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1.
Br J Cancer ; 2020 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-32372027

RESUMO

BACKGROUND: Nasopharyngeal carcinoma (NPC) is an important cancer in Hong Kong. We aim to utilise liquid biopsies for serial monitoring of disseminated NPC in patients to compare with PET-CT imaging in detection of minimal residual disease. METHOD: Prospective serial monitoring of liquid biopsies was performed for 21 metastatic patients. Circulating tumour cell (CTC) enrichment and characterisation was performed using a sized-based microfluidics CTC chip, enumerating by immunofluorescence staining, and using target-capture sequencing to determine blood mutation load. PET-CT scans were used to monitor NPC patients throughout their treatment according to EORTC guidelines. RESULTS: The longitudinal molecular analysis of CTCs by enumeration or NGS mutational profiling findings provide supplementary information to the plasma EBV assay for disease progression for good responders. Strikingly, post-treatment CTC findings detected positive findings in 75% (6/8) of metastatic NPC patients showing complete response by imaging, thereby demonstrating more sensitive CTC detection of minimal residual disease. Positive baseline, post-treatment CTC, and longitudinal change of CTCs significantly associated with poorer progression-free survival by the Kaplan-Meier analysis. CONCLUSIONS: We show the potential usefulness of application of serial analysis in metastatic NPC of liquid biopsy CTCs, as a novel more sensitive biomarker for minimal residual disease, when compared with imaging.

2.
World Neurosurg ; 2020 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-32389871

RESUMO

OBJECTIVE: The aim of this study was to investigate the national impact of demographic, hospital, and inpatient risk factors on post-traumatic hydrocephalus (PTH) development in pediatric patients who presented to the ED following a traumatic brain injury (TBI). METHODS: The Nationwide Emergency Department Sample database years 2010 to 2014 was queried. Patients (<21 years old) with a primary diagnosis of TBI and subsequent secondary diagnosis of PTH were identified using the International Classification of Diseases, Ninth Revision, Clinical Modification coding system. RESULTS: We identified 1,244,087 patients who sustained TBI, of which 930 (0.07%) developed PTH. The rates of subdural hemorrhage and subarachnoid hemorrhage were both significantly higher for the PTH cohort. On multivariate regression, age 6-10 years [OR:0.6, 95% CI: (0.38, 0.93), p=0.022], 11-15 years [OR:0.32, 95% CI: (0.21, 0.48), p<0.0001], and 16-20 years [OR:0.24, 95% CI: (0.15, 0.37), p<0.0001] were independently associated with decreased risk of developing hydrocephalus, compared to ages 0-5 years. Extended loss of consciousness with baseline return and extended loss of consciousness without baseline return were independently associated with increased risk of developing hydrocephalus. Respiratory complication [OR:28.35, 95% CI (15.75, 51.05), p<0.0001], hemorrhage [OR:37.12, 95% CI: (4.79, 287.58), p=0.0001], thromboembolic [OR:8.57, 95% CI: (1.31, 56.19), p=0.025], and neurological complication [OR:64.64, 95% CI: (1.39, 3010.2), p=0.033] were all independently associated with increased risk of developing hydrocephalus. CONCLUSIONS: Our study using the NEDS database demonstrates that various demographic, hospital, and clinical risk factors are associated with the development of hydrocephalus following traumatic brain injury.

3.
Brain Behav Immun ; 2020 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-32305573

RESUMO

Chemotherapy causes various side effects, including cognitive impairment, known as 'chemobrain'. In this study, we determined whether a novel acupuncture mode called electroacupuncture trigeminal nerve stimulation plus body acupuncture (EA/TNS + BA) could produce better outcomes than minimum acupuncture stimulation (MAS) as controls in treating chemobrain and other symptoms in breast cancer patients. In this assessor- and participant-blinded, randomized controlled trial, 93 breast cancer patients under or post chemotherapy were randomly assigned to EA/TNS + BA (n = 46) and MAS (n = 47) for 2 sessions per week over 8 weeks. The Montreal Cognitive Assessment (MoCA) served as the primary outcome. Digit span test was the secondary outcomes for attentional function and working memory. The quality of life and multiple functional assessments were also evaluated. EA/TNS + BA treated group had much better performance than MAS-treated group on reverse digit span test at Week 2 and Week 8, with medium effect sizes of 0.53 and 0.48, respectively, although no significant differences were observed in MoCA score and prevalence of chemobrain between the two groups. EA/TNS + BA also markedly reduced incidences of diarrhoea, poor appetite, headache, anxiety, and irritation, and improved social/family and emotional wellbeing compared to MAS. These results suggest that EA/TNS + BA may have particular benefits in reducing chemotherapy-induced working memory impairment and the incidence of certain digestive, neurological, and distress-related symptoms. It could serve as an effective intervention for breast cancer patients under and post chemotherapy (trial registration: https://www.clinicaltrials.gov: NCT02457039).

4.
Radiother Oncol ; 148: 73-81, 2020 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-32335365

RESUMO

INTRODUCTION: External beam radiotherapy (EBRT) is actively used for hepatocellular carcinoma (HCC) treatment in clinical practice but has not got attention in several guidelines owing to the lack of high-level evidences. We evaluated HCC treatment guidelines from the radiation oncology perspective using the Appraisal of Guidelines for Research and Evaluation (AGREE II) model, to provide information to choose suitable guidelines and for future guidelines developments. METHODS: Guidelines and consensuses for HCC management involving EBRT that have been published until May 2019 were included. Seven appraisers from 6 countries participated; all were radiation oncologists specialized in HCC. Guidelines were assessed using the AGREE II (December 2017 update), and we added an additional domain, "Radiotherapy Content," to evaluate the fidelity of evidence and participation of relevant specialists. Inconsistency among appraisers was evaluated, and standard deviations (SD) among the average scores of each domain were calculated. RESULTS: Eighteen guidelines or consensuses were included; 4 of them (NCCN, EASL, AASLD, and KLCSG)* were considered applicable without modification. Overall scores were evenly and significantly affected by all domain scores, with "Rigour of Development" showing the most significant correlation. The median scores were the highest for "Scope and Purpose" (63.9%) and "Clarity of Presentation" (65.7%) and the lowest for "Applicability" (36.1%). Inconsistency among appraisers was higher in "Editorial Independence" (median SD: 1.96) than in other domains. CONCLUSION: Although the median overall score was moderate (64.3%), further efforts are necessary as all domains had scores <50% except "Scope and Purpose" and "Clarity of Presentation". Future guidelines need to consider more on "Applicability" because modern HCC treatment requires multidisciplinary approaches involving up-to-date techniques and systemic agents. The independency of development and role of funders should be comprehensively described in future guidelines. *National Cancer Comprehensive Network, European Association for the Study of the Liver, American Association for the Study of the Liver Disease, Korean Liver Cancer Study Group.

5.
J Hepatol ; 2020 Mar 10.
Artigo em Inglês | MEDLINE | ID: mdl-32165253

RESUMO

BACKGROUND & AIMS: Few studies have been conducted to compare the efficacies of stereotactic body radiation therapy (SBRT) and radiofrequency ablation (RFA). Thus, in this multinational study, we compared the effectiveness of SBRT and RFA in patients with unresectable HCC. METHODS: The retrospective study cohort included 2,064 patients treated in 7 hospitals: 1,568 and 496 in the RFA and SBRT groups, respectively. More than half of the patients (56.5%) developed recurrent tumors, mainly after transarterial chemoembolization (44.8%). Propensity score matching was performed to adjust for clinical factors (n = 313 in each group). RESULTS: At baseline, the SBRT group had unfavorable clinical features compared to the RFA group, including BCLC stage (B-C 65% vs. 16%), tumor size (median 3.0 cm vs. 1.9 cm), and frequent history of liver-directed treatment (81% vs. 49%, all p <0.001). With a median follow-up of 27.7 months, the 3-year cumulative local recurrence rates in the SBRT and RFA groups were 21.2% and 27.9%, respectively (p <0.001). After adjusting for clinical factors, SBRT was related to a significantly lower risk of local recurrence than RFA in both the entire (hazard ratio [HR] 0.45, p <0.001) and matched (HR 0.36, p <0.001) cohorts. In subgroup analysis, SBRT was associated with superior local control in small tumors (≤3 cm) irrespective of location, large tumors located in the subphrenic region, and those that progressed after transarterial chemoembolization. Acute grade ≥3 toxicities occurred in 1.6% and 2.6% of the SBRT and RFA patients, respectively (p = 0.268). CONCLUSIONS: SBRT could be an effective alternative to RFA for unresectable HCC, particularly for larger tumors (>3 cm) in a subphrenic location and tumors that have progressed after transarterial chemoembolization. LAY SUMMARY: It is currently not known what the best treatment option is for patients with unresectable hepatocellular carcinoma. Here, we show that stereotactic body radiation therapy provides better local control than radiofrequency ablation, with comparable toxicities. Stereotactic body radiation therapy appears to be an effective alternative to radiofrequency ablation that should be considered when there is a higher risk of local recurrence or toxicity after radiofrequency ablation.

6.
Health Qual Life Outcomes ; 18(1): 29, 2020 Feb 17.
Artigo em Inglês | MEDLINE | ID: mdl-32066444

RESUMO

BACKGROUND: Despite the wide use of the Short-Form Supportive Care Needs Survey Questionnaire (SCNS-SF34), the measurement invariance of the SCNS-SF34 across the main groups-gender and age-which might be of interest in the application of the instrument has never been confirmed. To provide an accurate assessment tool to evaluate the unmet needs of Chinese cancer patients, the present study aimed to assess the measurement invariance of the SCNS-SF34 across gender and age groups and to assess the validity and reliability of the Chinese version of the SCNS-SF34. METHODS: The SCNS-SF34 was administrated to 1106 Chinese cancer patients. Other instruments included the Memorial Symptom Assessment Scale-Short Form (MSAS-SF), the Short-Form-12 Health Survey version 2 (SF-12 v2) and the Hospital Anxiety and Depression Scale (HADS). Factor structure, internal construct validity, convergent validity, known-group validity and internal consistency were assessed. RESULTS: Our data fit the original five-factor model. Multi-group confirmatory factor analysis indicated measurement invariance across age and gender groups. The domains of the SCNS-SF34 had moderate correlations with the corresponding domains of the MSAS-SF, the SF-12 v2 and the HADS, which supported convergent validity. Of the 34 items, 33 had an item-total correlation that was corrected for an overlap of > 0.4 to support the internal construct validity. The SCNS-SF34 aptly differentiated patients by age and gender. The Cronbach's alpha coefficient ranged from 0.64 to 0.87. CONCLUSIONS: We confirm the measurement invariance of the Chinese version of the SCNS-SF34 across gender and age group. It is a valid and reliable tool for evaluating the needs of Chinese patients with cancer.

7.
J Cutan Pathol ; 47(6): 548-553, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31943330

RESUMO

Perivascular epithelioid cell tumors (PEComas) are a group of lesions sharing the common features of co-expression of melanocytic and myogenic markers, with focal association of the cells with vascular walls. The PEComa group exhibits a wide range of morphologies. A "fibroma-like" variant of PEComa has been recently described. The case reported herein is that of an infant with tuberous sclerosis complex (TSC) presenting with a lip mass. Excisional biopsy showed a moderately cellular tumor composed of spindled to stellate cells embedded within a collagenized stroma. The cells showed focal perivascular accumulation and positivity for both melanocytic (HMB-45) and myogenic (desmin) markers. This is the fifth reported case of "fibroma-like" PEComa in literature and the youngest patient to date. All of the "fibroma-like" PEComas were found in patients with tuberous sclerosis-hence, the diagnosis of this entity should prompt a workup for TSC; conversely, a fibroma-like lesion in a patient with TSC or with TSC-related conditions should be evaluated using melanocytic and myogenic markers. Melanocytic and myogenic markers are also useful in differentiating "fibroma-like" PEComa from other differential diagnoses such as fibroma and benign fibrous histiocytoma.

9.
World Neurosurg ; 136: e347-e354, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31917315

RESUMO

OBJECTIVE: The aim of this study was to evaluate regional variations in the management, complications, and total cost of admission for adolescent idiopathic scoliosis (AIS) treated by elective posterior spinal surgery (PSF, ≥4 levels). METHODS: The Kids' Inpatient Database year 2012 was queried and adolescent patients (age 10-17 years old) with AIS undergoing elective PSF (≥4 levels) were selected. The primary outcome was regional variations for intraoperative and postoperative complications, length of surgery, and total cost of admission after elective PSF intervention. RESULTS: In our cohort of 3759 adolescent patients identified, 704 (18.7%) patients were treated in the Northeast, 917 (24.4%) in the Midwest, 1329 (35.4%) in the South, and 809 (21.5%) in the West (Northeast: n = 704; Midwest: n = 917; South: n = 1329; West: n = 809). The Northeast had the greatest complication rate, followed by the Midwest, South, and West region cohorts (Northeast: 27.7% vs. Midwest: 24.5% vs. South: 23.0% vs. West: 17.2%, P < 0.001). On average, length of surgery was shortest in the South (Northeast: 5.3 ± 2.7 days vs. Midwest: 5.3 ± 3.1 days vs. South: 4.9 ± 3.1 days vs. West: 5.3 ± 2.1 days, P < 0.001), while the total cost of admission was greatest in the West (Northeast: $51,760 ± $25,177 vs. Midwest: $55,201 ± $23,750 vs. South: $58,847 ± $28,227 vs. West: $60,636 ± $29,372, P < 0.001). CONCLUSIONS: Our study suggests that there may be regional variations in health care resource utilization in AIS patients undergoing multilevel posterior spinal fusions. Further study is warranted to determine the specific factors contributing to disparities in regional outcomes.


Assuntos
Disparidades em Assistência à Saúde/economia , Escoliose/cirurgia , Fusão Vertebral/economia , Fusão Vertebral/métodos , Adolescente , Criança , Feminino , Geografia , Custos de Cuidados de Saúde , Humanos , Masculino , Resultado do Tratamento
10.
Support Care Cancer ; 28(3): 1523-1533, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31280363

RESUMO

PURPOSE: The study adopted a randomized controlled trial to compare the effect of culturally compatible psychosocial interventions on multiple aspects of quality of life (QoL) for family caregivers of lung cancer patients. METHODS: 157 Chinese informal caregivers of lung cancer patients were recruited together with the family members for whom they were providing care, and randomly assigned to either integrative body-mind-spirit intervention (I-BMS) or cognitive behavioral therapy (CBT). Patient-caregiver dyads attended the same arm of intervention in separate groups for 8 weeks. Assessments of generic QoL, anxiety, depression, perceived stress, insomnia, and caregiving burden were measured before intervention (T0), within 1-week (T1), 8-week (T2), and 16-week (T3) post-intervention. RESULTS: Adopting the intention-to-treat analysis, family caregivers in receipt of both I-BMS and CBT exhibited a statistically significant improvement in generic QoL immediately following intervention and at follow-up assessments, with moderate effect size. Improvement of insomnia was found at T1 for both modes, which deteriorated at follow-up; both modes reduced anxiety and perceived stress at follow-up. No intervention effect was observed in depression and domains of caregiving burden. There was no significant interaction effect between intervention type and time. No main or interaction effect between sample background variables and intervention type was found to predict symptomatic changes at T1 and T3. CONCLUSIONS: Culturally attuned I-BMS and CBT exhibited equivalent effectiveness in improving psychological distress and generic QoL for family caregivers of lung cancer patients. To improve the evaluation of outcomes, future study could benefit from incorporating a usual care control.

11.
Mod Pathol ; 33(1): 138-152, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31383965

RESUMO

Female genital melanomas are rare. At diagnosis, most affected patients have advanced disease. Surgery remains the primary treatment, and adjuvant therapy is largely ineffective. Recently, immune checkpoints and the mitogen-activated protein kinase pathway have been explored as treatment targets. However, evaluation of these biomarkers in genital melanomas is limited. We evaluated the clinicopathological features of 20 vulvar, 32 vaginal, and three cervical melanomas and assessed programmed cell death ligand 1 (PD-L1) expression, CD8 tumor-infiltrating lymphocyte density, mismatch repair proteins, VE1 immunohistochemistry, and KIT and BRAF mutations. The median age of the patients was 66 years, and median tumor sizes were 25, 30, and 20 mm for vulvar, vaginal, and cervical tumors, respectively. Mean mitotic figures were 18, 19, and 30 per mm2. Thirty-seven patients (67%) had operable tumors. After a median follow-up of 15 months, only nine patients (16%) were alive. Eight of the nine survivors did not have lymph node metastasis. Using 5% as the threshold, PD-L1 expression was observed in 55%, 50%, and 33% of vulvar, vaginal, and cervical tumors, respectively, when the Roche SP263 antibody was used and 20%, 53%, and 0%, respectively, when the Dako 28-8 antibody was used. The median CD8 tumor-infiltrating lymphocyte density was significantly higher in vulvar/vaginal than cervical melanomas and correlated with PD-L1 expression. No cases exhibited loss of mismatch repair proteins. Five cases harbored KIT mutations, three of which were hotspots. BRAF V600E mutation was not detected. Univariable analysis showed that tumor size greater than or equal to 33 mm, mitotic figures of greater than or equal to 10 per mm2, lymph node metastasis, and low CD8+ tumor-infiltrating lymphocyte density were adverse prognostic factors. Thus, patients with genital melanomas have a poor prognosis, and evaluation of multiple biomarkers is necessary to identify patients who may benefit from immunotherapy or targeted therapy.

12.
Head Neck ; 42(2): 180-187, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31617636

RESUMO

BACKGROUND: This study analyzed the dose volume effects of re-irradiation for locally recurrent nasopharyngeal carcinoma (NPC) and attempts to determine the optimal dose for the best survival. METHODS: Ninety-one patients were studied. The local control, fatal complication, and overall survival were analyzed against the dose (in Equivalent Dose at 2 Gy/fractions) and recurrent gross tumor volume (GTV). RESULTS: The local control and fatal complication rate appear to increase with prescribed dose. The overall survival peaks at around 60 Gy10 . Local control decreases significantly with increasing GTV (P < .001) while overall survival shows similar trend (P = .06). No correlation was observed between the fatal complication rate and GTV volume. The dose response of local control appears to be stronger for smaller tumors. CONCLUSION: GTV volume plays a significant role in local control. A 60 Gy10 appears to be optimal for the best survival outcome; higher doses might be considered for small tumors.

13.
J Thorac Oncol ; 15(3): 324-343, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31733357

RESUMO

Stage III NSCLC represents a heterogeneous disease for which optimal treatment continues to pose a clinical challenge. Recent changes in the American Joint Commission on Cancer staging to the eighth edition has led to a shift in TNM stage grouping and redefined the subcategories (IIIA-C) in stage III NSCLC for better prognostication. Although concurrent chemoradiotherapy has remained standard-of-care for stage III NSCLC for almost 2 decades, contemporary considerations include the impact of different molecular subsets of NSCLC, and the roles of tyrosine kinase inhibitors post-definitive therapy and of immune checkpoint inhibitors following chemoradiotherapy. With rapid evolution of diagnostic algorithms and expanding treatment options, the need for interdisciplinary input involving multiple specialists (medical oncologists, radiation oncologists, pulmonologists, radiologists, pathologists and thoracic surgeons) has become increasingly important. The unique demographics of Asian NSCLC pose further challenges when applying clinical trial data into clinical practice. This includes differences in smoking rates, prevalence of oncogenic driver mutations, and access to health care resources including molecular testing, prompting the need for critical review of existing data and identification of current gaps. In this expert consensus statement by the Asian Thoracic Oncology Research Group, an interdisciplinary group of experts representing Hong Kong, Korea, Japan, Taiwan, Singapore, Thailand, Malaysia, and Mainland China was convened. Standard clinical practices for stage III NSCLC across different Asian countries were discussed from initial diagnosis and staging through to multi-modality approaches including surgery, chemotherapy, radiation, targeted therapies, and immunotherapy.

14.
Hematol Oncol Clin North Am ; 34(1): 109-125, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31739938

RESUMO

Radiotherapy is the most commonly used nonsurgical modality in treatment of lung cancers, non-small cell lung cancer (NSCLC) in particular. Radiation therapy has been increasingly used as definitive radical treatment, either alone or in combination with concurrent chemoradiation for locally advanced disease. More recently with the advent of novel radiation techniques and modalities such as stereotactic radiotherapy and proton therapy, radiotherapy can now be used as sole radical treatment of small solitary tumors. This article reviews the current indications and future directions of radiotherapy in lung cancer management.

15.
Sci Rep ; 9(1): 16919, 2019 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-31729410

RESUMO

Natural sensory signals have nonlinear structures dynamically composed of the carrier frequencies and the variation of the amplitude (i.e., envelope). How the human brain processes the envelope information is still poorly understood, largely due to the conventional analysis failing to quantify it directly. Here, we used a recently developed method, Holo-Hilbert spectral analysis, and steady-state visually evoked potential collected using electroencephalography (EEG) recordings to investigate how the human visual system processes the envelope of amplitude-modulated signals, in this case with a 14 Hz carrier and a 2 Hz envelope. The EEG results demonstrated that in addition to the fundamental stimulus frequencies, 4 Hz amplitude modulation residing in 14 Hz carrier and a broad range of carrier frequencies covering from 8 to 32 Hz modulated by 2 Hz amplitude modulation are also found in the two-dimensional frequency spectrum, which have not yet been recognized before. The envelope of the stimulus is also found to dominantly modulate the response to the incoming signal. The findings thus reveal that the electrophysiological response to amplitude-modulated stimuli is more complex than could be revealed by, for example, Fourier analysis. This highlights the dynamics of neural processes in the visual system.

16.
Org Biomol Chem ; 17(41): 9095-9123, 2019 10 23.
Artigo em Inglês | MEDLINE | ID: mdl-31596305

RESUMO

The Stille coupling between organostannanes and organohalides is an effective catalytic method for organic synthesis. Despite the ample amount of published results in this area, finding the optimal conditions for this transformation is often not straightforward. It was observed that this reaction could be accelerated with improved efficiency by the addition of a Cu(i) salt and fluoride. This review summarises the application of this simple protocol in the synthesis of natural products, their analogues and other biologically active molecules, from 2004 to 2018.


Assuntos
Produtos Biológicos/síntese química , Cobre/química , Fluoretos/química , Compostos Orgânicos de Estanho/química , Técnicas de Química Sintética/métodos
18.
Br J Cancer ; 121(8): 690-698, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31527689

RESUMO

BACKGROUND: Epstein-Barr virus (EBV)-associated nasopharyngeal carcinoma (NPC) in endemic regions may have undetectable plasma EBV DNA. METHODS: We prospectively recruited 518 patients with non-metastatic NPC and measured their pre-treatment plasma EBV DNA. The stage distribution and prognosis between pre-treatment plasma EBV DNA-negative (0-20 copies/ml) and EBV DNA-positive (>20 copies/ml) patients following radical treatment were compared. RESULTS: Seventy-eight patients (15.1%) were plasma EBV DNA-negative, and 62 in this subset (12.0%) had 0 copy/ml. Only 23/78 (29.5%) plasma EBV DNA-negative patients with advanced NPC (stage III-IVA) had strong EBV encoded RNA (EBER) positivity (score 3) in their tumours compared to 342/440 (77.7%) EBV DNA-positive patients of the same stages (p < 0.001). Though EBV DNA-negative patients had more early-stage disease (p < 0.001) and smaller volumes of the primary tumour and the positive neck nodes (p < 0.001), they had similar 5-year overall survival and cancer-specific survival to those EBV DNA-positive counterparts by stage. Similar results were also seen when plasma EBV DNA cut-off was set at 0 copy/ml. CONCLUSIONS: Patients with low-volume NPC may not be identified by plasma/serum tumour markers and caution should be taken in its utility as a screening tool for NPC even in endemic regions. CLINICAL TRIAL REGISTRATION: Clinicaltrials.gov Identifier: NCT02476669.

19.
J Phys Chem A ; 123(37): 8063-8070, 2019 Sep 19.
Artigo em Inglês | MEDLINE | ID: mdl-31408352

RESUMO

An efficient and accurate approach for using diffusion Monte Carlo (DMC) to study molecular clusters is described and applied to an investigation of (H2O)n with n = 1, 2, 3. In this approach, importance sampled DMC is used to describe the intramolecular degrees of freedom of the water monomers. The intermolecular degrees of freedom are treated using standard unguided DMC approaches. This hybrid approach allows us to use significantly smaller simulations to obtain converged zero-point energies and ground state wave functions than would be required for a fully unguided simulation of the same system. We demonstrate the efficiency, accuracy, and utility of this approach through a study of nine isotopologues of water trimer, focusing on how the ground state probability amplitude for these clusters samples the various low-energy minima on the potential surface.

20.
Ther Adv Med Oncol ; 11: 1758835919859990, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31285759

RESUMO

The management of advanced gastric cancer has improved over the past decade. There is more evidence to support the efficacy of systemic treatment in refractory gastric cancer beyond second-line treatment. Important randomized controlled trials of chemotherapies, targeted agents and immunotherapies have been reported. With the development of these novel therapies, clinicians can better individualize treatment for patients beyond progression on second-line therapy. However, there is no guideline on third-line therapy available for clinicians. This review discussed the efficacy and safety data from the pivotal trials of the agents proven to be effective in third-line settings, including the quality of study design, level of evidence and subgroup analysis, and how the data can help to guide clinicians on selecting the most appropriate third-line therapy for their patients.

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