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[This corrects the article DOI: 10.1371/journal.pone.0057413.].
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Aim: To synthesize novel chloroquine analogues and evaluate them for antimicrobial and cytotoxic potential. Methods: Novel analogues were synthesized from chloroquine by nucleophilic substitution reaction at the 4-amino position. Results: Analogue CS1 showed maximum antimicrobial potential (30.3 ± 0.15 mm zone) against Pseudomonas aeruginosa and produced a 19.2 ± 0.21 mm zone against Candida albicans, while CS0 produced no zone at the same concentration. Analogue CS9 has excellent cytotoxic potential (HeLa cell line), showing 100% inhibition (IC50 = 8.9 ± 1.2 µg/ml), compared with CS0 (61.9% inhibition at 30 µg/ml). Conclusion: These synthesized chloroquine analogues have excellent activity against different microbial strains and cervical cancer cell lines (HeLa) compared with their parent molecule.
[Box: see text].
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Antineoplásicos , Candida albicans , Cloroquina , Pruebas de Sensibilidad Microbiana , Pseudomonas aeruginosa , Humanos , Candida albicans/efectos de los fármacos , Cloroquina/farmacología , Cloroquina/química , Pseudomonas aeruginosa/efectos de los fármacos , Células HeLa , Antineoplásicos/farmacología , Antineoplásicos/química , Antineoplásicos/síntesis química , Antibacterianos/farmacología , Antibacterianos/química , Antibacterianos/síntesis química , Relación Estructura-Actividad , Antifúngicos/farmacología , Antifúngicos/química , Antifúngicos/síntesis química , Estructura Molecular , Ensayos de Selección de Medicamentos Antitumorales , Proliferación Celular/efectos de los fármacos , Antiinfecciosos/farmacología , Antiinfecciosos/química , Antiinfecciosos/síntesis químicaRESUMEN
INTRODUCTION: Conjunctival melanoma (CM) has genetic characteristics that are similar to primary cutaneous melanoma (PCM). The management of advanced CM with orbital metastasis was limited until the adoption of novel immunotherapy agents that significantly improved the survival of metastatic PCM. PURPOSE: To review and compare the immune checkpoint inhibitor (ICI) treatment response in cases reported in the English literature with orbital involvement secondary to CM versus PCM. In addition, we report a case of local recurrence of CM in a young female after successful treatment with ICI. METHODS: In addition to reviewing the chart of one patient who presented to our clinic, we conducted a comprehensive literature review to identify CM cases and cases with orbital metastasis secondary to advanced CM and PCM. Outcomes included patient demographics, response to ICI, and associated adverse effects. RESULTS: There were ten cases with orbital involvement, four were secondary to CM, and six were metastasis from PCM. Orbital metastasis from PCM regressed following treatment with ICI agents, whereas those secondary to CM resolved completely. There were 19 cases of CM without orbital invasion. Of the 29 cases identified, complete resolution of ocular melanoma was achieved in 15 patients, representing 52% of the cases collectively, and none of them reported recurrence except in our case. CONCLUSION: CM with orbital invasion responds well to ICIs, with manageable toxic effects. Despite the complete resolution, close observation is needed as the recurrence risk remains.
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Neoplasias de la Conjuntiva , Melanoma , Neoplasias Cutáneas , Humanos , Femenino , Melanoma/tratamiento farmacológico , Melanoma/patología , Neoplasias Cutáneas/patología , Inhibidores de Puntos de Control Inmunológico/uso terapéutico , Neoplasias de la Conjuntiva/tratamiento farmacológico , Neoplasias de la Conjuntiva/patología , Estudios RetrospectivosRESUMEN
Background and objective: Nanomaterials play significant roles in numerous industrial and engineering applications, like nuclear plants, paper production, thermal power plants, glass fibres, manufacturing of medicines, medical instruments, micro-electronics and polymer sheet extrusion. In view of such important applications, in this study, we discuss the magnetohydrodynamic flow of a nanofluid over an inclined surface by employing the Darcy-Forchheimer model. The Buongiorno model is applied to understand the various important aspects of the nanofluid. Radiation, magnetic field, dissipation and entropy generation in a chemically reactive flow are also discussed. Methodology: The governing nonlinear expressions were transformed into a dimensionless system through adequate transformations. The obtained non-dimensional systems were computed by the NDSolve approach. Results: Physical illustrations for the flow, temperature, concentration and entropy rate via emerging variables were examined. Here an enhancement in velocity was seen for the mixed convection variable, while opposite impacts on flow and temperature were noticed through the Hartman number. A higher Eckert number was obtained with a rise in temperature, while a decrease in concentration was noticed for the thermophoresis variable. An augmentation in the entropy rate was detected for radiation, while the thermal transport rate was boosted by thermophoresis.
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There are 1% to 2% of lymphoma cases that include the testis as primary testicular non-Hodgkin lymphoma (NHL). In 35% of cases, it involves both testes and is usually seen as a painless testicular mass. Therefore, in most cases, the management option is radical orchiectomy. The overall prognosis in these cases is poor, as most cases are associated with systemic disease. We report a case of a 42-year-old male who presented with painless right scrotal swelling for three months. The only serologic marker of solid tumors that was elevated was ßHCG; others were unremarkable. Ultrasonography was initially ordered as well and showed a heterogeneous intra-testicular lesion of relatively low echogenicity. According to the given age, epidemiology, and clinical presentation, the suspicion of a germ cell tumor was highly likely. Therefore, a right radical inguinal orchiectomy was done, and the specimen was sent for histopathology, which came back as B-cell non-Hodgkin lymphoma. The clinical presentation and the overall picture of the investigations made in this case mimicked a germ cell tumor presentation.
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Objective: Nanoliquid flows are widely utilized in industrial, petroleum, engineering, and pharmaceutical applications including electric cooling, drug delivery, nuclear reactor cooling, solar collectors, heat exchangers, magnetohydrodynamic power generators, aerospace, porous media, thermal storage systems, and many others. Darcy-Forchheimer magnetized hybrid nanoliquid subjected to a stretchable cylinder was addressed, and the Cattaneo-Christov heat flux analysis was considered. Herein, disulfido (dithioxo) molybdenum (MoS4) and cobalt ferrite (CoFe2O4) were considered as nanoparticles, and engine oil as a conventional liquid. The thermal relationship of heat generation and radiation was discussed, and the influence of the entropy rate was addressed. Methodology: Governing expressions were transformed into dimensionless forms. Simulation by the ND-solve technique was implemented. Conclusions: Features for the entropy rate, liquid flow, and temperature against emerging variables for nanoliquid (MoS4/engine oil) and hybrid nanoliquid (MoS4 + CoFe2O4/engine oil) were explored. The numerical results of the coefficient of skin friction and thermal transport rate for nanoliquid (MoS4/engine oil) and hybrid nanoliquid (MoS4 + CoFe2O4/engine oil) were examined. Reduction in velocity clearly occurred through a magnetic field, whereas the reverse impact held for the entropy rate. The thermal field and entropy rate against the curvature parameter were enhanced. A decrease in liquid flow occurred for higher porosity variables. An enhancement in the entropy rate was witnessed for radiation and porosity parameters. Higher radiation and thermal relaxation time variables resulted in enhancement of the thermal transport rate.
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Psychosis is a severe mental disorder characterized by abnormal thoughts and perceptions (e.g., hallucinations) occurring quintessentially in schizophrenia and in several other neuropsychiatric disorders. Schizophrenia is widely considered as a neurodevelopmental disorder that onsets during teenage/early adulthood. A multiplex consanguineous Pakistani family was afflicted with severe psychosis and apparent autosomal recessive transmission. The first-cousin parents and five children were healthy, whereas two teenage daughters were severely affected. Structured interviews confirmed the diagnosis of DSM-V schizophrenia. Probands and father underwent next-generation sequencing. All available relatives were subjected to confirmatory Sanger sequencing. Homozygosity mapping and directed a priori filtering identified only one rare variant [MAF < 5(10)-5] at a residue conserved across vertebrates. The variant was a non-catalytic deubiquitinase, USP53 (p.Cys228Arg), predicted in silico as damaging. Genome sequencing did not identify any other potentially pathogenic single nucleotide variant or structural variant. Since the literature on USP53 lacked relevance to mental illness or CNS expression, studies were conducted which revealed USP53 localization in regions of the hippocampus (CA 1-3) and granular dentate. The staining pattern was like that seen with GRIA2/GluA2 and GRIP2 antibodies. All three proteins coimmunoprecipitated. These findings support the glutamate hypothesis of schizophrenia as part of the AMPA-R interactome. If confirmed, USP53 appears to be one of the few Mendelian variants potentially causal to a common-appearing mental disorder that is a rare genetic form of schizophrenia.
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Trastornos Psicóticos , Esquizofrenia , Niño , Humanos , Animales , Ratones , Adulto , Adolescente , Esquizofrenia/genética , Consanguinidad , Ácido alfa-Amino-3-hidroxi-5-metil-4-isoxazol Propiónico , Trastornos Psicóticos/genética , Hipocampo , Proteasas Ubiquitina-Específicas/genéticaRESUMEN
Here, the magnetohydrodynamic bioconvective flow of a non-Newtonian nanomaterial over a stretched sheet is scrutinized. The characteristics of convective conditions are analyzed. Irreversibility analysis in the presence of gyrotactic micro-organisms is discussed. Energy expression is assisted with thermal radiation, heat generation and ohmic heating. Buongiorno's model is employed to discuss the characteristics of the nanoliquid through thermophoresis and random diffusions. Nonlinear expressions of the given model are transformed through adequate transformations. The obtained expressions have been computed by the Newton built in-shooting technique. Results of influential variables for velocity, concentration, microorganism field, temperature and entropy rate are graphically studied. Clearly, velocity reduction is witnessed for the bioconvection Rayleigh number and magnetic variable. A higher heat generation variable leads to augmentation of temperature. An increase in the magnetic variable results in entropy and temperature enhancement. A higher Peclet number results in microorganism field reduction. Temperature distribution rises for radiation and the thermal Biot number. A higher solutal Biot number intensifies the concentration. The entropy rate for radiation and diffusion variables is enhanced.
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Here, the hydromagnetic entropy optimized flow of a hybrid (Pb + Fe2O3/C2H6O2) nanoliquid by a curved stretchable surface is addressed. The Darcy-Forchheimer model is utilized for porous space. Lead (Pb) and ferric oxide (Fe2O3) are considered the nanoparticles and ethylene glycol (C2H6O2) as the base liquid. Thermal expression consists of dissipation and ohmic heating. Entropy generation is under consideration. The Cattaneo-Christov heat flux impact is discussed. Non-dimensional partial expressions by adequate transformations have been reduced to ordinary differential systems. The ND-solve technique is implemented for numerical solutions of dimensionless systems. Graphical illustrations of velocity, thermal field and entropy against influential variables for both nanoliquid (Pb/C2H6O2) and hybrid nanoliquid (Pb + Fe2O3/C2H6O2) are presented. Graphical illustrations of velocity, thermal field and entropy against sundry variables for both nanoliquid (Pb/C2H6O2) and hybrid nanoliquid (Pb + Fe2O3/C2H6O2) are presented. Influences of sundry variables on the Nusselt number and drag force for both nanoliquid (Pb/C2H6O2) and hybrid nanoliquid (Pb + Fe2O3/C2H6O2) are examined. A higher thermal relaxation time tends to intensify the heat transport rate and temperature. An increment in the magnetic variable leads to an enhancement of the entropy and thermal field. An improvement in liquid flow is seen for volume fraction variables. Velocity against the porosity variable and Forchheimer number is reduced. The Brinkman number leads to maximization of entropy generation.
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Structural coloring is a photostable and environmentally friendly coloring approach that harnesses optical interference and nanophotonic resonances to obtain colors with a range of applications including display technologies, colorful solar panels, steganography, décor, data storage, and anticounterfeiting measures. We show that optical coatings exhibiting the photonic Fano Resonance present an ideal platform for structural coloring; they provide full color access, high color purity, high brightness, controlled iridescence, and scalable manufacturing. We show that an additional oxide film deposited on Fano resonant optical coatings (FROCs) increases the color purity (up to 99%) and color gamut coverage range of FROCs to 61% of the CIE color space. For wide-area structural coloring applications, FROCs have a significant advantage over existing structural coloring schemes.
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OBJECTIVE: The aim of the present study is to determine the in vivo and in silico anti-inflammatory effect of Azadirachta indica (A. indica) in carrageenan-induced rats and its blood biomarkers. A. indica (Neem) is a widely used medicinal plant across the world, especially in Pakistan. Neem leaves have been traditionally used for the synthesis of drugs and treatment of a wide variety of diseases. MATERIALS AND METHODS: In this study, sixty albino rats (160-200 g) were divided into 4 groups: control (group I), standard (group II), ethanolic and aqueous (group III and IV) at doses of 50, 100, 200 and 400 mg/kg. RESULTS: Ethanolic and aqueous extracts showed maximum inhibition in paw size at the 5th hour (400 mg/kg). Similarly, biomarkers measured, including Interleukin-6 and C-reactive protein, exhibited significant anti-inflammatory activity at the highest dose of 400 mg/kg in both experimental groups but were more distinct in the group treated with ethanolic extracts. Correlation between C-reactive protein (CRP) and inter-leukin-6 (IL-6) showed positive correlation in group III, while negative in group IV. Similarly, positive and negative correlations were observed between CRP biomarkers and paw size in group III and IV, and the same results were also shown in the case of IL-6 and paw size. In molecular docking, the binding energy value of protein CRP and IL-1ß with the identified ligands quercetin and nimbosterol showed (-8.2 kcal/mol and -7.7 kcal/mol) the best binding affinity as compared to standard drug diclofenac with -7.0 kcal/mol binding energy respectively. CONCLUSIONS: In conclusion, in silico and in vivo analysis revealed that the extracts of A. indica leaves can be used as an effective drug to manage inflammation.
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Azadirachta , Extractos Vegetales , Ratas , Animales , Extractos Vegetales/uso terapéutico , Interleucina-6 , Proteína C-Reactiva , Azadirachta/química , Simulación del Acoplamiento Molecular , Edema/inducido químicamente , Edema/tratamiento farmacológico , Antiinflamatorios/farmacología , Antiinflamatorios/uso terapéutico , Biomarcadores , Hojas de la PlantaRESUMEN
Obsessive-compulsive disorder (OCD) affects 1-2% of children and is associated with functional impairment and diminished quality of life. Several treatments are efficacious: cognitive behavioral therapy (CBT) with exposure and response prevention, serotonin reuptake inhibitor (SRI) monotherapy, and combined treatment (SRI + CBT). Expert clinician-informed practice parameters suggest that youth with mild to moderate OCD should be treated initially with CBT yet SRIs are frequently employed as the first-line intervention or in combination with psychotherapy in applied practice. Empirical data to guide SRI discontinuation in pediatric OCD are very limited. This study, Promoting OCD Wellness and Resiliency (POWER), aims to address this gap through a two phase, double-blinded, placebo-controlled, randomized controlled non-inferiority trial with the purpose of evaluating whether youth with OCD on an SRI can discontinue their medication after successful CBT augmentation and maintain wellness for a period of 24 weeks during which they receive maintenance CBT that models standard-of-care. In this paper we describe the rationale and methodological design of the POWER study.
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Introduction Human papillomaviruses (HPV) are known to be the main culprit of cervical cancer. It is the fourth most common cancer among women worldwide. In recent years, it has begun to spread more widely in Saudi Arabia. Saudi Arabia's Ministry of Health recently added HPV vaccination for women to the list of recommended vaccinations. Aim This study aimed to assess Saudi females' knowledge regarding HPV infection, screening, and the available tools for prevention in Qassim, Saudi Arabia. Subject and methods This is a descriptive cross-sectional study conducted among women living in the Qassim region of Saudi Arabia. A self-administered pre-structured questionnaire was distributed among the targeted women using an online platform. The questionnaire includes socio-demographic characteristics (i.e. age, education, occupation, etc.) knowledge questionnaire and a questionnaire about the attitude toward HPV protection. The minimum required sample size was 385. This means 385 or more measurements/surveys are needed to have a confidence level of 95% that the real value is within ±5% of the measured/surveyed value. All females aged 18 years and above who are living in the Qassim region of Saudi Arabia were included in our study. Males are excluded from this study. All data analyses were performed using Statistical Product and Service Solutions (SPSS) (IBM SPSS Statistics for Windows, Version 26.0, Armonk, NY). Results Of the 387 women involved, 52.2% were aged between 18 and 25 years old. The prevalence of women who have heard of HPV was 49.1%. Fifty-four percent were willing to accept HPV vaccination if offered. The overall mean knowledge score was 3.56 (SD 2.51) out of 11 points. Poor knowledge levels constituted most of the women (71.1%), 24.5% had moderate knowledge and only 4.4% were considered good. Increased awareness was more prevalent in younger women, more educated, those who underwent Pap smear, and those who were willing to accept HPV vaccination. Conclusion The awareness of women toward HPV infection was deficient. Younger women who had a better education and who are willing to receive HPV vaccination were more likely to demonstrate better awareness levels toward HPV infection as compared to the rest of the women. More research is needed to establish the level of awareness among women in our region.
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BACKGROUND: Psychiatric disorders are characterized by alteration in emotions, mood and behavior. Genetics is known to play a significant role in the development of psychiatric disorders. Genome-wide association studies have identified several loci associated with psychiatric illnesses. We hypothesize the existence of rare variants following Mendelian recessive mode of inheritance. These variants can be identified in families with multiple affected individuals born to unaffected consanguineous parents. METHODS: We visited psychiatric outpatient departments of multiple hospitals in Lahore, Pakistan. We focused on psychosis, as it can occur in several DSM disorders such as schizophrenia, dementia and bipolar disorder. After clinical diagnosis by an American trained psychiatrist, detailed clinical assessments using Diagnostic Interview for Genetic Studies (DIGS), Diagnostic Interview for Psychosis and Affective Disorders (DI-PAD), Positive and Negative Syndrome Scale (PANSS), Hamilton Depression and Anxiety Rating Scale (HAM-D; HAM-A) were administered to all willing affected and unaffected participants. RESULTS: We identified eight pedigrees with two or more psychotic individuals in each family. Clinical diagnoses determined by their psychiatrists included ten individuals with schizophrenia; four individuals with psychosis and bipolar disorder; and two patients with "unspecified psychosis." The rating instruments rigorously confirmed the diagnosis of psychosis in the affected patients from the six families as well as the absence of psychotic disorders in unaffected individuals from the six families. We obtained DNA samples from willing members of all eight families for future genetic analyses. CONCLUSION: Our research highlights an alternative approach to discovery of rare recessively inherited genetic variants causing psychiatric disorders that have remained unidentified to date. These findings could illuminate underlying biological mechanisms leading toward development of targeted therapies in future.
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Trastornos Mentales , Trastornos Psicóticos , Esquizofrenia , Humanos , Consanguinidad , Estudio de Asociación del Genoma Completo , Trastornos Mentales/genética , Trastornos Psicóticos/diagnóstico , Trastornos Psicóticos/genética , Esquizofrenia/diagnósticoRESUMEN
PURPOSE: We describe a rare case of annular granuloma involving the eyelid of a child, a 6-year-old male, who presented with multiple subcutaneous nodular lesions involving the upper eyelid of the right eye. OBSERVATIONS: The slit-lamp examination of the eye was normal. Extra-ocular examination showed a lesion on the dorsal aspect of the right foot, which was resistant to treatment with topical corticosteroids. He underwent surgical excision of the eyelid nodules under general anesthesia. Histopathology with immunohistochemical staining of the excisional biopsy confirmed the diagnosis of annular granuloma, with positive Vimentin and CD68 stains in many palisading histiocytic cells, while Factor VIIIa, S100, and CD1a were negative. Tuberculosis was ruled out by negative Ziehl-Neelsen staining for acid-fast bacilli. CONCLUSIONS AND IMPORTANCE: This idiopathic granulomatous condition proved to be a benign, self-limiting cutaneous disease that can regress spontaneously. It affects the skin of the foot in more than 70% of all patients; however, involvement of the eyelid is extremely rare. We report this case to highlight such a rare entity and increase awareness regarding this dermatological condition among ophthalmologists.
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The present study compares the in vitro effects of nanoparticles loaded pentamidine drug and conventional pentamidine on Leishmania tropica. Herein, pentamidine-loaded chitosan nanoparticles (PTN-CNPs) have been synthesized through an ionic gelation method with sodium tripolyphosphate (TPP). Next, the physical characteristics of PTN-CNPs were determined through the surface texture, zeta potential, in vitro drug release, drug loading content (DLC), and encapsulation efficacy (EE) and compared its efficacy with free pentamidine (PTN) drug against promastigotes and axenic amastigotes forms of L. tropica in vitro. The PTN-CNPs displayed a spherical shape having a size of 88 nm, an almost negative surface charge (-3.09 mV), EE for PTN entrapment of 86%, and in vitro drug release of 92% after 36 h. In vitro antileishmanial activity of PTN-CNPs and free PTN was performed against Leishmania tropica KWH23 promastigote and axenic amastigote using 3-(4, 5- dimethylthiazol-2-yl)-2, 5-diphenyletetrazolium bromide (MTT) assay. It was observed that the effect of PTN-CNPs and free PTN on both forms of the parasite was dose and time dependent. Free PTN presented low efficacy even at higher dose (40 µg/ml) with 25.6 ± 1.3 and 26.5 ±1.4 mean viability rate of the promastigotes and axenic amastigotes, respectively after 72 hrs incubation. While PTN-CNPs showed strong antileishmanial effects on both forms of parasite with 16 ± 0.4 and 19 ± 0.7 mean viability rate at the same higher concentration (40 µg/ml) after 72 hrs incubation. Half maximal inhibitory concentration (IC50) values of PTN-CNPs toward promastigotes and amastigotes were obtained as 0.1375 µg/ml and 0.1910 µg/ml, respectively. In conclusion, PTN-CNPs effectively inhibited both forms of the L. tropica; however, its effect was more salient on promastigotes. This data indicates that the PTN-CNPs act as a target drug delivery system. However, further research is needed to support its efficacy in animal and human CL.
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Antiprotozoarios , Quitosano , Leishmania tropica , Nanopartículas , Animales , Humanos , Pentamidina/farmacología , Quitosano/farmacología , Antiprotozoarios/farmacología , Sistemas de Liberación de MedicamentosRESUMEN
Background Gastric cancer is one of the most prevalent cancers in the world and the third most common cause of death from cancer. The diagnosis and treatment are often complex and require a multifaceted approach. Hence, appropriate and timely management is essential for better patient outcomes. Our aim was to determine if rural inhabitation affects the mortality of patients with gastric adenocarcinoma. If such an association exists, we propose to ascertain whether this is related to delayed diagnosis, differing tumor characteristics, or treatment inequalities. Methods The Cox model was applied to gastric adenocarcinoma cases diagnosed during 2004-2011 in American residents aged 20+ years in the Surveillance, Epidemiology, and End Results (SEER) program to determine the impact of rurality on mortality. Binary logistic regression was used to compare the odds of not receiving surgical treatment for localized tumors between rural and urban areas. It was also used to measure the association of rurality with stage at diagnosis (non-metastatic vs. metastatic). Results There was a significant association of rurality on 5-year mortality [HR 1.14 (1.09-1.20), p < 0.01]. No significant association was observed between rural-urban residency and stage at diagnosis, with an odds ratio (OR) of 0.95 (0.87-1.03), p = 0.21. The median time from diagnosis to any first-course treatment was one month for both rural and urban counties. Rural residents were far more likely not to receive surgical treatment for localized tumors than their urban counterparts [OR 1.70 (1.41-2.05), p < 0.01]. A greater percentage of rural inhabitants had cardia tumors as compared to urban ones, 39.8% vs. 33.8% respectively. Non-cardia tumors were far less likely not to receive surgical treatment (i.e., more likely to receive surgical treatment) than cardia tumors [OR 0.35 (0.30-0.41), p < 0.01]. Conclusions Rurality is associated with worse gastric adenocarcinoma mortality. This may be due to a lesser probability of receiving surgical treatment for early-stage disease and differences in the primary site of the tumor between rural and urban counties, but not due to differences in stage at presentation. Future research should focus on improving health care access in rural communities.
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Background Appendiceal carcinoma has an insidious clinical presentation, and these tumors are rarely suspected prior to surgery, potentially leading to late diagnosis. The aim of this study is to investigate the prevalence of metastatic disease at initial presentation and potentially associated sociodemographic characteristics. Methods Patients were identified from the Surveillance, Epidemiology, and End Results (SEER) program using the International Classification of Diseases for Oncology-3 (ICD-O-3) histology/behavior codes between 2010 and 2015. Firth logistic regression was performed to determine the association of metastasis at presentation with tumor subtype, adjusted for age, race, sex, insurance and marital status, tumor grade, and tumor and nodal stage using the 7th edition of the American Joint Committee on Cancer (AJCC) staging system. Results We identified a total of 3,447 patients with known metastatic status. A total of 38.4% had metastatic disease at diagnosis. Compared to colonic-type adenocarcinoma (CA), mucinous adenocarcinoma (MA) and signet ring cell carcinoma (SC) were more likely to present with metastasis at diagnosis (OR: 2.34; 95% CI [1.80- 3.06]; OR: 1.93 [1.29-2.89], respectively), however, goblet cell carcinoma (GC) was less likely (OR: 0.59 [0.36-0.93]). Compared to tumors invading the submucosa (T1 stage), tumors invading deeper through the visceral peritoneum or nearby organs (T4 stage) were significantly more likely to present with metastatic disease (OR: 3.46 [2.24-5.51]). Tumors invading the muscularis propria (T2 stage) or deeper into the subserosa, or the mesoappendix (T3 stage) were less likely to present with metastatic disease (OR: 0.34 [0.16-0.71]); OR: 0.55 [0.34-0.91], respectively). Compared to no regional lymph node spread, four or more regional lymph node involvement (N2 stage) was more likely to present with metastatic disease (OR: 2.19 [1.53-3.16]). Men were less likely to present with metastatic disease (OR: 0.60 [0.48-0.73]). A total of 90.1% of CA, 84.2% of GC, 42.2% of MA, and 78.5% of SC patients with metastasis at diagnosis had extraperitoneal distant metastasis (M1b). Conclusions A significant proportion of patients with newly diagnosed appendiceal carcinoma presented with metastatic disease, concerning substantial diagnostic delay and potentiating the need for aggressive treatments. Predictors of metastatic disease included female sex, histologic subtype, and significant regional lymph node involvement. Future research should focus on earlier detection and explore tumor biology.
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Entropy optimization in convective viscous fluids flow due to a rotating cone is explored. Heat expression with heat source/sink and dissipation is considered. Irreversibility with binary chemical reaction is also deliberated. Nonlinear system is reduced to ODEs by suitable variables. Newton built in shooting procedure is adopted for numerical solution. Salient features velocity filed, Bejan number, entropy rate, concentration and temperature are deliberated. Numerical outcomes for velocity gradient and mass and heat transfer rates are displayed through tables. Assessments between the current and previous published outcomes are in an excellent agreement. It is noted that velocity and temperature show contrasting behavior for larger variable viscosity parameter. Entropy rate and Bejan number have reverse effect against viscosity variable. For rising values of thermal conductivity variable both Bejan number and entropy optimization have similar effect.
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In this work, we report on the creation of a black copper via femtosecond laser processing and its application as a novel electrode material. We show that the black copper exhibits an excellent electrocatalytic activity for hydrogen evolution reaction (HER) in alkaline solution. The laser processing results in a unique microstructure: microparticles covered by finer nanoparticles on top. Electrochemical measurements demonstrate that the kinetics of the HER is significantly accelerated after bare copper is treated and turned black. At -0.325 V (v.s. RHE) in 1 M KOH aqueous solution, the calculated area-specific charge transfer resistance of the electrode decreases sharply from 159 Ω cm2 for the untreated copper to 1 Ω cm2 for the black copper. The electrochemical surface area of the black copper is measured to be only 2.4 times that of the untreated copper and therefore, the significantly enhanced electrocatalytic activity of the black copper for HER is mostly a result of its unique microstructure that favors the formation and enrichment of protons on the surface of copper. This work provides a new strategy for developing high-efficient electrodes for hydrogen generation.