A Comparison of Folinic Acid, Fluorouracil and Irinotecan (FOLFIRI) plus Bevacizumab and FOLFIRI plus Aflibercept as Second-line Treatment for Metastatic Colorectal Cancer.

AIM: To compare the efficacy and safety of folinic acid, fluorouracil and irinotecan (FOLFIRI) plus bevacizumab or aflibercept in metastatic colorectal cancer (mCRC) patients pretreated with oxaliplatin-based chemotherapy. MATERIALS AND METHODS: We analysed the treatment outcomes of patients receiving FOLFIRI in combination with bevacizumab or aflibercept as second-line treatment for mCRC between October 2017 and March 2020. This analysis included 67 patients receiving FOLFIRI plus aflibercept and 83 receiving FOLFIRI plus bevacizumab. RESULTS: The overall response rate (ORR) was 13.6% (95% confidence interval 4.85-22.34) in the FOLFIRI-aflibercept group and 14.7% (95% confidence interval 6.68-22.71) in the FOLFIRI-bevacizumab group. This difference in ORR was not statistically significant. The median progression-free survival was 8.6 months in the FOLFIRI-bevacizumab group and 8.5 months in the FOLFIRI-aflibercept group (P = 0.752). Patients in the FOLFIRI-bevacizumab group showed a median overall survival of 12.4 months, whereas patients in the FOLFIRI-aflibercept group had a median overall survival of 13.7 months (P = 0.276). There were no significant differences in survival between the two treatment groups. The adverse events were also largely similar between the two groups. However, hypertension of grade 3 or more was more frequent in the FOLFIRI-aflibercept group. CONCLUSION: FOLFIRI plus bevacizumab and FOLFIRI plus aflibercept had similar anti-tumour activities and toxicity profiles when used as second-line therapy in mCRC patients. Based on these data, both aflibercept and bevacizumab are suitable anti-angiogenic agents when used in combination with FOLFIRI for mCRC.

Retrospective analysis of the association between tooth loss and dementia: a population-based matched case-control study.

OBJECTIVE: To clarify the association between multiple tooth loss and dementia. BASIC RESEARCH DESIGN: Case-control study based on the claims data from National Health Insurance Research Database (NHIRD). Patients were divided into two groups: the dementia groups and non-dementia group. For each case patient, one control patient was randomly selected and frequency matched by age (per 5 years) and sex. The case group comprised patients newly diagnosed with dementia, and the index date was the the date of dementia diagnosis, which became the baseline for comorbidity and age calculations. RESULTS: Among the 43,026 individuals, patients with dementia had a significantly higher extraction density at ages 60-69 (p ⟨ 0.0001) and 70-79 (p = 0.04) years compared with control patients. CONCLUSIONS: This population-based retrospective study demonstrated an association between tooth loss and dementia. Patients in Taiwan with more tooth extraction experience are likely to have an increased risk of dementia.

Long-term follow-up of intradermal injection of methylene blue for intractable, idiopathic pruritus ani.

BACKGROUND: While various medical treatments such as topical steroid ointment, antihistamine agent, and sedatives have been used for treating idiopathic intractable pruritus ani, they are not long-term solutions, due to the high recurrence rate. The aim of this study was to determine the effect of methylene-blue intradermal-injection therapy for treating patients with idiopathic intractable pruritus ani. Symptom improvement and recurrence rates were determined with a long-term follow-up. METHODS: A retrospective study was conducted from January 2011 to October 2013 on consecutive patients with intractable pruritus ani treated with methylene-blue intradermal injection. The therapy included 5 ml of 1% methylene blue and 15 ml of 1% lidocaine. Follow-up included a physical exam and satisfaction-score survey (1 = much worse, 2 = worse, 3 = no improvement, 4 = much better, 5 = gone completely) before treatment, 6 weeks after treatment, and 3 years after treatment to check patient status and recurrence rate. RESULTS: Of 103 treated patients, 96 were able to attend the 6-week follow-up visit. There were 58 (60.4%) males and 38 (39.6%) females with a mean age of 48.34 ± 10.21 years. Their mean satisfaction score at 6 weeks was 4.23 ± 0.86. Of the total of 96 patients, 9 (9.4%) patients scored 3 or less in their satisfactions score at 6 weeks. 62 (64.6%) patients were evaluated 3-year post-treatment. The satisfaction score at 3 years after treatment was 4.74 ± 0.57. Besides the 9 patients who initially failed treatment, 4 of the remaining 53 patients scored 3 or less in their satisfaction score surveys. Thus, the recurrence rate at 3 years was 7.5% (4/53). CONCLUSIONS: Methylene-blue intradermal injection can result in a high symptom improvement rate with low recurrence rate for patients with idiopathic pruritus ani.

Temporal changes in arthropod activity in tropical anthropogenic forests.

Arthropod communities in the tropics are increasingly impacted by rapid changes in land use. Because species showing distinct seasonal patterns of activity are thought to be at higher risk of climate-related extirpation, global warming is generally considered a lower threat to arthropod biodiversity in the tropics than in temperate regions. To examine changes associated with land use and weather variables in tropical arthropod communities, we deployed Malaise traps at three major anthropogenic forests (secondary reserve forest, oil palm forest, and urban ornamental forest (UOF)) in Peninsular Malaysia and collected arthropods continuously for 12 months. We used metabarcoding protocols to characterize the diversity within weekly samples. We found that changes in the composition of arthropod communities were significantly associated with maximum temperature in all the three forests, but shifts were reversed in the UOF compared with the other forests. This suggests arthropods in forests in Peninsular Malaysia face a double threat: community shifts and biodiversity loss due to exploitation and disturbance of forests which consequently put species at further risk related to global warming. We highlight the positive feedback mechanism of land use and temperature, which pose threats to the arthropod communities and further implicates ecosystem functioning and human well-being. Consequently, conservation and mitigation plans are urgently needed.

Tunable quad-band transmission response, based on single-layer metamaterials.

We investigated the electromagnetically induced transparency (EIT)-like effects in planar metamaterials (MMs) at microwave (GHz) frequencies. The specific MMs that were used in this study consist of cut-wire resonator/ring resonator, which achieved the dual EIT-like effects in a single-layer through the bright- and quasi-dark-mode coupling and the lattice mode coupling. In addition, by varying the distance between the two resonators, the quad-band EIT spectral response in the microwave region was obtained, and the group refractive index at the EIT-like resonance of proposed design reached up to 4,000. This study provides the design approach to the multispectral EIT-like effects and might suggest potential applications in a variety of fields, for example, low-loss slow-light device, multiple switching sensor, and other sensing devices.

Switching and extension of transmission response, based on bending metamaterials.

The electromagnetically-induced transparency (EIT)-like effects in planar and non-planar metamaterials (MMs) were investigated for microwave (GHz) frequencies. The specific MMs used in this study consisted of a cut-wire resonator and a ring resonator, where were placed on the top and the bottom layers, respectively. A transmission window was produced, due to the interference between bright- and bright-mode coupling. Using the numerical and the experimental results, we demonstrate that the bending of MM leads to enhanced transmission and bandwidth, as well as an additional EIT-like peak. This provides an effective way of realizing the tunable devices, including the switching sensors.

Purifying selection and genetic drift shaped Pleistocene evolution of the mitochondrial genome in an endangered Australian freshwater fish.

Genetic variation in mitochondrial genes could underlie metabolic adaptations because mitochondrially encoded proteins are directly involved in a pathway supplying energy to metabolism. Macquarie perch from river basins exposed to different climates differ in size and growth rate, suggesting potential presence of adaptive metabolic differences. We used complete mitochondrial genome sequences to build a phylogeny, estimate lineage divergence times and identify signatures of purifying and positive selection acting on mitochondrial genes for 25 Macquarie perch from three basins: Murray-Darling Basin (MDB), Hawkesbury-Nepean Basin (HNB) and Shoalhaven Basin (SB). Phylogenetic analysis resolved basin-level clades, supporting incipient speciation previously inferred from differentiation in allozymes, microsatellites and mitochondrial control region. The estimated time of lineage divergence suggested an early- to mid-Pleistocene split between SB and the common ancestor of HNB+MDB, followed by mid-to-late Pleistocene splitting between HNB and MDB. These divergence estimates are more recent than previous ones. Our analyses suggested that evolutionary drivers differed between inland MDB and coastal HNB. In the cooler and more climatically variable MDB, mitogenomes evolved under strong purifying selection, whereas in the warmer and more climatically stable HNB, purifying selection was relaxed. Evidence for relaxed selection in the HNB includes elevated transfer RNA and 16S ribosomal RNA polymorphism, presence of potentially mildly deleterious mutations and a codon (ATP6113) displaying signatures of positive selection (ratio of nonsynonymous to synonymous substitution rates (dN/dS) >1, radical change of an amino-acid property and phylogenetic conservation across the Percichthyidae). In addition, the difference could be because of stronger genetic drift in the smaller and historically more subdivided HNB with low per-population effective population sizes.

Factors Affecting the Incidence of Angel Wing in White Roman Geese: Stocking Density and Genetic Selection.

The present study investigated stocking density and genetic lines, factors that may alter the severity and incidence of angel wing (AW), in White Roman geese. Geese (n = 384) from two genetically selected lines (normal- winged line, NL, and angel-winged line, AL, respectively) and one commercial line (CL) were raised in four pens. Following common commercial practice, low-stocking-density (LD), medium-stocking-density, and high-stocking-density treatments were respectively administered to 24, 32, and 40 geese per pen at 0 to 3 weeks (1.92 m(2)/pen) and 4 to 6 weeks (13.2 m(2)/pen) of age and to 24, 30, and 36 geese at 7 to 14 weeks (20.0 m(2)/pen) of age. The results revealed that stocking density mainly affected body weight gain in geese younger than 4 weeks, and that geese subjected to LD had a high body weight at 2 weeks of age. However, the effect of stocking density on the severity score of AW (SSAW) and incidence of AW (IAW) did not differ significantly among the treatments. Differences were observed among the genetic stocks; that is, SSAW and IAW were significantly higher in AL than in NL and CL. Genetic selection generally aggravates AW, complicating its elimination. To effectively reduce IAW, stocking density, a suspected causal factor, should be lower than that presently applied commercially.

Pleistocene divergence across a mountain range and the influence of selection on mitogenome evolution in threatened Australian freshwater cod species.

Climatic differences across a taxon's range may be associated with specific bioenergetic demands and may result in genetics-based metabolic adaptation, particularly in aquatic ectothermic organisms that rely on heat exchange with the environment to regulate key physiological processes. Extending down the east coast of Australia, the Great Dividing Range (GDR) has a strong influence on climate and the evolutionary history of freshwater fish species. Despite the GDR acting as a strong contemporary barrier to fish movement, many species, and species with shared ancestries, are found on both sides of the GDR, indicative of historical dispersal events. We sequenced complete mitogenomes from the four extant species of the freshwater cod genus Maccullochella, two of which occur on the semi-arid, inland side of the GDR, and two on the mesic coastal side. We constructed a dated phylogeny and explored the relative influences of purifying and positive selection in the evolution of mitogenome divergence among species. Results supported mid- to late-Pleistocene divergence of Maccullochella across the GDR (220-710 thousand years ago), bringing forward previously reported dates. Against a background of pervasive purifying selection, we detected potentially functionally relevant fixed amino acid differences across the GDR. Although many amino acid differences between inland and coastal species may have become fixed under relaxed purifying selection in coastal environments rather than positive selection, there was evidence of episodic positive selection acting on specific codons in the Mary River coastal lineage, which has consistently experienced the warmest and least extreme climate in the genus.

Review of ultrasonography of malignant neck nodes: greyscale, Doppler, contrast enhancement and elastography.

Assessment of neck lymph nodes is essential in patients with head and neck cancers for predicting the patient's prognosis and selecting the appropriate treatment. Ultrasonography is a useful imaging tool in the assessment of neck lymph nodes. Greyscale ultrasonography assesses the size, distribution, and internal architecture of lymph nodes. Doppler ultrasonography evaluates the intranodal vascular pattern and resistance of lymph nodes. Contrast-enhanced ultrasonography provides information on lymph node parenchymal perfusion. Elastography allows qualitative and quantitative assessment of lymph node stiffness. This article reviews the value of greyscale, Doppler and contrast-enhanced ultrasonography as well as elastography in the assessment of malignant nodes in the neck.

Use of the INNO-LIA syphilis score assay in the resolution of discordant positive screening enzyme immunoassay results for the serological diagnosis of syphilis.

We studied the use of the INNO-LIA syphilis score assay in the resolution of discordant positive screening results of the Murex ICE Syphilis enzyme immunoassay (EIA) with the confirmatory results of both the Serodia Treponema pallidum particle agglutination (TPPA) and the fluorescent treponemal antibody-absorption (FTA-Abs) assays, for the serological diagnosis of syphilis. This was an observational study on the serum samples received by the Syphilis Laboratory, Hong Kong, during the period from January 2006 to December 2012. A total of 801 serum samples with discordant positive screening EIA results were used. Consensus results of such serum samples were derived from results of the EIA, TPPA and FTA-abs assays. The age range of the individuals was 14 to 104 years (median of 52). There were 369 males and 432 females. Of 378 serum samples, 139 showed agreement among positive results, 23 of 310 showed agreement among indeterminate results and 277 of 465 showed agreement among negative results. The proportions of agreement among positive, indeterminate and negative results were 0.37 (95% CI 0.32-0.42), 0.07 (95% CI 0.05-0.11) and 0.60 (95% CI 0.55-0.64), respectively; kappa 0.55 (95% CI 0.49-0.60). There were 60 serum samples with positive consensus results but negative INNO-LIA syphilis score results and 10 with negative consensus results but positive INNO-LIA syphilis score results. Although the INNO-LIA syphilis score assay can be considered a valid alternative confirmatory test for the serological diagnosis of syphilis, the present study showed that its use in the resolution of discordant positive screening EIA results was moderate. A more extensive characterization of serum samples with discordant reactive screening treponemal test results is necessary.

Unusual parotid gland lesions: a pictorial review.

This is a pictorial essay of unusual parotid gland lesions that may be encountered in routine clinical practice.

Genetic diversity of Vietnamese domestic chicken populations as decision-making support for conservation strategies.

The aims of this study were to assess the genetic diversity of 17 populations of Vietnamese local chickens (VNN) and one Red Jungle Fowl population, together with six chicken populations of Chinese origin (CNO), and to provide priorities supporting the conservation of genetic resources using 20 microsatellites. Consequently, the VNN populations exhibited a higher diversity than did CNO populations in terms of number of alleles but showed a slightly lower observed heterozygosity. The VNN populations showed in total seven private alleles, whereas no CNO private alleles were found. The expected heterozygosity of 0.576 in the VNN populations was higher than the observed heterozygosity of 0.490, leading to heterozygote deficiency within populations. This issue could be partly explained by the Wahlund effect due to fragmentation of several populations between chicken flocks. Molecular analysis of variance showed that most of genetic variation was found within VNN populations. The Bayesian clustering analysis showed that VNN and CNO chickens were separated into two distinct groups with little evidence for gene flow between them. Among the 24 populations, 13 were successfully assigned to their own cluster, whereas the structuring was not clear for the remaining 11 chicken populations. The contributions of 24 populations to the total genetic diversity were mostly consistent across two approaches, taking into account the within- and between-populations genetic diversity and allelic richness. The black H'mong, Lien Minh, Luong Phuong and Red Jungle Fowl were ranked with the highest priorities for conservation according to Caballero and Toro's and Petit's approaches. In conclusion, a national strategy needs to be set up for Vietnamese chicken populations, with three main components: conservation of high-priority breeds, within-breed management with animal exchanges between flocks to avoid Wahlund effect and monitoring of inbreeding rate.

Tunable dual-band perfect absorbers based on extraordinary optical transmission and Fabry-Perot cavity resonance.

Magnetic resonance is considered to be a necessary condition for metamaterial perfect absorbers, and dual-band absorbers can be composed of a pair of metallic layers with anti-parallel surface currents. We designed and fabricated a tunable dual-band perfect absorber based on extraordinary-optical-transmission (EOT) effect and Fabry-Perot cavity resonance. The idea and the mechanism are completely different from the absorber based on the near-field interaction. The important advantage of our structure is that we can switch a single-band absorber to a dual-band absorber by changing the distance between two metallic layers and/or incident angle. The peak originating from the EOT effect becomes significantly narrower, resulting in an increase of the Q-factor from 16.88 to 49. The dual-band absorber can be optimized to be insensitive to the polarization of the incident electromagnetic wave by slightly modifying the absorber structure.

A global analysis of molecular markers and phenotypic traits in local chicken breeds in Taiwan.

Molecular and phenotypic data have been combined to characterize the genetic diversity of six local chicken breeds maintained with a long-term conservation programme. Hua-Tung, Hsin-Yi, Ju-Chi and Quemoy originated from Taiwan, Shek-Ki is from South China, and Nagoya is from Japan. Molecular tools included 24 microsatellite markers, melanocortin 1 receptor (alpha melanocyte stimulating hormone receptor) (MC1R), the LEI0258 marker located within the major histocompatibility complex (MHC), and mitochondrial DNA. Performance was recorded on the same individuals for body weight, panting rate in summer and antibody response (antigens: Newcastle disease virus and sheep red blood cells). A multivariate method previously proposed for taxonomy was used to combine the different data sets. Melanocortin 1 receptor (alpha melanocyte stimulating hormone receptor) and the MCW330 marker contributed the most to the first axis of the multiple coinertia analysis of molecular markers. Melanocortin 1 receptor (alpha melanocyte stimulating hormone receptor) showed evidence of selection, probably related to its effect on feather colour. The MHC exhibited a large diversity, with 16 alleles of the LEI0258 marker. Immune response traits contributed the most to the principal component analysis of phenotypic data. Eight mitochondrial DNA haplotypes related to clades A, B, C and E were distributed across breeds and revealed an important contribution of Indian and European breeds to Ju-Chi, Quemoy and Hsin-Yi. Phenotypic data contributed less than molecular data to the combined analysis, and two markers, LEI0258 and LEI0228, contributed the most. The combined analysis could clearly discriminate all breeds, except Ju-Chi, which was similar to Quemoy for many criteria, except immune response.

Cystic change in thyroid nodules: a confounding factor for real-time qualitative thyroid ultrasound elastography.

OBJECTIVE: To evaluate real-time qualitative ultrasound elastography for focal thyroid masses undergoing fine-needle aspiration in a routine thyroid ultrasound clinic. MATERIALS AND METHODS: Ninety-four thyroid nodules scheduled for fine-needle aspiration cytology in a thyroid ultrasound clinic also underwent real-time freehand elastography. Colour-scaled elastograms were graded visually on the stiffness of the solid component of nodules relative to thyroid parenchyma using an elastography score (ES) scale from 1 (soft) to 4 (stiff). The ES for benign and malignant nodules and the influence of cystic change on ES were analysed using Chi-square with trend and Fishers exact tests, with a p<0.05 used to indicate statistical significance. RESULTS: There were 19 papillary carcinomas, five metastases, 57 hyperplastic nodules, and four follicular adenomas based on definitive cytology (n=54) or histology (n=31). Nine nodules were excluded due to indeterminate cytology and no histology. Of malignancies (all solid), two were ES=1, four were ES=2, eight were ES=3, and 10 were ES=4. Of benign nodules, 17 were ES=1, 17 were ES=2, 16 were ES=3, and 11 were ES=4. An ES>2 was more common in benign nodules with predominant cystic components (17/18) than mildly cystic (3/12) or completely solid (7/31) benign nodules (p=0.0004, p<0.0001). The ES was not significantly different between benign and malignant nodules (p=0.09) unless partially cystic nodules were excluded (p=0.005). For solid nodules, an ES>2 optimally predicted malignancy, achieving 74% sensitivity, 77% specificity, and 76% accuracy. CONCLUSION: Qualitative real-time thyroid elastography predicts malignancy only if predominantly cystic nodules are excluded, which may limit its utility in routine clinical practice.

Caspase-3-mediated degradation of condensin Cap-H regulates mitotic cell death.

Mitotic death is a major form of cell death in cancer cells that have been treated with chemotherapeutic drugs. However, the mechanisms underlying this form of cell death is poorly understood. Here, we report that the loss of chromosome integrity is an important determinant of mitotic death. During prolonged mitotic arrest, caspase-3 is activated and it cleaves Cap-H, a subunit of condensin I. The depletion of Cap-H results in the loss of condensin I complex at the chromosomes, thus affecting the integrity of the chromosomes. Consequently, DNA fragmentation by caspase-activated DNase is facilitated, thus driving the cell towards mitotic death. By expressing a caspase-resistant form of Cap-H, mitotic death is abrogated and the cells are able to reenter interphase after a long mitotic delay. Taken together, we provide new insights into the molecular events that occur during mitotic death.

Plasma carotenoids and risk of acute myocardial infarction in the Singapore Chinese Health Study.

BACKGROUND AND AIM: Modification of low-density lipoprotein due to oxidative stress is essential in the development of coronary atherosclerosis. Data of specific carotenoids except ß-carotene on cardioprotective effects in humans are limited. METHODS AND RESULTS: This study examined the associations between plasma concentrations of specific carotenoids and incidence of acute myocardial infarction. The study included 280 incident cases of acute myocardial infarction and 560 matched controls nested within the Singapore Chinese Health Study, a prospective cohort of 63,257 Chinese men and women aged 45-74 years old enrolled in 1993-1998 in Singapore. Retinol and carotenoids in prediagnostic plasma were quantified using high-performance liquid chromatography. High levels of plasma ß-cryptoxanthin and lutein were associated with decreased risk of acute myocardial infarction after adjustment for multiple risk factors for coronary heart disease. For ß-cryptoxanthin, the odds ratio (95% confidence interval) for the highest (Q5) versus the lowest (Q1) quintile was 0.67 (0.37-1.21) (P for trend=0.03). For lutein, the odds ratios (95% confidence intervals) for the combined Q2-Q3 and the combined Q4-Q5 versus Q1 were 0.71 (0.45-1.12) and 0.58 (0.35-0.94) respectively (P for trend=0.03). There was no statistically significant association between other carotenoids or retinol and risk of acute myocardial infarction. CONCLUSIONS: High plasma levels of ß-cryptoxanthin and lutein were associated with decreased risk of acute myocardial infarction. The findings of this study support a cardioprotective role of these two carotenoids in humans.

Comparison of inter- and intraobserver agreement and reliability between three different types of placental volume measurement technique (XI VOCAL, VOCAL and multiplanar) and validity in the in-vitro setting.

OBJECTIVES: To compare XI VOCAL (eXtended Imaging Virtual Organ Computer-aided AnaLysis) for three-dimensional (3D) ultrasound volumetry of the placenta and of phantom objects with a rotational method using VOCAL and with the multiplanar method. METHODS: We acquired 3D volume datasets from 32 fetuses at 11-14 weeks' gestation. Placental volume was calculated twice by each of two observers using XI VOCAL (with 5, 10, 15 and 20 slices), multiplanar (1-mm interval) and VOCAL (with 12 degrees, 18 degrees and 30 degrees rotation) methods. In addition, validity was assessed using the in-vitro setting with three phantom objects of known volume. RESULTS: Both inter- and intraobserver reliabilities were very high for all three methods. There was no systematic bias between any two methods except between XI VOCAL (10 slices) and the multiplanar (1-mm interval) method, with a smaller volume using the former method. The limits of agreement were wide between any two of the three methods. In the in-vitro setting, there was a trend towards less valid measurements with the XI VOCAL technique and fewer slices. With the same number of steps, measurements made with VOCAL (12 degrees and 18 degrees) were more valid than were those made with XI VOCAL (15 and 10 slices, respectively). CONCLUSION: XI VOCAL cannot be used interchangeably with VOCAL or multiplanar techniques in measuring placental volume at 11-14 weeks' gestation.