Direct replication of a glass micro Fresnel zone plate array by laser irradiation using an infrared transmissive mold.

It is not yet possible to fabricate micrometer-scale, glass optical components with nanometer-scale precision. Glass thermal imprinting enhances production efficiency. However, dimensional changes caused by shrinkage are inevitable because of phase transitions. Replication is very difficult when high-level pitch precision is essential. We used an infrared-transparent silicon mold and a CO2 laser to perform replica-type, thermal surface texturing at the nanoscale level; we analyzed a glass Fresnel zone plate array to this end. The Fresnel zone plate array was 10 × 10 mm2 in area and featured a 20 × 20 array. The individual Fresnel zone plate diameter was 500 µm and had 21 rings of minimum linewidth 2.9 µm and height 737 nm.

Cloning and characterization of α-L-rhamnosidase from Chloroflexus aurantiacus and its application in the production of isoquercitrin from rutin.

OBJECTIVE: This study was conducted to characterize recombinant α-L-rhamnosidase from Chloroflexus aurantiacus and apply the enzyme in the production of isoquercitrin from rutin. RESULTS: The α-L-rhamnosidase from C. aurantiacus was cloned and expressed in Escherichia coli BL21 and purified as a soluble enzyme. α-L-rhamnosidase purified from C. aurantiacus has a molecular mass of approximately 105 kDa and is predicted to exist as a homodimer with a native enzyme of 200 kDa. The purified enzyme exhibited the highest specific activity for rutin among the reported isoquercitrin producing α-L-rhamnosidases and was applied in the production of isoquercitrin from rutin. Under the optimised conditions of pH 6.0, 50 °C, 0.6 U mL-1 α-L-rhamnosidase, and 30 mM rutin, α-L-rhamnosidase from C. aurantiacus produced 30 mM isoquercitrin after 2 h with a 100% conversion yield and productivity of 15 mM h-1. CONCLUSIONS: We achieved a high productivity of isoquercitrin from rutin. Moreover, these results suggest that α-L-rhamnosidase from C. aurantiacus is an effective isoquercitrin producer.

Design methodology for micro-discrete planar optics with minimum illumination loss for an extended source.

Recently, studies have examined techniques for modeling the light distribution of light-emitting diodes (LEDs) for various applications owing to their low power consumption, longevity, and light weight. The energy mapping technique, a design method that matches the energy distributions of an LED light source and target area, has been the focus of active research because of its design efficiency and accuracy. However, these studies have not considered the effects of the emitting area of the LED source. Therefore, there are limitations to the design accuracy for small, high-power applications with a short distance between the light source and optical system. A design method for compensating for the light distribution of an extended source after the initial optics design based on a point source was proposed to overcome such limits, but its time-consuming process and limited design accuracy with multiple iterations raised the need for a new design method that considers an extended source in the initial design stage. This study proposed a method for designing discrete planar optics that controls the light distribution and minimizes the optical loss with an extended source and verified the proposed method experimentally. First, the extended source was modeled theoretically, and a design method for discrete planar optics with the optimum groove angle through energy mapping was proposed. To verify the design method, design for the discrete planar optics was achieved for applications in illumination for LED flash. In addition, discrete planar optics for LED illuminance were designed and fabricated to create a uniform illuminance distribution. Optical characterization of these structures showed that the design was optimal; i.e., we plotted the optical losses as a function of the groove angle, and found a clear minimum. Simulations and measurements showed that an efficient optical design was achieved for an extended source.

Effect of high hydrostatic pressure treatment on isoquercetin production from rutin by commercial α-L-rhamnosidase.

OBJECTIVES: To optimize conversion of rutin to isoquercetin by commercial α-L-rhamnosidase using high hydrostatic pressure (HHP). RESULTS: The de-rhamnosylation activity of α-L-rhamnosidase for isoquercetin production was maximal at pH 6.0 and 50 °C using HHP (150 MPa). The enzyme showed high specificity for rutin. The specific activity for rutin at HHP was 1.5-fold higher than that at atmospheric pressure. The enzyme completely hydrolysed 20 mM rutin in tartary buckwheat extract after 2 h at HHP, with a productivity of 10 mM h(-1). The productivity and conversion were 2.2- and 1.5-fold higher at HHP than at atmospheric pressure, respectively. CONCLUSIONS: This is the first report concerning the enzymatic hydrolysis of isoquercetin in tartary buckwheat at HHP.

Design methodology accounting for fabrication errors in manufactured modified Fresnel lenses for controlled LED illumination.

The increasing demand for lightweight, miniaturized electronic devices has prompted the development of small, high-performance optical components for light-emitting diode (LED) illumination. As such, the Fresnel lens is widely used in applications due to its compact configuration. However, the vertical groove angle between the optical axis and the groove inner facets in a conventional Fresnel lens creates an inherent Fresnel loss, which degrades optical performance. Modified Fresnel lenses (MFLs) have been proposed in which the groove angles along the optical paths are carefully controlled; however, in practice, the optical performance of MFLs is inferior to the theoretical performance due to fabrication errors, as conventional design methods do not account for fabrication errors as part of the design process. In this study, the Fresnel loss and the loss area due to microscopic fabrication errors in the MFL were theoretically derived to determine optical performance. Based on this analysis, a design method for the MFL accounting for the fabrication errors was proposed. MFLs were fabricated using an ultraviolet imprinting process and an injection molding process, two representative processes with differing fabrication errors. The MFL fabrication error associated with each process was examined analytically and experimentally to investigate our methodology.

A Real-World Retrospective Analysis of the Management of Advanced Urothelial Carcinoma in Canada.

Locally advanced or metastatic urothelial carcinoma (aUC) presents a significant challenge with high mortality rates. Platinum-based chemotherapy remains the established frontline standard of care, and a switch-maintenance strategy with immunotherapy has now emerged as a new standard for aUC patients without disease progression, following initial platinum therapy. Examining the treatment patterns is imperative, given the evolving therapeutic landscape. In this study, we conducted a retrospective medical chart review of 17 Canadian oncologists treating patients with aUC to assess unmet needs in Canadian aUC patient care. Data from 146 patient charts were analyzed, revealing important clinical insights about the management of aUC. A substantial proportion of patients (53%) presented with de novo metastatic disease, which was possibly influenced by pandemic-related care disruptions. Variability was evident in the cisplatin eligibility criteria, with a majority (70%) of oncologists utilizing a 50 mL/min threshold. Most favored four cycles of platinum-based chemotherapy to spare the bone marrow for future therapies and prevent patient fatigue. Notably, some eligible patients were kept under surveillance rather than receiving maintenance therapy, suggesting a potential gap in awareness regarding evidence-based recommendations. Furthermore, managing treatment-related adverse events was found to be one of the biggest challenges in relation to maintenance immunotherapy. In conclusion, our findings provide the first comprehensive overview of aUC treatment patterns in Canada following the approval of maintenance immunotherapy, offering insights into the decision-making process and underscoring the importance of evidence-based guidelines in aUC patient management.

Impact of Timing of Immunotherapy and Cytoreductive Nephrectomy in Metastatic Renal Cell Carcinoma: Real-World Data on Survival Outcomes from the CKCis Database.

Immunotherapy-based systemic treatment (ST) is the standard of care for most patients diagnosed with metastatic renal cell carcinoma (mRCC). Cytoreductive nephrectomy (CN) has historically shown benefit for select patients with mRCC, but its role and timing are not well understood in the era of immunotherapy. The primary objective of this study is to assess outcomes in patients who received ST only, CN followed by ST (CN-ST), and ST followed by CN (ST-CN). The Canadian Kidney Cancer information system (CKCis) database was queried to identify patients with de novo mRCC who received immunotherapy-based ST between January 2014 and June 2023. These patients were classified into three categories as described above. Cox proportional hazards models were used to assess the impact of the timing of ST and CN on overall survival (OS) and progression-free survival (PFS), after adjusting for the International Metastatic RCC Database Consortium (IMDC) risk group, age, and comorbidities. Best overall response and complications of ST and CN for these cohorts were collected. A total of 588 patients were included in this study: 331 patients received ST only, 215 patients received CN-ST, and 42 patients received ST-CN. Patient and disease characteristics including age, gender, performance status, IMDC risk category, comorbidity, histology, type of ST, and metastatic sites are reported. OS analysis favored patients who received ST-CN (hazard ratio [HR] 0.30, 95% confidence interval [CI] 0.13-0.68) and CN-ST (HR 0.68, CI 0.47-0.97) over patients who received ST only. PFS analysis showed a similar trend for ST-CN (HR 0.45, CI 0.26-0.77) and CN-ST (HR 0.9, CI 0.68-1.17). This study examined baseline features and outcomes associated with the use and timing of CN and ST using real-world data via a large Canadian real-world cohort. Patients selected to receive CN after ST demonstrated improved outcomes. There were no appreciable differences in perioperative complications across groups. Limitations include the small number of patients in the ST-CN group and residual confounding and selection biases that may influence the outcomes in patients undergoing CN.

Characterization of a recombinant mannobiose 2-epimerase from Spirochaeta thermophila that is suggested to be a cellobiose 2-epimerase.

A purified recombinant enzyme from Spirochaeta thermophila, that is suggested to be a cellobiose 2-epimerase, was a 47 kDa monomer with a specific activity of 29.2 U min(-1) for mannobiose. The epimerization activity of the recombinant enzyme for mannobiose was maximal at pH 7.0 and 60 °C with a half-life of 124 h. The enzyme exhibited a higher epimerization activity for mannose or the mannose moiety at the reducing end of ß- and α-1,4-glycosyl-mannose than for glucose or the glucose moiety of ß- and α-1,4-glycosyl-glucose. The enzyme was identified as a mannobiose 2-epimerase by evaluating its substrate specificity with not only glucose-containing sugars but also mannose-containing sugars. The activities of the reported cellobiose 2-epimerases from Caldicellulosiruptor saccharolyticus, Dictyoglomus turgidum and Ruminococcus marinus for mannobiose were higher than those for cellobiose, strongly suggesting that these enzymes are not cellobiose 2-epimerases but are mannobiose 2-epimerases.

Combination of Osimertinib with Concurrent Chemotherapy and Hormonal Therapy for Synchronous NSCLC, Hormone Receptor-Positive Breast Cancer, and Triple-Negative Breast Cancer: Case Report.

Patients presenting with multiple primary malignancies remain a growing challenge for physicians due to a lack of data for generalizable guidelines. Identification of driver mutations in carcinogenesis leads to the development of targeted treatment of many different cancer types, but its combination with other anti-cancer therapy is not well understood. We report a case of a 66-year-old woman who presented with triple-negative breast cancer, multifocal hormone receptor-positive breast cancer, primary epidermal growth factor receptor-mutated lung adenocarcinoma, possible primary lung adenocarcinoma of unspecified mutational status in the contralateral lung, and a solitary metastatic lesion in the brain from one of her primary cancers. She was treated with stereotactic radiosurgery and osimertinib in combination with carboplatin/nab-paclitaxel, doxorubicin/cyclophosphamide, and letrozole, with excellent clinical and radiographical response. We did not observe synergistic toxicity or unexpected adverse events from the treatment. To the best of our knowledge, this is the first report of concurrent osimertinib with these chemotherapy and hormonal therapy agents. As large-scale studies are difficult to conduct for these rare cases requiring exceptional treatment, it is important for physicians to build on the community's shared experience via case reports to better predict efficacy and safety of combining targeted agents with other conventional systemic treatments.

An Unconventional Regimen of Carboplatin and Paclitaxel in Metastatic Colorectal Carcinosarcoma: A Case Report and Review of Literature.

Colorectal carcinosarcoma is an exceedingly rare subtype of colorectal cancer that displays the histological and molecular features of both mesenchymal and epithelial tumors. Due to its rarity, there are no guidelines regarding the systemic treatment of this disease. This report describes a case of a 76-year-old woman with colorectal carcinosarcoma with extensive metastatic burden treated with carboplatin and paclitaxel. After four cycles of chemotherapy, the patient had an excellent clinical and radiographical response to treatment. To the best of our knowledge, this is the first report addressing the use of carboplatin and paclitaxel in this disease. We reviewed seven published case reports of metastatic colorectal carcinosarcoma where various systemic treatments were offered. Remarkably, there are no previously published reports where even a partial response was noted, which underscores the aggressiveness of this disease. While further studies are required to validate our experience and assess long-term outcomes, this case suggests an alternative treatment regimen for metastatic colorectal carcinosarcoma.

A screening method for ß-glucan hydrolase employing Trypan Blue-coupled ß-glucan agar plate and ß-glucan zymography.

A new screening method for ß-(1,3-1,6) glucan hydrolase was developed using a pure ß-glucan from Aureobaisidum pullulans by zymography and an LB-agar plate. Paenibacillus sp. was screened as a producer a ß-glucan hydrolase on the Trypan Blue-coupled ß-glucan LB-agar plate and the activity of the enzyme was analyzed by SDS-ß-glucan zymography. The ß-glucan was not hydrolyzed by Bacillus spp. strains, which exhibit cellulolytic activity on CMC zymography. The gene, obtaining by shotgun cloning and encoding the ß-glucan hydrolase of Paenibacillus sp. was sequenced.

Secondary Immune Thrombocytopenia Due to Mycoplasma pneumoniae Without Clinically Significant Evidence of Active Infection.

Immune thrombocytopenia (ITP) is a leading cause of isolated thrombocytopenia characterized by autoantibody-mediated destruction of platelets, impaired megakaryocyte function, and pathologic T-cell recognition of platelet antigens. Several triggers for ITP have been identified. Treatment of the inciting cause decreases the antibodies responsible for molecular mimicry, and these cases are usually associated with a better outcome with a decreased probability of progression to chronic ITP. Mycoplasma pneumoniae infection is known to have extrapulmonary manifestations, and growing evidence suggests it can be a cause of secondary ITP. Many of the described cases report evidence of a pulmonary infection with severe mucosal bleeding. Here, we describe an interesting case of a patient presenting with isolated thrombocytopenia with mild mucosal bleeding, later found to be positive for Mycoplasma immunoglobulin M without clinically significant evidence of active infection. Currently, mycoplasma testing is not routinely performed as a workup for ITP. However, clinicians may consider this before proceeding with more aggressive treatment for refractory ITP (i.e., prolonged immunosuppression, splenectomy). This case illustrates that mild/asymptomatic Mycoplasma infection can also be associated with ITP.

Massively parallel direct writing of nanoapertures using multi-optical probes and super-resolution near-fields.

Laser direct-writing enables micro and nanoscale patterning, and is thus widely used for cutting-edge research and industrial applications. Various nanolithography methods, such as near-field, plasmonic, and scanning-probe lithography, are gaining increasing attention because they enable fabrication of high-resolution nanopatterns that are much smaller than the wavelength of light. However, conventional methods are limited by low throughput and scalability, and tend to use electron beams or focused-ion beams to create nanostructures. In this study, we developed a procedure for massively parallel direct writing of nanoapertures using a multi-optical probe system and super-resolution near-fields. A glass micro-Fresnel zone plate array, which is an ultra-precision far-field optical system, was designed and fabricated as the multi-optical probe system. As a chalcogenide phase-change material (PCM), multiple layers of Sb65Se35 were used to generate the super-resolution near-field effect. A nanoaperture was fabricated through direct laser writing on a large-area (200 × 200 mm2) multi-layered PCM. A photoresist nanopattern was fabricated on an 8-inch wafer via near-field nanolithography using the developed nanoaperture and an i-line commercial exposure system. Unlike other methods, this technique allows high-throughput large-area nanolithography and overcomes the gap-control issue between the probe array and the patterning surface.

Toll-like receptors and interferon associated immune factors in viral haemorrhagic septicaemia virus-infected olive flounder (Paralichthys olivaceus).

Pattern recognition receptor (PRR) toll-like receptors (TLRs), antiviral agent interferon (IFN) and the effector IFN stimulated genes (ISGs) play pivotal role in antiviral innate immunity of a host. The present in-vivo experiment was conducted to investigate the role of these innate immune factors in early phase as well as during recovery of viral haemorrhagic septicaemia virus (VHSV) infection by quantitative real-time reverse transcriptase polymerase chain reaction. A less lethal VHSV infection was generated in olive flounder (Paralichthys olivaceus) and was sampled at 3, 6, and 12h post infection (hpi), and 1, 2, 4, and 7 days post infection (dpi). At 3 hpi, the VHSV N gene was detected in three out of five fish and all five fish showed a relative fold increase of TLR 2, TLR 7, interleukin 8 (IL 8), IFN regulatory factor 3 (IRF 3), IRF 7, and ISG 15. Viral copies rapidly increased at 12 hpi then remained high until 2 dpi. When viral copy numbers were high, a higher expression of immune genes IL 1ß, IRF 3, IRF 7, Type I IFN, ISG 15 and Mx was observed. Viral copies were drastically reduced in 4 and 7 dpi fish, and also the immune response was considerably reduced but remained elevated, except for ISG 15 which found equal to control in 7 dpi fish. A high degree of correlation was observed between immune genes and viral copy number in each of the sampled fish at 12 hpi. A fish with ascites sampled at 7 dpi displayed high viral copy but under-expressed immune genes except for Mx. When viral copies were high at 1 and 2 dpi, both TLR 2 and TLR 7 were down-regulated, perhaps indicating immune suppression by the virus. The quick and prolonged elevated expression of the immune genes indicates their crucial role in survival of host against VHSV.

Production of aglycon protopanaxadiol via compound K by a thermostable ß-glycosidase from Pyrococcus furiosus.

The production of compound K and aglycon protopanaxadiol (APPD) from ginsenoside Rd and ginseng root extract was performed using a recombinant ß-glycosidase from Pyrococcus furiosus. The activity for Rd was optimal at pH 5.5 and 95°C with a half-life of 68 h at 95°C. ß-Glycosidase converted Rb(1), Rb(2), Rc, and Rd to APPD via compound K. With increases in the enzyme activity, the productivities of compound K and APPD increased. The substrate concentration was optimal at 4.0 mM Rd or 10% (w/v) ginseng root extract; 4 mM of Rd was converted to 3.3 mM compound K with a yield of 82.5% (mol/mol) and a productivity of 2,010 mg l(-1) h(-1) at 1 h and was hydrolyzed completely to APPD with 364 mg l(-1) h(-1) after 5 h. Rb(1), Rb(2), Rc, and Rd at 3.9 mM in 10% ginseng root extract were converted to 3.1 mM compound K with 79.5% and 1,610 mg l(-1) h(-1) at 1.2 h and were hydrolyzed completely to APPD with 300 mg l(-1) h(-1) after 6 h. The concentrations and productivities of compound K and APPD in the present study are the highest ever reported.

Characterization of a recombinant cellobiose 2-epimerase from Caldicellulosiruptor saccharolyticus and its application in the production of mannose from glucose.

A putative N-acyl-D-glucosamine 2-epimerase from Caldicellulosiruptor saccharolyticus was cloned and expressed in Escherichia coli. The recombinant enzyme was identified as a cellobiose 2-epimerase by the analysis of the activity for substrates, acid-hydrolyzed products, and amino acid sequence. The cellobiose 2-epimerase was purified with a specific activity of 35 nmol min(-1) mg(-1) for D-glucose with a 47-kDa monomer. The epimerization activity for D-glucose was maximal at pH 7.5 and 75°C. The half-lives of the enzyme at 60°C, 65°C, 70°C, 75°C, and 80°C were 142, 71, 35, 18, and 4.6 h, respectively. The enzyme catalyzed the epimerization reactions of the aldoses harboring hydroxyl groups oriented in the right-hand configuration at the C2 position and the left-hand configuration at the C3 position, such as D-glucose, D-xylose, L-altrose, L-idose, and L-arabinose, to their C2 epimers, such as D-mannose, D-lyxose, L-allose, L-gulose, and L-ribose, respectively. The enzyme catalyzed also the isomerization reactions. The enzyme exhibited the highest activity for mannose among monosaccharides. Thus, mannose at 75 g l(-1) and fructose at 47.5 g l(-1) were produced from 500 g l(-1) glucose at pH 7.5 and 75°C over 3 h by the enzyme.

Antiobesity activity of fermented Angelicae gigantis by high fat diet-induced obese rats.

This study aimed to evaluate the effects of Monascus purpureus-fermented Angelicae gigantis Radix (FAG) on body weight gain, visceral fat accumulation, biochemical markers of obesity, and the mRNA expression levels of various genes involved in adipogenesis in a high-fat-diet (HFD)-induced rat model of obesity. Effect of nodakenin isolated from Angelicae gigantis on 3T3-L1 preadipocyte differentiation was also investigated in vitro. Male Sprague-Dawley rats were randomly divided into five groups (n = 6 per group) based on five dietary categories: HFD control, HFD + 2.5% (w/w) AG, HFD + 5% AG, HFD + 2.5% FAG, and HFD + 5% FAG. Present study investigated nodakenin isolated from AG and FAG roots by measuring fat accumulation in 3T3-L1 preadipocyte using Oil Red O staining. FAG administration effectively lowered the body weight gain, visceral fat accumulation, and hepatic and serum lipid and leptin concentrations in obese rats. In addition, FAG administration significantly reduced the mRNA expression levels of adipose tissue genes encoding adipocyte protein 2 (aP2), peroxisome proliferator-activated receptor γ 2 (PPARγ2), and CCAT/enhancer-binding protein α (C/EBPα) as compared with HFD group. Furthermore, nodakenin reduced the fat accumulation in differentiated 3T3-L1 adipocytes in a dose-dependent manner. FAG ameliorates HFD-induced obesity, probably by modulating multiple genes associated with adipogenesis in the visceral fat tissue of rats. Accordingly, fermented Angelicae gigantis may be an ideal candidate for obesity relief.

Venous thromboembolism in patients with multiple myeloma receiving daratumumab-based regimens: a post hoc analysis of phase 3 clinical trials.

It is unknown if daratumumab could affect venous thromboembolism (VTE) risks in patients with multiple myeloma (MM). In this study, individual participant data from three trials comparing daratumumab (DARA) and non-DARA regimens, the CASTOR, PULLOX and MAIA trial, were pooled into two groups. A total of 896 and 899 patients received DARA and non-DARA regimens, respectively. After a median follow-up of 13.9 and 13.5 months, there was no significant difference in VTE incidence between the two groups (hazard ratio 0.80, 95% confidence interval 0.57-1.13, p = 0.17). The two groups shared similar VTE risk factors. The SAVED score and IMPEDE-VTE score are two validated VTE risk-stratification tools in MM. In the DARA group, the SAVED score had better performance than the IMPEDE-VTE score in identifying high risk patients.

Risk of Non-Hodgkin's Lymphoma in HCV Patients in the United States Between 2013 and 2020: A Population-Based Study.

Hepatitis C virus (HCV) is a significant healthcare problem affecting ~1% of the United States population. Meta-analyses of epidemiological studies reported a strong association between non-Hodgkin's lymphoma (NHL) and HCV. Direct oncogenic properties of HCV proteins and chronic antigenic stimulation are possible etiologies. We explored if NHL's prevalence has changed since older HCV therapy based on interferon that shared antiviral and anti-lymphoma properties was replaced with interferon-free direct-acting antivirals (DAA). We reviewed data from a nationwide database (Explorys, IBM) that aggregates records from 26 health-care-systems. We identified patients with chronic hepatitis C infection between June 2013 and June 2020. The control group was gender, race, and age-matched HCV-negative population. Statistical analysis used the odds ratio (OR) with P value <.001 for significance. There were 940 cases of NHL of 129,970 patients in the HCV group versus 107,480 cases of NHL of 37,961,970 in the control cohort [OR 2.6, 95% confidence interval (CI) 2.4-2.7]. A positive association was present for chronic lymphocytic leukemia, follicular lymphoma, marginal zone lymphoma, lymphoplasmacytic lymphoma, diffuse large B-cell lymphoma, Burkitt's lymphoma, non-Hodgkin T-cell lymphoma, and primary cutaneous T-cell lymphoma. There were no differences in Mantle cell lymphoma. The increased risk of HCV-associated lymphoma was persistent across genders, Caucasians and African-Americans, and age groups. While the risk of NHL in the HCV-negative population was higher in Caucasians than African-Americans (OR 1.8, 95% CI 1.7-1.8), the risk of HCV-associated NHL was not different. Further prospective studies examining the risk of HCV-associated lymphoma following DAA are warranted.

Acute Liver Failure From Sickle Cell Hepatopathy Treated With Exchange Transfusion.

Sickle cell disease (SCD) is a qualitative hemoglobinopathy that can cause widespread sickling and vaso-occlusive events in all organ systems. Sickle cell hepatopathy is an umbrella term for various acute and chronic pathologies of the liver as a result of sickling in SCD patients. We present below the case of a 49-year-old woman who had an acute liver failure in the setting of a hepatic crisis with recovery after exchange transfusion. Hepatic involvement in SCD may be life-threatening. Understanding the etiology and severity of hepatic involvement by sickling is necessary for appropriate treatment.