of melanoma. However, it is difficult to accurately determine the actual Breslow depth before surgery using the existing ocular micrometer and biopsy technique. OBJECTIVES: To evaluate the use of 3D wide-field multispectral photoacoustic imaging to non-invasively measure depth and outline the boundary of melanomas for optimal surgical margin selection. METHODS: Six melanoma patients were examined in vivo using the 3D multispectral photoacoustic imaging system. For five cases of melanomas (one in situ, three nodular, and one acral lentiginous type melanoma), the spectrally unmixed photoacoustic depths were calculated and compared against histopathological depths. RESULTS: Spectrally unmixed photoacoustic depths and histopathological depths match well within a mean absolute error of 0.36 mm. In particular, the measured minimum and maximum depths in the in situ and nodular type of melanoma were 0.6 and 9.1 mm, respectively. In the 3D photoacoustic image of one metastatic melanoma, feeding vessels were visualized in the melanoma, suggesting the neovascularization around the tumour. CONCLUSIONS: The 3D multispectral photoacoustic imaging not only provides well-measured depth and sizes of various types of melanomas, it also visualizes the metastatic type of melanoma. Obtaining accurate depth and boundary information of melanoma before surgery would play a useful role in the complete excision of melanoma during surgery.


Assuntos
Melanoma , Técnicas Fotoacústicas , Neoplasias Cutâneas , Diagnóstico por Imagem , Humanos , Melanoma/diagnóstico por imagem , Projetos Piloto , Neoplasias Cutâneas/diagnóstico por imagem
18.
Osteoporos Int ; 31(3): 525-531, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31784788

RESUMO

In aged population, the association of thyroid hormones on physical performance, especially within their normal range, has yet to be elucidated. In this study, individuals with low serum free T3/free T4 were likely to have low muscle mass and impaired physical performance. PURPOSE: We aimed to evaluate the associations of muscle mass, strength, and physical performance with thyroid hormone in an aged euthyroid population from a community-based cohort. METHODS: We examined 918 men aged over 60 years and 1215 postmenopausal women from the Ansung cohort study. Appendicular skeletal muscle mass divided by square of height (ASM/ht2) was used as the muscle mass index. Hand grip strength was measured using a hydraulic dynamometer. Physical performance was assessed using the short physical performance battery (SPPB). RESULTS: Participants with higher tertiles of free T3 and free T3/free T4 were younger and had higher ASM/ht2, stronger hand grip strength, and higher SPPB scores than those in the lower tertiles. In adjusted models, men within higher tertiles of free T3 had higher ASM/ht2 compared with those within lower tertiles (p = 0.033), whereas subjects with higher tertiles of free T4 had lower ASM/ht2 compared with those within lower tertiles (p = 0.043). Subjects within higher tertiles of free T3/free T4 had higher ASM/ht2 (p < 0.001) and better physical performance (p = 0.048) than those within lower tertiles after adjustments. However, free T3, free T4, or free T3/free T4 was not related to hand grip strength after adjustment for covariates. CONCLUSION: Our results thus indicate that in an aged euthyroid population, low serum free T3/free T4 was a better index for low muscle mass and impaired physical performance than serum free T3 or free T4 alone.


Assuntos
Força da Mão , Vida Independente , Idoso , Estudos de Coortes , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Músculo Esquelético , Músculos , Desempenho Físico Funcional
19.
Phys Rev Lett ; 124(25): 252501, 2020 Jun 26.
Artigo em Inglês | MEDLINE | ID: mdl-32639790

RESUMO

Transverse single-spin asymmetries of very forward neutral pions generated in polarized p+p collisions allow us to understand the production mechanism in terms of perturbative and nonperturbative strong interactions. During 2017, the RHICf Collaboration installed an electromagnetic calorimeter in the zero-degree region of the STAR detector at the Relativistic Heavy Ion Collider (RHIC) and measured neutral pions produced at pseudorapidity larger than 6 in polarized p+p collisions at sqrt[s]=510 GeV. The large nonzero asymmetries increasing both in longitudinal momentum fraction x_{F} and transverse momentum p_{T} have been observed at low transverse momentum p_{T}<1 GeV/c for the first time, at this collision energy. The asymmetries show an approximate x_{F} scaling in the p_{T} region where nonperturbative processes are expected to dominate. A non-negligible contribution from soft processes may be necessary to explain the nonzero neutral pion asymmetries.

20.
Phys Rev Lett ; 125(11): 112502, 2020 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-32976004

RESUMO

A beam-normal single-spin asymmetry generated in the scattering of transversely polarized electrons from unpolarized nucleons is an observable related to the imaginary part of the two-photon exchange process. We report a 2% precision measurement of the beam-normal single-spin asymmetry in elastic electron-proton scattering with a mean scattering angle of θ_{lab}=7.9° and a mean energy of 1.149 GeV. The asymmetry result is B_{n}=-5.194±0.067(stat)±0.082 (syst) ppm. This is the most precise measurement of this quantity available to date and therefore provides a stringent test of two-photon exchange models at far-forward scattering angles (θ_{lab}→0) where they should be most reliable.

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