[Immunotherapy advances for lung cancer combined with chronic obstructive pulmonary disease].

Lung cancer is a major public health problem worldwide, with high rates of morbidity and mortality. It often coexists with chronic obstructive pulmonary disease (COPD), the diagnosis and management of which often receives insufficient attention. In particular, the presence of COPD has significant implications for the clinical management of lung cancer patients. This review systematically assesses the influence of COPD on the efficacy of immunotherapy and the occurrence of immune-related adverse events in patients with lung cancer, identifies existing challenges and proposes avenues for future research in this field.

A three-generation family cluster with COVID-19 infection: should quarantine be prolonged?

OBJECTIVES: Families are a transmission route for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) because of the close contact. Monitoring of the viral load will be a valuable method to reduce the optimal number of quarantine days, especially in presymptomatic and symptomatic carriers of their households. The traditional three-generation families living together are seen frequently in East Asia, including in Taiwan. STUDY DESIGN: We report on a family cluster with six individuals infected with coronavirus disease in Taiwan. METHODS: The current public policy in Taiwan is quarantine for at least 14 days, based on the incubation period, or until the patient has tested negative three days in a row using the SARS-CoV-2 reverse transcription polymerase chain reaction. Details on the onset date of clinical symptoms, throat swab conversion, and course of disease were collected from medical records retrospectively. RESULTS: In the household of this three-generation Taiwanese family, the infection rate was 60%. The ratio of males to females was 4:2, and the age range was 11-85 years. The prevalence of asymptomatic disease was 33.3% (2/6). The longest throat swab conversion time was 37 days, and the estimated course of disease from symptoms to first conversion of throat swab was 59 days. CONCLUSIONS: Large families, including three-generation families in a single dwelling, should be monitored when the index case is found. Presymptomatic and symptomatic family members could be quarantined for an appropriate duration which, in our experience, is 2 months.

Solid-state, ambient-operation thermally activated delayed fluorescence from flexible, non-toxic gold-nanocluster thin films: towards the development of biocompatible light-emitting devices.

Luminescent gold nanoclusters (AuNCs) with good biocompatibility have gained much attention in bio-photonics. In addition, they also exhibit a unique photo-physical property, namely thermally activated delayed fluorescence (TADF), by which both singlet and triplet excitons can be harvested. The combination of their non-toxic material property and unique TADF behavior makes AuNCs biocompatible nano-emitters for bio-related light-emitting devices. Unfortunately, the TADF emission is quenched when colloidal AuNCs are transferred to solid states under ambient environment. Here, a facile, low-cost and effective method was used to generate efficient and stable TADF emissions from solid AuNCs under ambient environment using polyvinyl alcohol as a solid matrix. To unravel the underlying mechanism, temperature-dependent static and transient photoluminescence measurements were performed and we found that two factors are crucial for solid TADF emission: small energy splitting between singlet and triplet states and the stabilization of the triplet states. Solid TADF films were also deposited on the flexible plastic substrate with patterned structures, thus mitigating the waveguide-mode losses. In addition, we also demonstrated that warm white light can be generated based on a co-doped single emissive layer, consisting of non-toxic, solution-processed TADF AuNCs and fluorescent carbon dots under UV excitation.

Rapid molecular diagnosis of the Gilbert's syndrome-associated exon 1 mutation within the UGT1A1 gene.

Gilbert's syndrome is suspected in patients with unconjugated hyperbilirubinemia caused by decreased activity of the UDP-glucuronosyltransferase 1A1 (UGT1A1) gene in the absence of abnormal liver function and hemolysis. The major genetic variants underlying Gilbert's syndrome are TATA-box repeats of the promoter region and exon 1 G211A of the coding region, particularly in Asians. The efficacy of DNA melting curve analysis, however, has not been established for the G211A mutation. For rapid and accurate molecular diagnosis of Gilbert's syndrome, DNA melting curve analysis was evaluated for its genotyping capability not only for TATA-box repeats of the UGT1A1 promoter, but also for G211A of UGT1A1 exon 1. TA repeats within the TATA-box sequence and the exon 1 G211A mutation of the UGT1A1 gene were analyzed by DNA melting curve analysis. To evaluate the assay reliability, direct sequencing or polyacrylamide gel electrophoresis was used as a comparative method. All homozygous and heterozygous polymorphisms of A(TA)7TAA within the TATA-box allele and of exon 1 G211A mutants of the UGT1A1 gene were successfully identified with DNA melting curve analysis. DNA melting curve analysis is, therefore, an effective molecular method for the rapid diagnosis of Gilbert's syndrome, as it detects not only TATA-box polymorphisms but also the exon 1 G211A mutation located within the UGT1A1 gene.

Interferon-based therapy reduces risk of stroke in chronic hepatitis C patients: a population-based cohort study in Taiwan.

BACKGROUND: Hepatitis C virus (HCV) infection has been linked to an increased risk of insulin resistance and carotid atherosclerosis. AIM: To investigate the association between HCV infection and stroke, and the effect of interferon-based therapy (IBT) on stroke risk in chronic hepatitis C (CHC) patients. METHODS: We conducted a retrospective cohort study that followed up 3113 subjects with a newly detected HCV infection and 12 452 age- and gender-matched subjects without HCV infection selected from a random sample of 10(6) beneficiaries from the Taiwan National Health Insurance Program up to 5 years. Use of IBT was defined as treatment with interferon alpha, pegylated interferon alpha-2a or pegylated interferon alpha-2b for at least 3 months. The hazard ratio (HR) for newly detected stroke was calculated for subjects with HCV compared to those without HCV, and for IBT-treated HCV patients compared to non-IBT-treated HCV patients while adjusting for possible confounding factors. RESULTS: The overall person-years of follow-up were 8624.11 in patients with HCV, 54,533.69 in patients without HCV, 666.65 in IBT-treated patients, and 7886.49 in nontreated patients. The multivariable-adjusted hazard ratio (HR) for newly detected stroke was 1.23 for subjects with HCV compared to the age- and sex-matched subjects without HCV (adjusted HR = 1.23, 95% CI = 1.06-1.42, P = 0.008). Moreover, use of IBT significantly reduced the risk of stroke in HCV patients (adjusted HR = 0.39, 95% CI = 0.16-0.95, P = 0.039) after adjusting for known prognostic factors. CONCLUSIONS: Interferon-based therapy may reduce the long-term risk of stroke in patients with chronic HCV infection.

Differentiation of bacteria cell wall using Raman scattering enhanced by nanoparticle array.

We have fabricated surface-enhanced Raman scattering (SERS) substrates based on arrays of silver nanoparticles grown on porous anodic alumina templates. Using this nanotechnology platform, label-free and high-speed detection of bacteria are achieved. SERS spectra of various bacteria including Staphylococcus Aureus (Gram-positive bacterium), Klebsiella Pneumoniae (Gram-negative bacterium), and Mycobacterium Smegmatis (Mycobacterium) were recorded. The highly reproducible SERS-based technological platform is capable of differentiating different kinds of bacteria by PCA, LDA, clustering analysis, and SVM methods, which provides promising opportunity for biosensing of clinical microbes.

Measurement of the parity-violating asymmetry in inclusive electroproduction of π- near the Δ0 resonance.

The parity-violating (PV) asymmetry of inclusive π- production in electron scattering from a liquid deuterium target was measured at backward angles. The measurement was conducted as a part of the G0 experiment, at a beam energy of 360 MeV. The physics process dominating pion production for these kinematics is quasifree photoproduction off the neutron via the Δ0 resonance. In the context of heavy-baryon chiral perturbation theory, this asymmetry is related to a low-energy constant d(Δ)- that characterizes the parity-violating γNΔ coupling. Zhu et al. calculated d(Δ)- in a model benchmarked by the large asymmetries seen in hyperon weak radiative decays, and predicted potentially large asymmetries for this process, ranging from A(γ)-=-5.2 to +5.2 ppm. The measurement performed in this work leads to A(γ)-=-0.36±1.06±0.37±0.03 ppm (where sources of statistical, systematic and theoretical uncertainties are included), which would disfavor enchancements considered by Zhu et al. proportional to V(ud)/V(us). The measurement is part of a program of inelastic scattering measurements that were conducted by the G0 experiment, seeking to determine the N-Δ axial transition form factors using PV electron scattering.

Increasing insulin resistance is associated with increased severity and prevalence of gastro-oesophageal reflux disease.

BACKGROUND: The diagnosis of gastro-oesophageal reflux disease (GERD) is based on reflux symptoms. Although metabolic syndrome has been linked to erosive oesophagitis (EO), the impact of insulin resistance, the core of the metabolic syndrome, on reflux symptoms remains to be elucidated. AIM: To assess the effects of insulin resistance on GERD, including both endoscopic findings and symptoms. METHODS: A total of 743 sonographic noncirrhotic adult subjects, who underwent an upper gastrointestinal endoscopic examination, completed a gastro-oesophageal reflux questionnaire and had available fasting insulin data were included. Endoscopic findings were classified according to the Los Angeles classification. Homeostatic model assessment-insulin resistance (HOMA-IR) index was used to evaluate the status of insulin resistance. Univariate and multivariate approaches were used to evaluate the associations between insulin resistance and GERD. RESULTS: Older age, male gender, smoking and alcohol consumption increased the prevalence of EO, but not GERD symptoms. A large waist circumference, high fasting blood glucose levels and high number of metabolic syndrome components were associated with increased prevalence of both EO and GERD symptoms, while high blood pressure was associated with increased prevalence of EO only. Moreover, higher scores in the gastro-oesophageal reflux questionnaire were associated with higher HOMA-IR index, and higher HOMA-IR index was associated with increased prevalence of EO (adjusted odds ratio 1.14, 95% CI 1.03-1.26, P = 0.012). CONCLUSIONS: Our findings demonstrate clear associations between insulin resistance, metabolic syndrome and GERD. Whether reducing insulin resistance may improve GERD symptoms or EO deserves prospective study.

Transverse beam spin asymmetries at backward angles in elastic electron-proton and quasielastic electron-deuteron scattering.

We have measured the beam-normal single-spin asymmetries in elastic scattering of transversely polarized electrons from the proton, and performed the first measurement in quasielastic scattering on the deuteron, at backward angles (lab scattering angle of 108°) for Q² = 0.22 GeV²/c² and 0.63 GeV²/c² at beam energies of 362 and 687 MeV, respectively. The asymmetry arises due to the imaginary part of the interference of the two-photon exchange amplitude with that of single-photon exchange. Results for the proton are consistent with a model calculation which includes inelastic intermediate hadronic (πN) states. An estimate of the beam-normal single-spin asymmetry for the scattering from the neutron is made using a quasistatic deuterium approximation, and is also in agreement with theory.

Sensitive measurement of quantity dynamics of FLT3 internal tandem duplication at early time points provides prognostic information.

BACKGROUND: The level of minimal residual disease (MRD) in acute myeloid leukemia (AML) at early time points (TPs) may be an important prognostic factor. Although internal tandem duplication of FLT3 (FLT3-ITD) as an MRD marker has been questioned for its instability based on semi-quantitative methods, we hypothesized that FLT3-ITD dynamics measured by sensitive quantitative real-time PCR at early TPs before appearance of instability may provide prognostic information. PATIENTS AND METHODS: We measured mutant quantity in 493 serial samples from 55 patients with a median follow-up time of 64.8 months. The FLT3-ITD quantities after induction (TP1) and after the first post-induction chemotherapy (TP2) were analyzed. RESULTS: We found that lower FLT3-ITD levels at TP2 predicted longer overall survival (OS) and disease-free survival (DFS) regardless of cytogenetic risk. Multivariate analysis showed that ≥3 log reduction of FLT3-ITD at TP2 independently predicted better DFS and a trend toward better OS. FLT3-ITD disappeared at relapse in 16.7% of patients and none in those harboring mutant NPM1 compared with 29.4% in those with wild-type NPM1 (P = 0.032). CONCLUSIONS: Though the mutation may disappear at relapse in a few patients, FLT3-ITD levels at early TPs after chemotherapy provide prognostic information. FLT3-ITD is significantly more stable in those with mutant NPM1.

Strange quark contributions to parity-violating asymmetries in the backward angle G0 electron scattering experiment.

We have measured parity-violating asymmetries in elastic electron-proton and quasielastic electron-deuteron scattering at Q2=0.22 and 0.63 GeV2. They are sensitive to strange quark contributions to currents in the nucleon and the nucleon axial-vector current. The results indicate strange quark contributions of approximately < 10% of the charge and magnetic nucleon form factors at these four-momentum transfers. We also present the first measurement of anapole moment effects in the axial-vector current at these four-momentum transfers.

Results of up to 2 years of entecavir vs lamivudine therapy in nucleoside-naïve HBeAg-positive patients with chronic hepatitis B.

Entecavir is a potent inhibitor of hepatitis B virus (HBV) polymerase. The efficacy and safety of entecavir in nucleoside-naïve patients with hepatitis B virus e antigen (HBeAg)-positive chronic hepatitis B was established in a large, international, double-dummy study (ETV-022) where patients were randomized to entecavir 0.5 mg/day (n = 354) or lamivudine 100 mg/day (n = 355) once daily. ETV-022 had a 52-week blinded treatment phase, followed by an extended blinded treatment phase for up to 44 additional weeks (96 weeks total). Treatment was discontinued for patients achieving a protocol-defined response as determined by patient management criteria that intended to test the possibility of finite therapy, which has not previously been studied for entecavir or other anti-HBV agents in a large trial. Early results from this study have been previously presented/published separately. This paper compiles the results of up to 2 years of treatment for protocol-defined responders, virologic responders and nonresponders. For responders who discontinued therapy (per protocol), 24-week off-treatment evaluation is presented to provide a more 'complete picture' of what clinicians can expect when treating nucleoside-naïve HBeAg-positive patients with chronic hepatitis B. For patients who discontinued therapy because of nonresponse (nonresponders) and subsequently entered the rollover study ETV-901, follow-up results, including resistance profile, are provided.

New allele name of some HLA-DRB1*1401: HLA-DRB1*1454.

The primary function of MHC polymorphism is considered as the foundation of self-defense mechanism of the host in surveillance against countless diverse invading pathogens. However, this biological function can also elicit undesirable immunological responses that jeopardize transplantations when compatibility between donors and recipients is unfavourable.

Quantitative rat liver function test by galactose single point method.

The purpose of this study was to investigate the galactose single point (GSP) method, a residual liver function test recently recommended by the US Food and Drug Administration, which can be a useful tool for rat liver function measurement. Rats were treated either with carbon tetrachloride (CCl(4)) alone (1 mL/kg, intraperitoneally [i.p.]) for one day or with isoniazid (INH) alone (150 mg/kg, i.p.) or (in order to ameliorate the effects of INH) with a combination of INH and bis-p-nitrophenyl phosphate (BNPP) (25 mg/kg, i.p.) for 21 days. Hepatotoxicity was assayed by plasma aspartate aminotransferase (AST) and alanine aminotransferase (ALT) activities and scores of histological activity index-necroinflammation (HAI-NI) of the respective liver specimens. The GSP method in rats was defined by the galactose blood level after 60 min. Significant differences in GSP values were observed between controls and the CCl(4)-treated rats. After 21 days of treatment, no significant changes in AST and ALT values were observed among the control, INH and INH-BNPP groups. There were significant differences in average GSP values for controls (P < 0.001) and INH-BNPP (P < 0.001) compared with INH alone. Highly significant correlations (P < 0.001) were obtained between GSP and scores of HAI-NI for all the groups. GSP was concluded to be a more sensitive biomarker of INH-induced hepatotoxicity than AST or ALT in the rats. The GSP method has been proved to be a simple and useful tool for the quantitative determination of liver function in rats, which can possibly be extended to other animals.

Sodium trimer ordering on a NaxCoO2 surface.

Sodium ion ordering on an in situ cleaved NaxCoO2 (x=0.84) surface has been studied by ultrahigh vacuum scanning tunneling microscopy at room temperature. Three main phases, with p(3 x 3), ( radical7 x radical7), and (2 radical3 x 2 radical3) hexagonal unit cells and a surface Na concentration of 1/3, 3/7, 1/2, respectively, were identified. One surprising finding is that Na trimers act as the basic building blocks that order in long range. The stability of Na trimers is attributed to the increased Na coordination with oxygen as indicated by ab initio calculations, and possibly at finite temperature by configuration entropy.

Transverse beam spin asymmetries in forward-angle elastic electron-proton scattering.

We have measured the beam-normal single-spin asymmetry in elastic scattering of transversely polarized 3 GeV electrons from unpolarized protons at Q2=0.15, 0.25 (GeV/c)2. The results are inconsistent with calculations solely using the elastic nucleon intermediate state and generally agree with calculations with significant inelastic hadronic intermediate state contributions. A(n) provides a direct probe of the imaginary component of the 2gamma exchange amplitude, the complete description of which is important in the interpretation of data from precision electron-scattering experiments.

Positioning a safe gastric puncture point before percutaneous endoscopic gastrostomy.

To position a safe gastric puncture point prior to the percutaneous endoscopic gastrostomy (PEG) a technique using an abdominal plain film with a gastric insufflation was assessed. After insufflated with 500 ml of air, an abdominal plain film was obtained before PEG in 84 patients. The body of the stomach near the angularis, equidistant from the greater and lesser curves, was defined as the optimal gastric puncture point. The location of the puncture points varied greatly, being situated over the right upper quadrant in 31% of patients, left upper in 59%, right lower in 5% and left lower quadrant in 5% of patients. The marked puncture points on abdominal film in some patients were shown to be partially covered by colon or small bowel loop, lie high under the costal margin, or low beneath the umbilicus. An abdominal plain film utilising a gastric insufflation technique prior to PEG may help to determine optimal gastric puncture site selection. Use this technique in clinical practice might hasten procedural time, provide better assurance to the clinical doctor, and provide an added margin of safety for the patient.

Effects of music on gastric myoelectrical activity in healthy humans.

The aim was to study the effects of listening to music on gastric myoelectrical activity in healthy humans. Gastric myoelectrical activity was recorded using surface electrogastrography from 17 healthy volunteers before and for 30 min after they listened to music. All subjects listened to the same music. Ten perceived the music as enjoyable and seven did not. The percentages of normal slow wave, dominant frequency and dominant power did not differ significantly between baseline and during music intervention. An analysis of covariance model that included the subjects' feelings about the music and dominant power showed significantly higher dominant power during music intervention in subjects who enjoyed the music (p < 0.01). In the individuals who enjoyed the music, dominant power (55.0 +/- 9.2 dB) was significantly higher during music intervention than at baseline (49.5 +/- 6.8 dB, p = 0.03). In the subjects who did not enjoy the music, dominant power was significantly lower during music intervention than at baseline (48.8 +/- 6.8 and 55.7 +/- 6.2 dB, respectively; p < 0.01). Listening to enjoyable music increases the amplitude of gastric myoelectrical activity in healthy humans. Music therapy may improve gastric motility and may be used to stimulate gastric emptying.