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We present a dynamic density functional theory for modeling the effects of applied electric fields on the local structure of polymers with added salt (polymer electrolytes). Time-dependent equations for the local electrostatic potential and volume fractions of polymer, cation, and anion of added salt are developed using the principles of linear irreversible thermodynamics. For such a development, a field theoretic description of the free energy of polymer melts doped with salts is used, which captures the effects of local variations in the dielectric function. Connections of the dynamic density functional theory with experiments are established by relating the three phenomenological Onsager's transport coefficients of the theory to the mutual diffusion of electrolyte, ionic conductivity, and transference number of one of the ions. The theory is connected with a statistical mechanical model developed by Bearman and Kirkwood [J. Chem. Phys. 28, 136 (1958)] after relating the three transport coefficients to friction coefficients. The steady-state limit of the dynamic density functional theory is used to understand the effects of dielectric inhomogeneity on the phase separation in polymer electrolytes. The theory developed here provides not only a way to connect with experiments but also to develop multi-scale models for studying connections between local structure and ion transport in polymer electrolytes.
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The evidence on bladder cancer in the young population remains fragmented due to lack of literature and conflicting results from the existing studies. We aim to elucidate such conflicting data and define the clinicopathologic characteristics, management trends, and outcomes of urothelial bladder carcinoma in young adults as compared to their older counterparts. This was a retrospective, single-center study involving patients with primary urothelial bladder cancer who underwent treatment at our center from March 2017 to March 2022. For analysis, patients were stratified into three subgroups based on age: group A, 18-40 years; group B, > 40 years; and group C, > 60 years. Group A with younger patients was compared with groups B and C. A total of 471 eligible patients (422 males and 49 females) were included in the study with a median age of 44 years. Group A had significantly lower recurrence and progression rates as compared to group B (31% vs 57.1%, p = 0.002 and 9.5% vs 19.2%, p = 0.04, respectively). Group A had significantly more recurrence-free survival (RFS) than group B (5-year-RFS = 68.03% vs 32.58%, p = 0.01). Similarly, group A also had lower recurrence (31% vs 62.6%, p < 0.001) and progression (9.5% vs 28.6%, p = 0.015) rates as compared to group C as well as better RFS (5-year-RFS = 68.03% vs 19.00%, p = 0.04) and progression-free survival (5-year-PFS = 83.1% vs 62.8%, p = 0.03) in comparison to group C. Age and tumor grade were found to be independent predictors of recurrence-free and progression-free survival. We concluded that high-grade disease is more common than low-grade disease both in younger and older patients. Younger patients fare better in terms of recurrence and progression when compared to their older counterparts.
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PURPOSE: Standard neoadjuvant chemotherapy (NACT) for locally advanced esophageal/gastroesophageal junction squamous cancer (LAEGSC), 5-fluorouracil (5FU)+platinum, is toxic and logistically challenging; alternative regimens are needed. PATIENTS AND METHODS: Phase III randomized open-label non-inferiority trial at Tata Memorial Center, India, in resectable LAEGSC. Patients were randomized 1:1 to three cycles of 3-weekly platinum (cisplatin 75 mg/m2 or carboplatin AUC 6) with paclitaxel 175 mg/m2 (day 1) or 5FU 1000 mg/m2 continuous infusion (days 1-4), followed by surgery. RESULTS: Between August 2014 and June 2022, we enrolled 420 patients; 210 to each arm. Significantly more patients on paclitaxel + platinum (194 (92.3%)] received all 3 chemotherapy cycles than on 5FU+platinum (170 [85.9%]), P = .009. 5FU + platinum caused more grade ≥ 3 toxicities (124 [69.7%]) than paclitaxel + platinum (97 [51.9%]), P = .001. Surgery was performed in 131 (62.4%) patients on 5FU + platinum vs 139 (66.2%) on paclitaxel + platinum, P = .415. Paclitaxel + platinum resulted in higher pathologic primary tumor clearance (33 [25.8%]) vs 17 [15%]; P = .04), and pathologic complete responses in 21.9% compared to 12.4% from 5FU + platinum, P = .053. Median OS was 27.5 months (95% CI, 18.6-43.5) from paclitaxel + platinum, which was non-inferior to 27.1 months (95% CI, 18.8-40.7) from 5FU + platinum; HR, 0.89 (95% CI, 0.72-1.09); P = .346. CONCLUSION: Neoadjuvant paclitaxel + platinum chemotherapy is safer, and results in similar R0 resections, higher pathologic tumor clearance and non-inferior survival, compared to 5FU + platinum. Paclitaxel + platinum should replace 5FU + platinum as NACT for resectable LAEGSC. CLINICAL TRIALS REGISTRY INDIA NUMBER: CTRI/2014/04/004516.
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BACKGROUND: Pre-vascular facial nodes (PV-FNs; perifacial lymph nodes) are supra-mandibular lymph nodes above the inferior border of the mandible. These are not part of routine neck dissection done for OCSCC. These lymph nodes can be sentinel station for metastatic lymph nodes from gingivobuccal complex cancers and are missed during routine neck dissection. It is imperative to include this sentinel station in routine neck dissection to prevent nodal recurrences. MATERIALS AND METHODS: One hundred thirty-seven patients with GBCC (T1-T4) were prospectively recruited between May 2020 and June 2022 with the intent to evaluate the incidence of PV-FN metastases and clinicopathological factors predicting them. RESULTS: PV-FN metastases were seen in 26 patients (18.9%; 26/137). The occult metastasis rate was 8.7% (12/137). On multivariate analysis, pathological T4 stage (pT4), LVE positivity, and intermediate-high BGS were statistically significant predictors of PV-FN metastases in our study. CONCLUSIONS: Incidence of PV-FN metastasis is high (18.9%) in GBCC, which can be potentially the first sentinel station in the lymphatic drainage pattern for this sub-site. Meticulous clearance of this nodal basin is of paramount importance during neck dissection to prevent nodal recurrences. LEVEL OF EVIDENCE: Level 2 (CEBM-Level of Evidence-2.1) Laryngoscope, 2024.
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n-Type doping for improving the electrical characteristics and air stability of n-type organic semiconductors (OSCs) is important for realizing advanced future electronics. Herein, we report a selection method for an effective n-type dopant with an optimized structure and thickness based on anthracene cationic dyes with high miscibility induced by a molecular structure similar to that of OSCs. Among the doped OSCs evaluated, rhodamine B (RhoB)-doped OSC exhibits the highest density, a smallest roughness of 2.69 nm, a phase deviation of 0.85° according to atomic force microscopy measurements, and the highest electron mobility (µ), showing its high miscibility. Surface doping of RhoB affords the lowest contact resistance of 2.01 × 105 Ω cm compared to bulk and contact doping, resulting in an effective doping structure. The RhoB-doped OSC retains 81.63% of the original µ value of 6.13 × 10-2 cm2 V-1 s-1 after 15 days, whereas pristine OSC shows a lower µ of 2.33 × 10-2 cm2 V-1 s-1 and maintains only 4.41% of the original value after 15 days. Our findings demonstrate that this methodology is effective for the selection of a high-performance n-type dopant for OSCs toward the development of high-performance and air-stable n-type organic electronics.
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We study responses of thermally annealed ultrathin films deposited on silicon substrates and containing polyzwitterions to applied electric fields by using specular neutron reflectometry (NR). In particular, we applied 7 kV under vacuum at 150 °C on the films containing poly(1-(3-sulfonatopropyl)-2-vinylpyridinium) (P2VPPS) and its blends with either a deuterated ionic liquid (EMIMBF4-d11), potassium bromide (KBr), or deuterated sodium polystyrenesulfonate (NaPSS-d7). The voltage was applied over an air gap, and the in situ neutron reflectivity measurements allowed us to measure changes in the films. In all the cases, we measured decreases in thicknesses of the films, which varied up to â¼8% depending on the added salt. Posteriori X-ray reflectivity (XRR) measurements on the same films at room temperature reveal that these films were highly hygroscopic, which led to the presence of water in these films. Analysis of the NR and the XRR revealed that the decrease in the thickness of the films in the neutron reflectivity experiments on heating resulted from the loss of water and the ionic liquid but not from electrostrictive effects. The in situ NR and posteriori XRR experiments revealed not only the hygroscopic nature of these films but also depth-resolved structural rearrangements due to the applied electric fields in the films containing electrolytes and polyelectrolytes. This work shows that a combination of NR and XRR can be used to distinguish between mass loss and electrostriction in films containing charged polymers such as polyzwitterions.
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We employ polymer integral equation theory to study a simplified model of semiflexible polymerized ionic liquids (PolyILs) that interact via hard core repulsions and short range screened Coulomb interactions. The multi-scale structure in real and Fourier space of PolyILs (ions chosen to mimic Li, Na, K, Br, PF6, and TFSI) are determined as a function of melt density, Coulomb interaction strength, and ion size. Comparisons with a homopolymer melt, a neutral polymer-solvent-like athermal mixture, and an atomic ionic liquid are carried out to elucidate the distinct manner that ions mediate changes of polymer packing, the role of excluded volume effects, and the influence of chain connectivity, respectively. The effect of Coulomb strength depends in a rich manner on ion size and density, reflecting the interplay of steric packing, ion adsorption, and charge layering. Ion-mediated bridging of monomers is found, which intensifies for larger ions. Intermediate range charge layering correlations are characterized by a many-body screening length that grows with PolyIL density, cooling, and Coulomb strength, in disagreement with Debye-Hückel theory, but in accord with experiments. Qualitative differences in the collective structure, including an ion-size-dependent bifurcation of the polymer structure factor peak and pair correlation function, are predicted. The monomer cage order parameter increases significantly, but its collective ion counterpart decreases, as ions become smaller. Such behaviors allow one to categorize PolyILs into two broad classes of small and large ions. Dynamical implications of the predicted structural results are qualitatively discussed.
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Introduction: In the United States (US), prophylactic treatment with the antiemetic trimethobenzamide has been used before initiating apomorphine therapy. However, US trimethobenzamide stores have been depleted, leaving uncertainty regarding whether antiemetic pretreatment is needed. Methods: This modified Delphi panel aimed to inform circumstances when apomorphine is initiated without antiemetic pretreatment. During Round 1, a panel of 9 US movement disorder specialists rated the appropriateness of prescribing apomorphine therapy with and without antiemetic pretreatment across 192 patient scenarios and were able to review their scores in relation to other scores. During the Round 2, consensus was defined for each scenario as either strong (>75 % agreement) or moderate (66 % agreement). Results: There was strong consensus on 118 of 192 scenario's (97 as appropriate and 21 as inappropriate), moderate consensus on 29 scenarios, some agreement on 32 scenarios, and lack of agreement on 13 scenarios. In the absence of an antiemetic, there was strong consensus that titration schedules should be flexible and based on dose response. However, the group only reached moderate consensus on the speed of titration, highlighting the need for more systematic information on this area. In the presence of an antiemetic, panelists considered usual initial dosing and flexible titration to be appropriate in most scenarios except for when the patient is already experiencing dopaminergic adverse events. Conclusions: Experts generally reached consensus that apomorphine can usually be prescribed without antiemetic pretreatment. Recommendations described here reflect the areas of greatest agreement among a panel of experts based on current available evidence.
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Introduction: The blood-based inflammatory marker, neutrophil-to-lymphocyte ratio (NLR), is a reliable prognostic biomarker for several cancers. Although the literature supports the correlation between preoperative NLR, clinicopathological characteristics, and oncological outcomes in upper tract urothelial carcinoma (UTUC), the cutoff of NLR is still debated. This study aimed to determine the prognostic value of NLR in patients with UTUC. Methods: This was a retrospective analysis of prospectively collected data from July 2012 to December 2022 evaluating patients with UTUC who underwent radical nephroureterectomy (RNU). NLR was calculated using the neutrophil and lymphocyte counts obtained a day before the surgery and the cutoff value was set as 2.5. Kaplan-Meier and Cox's proportional hazards regression were used to analyze the association between NLR and the oncological outcomes. Results: The study included 91 patients (78 males, 13 females) in the final analysis with a median follow-up of 49 months (8-130). The mean age of the patients with NLR <2.5 and NLR ≥2.5 was 56.88 years and 56.35 years, respectively, and the pathological stage was pT1 in 48%, pT2 in 20.88%, pT3 in 27.47%, and pT4 in 3.30% of the patients. Multivariable Cox regression analysis showed that the preoperative NLR ≥2.5 was significantly associated (Hz = 7.17) with higher T stage, lymphovascular invasion, necrosis, nodal involvement, adjuvant chemotherapy, and worse overall survival (OS) (Hz = 9.87). The Kaplan-Meier analysis revealed an improved OS in patients with NLR <2.5, but a statistically significant difference in the recurrence-free survival was not found. Conclusions: Preoperative NLR is an easily available, inexpensive, and important prognostic biomarker of survival in patients with UTUC and has a potential role in risk stratification by predicting adverse clinicopathological characteristics.
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During meiosis, nucleoprotein filaments of the strand exchange proteins RAD51 and DMC1 are crucial for repairing SPO11-generated DNA double-strand breaks (DSBs) by homologous recombination (HR). A balanced activity of positive and negative RAD51/DMC1 regulators ensures proper recombination. Fidgetin-like 1 (FIGNL1) was previously shown to negatively regulate RAD51 in human cells. However, FIGNL1's role during meiotic recombination in mammals remains unknown. Here, we decipher the meiotic functions of FIGNL1 and FIGNL1 Interacting Regulator of Recombination and Mitosis (FIRRM) using male germline-specific conditional knock-out (cKO) mouse models. Both FIGNL1 and FIRRM are required for completing meiotic prophase in mouse spermatocytes. Despite efficient recruitment of DMC1 on ssDNA at meiotic DSB hotspots, the formation of late recombination intermediates is defective in Firrm cKO and Fignl1 cKO spermatocytes. Moreover, the FIGNL1-FIRRM complex limits RAD51 and DMC1 accumulation on intact chromatin, independently from the formation of SPO11-catalyzed DSBs. Purified human FIGNL1ΔN alters the RAD51/DMC1 nucleoprotein filament structure and inhibits strand invasion in vitro. Thus, this complex might regulate RAD51 and DMC1 association at sites of meiotic DSBs to promote proficient strand invasion and processing of recombination intermediates.
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Proteínas de Ciclo Celular , Roturas del ADN de Doble Cadena , Proteínas de Unión al ADN , Meiosis , Ratones Noqueados , Recombinasa Rad51 , Espermatocitos , Recombinasa Rad51/metabolismo , Recombinasa Rad51/genética , Animales , Masculino , Meiosis/genética , Proteínas de Ciclo Celular/metabolismo , Proteínas de Ciclo Celular/genética , Humanos , Ratones , Espermatocitos/metabolismo , Proteínas de Unión al ADN/metabolismo , Proteínas de Unión al ADN/genética , Recombinación Homóloga , Proteínas Nucleares/metabolismo , Proteínas Nucleares/genética , Daño del ADN , Endodesoxirribonucleasas/metabolismo , Endodesoxirribonucleasas/genética , Cromatina/metabolismo , Proteínas de Unión a Fosfato/metabolismo , Proteínas de Unión a Fosfato/genéticaRESUMEN
This paper aims to integrate and empirically assess the antecedents and consequents of circular economy (CE) adoption to remove ambiguity existing in the literature and clarify divergent views. This study uses meta-analysis methodology to validate the research framework, considering 106 empirical studies with 210 effect sizes. Based on these studies, we establish twelve antecedents and three consequents related to CE. Antecedents are categorized in a technological-organizational-environmental framework and consequents in the sustainability outcomes. The result suggests that organisational factors are more prominent in driving CE practices, followed by environmental and technological factors. In the organisational category, the three most influencing factors are managing product returns, green manufacturing, and environmental strategy. In the environmental category, coercive pressure is the most influential factor, followed by mimetic and social pressures. Emerging I4.0 technologies are the most prominent factor in the technological category. Our study suggests that CE helps to achieve sustainable performance by significantly enabling economic, environmental, and social outcomes. This study further analyses how contextual factors such as national culture (masculinity) and economic regions influence the various relationships with CE using subgroup analysis. The moderation results show that low masculine culture and developing economies are more effectively using the I4.0 technologies to drive CE adoption than high masculine culture and developed economies. Additionally, different dimensions of sustainability are also influenced by the variations in masculinity and economic regions.
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Conservación de los Recursos Naturales , Humanos , TecnologíaRESUMEN
OBJECTIVES: Perimarginal nodes (PMN) lie in close relationship with marginal mandibular nerve (MMN), in the lymphatic drainage pathway of gingivo-buccal cancers (GBC), above the lower border of mandible and remain unaddressed in conventional neck dissection. We have aimed to define the boundaries of perimarginal node dissection, explore incidence of PMN metastasis and its correlation with histopathological characteristics. MATERIALS AND METHODS: A prospective study was conducted on 112 consecutive patients of GB carcinoma. PMN dissection was performed in an anatomically defined quadrangle. Prospective clinical characteristics included subsite, tumor and nodal stage, location of primary and clinical skin involvement. Histopathological characteristics analyzed included grade, size, pathological tumor, nodal stage, skin and/or bone involvement, depth of invasion, Brandwein Gensler histological risk score and lympho-vascular emboli. MMN function was graded at 3 and 6 months post-operatively. RESULTS: The PMN were identified histologically in 75.89 % patients. 15.2 % patients harboured metastasis in PMN. 16.7 % patients had clinically occult metastasis with 11.7 % having isolated PMN metastasis. None of the pre-operative clinical factors was found to be significant in predicting incidence of metastasis. Higher nodal burden (p = 0.01) and pathological skin involvement (p = 0.03) were found statistically significant on multivariable analysis. At 6 months follow-up, none of the patients had any MMN functional deformity at rest. CONCLUSION: There is a high incidence of occult PMN metastasis from gingivo-buccal complex cancer. High nodal stage and pathological skin involvement are independent predictors for PMN metastasis. PMN dissection must be performed in all cases of GB cancer.
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Statistical analysis is essential for minimizing the time, cost, and number of experiments needed to get the maximum output. In this work, the removal of cadmium bivalent (Cd (II)) ions was optimized using Box-Behnken design methodology. The effects of pH, concentration, time, and temperature were investigated for the removal of cadmium. Maximum removal (85.70%) was achieved at pH of 5.34, initial Cd(II) ions concentration 46.61,contact time 166.09 (min), and at 59.40 oC temperature on Punica Granatum carpellary membrane powder (PGCMP) and 88.61% removal was achieved on its modified forms (MPGCMP) at pH of 5.79, initial Cd(II) ions concentration 65.70,contact time 178.96, and at 59.91 oC temperature. The model was validated by analyzing variance (ANOVA). The practical data was well fitted to the quadratic model. PGCMP and MPGCMP were found to be naturally occurring, environmentally friendly adsorbents for the mitigation of Cd (II) ions as well as other toxic heavy metals from drinkable or wastewater.
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Accurately predicting agricultural commodity prices is crucial for India's economy. Traditional parametric models struggle with stringent assumptions, while machine learning (ML) approaches, though data-driven, lack automatic feature extraction. Deep learning (DL) models, with advanced feature extraction and predictive abilities, offer a promising solution. However, their application to agricultural price data ignored the exogenous factors. Hence, the study explored advanced versions of the well-known univariate models, NBEATSX and TransformerX. The research employed price data for essential crops like Tomato, Onion, and Potato (TOP) from major Indian markets and complemented it with corresponding weather data (precipitation and temperature). To provide a comprehensive analysis, the study also evaluated traditional statistical methods (ARIMAX and MLR) and a suite of ML algorithms (ANN, SVR, RFR, and XGBoost). The performance of these models was rigorously evaluated using error metrics like RMSE, MAE, sMAPE, MASE and QL. The findings were significant indicating DL models, particularly when augmented with exogenous variables, consistently outshone other methods with NBEATSX and TransformerX showing an average RMSE of 110.33 and 135.33, MAE of 60.08 and 74.92, sMAPE of 22.14 and 24.00, MASE of 1.02 and 1.32 and QL of 30.04 and 34.07, respectively. They exhibited lower error metrics, as compare to the statistical and ML models underscoring their effectiveness and potential in agricultural crop price forecasting. This study not only bridged a crucial research gap but also highlighted the robust potential of DL models in enhancing the accuracy of agricultural commodity price predictions in India.
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BACKGROUND: Patients with head and neck cancers (HNCs) are at an increased risk of developing functional symptoms associated with eating, speaking, and breathing along with symptoms caused by a fungating tumour (e.g., cosmetic change, malodor, and bleeding). These may substantially reduce their physical functioning and quality of life (QoL). This observational study aimed to find out the QoL in patients with HNC in a tertiary care oncology centre. METHODS: A prospective observational study was conducted in adult patients diagnosed with HNC. The patients were divided depending upon their disease extent into early, advanced, and very advanced local disease. The physical, cognitive, emotional, financial and social domains were assessed using a validated Hindi version of the European Organisation for Research and Treatment of cancer (EORTC)- QoL 30 and EORTC H&N 35 at baseline and 3 months. RESULTS: A total of 100 patients were assessed with a mean age of 49.3 ± 12.4 years. Most of the patients had carcinoma buccal mucosa (42%) followed by carcinoma tongue (17%). The patients experienced difficulties with physical functioning and deterioration in emotional functioning. Pain and fatigue were the major problematic symptoms especially in advanced disease patients resulting in poor QoL. There was a significant improvement in various domains of QoL at 3 months follow-up in those with advanced disease. The fatigue scores at baseline and follow-up showed a positive correlation with other symptoms. CONCLUSION: Patients with HNC have a high symptom burden that leads to poor QoL. Appropriate palliative care interventions help to decrease symptom burden and prevent deterioration of their QoL in patients with HNC.
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The controlled environment ecosystem is a meticulously designed plant growing chamber utilized for cultivating biofortified crops and microgreens, addressing hidden hunger and malnutrition prevalent in the growing population. The integration of speed breeding within such controlled environments effectively eradicates morphological disruptions encountered in traditional breeding methods such as inbreeding depression, male sterility, self-incompatibility, embryo abortion, and other unsuccessful attempts. In contrast to the unpredictable climate conditions that often prolong breeding cycles to 10-15 years in traditional breeding and 4-5 years in transgenic breeding within open ecosystems, speed breeding techniques expedite the achievement of breeding objectives and F1-F6 generations within 2-3 years under controlled growing conditions. In comparison, traditional breeding may take 5-10 years for plant population line creation, 3-5 years for field trials, and 1-2 years for variety release. The effectiveness of speed breeding in trait improvement and population line development varies across different crops, requiring approximately 4 generations in rice and groundnut, 5 generations in soybean, pea, and oat, 6 generations in sorghum, Amaranthus sp., and subterranean clover, 6-7 generations in bread wheat, durum wheat, and chickpea, 7 generations in broad bean, 8 generations in lentil, and 10 generations in Arabidopsis thaliana annually within controlled environment ecosystems. Artificial intelligence leverages neural networks and algorithm models to screen phenotypic traits and assess their role in diverse crop species. Moreover, in controlled environment systems, mechanistic models combined with machine learning effectively regulate stable nutrient use efficiency, water use efficiency, photosynthetic assimilation product, metabolic use efficiency, climatic factors, greenhouse gas emissions, carbon sequestration, and carbon footprints. However, any negligence, even minor, in maintaining optimal photoperiodism, temperature, humidity, and controlling pests or diseases can lead to the deterioration of crop trials and speed breeding techniques within the controlled environment system. Further comparative studies are imperative to comprehend and justify the efficacy of climate management techniques in controlled environment ecosystems compared to natural environments, with or without soil.
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Cellulose reducing ends are believed to play a vital role in the cellulose recalcitrance to enzymatic conversion. However, their role in insoluble cellulose accessibility and hydrolysis is not clear. Thus, in this study, reducing ends of insoluble cellulose derived from various sources were modified by applying reducing and/or oxidizing agents. The effects of cellulose reducing ends modification on cellulose reducing ends, cellulose structure, and cellulose accessibility to cellulase were evaluated along with the impact on cellulose hydrolysis with complete as well purified cellulase components. Sodium borohydride (NaBH4) reduction and sodium chlorite-acetic acid (SC/AA) oxidation were able to modify more than 90% and 60% of the reducing ends, respectively, while the bicinchoninic acid (BCA) reagent applied for various cycles oxidized cellulose reducing ends to various extents. X-ray diffractograms of the treated solids showed that these treatments did not change the cellulose crystalline structure and the change in crystallinity index was insignificant. Surprisingly, it was found that the cellulose reducing ends modification, either through selective NaBH4 reduction or BCA oxidation, had a negligible impact on cellulose accessibility as well on cellulose hydrolysis rates or final conversions with complete cellulase at loadings as low as 0.5 mg protein/g cellulose. In fact, in contrast to what is traditionally believed, modifications of cellulose reducing ends by these two methods had no apparent impact on cellulose conversion with purified cellulase components and their synergy. However, SC/AA oxidation resulted in significant drop in cellulose conversion (10%-50%) with complete as well purified cellulase components. Nonetheless, further research revealed that the cause for drop in cellulose conversion for the SC/AA oxidation case was due to primary hydroxyl groups (PHGs) oxidation and not the oxidation of reducing ends. Furthermore, it was found that the PHGs modification affects cellulose accessibility and slows the cellulase uptake as well resulting in significant drop in cellulose conversions.
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Celulasa , Celulosa , Oxidación-Reducción , Celulosa/química , Celulosa/metabolismo , Hidrólisis , Celulasa/química , Celulasa/metabolismoRESUMEN
OBJECTIVE: The 2x2 factorial design is an effective method that allows for multiple comparisons, especially in the context of interactions between different interventions, without substantially increasing the required sample size. In view of the considerable preclinical evidence for Curcumin and Metformin in preventing the development and progression of head and neck squamous cell carcinoma (HNSCC), this study describes the protocol of the clinical trial towards applying the drug combination in prevention of second primary tumors. METHODS: We have applied the trial design to a large phase IIB/III double-blind, multi-centric, placebo-controlled, randomized clinical trial to determine the safety and efficacy of Metformin and Curcumin in the prevention of second primary tumours (SPT) of the aerodigestive tract following treatment of HNSCC (n=1,500) [Clinical Registry of India, CTRI/2018/03/012274]. Patients recruited in this trial will receive Metformin (with placebo), Curcumin (with placebo), Metformin, and Curcumin or placebo alone for a period of 36 months. The primary endpoint of this trial is the development of SPT, while the secondary endpoints are toxicities associated with the agents, incidence of recurrence, and identifying potential biomarkers. In this article, we discuss the 2x2 factorial design and how it applies to the head and neck cancer chemoprevention trial. CONCLUSION: 2x2 factorial design is an effective trial design for chemoprevention clinical trials where the effectiveness of multiple interventions needs to be tested parallelly.
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Curcumina , Neoplasias de Cabeza y Cuello , Metformina , Neoplasias Primarias Secundarias , Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Curcumina/uso terapéutico , Método Doble Ciego , Estudios de Seguimiento , Neoplasias de Cabeza y Cuello/prevención & control , Neoplasias de Cabeza y Cuello/tratamiento farmacológico , Metformina/uso terapéutico , Neoplasias Primarias Secundarias/prevención & control , Pronóstico , Ensayos Clínicos Controlados Aleatorios como Asunto , Proyectos de Investigación , Carcinoma de Células Escamosas de Cabeza y Cuello/prevención & control , Carcinoma de Células Escamosas de Cabeza y Cuello/tratamiento farmacológico , Ensayos Clínicos Fase II como Asunto , Estudios Multicéntricos como Asunto , Ensayos Clínicos Fase III como AsuntoRESUMEN
Hamman's syndrome or Macklin phenomenon - spontaneous pneumomediastinum - is an uncommon condition that often gets missed due to the lack of awareness. It may rarely be associated with diabetic ketoacidosis (DKA) due to repeated vomiting or Kussmaul breathing associated with it. This condition is self-resolving, and improvement in symptoms is usually observed with appropriate management of DKA. Secondary pneumomediastinum is relatively more common, but spontaneous pneumomediastinum, which is rare, is often diagnosed incidentally. Here, we describe a case of a 24-year-old gentleman where this condition was found incidentally during the examination and was confirmed through imaging (X-ray and CT scans) and resolved with successful management of DKA.
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CONTEXT.: Salivary gland (SG) neoplasms (SGNs) display considerable immunophenotypic diversity. A significant proportion of SG carcinomas develop metastases with increased diagnostic difficulty at metastatic sites. Transcriptional repressor GATA binding 1 (TRPS1), a novel immunohistochemical marker for breast cancer, has been found to stain certain SGNs. OBJECTIVE.: To investigate TRPS1 and SRY-related HMG-box 10 (SOX10) immunoexpression in various SGNs and non-SG carcinomas, head and neck paragangliomas, and head and neck mucosal melanomas. DESIGN.: TRPS1 immunoreactivity score (IRS) was determined as negative or low, intermediate, or high positive; SOX10 was reported as negative or positive. RESULTS.: One hundred forty-eight SGNs, 5 breast carcinomas, 105 nonbreast-non-SG carcinomas, including 33 head and neck squamous cell carcinomas (HNSCCs), 6 head and neck paragangliomas, and 6 head and neck mucosal melanomas, were assessed for TRPS1. All 23 benign SGNs showed TRPS1 positivity, with the majority having high-positive IRS (17 of 23 cases; 74%). Among 125 SG carcinomas, 115 of 125 (92%) were TRPS1 positive, with high-positive IRS in 94 of 125 (75%), intermediate positive in 15 of 125 (12%), and low positive in 6 of 125 (5%). Among nonbreast-non-SG carcinomas, HNSCC, lung, thyroid, kidney, and ovarian carcinomas showed frequent TRPS1 staining. Nearly half of HNSCCs had high (11 of 18; 33%) or intermediate (4 of 18; 12%) positive IRS. Mean IRS in SG carcinomas was significantly higher than that in nonbreast-non-SG carcinomas (P < .001). None of the TRPS1-positive nonbreast-non-SG carcinomas expressed SOX10. CONCLUSIONS.: TRPS1 is positive in most benign and malignant SGNs. Its expression in several nonbreast-non-SG carcinomas indicates that it lacks specificity for breast and SG carcinomas, even if considering only high-positive IRS. Addition of SOX10 can increase discriminatory utility of TRPS1.