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1.
Brief Bioinform ; 25(3)2024 Mar 27.
Artigo em Inglês | MEDLINE | ID: mdl-38701420

RESUMO

The relationship between genotype and fitness is fundamental to evolution, but quantitatively mapping genotypes to fitness has remained challenging. We propose the Phenotypic-Embedding theorem (P-E theorem) that bridges genotype-phenotype through an encoder-decoder deep learning framework. Inspired by this, we proposed a more general first principle for correlating genotype-phenotype, and the P-E theorem provides a computable basis for the application of first principle. As an application example of the P-E theorem, we developed the Co-attention based Transformer model to bridge Genotype and Fitness model, a Transformer-based pre-train foundation model with downstream supervised fine-tuning that can accurately simulate the neutral evolution of viruses and predict immune escape mutations. Accordingly, following the calculation path of the P-E theorem, we accurately obtained the basic reproduction number (${R}_0$) of SARS-CoV-2 from first principles, quantitatively linked immune escape to viral fitness and plotted the genotype-fitness landscape. The theoretical system we established provides a general and interpretable method to construct genotype-phenotype landscapes, providing a new paradigm for studying theoretical and computational biology.


Assuntos
COVID-19 , Aprendizado Profundo , Genótipo , Fenótipo , SARS-CoV-2 , SARS-CoV-2/genética , SARS-CoV-2/imunologia , Humanos , COVID-19/virologia , COVID-19/genética , COVID-19/imunologia , Biologia Computacional/métodos , Algoritmos , Aptidão Genética
2.
Cancer ; 2024 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-38985726

RESUMO

BACKGROUND: Dermatofibrosarcoma protuberans (DFSP) is a cutaneous sarcoma with an infiltrative growth pattern that makes it challenging to clear margins. High quality data regarding DFSP natural history, management, and outcomes are limited. METHODS: Data were retrospectively collected for adult DFSP patients who underwent resection at 10 institutions in eight countries. Demographics, tumor characteristics, treatment strategies, and outcomes were analyzed. RESULTS: Analysis included 347 patients consisting of young (median, 42 years), White (76.2%), males (54.2%) with truncal lesions (57.3%). The majority (76.8%) were symptomatic at presentation. Preoperative imaging was used in 55.9% of cases. Diagnosis was established with excisional biopsy in 50.9% versus incisional biopsy in 25.0% of cases. Despite planned margins of >1.0 cm in 67.4% of cases, only 69.0% of patients achieved R0 resection. Twenty-two percent of patients underwent at least one re-excision. R0 resection was achieved at a second procedure in 80.2% and a third procedure in 86.2%. Ultimately, R0 resection was feasible in 89.5% of all patients. Fibrosarcomatous transformation (FST) was observed in 12.6%. In total, 6.6% (N = 23) recurred (17 local, six distant). Of the six distant recurrences, 50.0% had FST. With a median follow-up of 47.0 months, disease-specific survival rate was 98.8%. In multivariable analysis, R0 margins at index resection were associated with wider circumferential margins and non-FST histology. CONCLUSIONS: In this international, multicenter collaborative, DFSP practice patterns were heterogeneous but achieved favorable recurrence rates and survival. Multiple excisions to clear margins remain commonplace and can inform future efforts to optimize margin selection.

3.
BMC Cancer ; 24(1): 1068, 2024 Aug 29.
Artigo em Inglês | MEDLINE | ID: mdl-39210306

RESUMO

BACKGROUND: Disulfidptosis is an emerging form of cellular death resulting from the binding of intracellular disulfide bonds to actin cytoskeleton proteins. This study aimed to investigate the expression and prognostic significance of hub disulfidptosis-related lncRNAs (DRLRs) in R0 resected hepatocellular carcinoma (HCC) as well as their impact on the malignant behaviour of HCC cells. METHODS: A robust signature for R0 resected HCC was constructed using least absolute shrinkage and selection operator (LASSO) and multivariate Cox regression and was validated in an independent internal validation cohort to predict the prognosis of R0 HCC patients. Comprehensive bioinformatics analysis was performed on the hub DRLRs (KDM4A-AS1, MKLN1-AS, and TMCC1-AS1), followed by experimental validation using quantitative real-time polymerase chain reaction (qRT‒PCR) and cellular functional assays. RESULTS: The signature served as an independent prognostic factor applicable to R0 HCC patients across different age groups, tumour stages, and pathological characteristics. Gene Ontology (GO) and gene set enrichment analysis (GSEA) revealed hub pathways associated with this signature. The high-risk group presented an increased abundance of M0 macrophages and activated memory CD4 T cells as well as elevated macrophage and major histocompatibility complex (MHC) class I expression. High-risk R0 HCC patients also presented increased tumour immune dysfunction and exclusion scores (TIDEs), mutation frequencies, and tumour mutational burdens (TMBs). Drug sensitivity analysis revealed that high-risk patients were more responsive to drugs, including GDC0810 and osimertinib. High expression levels of the three hub DRLRs were detected in R0 HCC tissues and HCC cell lines. Functional assays revealed that the three hub DRLRs enhanced HCC cell proliferation, migration, and invasion. CONCLUSIONS: A signature was constructed on the basis of three DRLRs, providing novel insights for personalized precision therapy in R0 HCC patients.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , RNA Longo não Codificante , Humanos , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/patologia , Carcinoma Hepatocelular/cirurgia , Carcinoma Hepatocelular/mortalidade , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/cirurgia , RNA Longo não Codificante/genética , Prognóstico , Masculino , Biomarcadores Tumorais/genética , Feminino , Regulação Neoplásica da Expressão Gênica , Pessoa de Meia-Idade , Proliferação de Células/genética , Linhagem Celular Tumoral , Biologia Computacional/métodos
4.
J Surg Oncol ; 129(7): 1235-1244, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38419193

RESUMO

BACKGROUND: Surgeons rarely perform elective total pancreatectomy (TP). Our study seeks to report surgical outcomes in a contemporary series of single-stage (SS) TP patients. METHODS: Between the years 2013 to 2023 we conducted a retrospective review of 60 consecutive patients who underwent SSTP. Demographics, pathology, treatment-related variables, and survival were recorded and analyzed. RESULTS: SSTP consisted of 3% (60/1859) of elective pancreas resections conducted. Patient median age was 68 years. Ninety percent of these patients (n = 54) underwent SSTP for pancreatic ductal adenocarcinoma (PDAC). Conversion from a planned partial pancreatectomy to TP occurred intraoperatively in 31 (52%) patients. Fifty-nine patients (98%) underwent an R0 resection. Median length of hospital stay was 6 days. The majority of morbidities were minor, with 27% patients (n = 16) developing severe complications (Clavien-Dindo ≥3). Thirty and ninety-day mortality rates were 1.67% (one patient) and 5% (three patients), respectively. Median survival for the entire cohort was 24.4 months; 22.7 months for PDAC patients, with 1-, 3-, and 5-year survival of 68%, 43%, and 16%, respectively. No mortality occurred in non-PDAC patients (n = 6). CONCLUSION: Elective single-stage total pancreatectomy can be a safe and appropriate treatment option. SSTP should be in the armamentarium of surgeons performing pancreatic resection.


Assuntos
Carcinoma Ductal Pancreático , Pancreatectomia , Neoplasias Pancreáticas , Humanos , Pancreatectomia/métodos , Pancreatectomia/mortalidade , Masculino , Feminino , Idoso , Estudos Retrospectivos , Neoplasias Pancreáticas/cirurgia , Neoplasias Pancreáticas/mortalidade , Neoplasias Pancreáticas/patologia , Pessoa de Meia-Idade , Carcinoma Ductal Pancreático/cirurgia , Carcinoma Ductal Pancreático/mortalidade , Carcinoma Ductal Pancreático/patologia , Idoso de 80 Anos ou mais , Adulto , Resultado do Tratamento , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Taxa de Sobrevida , Seguimentos , Tempo de Internação/estatística & dados numéricos
5.
J Am Acad Dermatol ; 2024 Jul 09.
Artigo em Inglês | MEDLINE | ID: mdl-38980249

RESUMO

The rising global popularity of cosmetic and corrective tattoos has concurrently led to an increased demand for their removal. While in the past, methods like surgical excision, chemical destruction, and dermabrasion were employed, lasers have emerged as a reliable and effective tool for tattoo removal. Increasing technological options and combination treatment strategies have raised the importance of understanding the various approaches to laser tattoo removal along with their respective clinical impact. This CME aims to describe the multifaceted aspects of laser tattoo removal, including the method selection, application principles, and safety considerations. Furthermore, it addresses the factors considered when selecting the most suitable laser to achieve optimal treatment outcomes.

6.
World J Surg Oncol ; 22(1): 113, 2024 Apr 26.
Artigo em Inglês | MEDLINE | ID: mdl-38664776

RESUMO

BACKGROUND: The standard curative treatments for extremity soft tissue sarcoma (ESTS) include surgical resection with negative margins and perioperative radiotherapy. However, the optimal resection margin remains controversial. This study aimed to evaluate the outcomes in ESTS between microscopically positive margin (R1) and microscopically negative margin (R0) according to the Union for International Cancer Control (UICC) (R + 1 mm) classification. METHODS: Medical records of patients with localized ESTS who underwent primary limb-sparing surgery and postoperative radiotherapy between 2004 and 2015 were retrospectively reviewed. Patients were followed for at least 5 years or till local or distant recurrence was diagnosed during follow-up. Outcomes were local and distal recurrences and survival. RESULTS: A total of 52 patients were included in this study, in which 17 underwent R0 resection and 35 underwent R1 resection. No significant differences were observed in rates of local recurrence (11.4% vs. 35.3%, p = 0.062) or distant recurrence (40.0% vs. 41.18%, p = 0.935) between R0 and R1 groups. Multivariate analysis showed that distant recurrences was associated with a Fédération Nationale des Centres de Lutte Contre le Cancer (FNCLCC) grade (Grade III vs. I, adjusted hazard ratio (aHR): 12.53, 95% confidence interval (CI): 2.67-58.88, p = 0.001) and tumor location (lower vs. upper extremity, aHR: 0.23, 95% CI: 0.07-0.7, p = 0.01). Kaplan-Meier plots showed no significant differences in local (p = 0.444) or distant recurrent-free survival (p = 0.161) between R0 and R1 groups. CONCLUSIONS: R1 margins, when complemented by radiotherapy, did not significantly alter outcomes of ESTS as R0 margins. Further studies with more histopathological types and larger cohorts are necessary to highlight the path forward.


Assuntos
Extremidades , Margens de Excisão , Recidiva Local de Neoplasia , Sarcoma , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Sarcoma/cirurgia , Sarcoma/patologia , Sarcoma/radioterapia , Sarcoma/mortalidade , Estudos Retrospectivos , Recidiva Local de Neoplasia/patologia , Recidiva Local de Neoplasia/epidemiologia , Recidiva Local de Neoplasia/cirurgia , Extremidades/patologia , Extremidades/cirurgia , Adulto , Seguimentos , Taxa de Sobrevida , Idoso , Prognóstico , Radioterapia Adjuvante/métodos , Radioterapia Adjuvante/estatística & dados numéricos , Tratamentos com Preservação do Órgão/métodos , Tratamentos com Preservação do Órgão/estatística & dados numéricos , Adulto Jovem , Neoplasias de Tecidos Moles/cirurgia , Neoplasias de Tecidos Moles/patologia , Neoplasias de Tecidos Moles/radioterapia , Neoplasias de Tecidos Moles/mortalidade , Adolescente
7.
Proc Natl Acad Sci U S A ; 118(41)2021 10 12.
Artigo em Inglês | MEDLINE | ID: mdl-34615712

RESUMO

Zoonotic spillover and hybridization of parasites are major emerging public and veterinary health concerns at the interface of infectious disease biology, evolution, and control. Schistosomiasis is a neglected tropical disease of global importance caused by parasites of the Schistosoma genus, and the Schistosoma spp. system within Africa represents a key example of a system where spillover of animal parasites into human populations has enabled formation of hybrids. Combining model-based approaches and analyses of parasitological, molecular, and epidemiological data from northern Senegal, a region with a high prevalence of schistosome hybrids, we aimed to unravel the transmission dynamics of this complex multihost, multiparasite system. Using Bayesian methods and by estimating the basic reproduction number (R0 ), we evaluate the frequency of zoonotic spillover of Schistosoma bovis from livestock and the potential for onward transmission of hybrid S. bovis × S. haematobium offspring within human populations. We estimate R0 of hybrid schistosomes to be greater than the critical threshold of one (1.76; 95% CI 1.59 to 1.99), demonstrating the potential for hybridization to facilitate spread and establishment of schistosomiasis beyond its original geographical boundaries. We estimate R0 for S. bovis to be greater than one in cattle (1.43; 95% CI 1.24 to 1.85) but not in other ruminants, confirming cattle as the primary zoonotic reservoir. Through longitudinal simulations, we also show that where S. bovis and S. haematobium are coendemic (in livestock and humans respectively), the relative importance of zoonotic transmission is predicted to increase as the disease in humans nears elimination.


Assuntos
Número Básico de Reprodução/estatística & dados numéricos , Gado/parasitologia , Schistosoma haematobium/patogenicidade , Esquistossomose Urinária/transmissão , Esquistossomose Urinária/veterinária , Animais , Bovinos/parasitologia , Cabras/parasitologia , Humanos , Doenças Negligenciadas/parasitologia , Senegal/epidemiologia , Ovinos/parasitologia , Zoonoses/parasitologia , Zoonoses/transmissão
8.
Ecotoxicology ; 33(7): 801-817, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-39003411

RESUMO

Two monophyletic Daphnia species (Daphnia magna and D. similis) were exposed to a sub-lethal concentration of Pb (50 µg/L) for nine generations under two food regimes (usual and restricted) and analyzed for acetylcholinesterase (AChE) activity, first reproduction delay, lifespan, and net reproductive rate (R0) at the subcellular, individual, and population levels, respectively. In the sixth generation, Pb-acclimated neonates were moved to clean media for three more generations to check for recovery. The net reproductive rate (R0) of D. magna was not affected by Pb. However, Pb stimulated reproduction, reduced lifespan, and decreased AChE activity. First reproduction delay and lifespan did not improve during the recovery process, suggesting a possible genetic adaptation. Food restriction reduced R0, lifespan, delayed hatching, and increased AChE activity; the opposite outcomes were observed for D. similis. The full recovery shown by R0 suggests the physiological acclimation of D. similis. Under food restriction, the animals exhibited a reduction of R0 and lifespan, delayed first reproduction, and increased AChE activity; however, there was no effect of Pb. The recovery process under food restriction showed that D. similis might not cope with Pb exposure, indicating a failed recovery. Such outcomes indicate that one model species' sensitivity may not represent another's sensitivity.


Assuntos
Daphnia , Chumbo , Reprodução , Poluentes Químicos da Água , Animais , Daphnia/fisiologia , Daphnia/efeitos dos fármacos , Chumbo/toxicidade , Poluentes Químicos da Água/toxicidade , Reprodução/efeitos dos fármacos , Acetilcolinesterase/metabolismo , Longevidade/efeitos dos fármacos
9.
Molecules ; 29(9)2024 Apr 25.
Artigo em Inglês | MEDLINE | ID: mdl-38731473

RESUMO

Chalkophomycin is a novel chalkophore with antibiotic activities isolated from Streptomyces sp. CB00271, while its potential in studying cellular copper homeostasis makes it an important probe and drug lead. The constellation of N-hydroxylpyrrole, 2H-oxazoline, diazeniumdiolate, and methoxypyrrolinone functional groups into one compact molecular architecture capable of coordinating cupric ions draws interest to unprecedented enzymology responsible for chalkophomycin biosynthesis. To elucidate the biosynthetic machinery for chalkophomycin production, the chm biosynthetic gene cluster from S. sp. CB00271 was identified, and its involvement in chalkophomycin biosynthesis was confirmed by gene replacement. The chm cluster was localized to a ~31 kb DNA region, consisting of 19 open reading frames that encode five nonribosomal peptide synthetases (ChmHIJLO), one modular polyketide synthase (ChmP), six tailoring enzymes (ChmFGMNQR), two regulatory proteins (ChmAB), and four resistance proteins (ChmA'CDE). A model for chalkophomycin biosynthesis is proposed based on functional assignments from sequence analysis and structure modelling, and is further supported by analogy to over 100 chm-type gene clusters in public databases. Our studies thus set the stage to fully investigate chalkophomycin biosynthesis and to engineer chalkophomycin analogues through a synthetic biology approach.


Assuntos
Família Multigênica , Peptídeo Sintases , Policetídeo Sintases , Streptomyces , Streptomyces/genética , Streptomyces/enzimologia , Streptomyces/metabolismo , Policetídeo Sintases/genética , Policetídeo Sintases/metabolismo , Policetídeo Sintases/química , Peptídeo Sintases/metabolismo , Peptídeo Sintases/genética , Peptídeo Sintases/química , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Proteínas de Bactérias/química
10.
J Med Virol ; 95(3): e28683, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-36929727

RESUMO

An ongoing outbreak of monkeypox virus (MPXV) was first reported in the United Kingdom on 6 May 2022. As of 17 November, there had been a total of 80 221 confirmed MPXV cases in over 110 countries. Based on data reported between 6 May and 30 June 2022 in the United Kingdom, Spain, and Germany, we applied a deep learning approach using convolutional neural networks to evaluate the parameters of the 2022 MPXV outbreak. The basic reproduction number (R0 ) of MPXV was estimated to be 2.32 in the United Kingdom, which indicates the active diffusion of MPXV since the beginning of the outbreak. The data from Spain and Germany produced higher median R0 values of 2.42 and 2.88, respectively. Importantly, the estimated R0 of MPXV in the three countries tends to the previously calculated R0 of smallpox (3.50 to 6.00). Furthermore, the incubation (1/ε) and infectious (1/γ) period was predicted between 9 and 10 days and 4-5 days, respectively. The R0 value derived from MPXV is consistent with the significantly increasing number of cases, indicating the risk of a rapid spread of MPXV worldwide, which would provide important insights for the prevention and control of MPXV epidemic.


Assuntos
Epidemias , Mpox , Humanos , Mpox/epidemiologia , Surtos de Doenças , Número Básico de Reprodução , Alemanha/epidemiologia , Monkeypox virus
11.
J Med Virol ; 95(10): e29153, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-37804388

RESUMO

The transmissibility is a crucial feature for norovirus, yet its quantitative estimation has been limited. Our objective was to estimate the basic reproduction number (R0 ) of norovirus and investigate its variation characteristics. Norovirus outbreaks reported from September 2016 to August 2021 in Beijing were analyzed. The susceptible-infected-removed compartment model was established to estimate R0 . Linear regression models and logistic regression models were used to explore the factors affecting the transmissibility of norovirus. The overall median R0 of norovirus was estimated as 2.1 (interquartile range [IQR] 1.8-2.5), with 650 norovirus outbreaks. The transmissibility of norovirus varied by year, outbreak setting and genotype. The R0 of norovirus during September 2019 to August 2020 (median 2.1, IQR 1.8-2.4) and September 2020 to August 2021 (median 2.0, IQR 1.7-2.3) was lower than that of September 2016 to August 2017 (median 2.3, IQR 1.8-2.7) (ß = 0.94, p = 0.05; ß = 0.93, p = 0.008). The R0 of norovirus for all other settings was lower than that for kindergarten (median 2.4, IQR 2.0-2.9) (primary school: median 2.0, IQR 1.7-2.4, ß = 0.94, p = 0.001; secondary school: median 1.7, IQR 1.5-2.0, ß = 0.87, p < 0.001; college: median 1.7, IQR 1.5-1.8, ß = 0.89, p = 0.03; other closed settings: median 1.8, IQR 1.5-2.0, ß = 0.90, p = 0.004). GⅡ.2[P16] outbreaks had a median R0 of 2.2 (IQR 1.8-2.7), which was higher than that for GⅡ.6[P7] outbreaks (median 1.8, IQR: 1.8-2.0, odds ratio = 0.19, p = 0.03; GⅡ.2[P16] as reference) and mixed-genotype outbreaks (median 1.7, IQR: 1.5-1.8, ß = 0.92, p = 0.02; mixed-genotype as reference). In kindergartens and primary schools, norovirus shows increased transmissibility, emphasizing the vulnerable population and high-risk settings. Furthermore, the transmissibility of norovirus may change over time and with virus evolution, necessitating additional research to uncover the underlying mechanisms.


Assuntos
Infecções por Caliciviridae , Gastroenterite , Norovirus , Humanos , Pequim/epidemiologia , Norovirus/genética , Gastroenterite/epidemiologia , Infecções por Caliciviridae/epidemiologia , China/epidemiologia , Surtos de Doenças , Genótipo
12.
Ann Surg Oncol ; 30(8): 5093-5102, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37140750

RESUMO

BACKGROUND: The efficacy of neoadjuvant chemotherapy with gemcitabine plus S-1 (NAC-GS) in the prognosis of patients with resectable pancreatic ductal adenocarcinoma (PDAC) has been reported. NAC-GS is now assumed to be a standard regimen for resectable PDAC in Japan. However, the reason for this improvement in prognosis remains unclear. METHODS: In 2019, we introduced NAC-GS for resectable PDAC. From 2015 to 2021, 340 patients were diagnosed with resectable PDAC (anatomical and biological [carbohydrate antigen (CA) 19-9 < 500 U/mL]) and were divided according to the treatment period (upfront surgery [UPS] group, 2015-2019, n = 241; NAC-GS group, 2019-2021, n = 80). We used "intention-to-treat" analysis to compare the clinical outcomes of NAC-GS to those of UPS. RESULTS: Of the 80 patients with NAC-GS, 75 (93.8%) completed two cycles of NAC-GS, and the resection rate of the NAC-GS group was comparable to that of the UPS group (92.5 vs. 91.3%, P = 0.73). The R0 resection rate was significantly higher in the NAC-GS group than in the UPS group (91.3 vs. 82.6%, P = 0.04), even though the surgical burden was smaller. Progression-free survival tended to be better (hazard ratio [HR] = 0.70, P = 0.06), and overall survival was significantly better in the NAC-GS group than in the UPS group (HR 0.55, P = 0.02). CONCLUSIONS: NAC-GS provided improvements in microscopic invasion leading to a high R0 rate and smooth administration and completion of adjuvant therapy, which might lead to an improved prognosis in patients with resectable PDAC.


Assuntos
Carcinoma Ductal Pancreático , Neoplasias Pancreáticas , Humanos , Gencitabina , Terapia Neoadjuvante , Carcinoma Ductal Pancreático/tratamento farmacológico , Carcinoma Ductal Pancreático/cirurgia , Neoplasias Pancreáticas/tratamento farmacológico , Neoplasias Pancreáticas/cirurgia , Neoplasias Pancreáticas/patologia , Resultado do Tratamento , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Pancreáticas
13.
BMC Cancer ; 23(1): 49, 2023 Jan 14.
Artigo em Inglês | MEDLINE | ID: mdl-36641427

RESUMO

BACKGROUND: With the advent of intensive combination regimens, an increasing number of patients with unresectable pancreatic cancer (UPC) have regained the opportunity for surgery. We investigated the clinical benefits and prognostic factors of conversion surgery (CS) in UPC patients. METHODS: We retrospectively enrolled patients with UPC who had received CS following first-line systemic treatment in our center between 2014 to 2022. Treatment response, safety of the surgical procedure and clinicopathological data were collected. We analyzed the prognostic factors for postoperative survival among UPC patients who had CS. RESULTS: Sixty-seven patients with UPC were enrolled (53 with locally advanced pancreatic cancer (LAPC) and 14 with metastatic pancreatic cancer (MPC)). The duration of preoperative systemic treatment was 4.17 months for LAPC patients and 6.52 months for MPC patients. All patients experienced a partial response (PR) or had stable disease (SD) preoperatively according to imaging. Tumor resection was unsuccessful in four patients and, finally, R0 resection was obtained in 81% of cases. Downstaging was determined pathologically in 87% of cases; four patients achieved a complete pathological response. Median postoperative-progression-free survival (PO-PFS) was 9.77 months and postoperative overall survival (PO-OS) was 31.2 months. Multivariate logistic regression analyses revealed that the resection margin and postoperative changes in levels of tumor markers were significant prognostic factors for PO-PFS. No factors were associated significantly with PO-OS according to multivariate analyses. CONCLUSIONS: CS is a promising strategy for improving the prognosis of UPC patients. The resection margin and postoperative change in levels of tumor markers are the most important prognostic factors for prolonged PFS. Multidisciplinary treatment in high-volume centers is strongly recommended. Prospective studies must be undertaken to resolve the various problems regarding optimal regimens, the duration of treatment, and detailed criteria for CS.


Assuntos
Biomarcadores Tumorais , Neoplasias Pancreáticas , Humanos , Intervalo Livre de Progressão , Estudos Prospectivos , Estudos Retrospectivos , Margens de Excisão , Neoplasias Pancreáticas/patologia , Prognóstico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Pancreáticas
14.
Colorectal Dis ; 25(7): 1423-1432, 2023 07.
Artigo em Inglês | MEDLINE | ID: mdl-37246309

RESUMO

AIM: Extended total mesorectal excision (eTME) is a complex procedure involving en bloc resection of the structures surrounding the various quadrants of the rectum. This study, presenting the largest series so far of patients undergoing eTME, aimed to assess the surgical and survival outcomes of patients following treatment with eTME and to compare these outcomes with historical data on pelvic exenteration. METHOD: The study is a retrospective review of all patients with locally advanced rectal cancer requiring an eTME (2014-2020). The database includes the demographic profile, operative details, histopathological features and follow-up. RESULTS: One hundred and sixty three patients who underwent eTME were analysed. The overall Clavien-Dindo complication rate of > IIIa was 21.1%. The anterior quadrant was the most common anatomical site resected (68.5%). The R1 resection rate was 10.4%. After a median follow-up of 28 months, there were 51 recurrences in the study and twenty two deaths were recorded. The local recurrence rate was 7.3% among the study population. The disease-free survival (DFS) and overall survival were 66.7% and 80.4%, respectively, at 3 years. The majority of the recurrences were distant metastasis (84.3%). In univariate analysis, the quadrant involved did not affect survival. In multivariate analysis, signet ring histology, metastatic presentation, inadequate tumour response and R1 resection affected DFS. CONCLUSION: The recurrence pattern, R1 resection rate and survival outcomes of patients in the present study were comparable with those for patients undergoing an exenteration. Therefore, eTME is probably a safe alternative to pelvic exenterations when R0 resection is achievable and when the procedure is performed in high-volume specialist tertiary care centres.


Assuntos
Exenteração Pélvica , Neoplasias Retais , Humanos , Reto/cirurgia , Reto/patologia , Resultado do Tratamento , Neoplasias Retais/patologia , Intervalo Livre de Doença , Estudos Retrospectivos , Exenteração Pélvica/métodos , Recidiva , Recidiva Local de Neoplasia/patologia
15.
Surg Endosc ; 37(2): 1293-1302, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-36192659

RESUMO

BACKGROUND: Endoscopic submucosal dissection (ESD) has gained increasing popularity in the management of complicated colorectal polyps. However, clinical outcomes for ESD have remained highly inconsistent worldwide. This study investigated and analysed factors that significantly affect ESD outcomes. METHODS: We conducted a single-centred retrospective study on 220 colorectal polyps removed by ESD from 1st January 2016 to 31st December 2020. Data were collected and retrieved from clinical records. Variables studied included patient demographics, ESD technicalities and polyp characteristics. The primary outcome was completeness of resection based on en bloc and R0 resection rates. The secondary outcomes were recurrence, complications and hospital stay. Further analysis was performed for significant outcome determining factors. RESULTS: The en bloc resection and R0 resection rates were 97.3% and 65% respectively. Intraprocedural and delayed perforation rates were 3.2% and 0.5% respectively. Intraprocedural and delayed bleeding rates were both 1.8%. Post-polypectomy syndrome rate was 2.7%. The median hospital stay was 4 days. Submucosal fibrosis was a significant determining factor for lower en bloc resection (p = 0.004), lower R0 resection (p = 0.002), intraprocedural perforation (p = 0.001), intraprocedural bleeding (p = 0.025) and post-polypectomy syndrome (p = 0.039). Hybrid snaring was associated with lower en bloc resection (p < 0.001), while longer ESD time was associated with lower R0 resection (p = 0.003) and post-polypectomy syndrome (p = 0.025). Other significant factors for post-polypectomy syndrome included young age (p = 0.021) and large polyp size (p = 0.018). Secondary analysis showed that submucosal fibrosis was significantly associated with non-granular lesions (p < 0.001) and prior biopsy (p = 0.003). CONCLUSION: Submucosal fibrosis, hybrid snaring, ESD time, age and polyp size were significant outcome determining factors for ESD. By identifying these factors, strategies may be formulated to improve ESD outcomes.


Assuntos
Doenças do Colo , Pólipos do Colo , Neoplasias Colorretais , Ressecção Endoscópica de Mucosa , Fibrose Oral Submucosa , Humanos , Neoplasias Colorretais/cirurgia , Estudos Retrospectivos , Complicações Pós-Operatórias , Resultado do Tratamento
16.
BMC Public Health ; 23(1): 404, 2023 02 28.
Artigo em Inglês | MEDLINE | ID: mdl-36855085

RESUMO

OBJECTIVE: To summarise the dynamic characteristics of COVID-19 transmissibility; To analyse and quantify the effect of control measures on controlling the transmissibility of COVID-19; To predict and compare the effectiveness of different control measures. METHODS: We used the basic reproduction number ([Formula: see text]) to measure the transmissibility of COVID-19, the transmissibility of COVID-19 and control measures of 176 countries and regions from January 1, 2020 to May 14, 2022 were included in the study. The dynamic characteristics of COVID-19 transmissibility were summarised through descriptive research and a Dynamic Bayesian Network (DBN) model was constructed to quantify the effect of control measures on controlling the transmissibility of COVID-19. RESULTS: The results show that the spatial transmissibility of COVID-19 is high in Asia, Europe and Africa, the temporal transmissibility of COVID-19 increases with the epidemic of Beta and Omicron strains. Dynamic Bayesian Network (DBN) model shows that the transmissibility of COVID-19 is negatively correlated with control measures. Restricting population mobility has the strongest effect, nucleic acid testing (NAT) has a strong effect, and vaccination has the weakest effect. CONCLUSION: Strict control measures are essential for controlling the COVID-19 outbreak; Restricting population mobility and nucleic acid testing (NAT) have significant impacts on controlling the COVID-19 transmissibility, while vaccination has no significant impact. In light of these findings, future control measures may include the widespread use of new NAT technology and the promotion of booster immunization.


Assuntos
COVID-19 , Ácidos Nucleicos , Humanos , Teorema de Bayes , COVID-19/epidemiologia , COVID-19/prevenção & controle , África/epidemiologia , Ásia
17.
Risk Anal ; 43(1): 129-143, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-35704273

RESUMO

Early in the pandemic of coronavirus disease 2019 (COVID-19), face masks were used extensively by the general public in several Asian countries. The lower transmission rate of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in Asian countries compared with Western countries suggested that the wider community use of face masks has the potential to decrease transmission of SARS-CoV-2. A risk assessment model named Susceptible, Exposed, Infectious, Recovered (SEIR) model is used to quantitatively evaluate the potential impact of community face masks on SARS-CoV-2 reproduction number (R0 ) and peak number of infectious persons. For a simulated population of one million, the model showed a reduction in R0 of 49% and 50% when 60% and 80% of the population wore masks, respectively. Moreover, we present a modified model that considers the effect of mask-wearing after community vaccination. Interestingly mask-wearing still provided a considerable benefit in lowering the number of infectious individuals. The results of this research are expected to help public health officials in making prompt decisions involving resource allocation and crafting legislation.


Assuntos
COVID-19 , Doenças Transmissíveis , Humanos , COVID-19/prevenção & controle , Pandemias/prevenção & controle , SARS-CoV-2 , Máscaras
18.
Chaos Solitons Fractals ; 166: 112920, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36440088

RESUMO

The world experienced the life-threatening COVID-19 disease worldwide since its inversion. The whole world experienced difficult moments during the COVID-19 period, whereby most individual lives were affected by the disease socially and economically. The disease caused millions of illnesses and hundreds of thousands of deaths worldwide. To fight and control the COVID-19 disease intensity, mathematical modeling was an essential tool used to determine the potentiality and seriousness of the disease. Due to the effects of the COVID-19 disease, scientists observed that vaccination was the main option to fight against the disease for the betterment of human lives and the world economy. Unvaccinated individuals are more stressed with the disease, hence their body's immune system are affected by the disease. In this study, the S V E I H R deterministic model of COVID-19 with six compartments was proposed and analyzed. Analytically, the next-generation matrix method was used to determine the basic reproduction number ( R 0 ). Detailed stability analysis of the no-disease equilibrium ( E 0 ) of the proposed model to observe the dynamics of the system was carried out and the results showed that E 0 is stable if R 0 < 1 and unstable when R 0 > 1 . The Bayesian Markov Chain Monte Carlo (MCMC) method for the parameter identifiability was discussed. Moreover, the sensitivity analysis of R 0 showed that vaccination was an essential method to control the disease. With the presence of a vaccine in our S V E I H R model, the results showed that R 0 = 0 . 208 , which means COVID-19 is fading out of the community and hence minimizes the transmission. Moreover, in the absence of a vaccine in our model, R 0 = 1 . 7214 , which means the disease is in the community and spread very fast. The numerical simulations demonstrated the importance of the proposed model because the numerical results agree with the sensitivity results of the system. The numerical simulations also focused on preventing the disease to spread in the community.

19.
Ecol Lett ; 25(5): 1290-1304, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35257466

RESUMO

The ongoing explosion of fine-resolution movement data in animal systems provides a unique opportunity to empirically quantify spatial, temporal and individual variation in transmission risk and improve our ability to forecast disease outbreaks. However, we lack a generalizable model that can leverage movement data to quantify transmission risk and how it affects pathogen invasion and persistence on heterogeneous landscapes. We developed a flexible model 'Movement-driven modelling of spatio-temporal infection risk' (MoveSTIR) that leverages diverse data on animal movement to derive metrics of direct and indirect contact by decomposing transmission into constituent processes of contact formation and duration and pathogen deposition and acquisition. We use MoveSTIR to demonstrate that ignoring fine-scale animal movements on actual landscapes can mis-characterize transmission risk and epidemiological dynamics. MoveSTIR unifies previous work on epidemiological contact networks and can address applied and theoretical questions at the nexus of movement and disease ecology.


Assuntos
Ecologia , Movimento , Animais , Surtos de Doenças
20.
Emerg Infect Dis ; 28(7): 1345-1354, 2022 07.
Artigo em Inglês | MEDLINE | ID: mdl-35580960

RESUMO

Outbreaks of SARS-CoV-2 infection frequently occur in hospitals. Preventing nosocomial infection requires insight into hospital transmission. However, estimates of the basic reproduction number (R0) in care facilities are lacking. Analyzing a closely monitored SARS-CoV-2 outbreak in a hospital in early 2020, we estimated the patient-to-patient transmission rate and R0. We developed a model for SARS-CoV-2 nosocomial transmission that accounts for stochastic effects and undetected infections and fit it to patient test results. The model formalizes changes in testing capacity over time, and accounts for evolving PCR sensitivity at different stages of infection. R0 estimates varied considerably across wards, ranging from 3 to 15 in different wards. During the outbreak, the hospital introduced a contact precautions policy. Our results strongly support a reduction in the hospital-level R0 after this policy was implemented, from 8.7 to 1.3, corresponding to a policy efficacy of 85% and demonstrating the effectiveness of nonpharmaceutical interventions.


Assuntos
COVID-19 , Infecção Hospitalar , Número Básico de Reprodução , COVID-19/epidemiologia , COVID-19/prevenção & controle , Infecção Hospitalar/epidemiologia , Infecção Hospitalar/prevenção & controle , Humanos , Controle de Infecções/métodos , SARS-CoV-2
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