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Abstract Distinct crustal remanent magnetic anomalies are a strong indicator of rocks with stable natural remanent magnetization (NRM) carriers. The latter are able to store information on the history of a rock over long geological periods, and can therefore be used for a variety of applications in the field of paleomagnetism and rock magnetism. Typically, paleomagnetic and rock‐magnetic studies rely on rocks bulk magnetic properties. With the advent of high‐resolution magnetometric scanning techniques, it is now possible to map magnetic sources at the mineral scale, identify the different magnetic carriers, and analyze the effect of geometry, microstructures, and composition on their magnetic response. We investigate the stability of discrete remanent magnetization sources of a microcline–sillimanite gneiss sample from Russell Belt with a strong NRM, by scanning the sample before, and after alternating field demagnetization to 100 mT. We quantified changes in the magnetization intensity and direction by inverting the magnetic scan data. Here, we confirm that the exsolved titanohematite with ilmenite lamellae is the major source of magnetization, and the coexisting multidomain hematite grains contribute little to the NRM, or the magnetic anomalies. The microstructures in the titanohematite control local magnetic properties at the mineral scale. Magnetic modeling results suggest a consistent average magnetization direction before and after demagnetization at both the grain and thin section scale, with a decrease in the magnetization intensity of ≈30%. Results are consistent with previous bulk magnetic measurements and the likelihood to use high‐resolution magnetometric techniques in future magnetic studies is high.

This paper describes a method to estimate the direction from which the signal molecule reaches the sensor by using living cells. In this context, biohybrid sensors that utilize a sophisticated sensing system of cells can potentially offer high levels of chemical-detection sensitivity and selectivity. However, biohybrid-sensor-based chemical-source-direction estimation has not received research attention because the cellular response to chemicals has not been examined in the context of directional information. In our approach, we fabricated a device that can limit the interface between the cell-laden hydrogel and the chemical solution of interest to enhance the time difference over which the chemical solution reaches the cells. Chemical detection by cells that express specific receptors is reflected as the fluorescence of the calcium indicator within the cells. Our device has eight chambers that each house 3D cell-laden collagen hydrogels facing circularly outward. The device also works as a cover to prevent chemicals from permeating the hydrogel from above. In our study, by observing the time course of the fluorescence emission of each chamber, we were able to successfully estimate the chemical-source direction within an error range of 7–13°. Our results suggest that a combination of microstructure devices embedded with living cells can be used to exploit cell functionalities to yield chemical-source directional information.

The development of small sized laser operating above room temperature is important in the realization of optical integrated circuits. Recently, micro-lasers consisting of photonic crystals (PhCs) and whispering gallery mode cavities have been demonstrated. Optically pumped laser devices could be easily designed using photonic crystal-slab waveguides (PhC-WGs) with an air-bridge type structure. In this study, we observe lasing at 1.3μm from two-photon pumped InAs-quantum-dots embedded GaAs PhC-WGs above room temperature. This type of compact laser shows promise as a new light source in ultra-compact photonics integrated circuits.

The levels of rheumatoid factor (RF), antinuclear antibody (ANA), and composition of peripheral lymphocyte subsets in 515 dogs were examined. Of these sample cases, 33 cases were diagnosed as immune-mediated fever that presented with high C-reactive protein (CRP), 31 cases were diagnosed with Hansen's Type 1 disc herniation and the remaining 415 cases were clinically healthy dogs, and served as controls. In the cases diagnosed with immune-mediated fever, 84% of the dogs tested positive to either RF or ANA (RF positive 60.6%; ANA positive 24.2%). By contrast, 16.2% of the healthy dogs were positive for either RF or ANA (RF positive 14.9%; ANA 1.3%). The CD4/CD8 ratio for peripheral lymphocyte was high for all analysed cases diagnosed with immune-mediated fever, and was significantly higher than those of healthy controls. These results indicate that the abnormal levels of lymphocytes may be an effective indicator for immune-mediated disease coupled to immune-mediated fever.

The phenomena associated with the adsorption/desorption of ammonium, nitrate and phosphate ions by an electrical double layer capacitor (EDLC) were examined as a new application of this device for the removal of environmental pollutants from freshwater rivers, lakes and marshes. An electrode modified by introducing acidic functional groups onto its surface was used as the negative electrode of an EDLC, and this resulted in a 1.7-times increase in the amount of ammonium ions removed compared with that of an unmodified electrode. However, when the quantity of functional groups was increased to over 1.5 mmol/g, the amount of ammonium ions removed gradually decreased due to steric hindrance of the functional groups on the surface of the electrode and/or redox reactions with these groups. Similarly, it was found that the EDLC easily adsorbed nitrate ions but did not easily desorb them, whereas the opposite was the case for phosphate ions. The relationship between these phenomena and the pH pzc (pH value at the point of zero charge) of the electrode in nitrate and phosphate solutions is presented.

Abstract Single-cell Hi-C analysis of diploid human cells is difficult because of the lack of dense chromosome contact information and the presence of homologous chromosomes with very similar nucleotide sequences. Thus here, we propose a new algorithm to reconstruct the three-dimensional (3D) chromosomal architectures from the Hi-C dataset of single diploid human cells using allele-specific single-nucleotide variations (SNVs). We modified our recurrence plot-based algorithm, which is suitable for the estimation of the 3D chromosome structure from sparse Hi-C datasets, by newly incorporating a function of discriminating SNVs specific to each homologous chromosome. Here, we eventually regard a contact map as a recurrence plot. Importantly, the proposed method does not require any imputation for ambiguous segment information, but could efficiently reconstruct 3D chromosomal structures in single human diploid cells at a 1-Mb resolution. Datasets of segments without allele-specific SNVs, which were considered to be of little value, can also be used to validate the estimated chromosome structure. Introducing an additional mathematical measure called a refinement further improved the resolution to 40-kb or 100-kb. The reconstruction data supported the notion that human chromosomes form chromosomal territories and take fractal structures where the dimension for the underlying chromosome structure is a non-integer value.

Background: The Global Anticoagulant Registry in the FIELD–Atrial Fibrillation (GARFIELD-AF) is an ongoing prospective noninterventional registry, which is providing important information on the baseline characteristics, treatment patterns, and 1-year outcomes in patients with newly diagnosed non-valvular atrial fibrillation (NVAF). This report describes data from Indian patients recruited in this registry. Methods and results: A total of 52,014 patients with newly diagnosed AF were enrolled globally; of these, 1388 patients were recruited from 26 sites within India (2012–2016). In India, the mean age was 65.8 years at diagnosis of NVAF. Hypertension was the most prevalent risk factor for AF, present in 68.5% of patients from India and in 76.3% of patients globally (P

Southern Amazonia is one of the less-explored regions by anuran taxonomists. We describe a small new species of snouted treefrog, genus Scinax, from this region, from a fluvial archipelago in the Juruena River, state of Mato Grosso, Brazil. The description is based on external morphology of adults and tadpoles, advertisement call and molecular data. The species is phylogenetically related to other snouted treefrogs of the Scinax cruentomma species group and shows the most southeastern distribution in Amazonia among its close relatives. It is distinguished from congeners mainly by its larger adult body size and bilobate vocal sac that reaches the level of the pectoral fold, a reddish-brown horizontal stripe on the iris, dark melanophores or blotches on the vocal sac and the throat of females, and the uniformly brown posterior portion of the thigh. The advertisement call comprises one pulsed note emitted at regular intervals, with a duration of 189-227 ms, 30-35 pulses/note and a dominant frequency of 2,250-2,344 Hz. The type locality is suffering several environmental impacts, including illegal mining, overfishing, unsustainable agriculture, uncontrolled logging and degradation associated with the construction of new hydroelectric dams. Further study of the biology and regional distribution of the new species is required to propose mitigation measures needed for its conservation.

Summary: Cells cease to proliferate above their growth-permissible temperatures, a ubiquitous phenomenon generally attributed to heat damage to cellular macromolecules. We here report that, in the presence of rapamycin, a potent inhibitor of Target of Rapamycin Complex 1 (TORC1), the fission yeast Schizosaccharomyces pombe can proliferate at high temperatures that usually arrest its growth. Consistently, mutations to the TORC1 subunit RAPTOR/Mip1 and the TORC1 substrate Sck1 significantly improve cellular heat resistance, suggesting that TORC1 restricts fission yeast growth at high temperatures. Aiming for a more comprehensive understanding of the negative regulation of high-temperature growth, we conducted genome-wide screens, which identified additional factors that suppress cell proliferation at high temperatures. Among them is Mks1, which is phosphorylated in a TORC1-dependent manner, forms a complex with the 14-3-3 protein Rad24, and suppresses the high-temperature growth independently of Sck1. Our study has uncovered unexpected mechanisms of growth restraint even below the temperatures deleterious to cell physiology.

The TAQing system is upgraded and optimised as the foreign-DNA-free genome engineering technology, TAQing2.0. Genomic rearrangements are randomly induced by introducing the TaqI restriction endonuclease into non-sporulating industrial yeast with cell-penetrating peptides, leading to generation of mutants with altered phenotypes.

Cellular adaptation to stressful environments such as starvation is essential to the survival of microbial communities, but the uniform response of the cell community may lead to entire cell death or severe damage to their fitness. Here, we demonstrate an elaborate response of the yeast community against glucose depletion, in which the first adapted cells kill the latecomer cells. During glucose depletion, yeast cells release autotoxins, such as leucic acid and L-2keto-3methylvalerate, which can even kill the clonal cells of the ones producing them. Although these autotoxins were likely to induce mass suicide, some cells differentiated to adapt to the autotoxins without genetic changes. If nondifferentiated latecomers tried to invade the habitat, autotoxins damaged or killed the latecomers, but the differentiated cells could selectively survive. Phylogenetically distant fission and budding yeast shared this behavior using the same autotoxins, suggesting that latecomer killing may be the universal system of intercellular communication, which may be relevant to the evolutional transition from unicellular to multicellular organisms.

We report on the presence of scale mites (Trombidiformes: Pterygosomatidae) parasitizing three species of lizards in Timor-Leste. Geckobia bataviensis Vitzthum, 1926 was found associated with the Common House Gecko, Hemidactylus frenatus Duméril & Bibron, 1836, and the Indopacific Tree Gecko, Hemiphyllodactylus typus Bleeker, 1860, whereas Pterygosoma dracoensis Jack, 1962 was found on the patagia of a Timor Flying Dragon, Draco timoriensis Kuhl, 1820. The association of G. bataviensis with H. frenatus was well documented previously, but this is the first properly documented record of this mite for Timor-Leste. Our report of G. bataviensis on H. typus is the first association of this mite with this gecko. This is the second report of P. dracoensis on D. timoriensis and the first for Timor-Leste.

Boana icamiaba is an Amazonian anuran species reported for sites in the mid-lower Madeira-Rio Tapajós River and lower Tapajós-Rio, and Xingu River interfluves – municipalities of Juruti, Altamira, Santarém, and Itaituba, state of Pará, northern Brazil. We provided the first records of Boana icamiaba for the states of Mato Grosso and Rondônia, central and northern Brazil, which enlarges the knowledge on its distribution in approximately 470 km southmost and circa 886 km southwestmost from the nearest previously recorded locality.

Serum levels of 7 alpha-hydroxycholesterol and activities of hepatic microsomal cholesterol 7 alpha-hydroxylase in surgical patients were analyzed by capillary gas-liquid chromatography-selected ion monitoring technique using a new internal standard, 5 alpha-cholestane-3 beta, 7 beta-diol. We found that concentrations of 7 alpha-hydroxycholesterol obtained after alkaline hydrolysis were higher than those without alkaline hydrolysis, indicating that a considerable amount of 7 alpha-hydroxycholesterol in human serum is present in esterified form. Esterified 7 alpha-hydroxycholesterol could also be quantitatively hydrolyzed with cholesterol esterase, suggesting that fatty acid is bound at the 3 beta-position of the cholestenediol. The serum levels of esterified and free 7 alpha-hydroxycholesterol in patients with cholelithiasis were 198.0 +/- 90.3 and 48.3 +/- 19.8 pmol/ml (mean +/- SD), respectively, and were similar to those in patients without hepatobiliary diseases. After treatment with chenodeoxycholic acid (300 mg per day) for 7 to 10 days, esterified and free 7 alpha-hydroxycholesterol levels decreased to 64.9 +/- 33.6 and 20.5 +/- 11.1 pmol/ml, respectively. Activity of cholesterol 7 alpha-hydroxylase was also inhibited. Treatment with ursodeoxycholic acid (600 mg per day) for 7 to 10 days had no inhibitory effect on serum 7 alpha-hydroxycholesterol levels and the enzyme activity. In all groups, high correlations were found between the activity of cholesterol 7 alpha-hydroxylase and serum levels of 7 alpha-hydroxycholesterol: free (r = 0.71, n = 38, P less than 0.001); esterified (r = 0.87, n = 38, P less than 0.001); total (r = 0.87, n = 38, P less than 0.001). Esterified and total 7 alpha-hydroxycholesterol was more highly correlated with the enzyme activity than the free form. We conclude that a significant amount of 3 beta-acyl esters of 7 alpha-hydroxycholesterol is present in human serum and that serum levels of esterified and/or total 7 alpha-hydroxycholesterol are likely to reflect the activity of hepatic cholesterol 7 alpha-hydroxylase and thus the amount of primary bile acids synthesized in the liver.

O Mapa de Águas Subterrâneas do Estado de São Paulo, elaborado em conjunto pelo Departamento de Águas e Energia Elétrica do Estado de São Paulo (DAEE), Instituto Geológico (IG-SMASP), Instituto de Pesquisas Tecnológicas do Estado de São Paulo (IPT), e Serviço Geológico do Brasil (CPRM), é aqui apresentado. O trabalho teve por objetivo realizar o zoneamento dos aqüíferos sedimentares em termos de vazões exploráveis, e dos aqüíferos fraturados em termos de vazões prováveis. Os métodos utilizados variaram em função dos dados disponíveis e do tipo de aqüífero. Dentre os aqüíferos sedimentares, aqueles que permitem extrações maiores, em ordem decrescente, são Guarani, Taubaté e Bauru; os que apresentam menores potenciais são São Paulo, Tubarão e Litorâneo. Dos aqüíferos fraturados, os de maior potencial são o Serra Geral e o pré-Cambriano Cárstico. O Aqüífero Pré- Cambriano não cárstico, composto de rochas metamórficas e graníticas, foi subdividido em 3 classes de potencialidade distinta, cujos limites correspondem em parte aos dos terrenos pré-cambrianos e em parte a estruturas tectônicas rúpteis regionais.

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Nine fecal samples from four healthy subjects were examined for their ability to transform chenodeoxy-cholic acid (CDCA) and ursodeoxycholic acid (UDCA) in in vitro anaerobic broth cultures. Seven samples converted CDCA and UDCA into each other (more than 50% of CDCA was converted into UDCA while 10% or less of UDCA was converted into CDCA), and produced 7-keto-lithocholic acid and lithocholic acid equally from both acids. No alteration of the 7 beta-hydroxy group of UDCA was demonstrated by two fecal samples that failed to perform mutual 7-epimerization, suggesting the conversion of UDCA into lithocholic acid via CDCA. The 3 alpha-hydroxy groups of these substrate and metabolite bile acids were invariably partially epimerized to 3 beta-hydroxy groups by all the fecal samples. Evidence is presented for the prevalence of these 7- and 3-epimerizing organisms among the human intestinal flora.

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Microorganisms possess remarkable locomotion abilities, making them potential candidates for micromachine propulsion. Here, the use of Chlamydomonas Reinhardtii (CR) is explored, a motile green alga, as a micromotor by harnessing its propulsive force with microtraps. The objectives include developing the microtrap structure, evaluating trapping efficiency, and investigating the movement dynamics of biohybrid micromachines driven by CR. Experimental analysis demonstrates that trap design significantly influences trapping efficiency, with a specific trap configuration (multi-ring structure with diameters of 7 µm - 10 µm - 13 µm) showing the highest effectiveness. The micromachine empowered with two CRs facing the same direction exhibits complex, random-like motion with yaw, pitch, and roll movements, while the micromachine with four CRs in a circular position each facing the tangential direction of the circle demonstrates controlled rotational motion. These findings highlight the degree of freedom and movement potential of biohybrid micromachines., (© 2024 The Author(s). Small published by Wiley‐VCH GmbH.)

Objectives: Thoracoscopic sympathectomy is an effective treatment for palmar hyperhidrosis. However, compensatory hyperhidrosis occurs frequently as a postoperative complication of the procedure. The goal of this study was to elucidate the clinical significance of thoracoscopic sympathectomy using our surgical procedure., Methods: Consecutive 151 patients who underwent thoracoscopic sympathectomy for palmar hyperhidrosis were studied. In addition, to investigate patients' satisfaction and long-term quality of life, 111 patients were asked to complete a mailing questionnaire survey, and 84 responded (response rate of 75.7%)., Results: All of the 151 patients reported a reduction in palmar sweating during the immediate postoperative period. None of the patients had pneumothorax, hemothorax, Horner's syndrome, or worsening of bradycardia. Based on the questionnaire, the surgical success rate was 98.8%. None of the patients had a recurrence of palmar hyperhidrosis during the long-term postoperative period. However, compensatory hyperhidrosis was reported in 82 patients (97.6%). In total, 94.0% of patients had high levels of postoperative satisfaction., Conclusions: Thoracoscopic sympathectomy is an effective surgical treatment for palmar hyperhidrosis. By contrast, the careful preoperative explanation of compensatory hyperhidrosis is considered to be very important., (© 2024. The Author(s).)

Introduction: Fluorouracil, leucovorin, irinotecan, and oxaliplatin (FOLFIRINOX) improve overall survival (OS) and progression-free survival (PFS) in patients with pancreatic cancer, compared with gemcitabine (GEM). However, whether PFS is a surrogate marker of OS in pancreatic cancer chemotherapy focusing on FOLFIRINOX or GEM plus nab-paclitaxel remains unknown. We aimed to verify whether PFS can be a surrogate marker of OS in prognosis prediction., Methods: This was an integrated analysis of the NAPOLEON study and retrospective cohort of the NAPOLEON-2 study-a multicenter observational study conducted in Japan, using real-world data. The primary and secondary endpoints were OS and PFS, respectively. The correlation between OS and PFS in first- and second-line treatments was assessed using Method of Moments estimation. An analysis was performed in patients with confirmed OS at the end of follow-up. The NAPOLEON-2 cohort included only patients who received 5-fluorouracil, leucovorin, and nanoliposomal irinotecan (NFF) as second-line treatment., Results: Among 479 patients, the correlation between PFS and OS from first- and second-line chemotherapies was calculated in 310 and 225 patients, respectively. The R-squared values for the correlation between PFS and OS from first- and second-line chemotherapies were 0.74 and 0.76, respectively. There was no statistically significant difference in first-line treatment between the FOLFIRINOX and gemcitabine plus nab-paclitaxel groups (P=0.92). Therefore, the FOLFIRINOX group may not have shown a stronger correlation than the NFF group., Conclusion: PFS can be a surrogate marker of OS in first- and second-line therapies. Appropriate prognostic estimation might contribute to proper treatment selection., (S. Karger AG, Basel.)

Overconsumption of sucrose or fat is widely acknowledged as a prominent feature of unhealthy dietary patterns. Both factors commonly co-occur and are recognized as hallmarks of the Western diet, which is an important contributor to non-communicative diseases. In this study, we investigated the hazards of high sucrose or fat intake, either alone or in combination. Wistar rats were divided into four groups and fed a control starch diet, high-sucrose diet, high-fat diet, or high-sucrose/fat diet for 30 days. High fat intake increased body weight and visceral and subcutaneous adipose tissue weights. Both high-sucrose and -fat diets were associated with increased plasma triglyceride and glucose levels, and high sucrose also elevated plasma cholesterol levels. The combination of high sucrose and fat synergistically elevated plasma triglyceride levels. The high-sucrose diet increased liver weight and hepatic total lipid and triglyceride levels, whereas this increase was suppressed by the high-fat diet. The high sucrose increased the mRNA levels of hepatic genes involved in fatty acid synthesis and transport (ACLY, ACACA, FAS, ELOVL6, SCD1, SREBP1, and CD36), whereas the high fat suppressed the high sucrose-induced expression of these genes. We observed that high sucrose and fat contents differently exerted their effects on hyperlipidemia and fatty liver. Furthermore, high fat aggravated hyperlipidemia and suppressed fatty liver induced by high sucrose.

Left-right asymmetry in paired organs is well documented across various species, including the claws of fiddler crabs and snail-eating snakes' dentition. However, the mechanisms underlying these asymmetries remain largely elusive. This study investigates Doubledaya bucculenta (Coleoptera: Erotylidae), a lizard beetle species known for pronounced left-sided asymmetry in adult female mandible and gena. Given that insect mouthparts comprise multiple functionally significant appendages, we aimed to clarify the degree of asymmetry extending beyond the mandibles and genae. Phenotypic morphology was assessed through trait measurement and asymmetry index calculations. Our detailed morphometric analyses revealed left-longer asymmetry not only in mandibles and genae but also in maxillae and labium. Notably, the degree of asymmetry in other mouthparts was generally less pronounced compared to that in outer mandibles, suggesting a potential influence of left mandible development on other mouthparts. Additionally, male mandibles exhibited region-specific asymmetry, potentially indicative of constrained evolutionary adaptations. This study enhances a comprehensive understanding of adult phenotype morphology and offers insights into the developmental basis of asymmetrical mouthparts.

In eukaryotes, DNA is housed within the cell nucleus. Molecules required for the formation of a nucleus have been identified using in vitro systems with frog egg extracts and in vivo imaging of somatic cells. However, little is known about the physicochemical factors and conditions required for nuclear formation in mouse oocytes. In this study, using a reconstitution approach with purified DNA, we aimed to determine factors, such as the amount and timing of DNA introduction, required for the formation of nuclei with nuclear transport activity in mouse oocytes. T4 phage DNA (~166 kbp) was microinjected into strontium-activated oocytes to evaluate the conditions appropriate for nuclear formation. Microinjection of 100-500 ng/μL of T4 DNA, but not 20 ng/μL, was sufficient for the formation of nucleus-like structures. Furthermore, microinjection of DNA during metaphase II to telophase II, but not during interphase, was sufficient. Electron and fluorescence microscopy showed that T4 DNA-induced nucleus-like structures had nuclear lamina and nuclear pore complex structures similar to those of natural nuclei, as well as nuclear import activity. These results suggest that exogenous DNA can form artificial nuclei with nuclear transport functions in mouse oocytes, regardless of the sequence or source of the DNA., (© 2024 Molecular Biology Society of Japan and John Wiley & Sons Australia, Ltd.)

Background & Aims: Excess sucrose intake induces metabolic syndrome. In human, abnormal lipids metabolism like obesity, hyperlipidemia and fatty liver are induced. However, excess sucrose causes different phenotypes in different species. Based on our previous study, excess sucrose induced fatty liver and hyperlipidemia in rats. The phenotypes and mechanism of abnormal lipid metabolism in mice is unclear. We investigated the different phenotypes in 5 strains of mice and the relationship between gut microbiome and abnormal lipid metabolism in C57BL/6N mice., Methods: We examined the effect of a high sucrose diet in 5 different strains of mice. Besides, to find out the relationship between gut microbiome and metabolic disorder induced by excess sucrose, C57BL/6N mice were fed with a high sucrose diet with or without antibiotics cocktail., Results: A high sucrose diet induced obesity and fatty liver in inbred mice, whereas did not induce hyperlipidemia in all strains of mice. Moreover, a high sucrose diet changed the composition of gut microbiota in C57BL/6N mice. Antibiotics treatment alleviated the abnormal lipid metabolism induced by high sucrose diet by changing the composition of gut short chain fatty acids., Conclusions: These results indicates that the phenotypes of metabolic syndrome are influenced by genetic factors. Furthermore, the dysbiosis of gut microbiome caused by excess sucrose may contribute to the development of abnormal lipid metabolism via its metabolites., Competing Interests: Declaration of competing interest The authors declare no competing interests., (Copyright © 2024 European Society for Clinical Nutrition and Metabolism. Published by Elsevier Ltd. All rights reserved.)

Physical inactivity as well as breakfast skipping is known as risk factor for various metabolic diseases, such as obesity and type 2 diabetes. We have previously reported that a breakfast skipping model, in which the timing of feeding is delayed, induces abnormal lipid metabolism by altering the circadian rhythm of lipid metabolism-related genes in rats. The purpose of this study was to elucidate the synergistic effect of physical inactivity and breakfast skipping on lipid metabolism. We adopted sciatic neurectomized rats as physically inactive models, because we confirmed that the rats mildly decreased their spontaneous locomotor activity compared to sham-operated rats. And then the physically inactive model rats were fed a mild high-fat diet during zeitgeber time (ZT) 12-0 in the control group and ZT16-0 in the breakfast skipping group for 11 days. Body weight gain and total food intake were similar in both groups. Breakfast skipping induced a significant visceral fat accumulation, which was not observed in our previous breakfast skipping or physically inactive studies. The mRNA levels of clock and lipogenesis-related genes were altered by breakfast skipping in the liver and epididymal adipose tissue, and serum insulin level was altered by breakfast skipping. These results suggest that physical inactivity and breakfast skipping synergistically induces drastic visceral fat accumulation due to the alteration of circadian clock and lipid metabolism in the liver and adipose tissue. Therefore, regular feeding timing plays an important role in the health of a sedentary modern society., (© 2024. The Author(s).)

Background: The overall mortality and morbidity benefit in patients with heart failure with a reduced ejection fraction is greatest with a treatment combination of sacubitril/valsartan, beta-blockers, mineralocorticoid-receptor antagonists, and sodium-glucose transporter-2 inhibitors, termed the "fantastic four" or "quadruple therapy." The addition of vericiguat (an oral soluble guanylate cyclase stimulator) is believed to aid in managing worsening heart failure after quadruple therapy. Among childhood and young adult cancer survivors, cardiovascular complications that develop more than 10 years after anthracycline-based chemotherapy have a poor prognosis. Therefore, this study reports the efficacy of multidrug regimen based on quadruple therapy for worsening heart failure in cancer survivors with anthracycline-induced cardiomyopathy., Case Presentation: A survivor of cancer as a young adult who received high-dose anthracycline chemotherapy presented with acute decompensated heart failure 20 years post-chemotherapy and worsening heart failure 1.5 years after discharge. The patient showed signs of improvement after a step-wise introduction of carvedilol, empagliflozin, sacubitril/valsartan, ivabradine, and spironolactone for worsening heart failure. Vericiguat was accelerated owing to the risk of more severe cardiovascular events associated with ongoing aortic stenosis and the poor prognosis of anthracycline-induced cardiomyopathy. Heart failure symptoms continued to improve, with significant cardiac reverse remodeling, and the patient successfully underwent aortic valve replacement for severe aortic stenosis., Conclusions: Our case highlighted that multidrug treatment with add-on vericiguat and ivabradine based on quadruple therapy can potentially treat worsening heart failure in young adult cancer survivors with severe anthracycline-induced cardiomyopathy., (© 2024. The Author(s).)

Background: Biliary tract cancer (BTC) comprises a heterogeneous group of malignancies with poor prognosis because of the limited treatment options. With the recent advances of next generation sequencing technologies, comprehensive genomic profiling (CGP) tests have been widely introduced into daily clinical practice., Patients and Methods: We performed a retrospective, multicenter, observation cohort study. The genomic and clinical data of 85 BTC patients, who underwent CGP testing from August 2021 to September 2023, were analyzed., Results: There were 62 (73%) cases in which treatment recommendations were raised during expert meetings, including 34 intrahepatic cholangiocarcinoma (ICC), 20 extrahepatic cholangiocarcinoma (ECC) and 8 gall bladder carcinoma (GBC). The drug accessibility rate of the BTC patients was 15.3% (13 cases): ten ICCs, two ECCs, and one GBC. Five ICC patients (three male and two female) with the FGFR2 fusion gene were treated with pemigatinib. Those patients who received a genomically matched therapy had significantly longer median overall survival than those patients who not received. (n = 13; not reached [95% CI not reached-not reached] vs n = 72; 8.6 months [95% CI 6.6-10.0]; hazard ratio 0.24 [95% CI 0.12-0.49], p = 0.013). The median observation period of pemigatinib treatment was 15.4 months (range 10.1-27.4). The responses were classified as PR in three patients, SD in one patient and PD in one patient. The median progression free survival is 9.0 months. No patient had grade 3/4 AEs requiring discontinuation of the treatment., Conclusion: The drug accessibility rate of ICC is high and pemigatinib is effective and well-tolerated in ICC patients harboring FGFR2 gene fusions., (© 2024. The Author(s) under exclusive licence to Japan Society of Clinical Oncology.)

The Order Lepidoptera contains nearly 160,000 described species and most of them are specialist herbivores that use restricted plant species as hosts. Speciation that originated from host shift is one of the important factors for the diversification of Lepidoptera. Because plants prepare secondary metabolites for defense against herbivores, with varying profiles of the components among different plant taxa, the specialist herbivores need to be adapted to the toxic substances unique to their host plants. Swallowtail butterflies of the genus Papilio consist of over 200 species. Approximately 80% of them utilize Rutaceae plants, and among the remaining species, a specific subgroup uses phylogenetically distant Apiaceae plants as larval hosts. Rutaceae and Apiaceae commonly contain toxic secondary metabolites, furanocoumarins, and molecular phylogenetic studies support the concept that Apiaceae feeders were derived from Rutaceae feeders. Molecular mechanisms underlying furanocoumarin tolerance in Papilio butterflies have been investigated almost exclusively in an Apiaceae feeder by an in vitro assay. In contrast, there is little information regarding the Rutaceae feeders. Here, we focused on a Rutaceae feeder, Papilio xuthus, and identified two furanocoumarin-responsive cytochrome P450-6B (CYP6B) genes, of which one was an ortholog of a furanocoumarin-metabolizing enzyme identified in the Apiaceae-feeding Papilio while the other was previously unreported. We further conducted in vivo functional analysis using the CRISPR/Cas9 system, revealing a contribution of these CYP6Bs to furanocoumarin tolerance of P. xuthus larvae. Our findings suggest that co-option of furanocoumarin-metabolizing CYP6B enzymes at least partially contributed to the host shift from Rutaceae to Apiaceae in Papilio butterflies., Competing Interests: Competing interests The authors declare no competing or financial interests., (© 2024. Published by The Company of Biologists Ltd.)

Taurine can ameliorate hypercholesterolemia by facilitating cholesterol efflux and increasing cytochrome P450 7A1 (CYP7A1) without clear underlying molecular mechanisms. This study aims to elucidate the molecular action of taurine in diet-induced hypercholesterolemia. Male Wistar rats were fed a high cholesterol diet containing 5% taurine for 14 days. Three-dimensional primary hepatocytes from rats were exposed to 10 mM taurine for 24 h. Transcriptome analyses of both the liver and hepatocytes were performed using DNA microarray. Taurine significantly decreased serum cholesterol levels and increased hepatic CYP7A1 mRNA levels and transcription rates in rats. Taurine altered the expression of seventy-seven genes in the liver, involving lipid, drug, amino acid metabolism, and gluconeogenesis pathways. The small heterodimer partner (SHP), a transcription factor regulated by taurine, was suppressed. "Network analysis" revealed a negative correlation between the SHP and induction of CYP7A1 and cytochrome P450 8B1 (CYP8B1). However, CYP7A1 and CYP8B1 levels were not altered by taurine in 3D-primary hepatocytes. Venn diagram analyses of the transcriptomes in both hepatocytes and the liver indicated a consistent upregulation of organic anion transporting polypeptide 2 (OATP2) and betaine homocysteine methyltransferase (BHMT). Taurine ameliorated hypercholesterolemia in rats fed a high cholesterol diet by directly enhancing the hepatic expression of BHMT and OATP2, which modulated the SHP and induced CYP7A1 and CYP8B1, thereby promoting cholesterol catabolism and lowering blood cholesterol levels.

In the present study, we examined the immediate effect of allowing healthy participants to view their mirror-reflected body image on static and dynamic balance. We placed a mirror to allow participants to frontally view their own body image while maintaining a quiet stance or while engaged in a dynamic postural standing task. On measures of body sway during quiet stance, there were no effects of this visual feedback, supporting the view that human beings have no central mechanism for viewing the mirror-reflected body image to control body sway during quiet stance. However, the body deviated forward during quiet stance while viewing the mirror-reflected body image, indicating that viewing the mirror-reflected body image contributed to the anterior-posterior positioning of the body, as mediated by an ankle control strategy. For the dynamic standing task, viewing the body image induced unstable peaks of rhythmic lateral shifting of the body weight over the feet. This indicates that viewing the body image caused unstable motor commands for rhythmic lateral weight shifting. When participants made a transition from a bipedal to a unipedal stance in response to a cue, viewing the body image shortened the onset latency of the body sway. Accordingly, viewing the body image seemed to accelerate the motor execution involved in lateral weight shifting, possibly due to predictive activation of the motor system before movement onset. Considered collectively, we found static and dynamic stance balance to be influenced by viewing one's mirror-reflected body image. Viewing the mirror-reflected body image may be a means of changing static and dynamic balance in patients with impaired postural control., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

The purpose of the present study was to examine whether spatial or temporal prediction of the tactile stimulus contributes to tactile sensitivity. To investigate the effect of spatial prediction on tactile sensitivity, electrical stimuli were provided for the digit nerve in one of five fingers, and advanced notice of the stimulating finger was provided before the stimulus in some trials but not in others. There was no significant effect of spatial prediction on the intensity at the perceptual threshold of the digit nerve stimulus. This indicates that spatial prediction of the tactile stimulus does not influence tactile sensitivity. To examine the effect of temporal prediction, an auditory warning cue was provided 0, 1, or 10 s before the electrical stimulus to the digit nerve. The stimulus intensity at the perceptual threshold in the trials with the 1 s warning cue was lower than those with the 0 s warning cue. This indicates that temporal prediction enhances tactile sensitivity. The stimulus intensity at the perceptual threshold in the trials with the 1 s warning cue was lower than those with the 10 s warning cue. This means that the contribution of temporal prediction to the tactile sensitivity is greater as the warning cue is closer to the time of the stimulus. This finding may be explained by a defense mechanism activated when humans predict that a tactile stimulus is coming soon.

We report an estimation of the injected mass composition of ultrahigh energy cosmic rays (UHECRs) at energies higher than 10 EeV. The composition is inferred from an energy-dependent sky distribution of UHECR events observed by the Telescope Array surface detector by comparing it to the Large Scale Structure of the local Universe. In the case of negligible extragalactic magnetic fields (EGMFs), the results are consistent with a relatively heavy injected composition at E∼10  EeV that becomes lighter up to E∼100  EeV, while the composition at E>100  EeV is very heavy. The latter is true even in the presence of highest experimentally allowed extragalactic magnetic fields, while the composition at lower energies can be light if a strong EGMF is present. The effect of the uncertainty in the galactic magnetic field on these results is subdominant.

This study aimed to compare second-line treatment outcomes for patients with unresectable pancreatic cancer previously treated with gemcitabine plus nab-paclitaxel (GnP) therapy. We conducted an integrated analysis of two retrospective studies included 318 patients receiving nanoliposomal irinotecan + 5-fluorouracil/folinic acid (NFF) (n = 102), S-1 (n = 57), or FOLFIRINOX (n = 14) as second-line treatment. Median overall survival (OS) in the NFF group was 9.08 months, significantly better than S-1 (4.90 months, P = 0.002). FOLFIRINOX had a median OS of 4.77 months, not statistically different from NFF. Subgroup analyses of OS indicated NFF was generally superior, however, a statistical interaction was observed between the treatment regimen in serum Alb < 3.5 g/dL (P = 0.042) and serum CRP ≥ 0.3 mg/dL (P = 0.006). Median progression-free survival (PFS) was 2.93 months for NFF, significantly better than S-1 (2.53 months, P = 0.024), while FOLFIRINOX had a comparable PFS (3.04 months, P = 0.948). Multivariate analysis identified the serum CRP, serum CA19-9, duration of first-line GnP therapy, and use (yes/no) of S-1 for second-line treatment as independent predictors for OS. This study concludes that second-line NFF therapy demonstrated a more favorable OS compared to S-1 therapy, however, it is still important to consider the patient background characteristics while selecting the most appropriate treatment., (© 2024. The Author(s).)

We report here a case of postoperative recurrent adenosquamous carcinoma (ASC) of the esophagogastric junction (EGJ) treated with S-1 therapy. A 79-year-old woman was diagnosed with carcinoma of the EGJ. Thoracoscopic subtotal esophagectomy was performed, and pathological examination revealed advanced ASC with lymph node metastasis. Five months after surgery, multiple lung metastases and multiple lymph node metastases were observed, and the patient was treated with S-1 monotherapy, which showed partial response and may be effective for advanced ASC of the EGJ. On the other hand, immunohistological analysis of the tumors showed a relatively wide range of areas that could differentiate into both adenocarcinoma and squamous cell carcinoma, suggesting that tumor cells with multidifferentiation potential, or at least the ability to differentiate into both adeno-epithelial and squamous epithelial cells, were the likely source of the tumors., Competing Interests: None declared., (Published by Oxford University Press and JSCR Publishing Ltd. © The Author(s) 2024.)

Background: Despite the better prognosis associated with human papillomavirus (HPV)-positive oropharyngeal squamous cell carcinoma (OPSCC), some patients experience relapse and succumb to the disease; thus, there is a need for biomarkers identifying these patients for intensified treatment. Leucine-rich repeats and immunoglobulin-like domain (LRIG) protein 1 is a negative regulator of receptor tyrosine kinase signaling and a positive prognostic factor in OPSCC. Studies indicate that LRIG1 interacts with the LIM domain 7 protein (LMO7), a stabilizer of adherence junctions. Its role in OPSCC has not been studied before., Methods: A total of 145 patients diagnosed with OPSCC were enrolled. Immunohistochemical LMO7 expression and staining intensity were evaluated in the tumors and correlated with known clinical and pathological prognostic factors, such as HPV status and LRIG1, CD44, Ki67, and p53 expression., Results: Our results show that high LMO7 expression is associated with significantly longer overall survival (OS) (p = 0.044). LMO7 was a positive prognostic factor for OS in univariate analysis (HR 0.515, 95% CI: 0.267-0.994, p = 0.048) but not in multivariate analysis. The LMO7 expression correlated with LRIG1 expression (p = 0.048), consistent with previous findings. Interestingly, strong LRIG1 staining intensity was an independent negative prognostic factor in the HPV-driven group of tumors (HR 2.847, 95% Cl: 1.036-7.825, p = 0.043)., Conclusions: We show for the first time that high LMO7 expression is a positive prognostic factor in OPSCC, and we propose that LMO7 should be further explored as a biomarker. In contrast to previous reports, LRIG1 expression was shown to be an independent negative prognostic factor in HPV-driven OPSCC., (© 2024. The Author(s).)

A 62-year-old man visited his primary care physician with the complaints of loss of appetite and fatigue. He was admitted to our hospital based on a diagnosis of acute kidney injury, Fanconi syndrome as indicated by hypokalemia, hypouricemia, hypophosphatemia, elevated glucose levels in urine, and aminoaciduria. He had been taking multiple supplements, including Red Yeast Rice Cholesterol Help®, for one and a half years. After admission, all the supplements were stopped. Blood samples were collected; however, the samples were negative for diseases that could cause Fanconi syndrome. Renal biopsy revealed renal proximal tubular damage, mainly characterized by simplification of the proximal tubular epithelium. The mycotoxin, citrinin, which is reported to be produced by the mold used for producing red yeast rice, but not the mold Monascus pilosus used for Red Yeast Rice Cholesterol Help ® , reportedly causes proximal tubular damage. However, although the causative agent has not been identified, it was thought that a substance similar to citrinin, produced by the mold used for Red Yeast Rice Cholesterol Help®, caused proximal tubular damage, leading to acute kidney injury and Fanconi syndrome. Hence, all supplements were stopped, and the patient was treated with oral potassium and phosphorus preparations, leading to gradual recovery of his kidney function. We herein report the first case of acute kidney injury and Fanconi syndrome in a patient taking multiple health supplements, including Red Yeast Rice Cholesterol Help®. Early discontinuation of the oral supplements was probably useful in improving the patient's kidney function., (© 2024. The Author(s), under exclusive licence to Japanese Society of Nephrology.)

The development of a compact and affordable fluorescence microscope can be a formidable challenge for growing needs in on-site testing and detection of fluorescent labeled biological systems, especially for those who specialize in biology rather than in engineering. In response to such a situation, we present an open-source miniature fluorescence microscope using Raspberry Pi. Our fluorescence microscope, with dimensions of 19.2 × 13.6 × 8.2 cm 3 (including the display, computer, light-blocking case, and other operational requirements), not only offers cost-effectiveness (costing less than $500) but is also highly customizable to meet specific application needs. The 12.3-megapixel Raspberry Pi HQ Camera captures high-resolution imagery, while the equipped wide-angle lens provides a field of view measuring 21 × 15 mm 2 . The integrated wireless LAN in the Raspberry Pi, along with software-controllable high-powered fluorescence LEDs, holds potential for a wide range of applications. This open-source fluorescence microscope offers biohybrid sensor developers a versatile tool to streamline unfamiliar mechanical design tasks and open new opportunities for on-site fluorescence detections., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Author(s).)

Purpose: Partial rotator cuff tears can cause shoulder pain and dysfunction and are more common than complete tears. However, few studies examine partial injuries in small animals and, therefore a robust, clinically relevant model may be lacking. This study aimed to fully characterize the established rat model of partial rotator cuff injury over time and determine if it models human partial rotator cuff tears., Methods: We created a full-thickness, partial-width injury at the supraspinatus tendon-bone interface bilaterally in 31 Sprague-Dawley rats. Rats were euthanized immediately, and at 2-, 3-, 4-, and 8-weeks after surgery. Fourteen intact shoulders were used as controls. Samples were assessed biomechanically, histologically, and morphologically., Results: Biomechanically, load to failure in controls and 8 weeks after injury was significantly greater than immediately and 3 weeks after injury. Load to failure at 8 weeks was comparable to control. However, the locations of failure were different between intact shoulders and partially injured samples. Bone mineral density at 8 weeks was significantly greater than that at 2 and 3 weeks. Although no animals demonstrated propagation to complete tear and the injury site remodeled histologically, the appearance at 8 weeks was not identical to that in the controls., Conclusions: The biomechanical properties and bone quality decreased after the injury and was restored gradually over time with full restoration by 8 weeks after injury. However, the findings were not equivalent to the intact shoulder. This study demonstrated the limitations of the current model in its application to long-term outcome studies, and the need for better models that can be used to assess chronic partial rotator cuff injuries., Clinical Relevance: There is no small animal model that mimics human chronic partial rotator cuff tears, which limits our ability to improve care for this common condition., (Copyright © 2024 American Society for Surgery of the Hand. Published by Elsevier Inc. All rights reserved.)

Nanoliposomal irinotecan with fluorouracil and folinic acid (NFF) is a standard regimen after gemcitabine-based therapy for patients with unresectable or recurrent pancreatic cancer. However, there are limited clinical data on its efficacy and safety in the real-world. We therefore initiated a retrospective and prospective observational study (NAPOLEON-2). The results of the retrospective part were reported herein. In this retrospective study, we evaluated 161 consecutive patients who received NFF as second-or-later-line regimen. The main endpoint was overall survival (OS), and the other endpoints were response rate, disease control rate, progression-free survival (PFS), dose intensity, and adverse events (AEs). The median age was 67 years (range, 38-85 years). The median OS and PFS were 8.1 and 3.4 months, respectively. The objective response and disease control rates were 5% and 52%, respectively. The median relative dose intensity was 81.6% for nanoliposomal irinotecan and 82.9% for fluorouracil. Grade 3 or 4 hematological and nonhematological AEs occurred in 47 and 42 patients, respectively. Common grade 3 or 4 AEs included neutropenia (24%), anorexia (12%), and leukocytopenia (12%). Subanalysis of patients treated with second-line and third-or-later-line demonstrated no statistical significant difference in OS (7.6 months vs. 9.1 months, respectively; hazard ratio, 0.92; 95% confidence interval, 0.64-1.35; p = 0.68). In conclusion, NFF has acceptable efficacy and safety profile even in real-world clinical settings. The prospective study is in progress to validate these findings., (© 2024. The Author(s).)

This study examined whether tactile gating induced by the descending motor command to one finger spreads out to the other fingers to which the command is not delivered and whether this gating is dependent on the target finger to which the command is delivered. The change in perceptual threshold to the digital nerve stimulation of one finger induced by tonic contraction of the first dorsal interosseous or abductor digiti minimi muscle was examined. The perceptual threshold to the digital nerve stimulation of the thumb or little finger was increased by tonic contraction of the abductor digiti minimi muscle. This finding indicates that the descending motor command to the prime mover of the little finger abduction induces tactile gating not only in the finger to which the command is delivered but also in the other finger to which the command is not delivered. Tonic contraction of the first dorsal interosseous muscle did not change the perceptual threshold to the digital nerve stimulation in any finger. This finding means that tactile gating occurs particularly when the descending motor command is delivered to the dependent finger. Spreading out of tactile gating of one finger, to which the descending motor command is not delivered, is likely mediated by surround inhibition.

Reproducing instructed movements is crucial for practice in motor learning. In this study, we compared the short-term reproduction of active pelvis movements with visual feedback and passive movement with the therapist's hands in an upright stance. Sixteen healthy males (M age = 34.1; SD = 10.2 years) participated in this study. In one condition, healthy males maintained an upright stance while a physical therapist moved the participant's pelvis (passive movement instruction), and in a second condition, the participant actively moved their pelvis with visual feedback of the target and the online trajectory of the center of pressure (active movement instruction). Reproduction errors (displacement of the center of pressure in the medial-lateral axis) 10 s after the passive movement instruction were significantly greater than after the active movement instruction ( p < 0.001), but this difference disappeared 30 s after the instruction ( p = 0.118). Error of movement reproduction in the anterior-posterior axis after the passive movement instruction was significantly greater than after the active movement instruction, no matter how long the retention interval was between the instruction and reproduction phases ( p = 0.025). Taken together, active pelvis movements with visual feedback, rather than passive movement with the therapist's hand, is better to be used for instructing pelvis movements.

The linear ubiquitin assembly complex (LUBAC) consists of HOIP, HOIL-1 and SHARPIN and is essential for proper immune responses. Individuals with HOIP and HOIL-1 deficiencies present with severe immunodeficiency, autoinflammation and glycogen storage disease. In mice, the loss of Sharpin leads to severe dermatitis due to excessive keratinocyte cell death. Here, we report two individuals with SHARPIN deficiency who manifest autoinflammatory symptoms but unexpectedly no dermatological problems. Fibroblasts and B cells from these individuals showed attenuated canonical NF-κB responses and a propensity for cell death mediated by TNF superfamily members. Both SHARPIN-deficient and HOIP-deficient individuals showed a substantial reduction of secondary lymphoid germinal center B cell development. Treatment of one SHARPIN-deficient individual with anti-TNF therapies led to complete clinical and transcriptomic resolution of autoinflammation. These findings underscore the critical function of the LUBAC as a gatekeeper for cell death-mediated immune dysregulation in humans., (© 2024. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

Background/aim: Capecitabine plus oxaliplatin (CapeOX) therapy is used as an adjuvant chemotherapy regimen for patients with colorectal cancer (CRC). Although oxaliplatin induces thrombocytopenia, the risk factors for thrombocytopenia in oxaliplatin-treated patients with CRC are not well established. We aimed to investigate the risk factors for thrombocytopenia in CapeOX-treated patients with CRC. In addition, we evaluated platelet counts and non-invasive liver fibrosis indices, specifically the aspartate aminotransferase-to-platelet ratio index (APRI) and the fibrosis-4 index (FIB-4), during CapeOX therapy in these patients., Patients and Methods: Between July 2017 and June 2020, we enrolled CapeOX-treated patients with high-risk stage II or stage III CRC at seven hospitals collaborating with the Division of Oncology, Aichi Prefectural Society of Hospital Pharmacists (Aichi prefecture, Japan). In this retrospective study, we investigated patients' backgrounds, laboratory data, concomitant medications, number of cycles of CapeOX and oxaliplatin, cumulative dose of oxaliplatin, and administration period. The cut-off values were calculated using receiver operating characteristic analysis of platelet counts and APRI and FIB-4 scores., Results: Fifty-five patients without thrombocytopenia and 44 patients with thrombocytopenia were enrolled. During CapeOX therapy, the thrombocytopenia group showed a significant decrease in platelet count and a significant increase in APRI and FIB-4 scores compared to the non-thrombocytopenia group. Baseline albumin level ≤3.5 g/dl and platelet count ≤238×10 3 /μl were independently associated with ≥grade 2 thrombocytopenia in CapeOX-treated patients., Conclusion: Baseline albumin level and platelet count may be useful for predicting thrombocytopenia in CapeOX-treated patients with high-risk stage II or stage III CRC., (Copyright © 2024, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background : Previous neuroimaging studies have identified brain regions related to respiratory motor control and perception. However, little is known about the resting-state functional connectivity (FC) associated with respiratory impairment. We aimed to determine the FC involved in mild respiratory impairment without altering transcutaneous oxygen saturation. Methods : We obtained resting-state functional magnetic resonance imaging data from 36 healthy volunteers during normal respiration and mild respiratory impairment induced by resistive load (effort breathing). ROI-to-ROI and seed-to-voxel analyses were performed using Statistical Parametric Mapping 12 and the CONN toolbox. Results : Compared to normal respiration, effort breathing activated FCs within and between the sensory perceptual area (postcentral gyrus, anterior insular cortex (AInsula), and anterior cingulate cortex) and visual cortex (the visual occipital, occipital pole (OP), and occipital fusiform gyrus). Graph theoretical analysis showed strong centrality in the visual cortex. A significant positive correlation was observed between the dyspnoea score (modified Borg scale) and FC between the left AInsula and right OP. Conclusions : These results suggested that the FCs within the respiratory sensory area via the network hub may be neural mechanisms underlying effort breathing and modified Borg scale scores. These findings may provide new insights into the visual networks that contribute to mild respiratory impairments.

The ever-stricter regulations on animal experiments in the field of cosmetic testing have prompted a surge in skin-related research with a special focus on recapitulation of the in vivo skin structure in vitro. In vitro human skin models are seen as an important tool for skin research, which in recent years attracted a lot of attention and effort, with researchers moving from the simplest 2-layered models (dermis with epidermis) to models that incorporate other vital skin structures such as hypodermis, vascular structures, and skin appendages. In this study, we designed a microfluidic device with a reverse flange-shaped anchor that allows culturing of an in vitro skin model in a conventional 6-well plate and assessing its barrier function without transferring the skin model to another device or using additional contraptions. Perfusion of the skin model through vascular-like channels improved the morphogenesis of the epidermis compared with skin models cultured under static conditions. This also allowed us to assess the percutaneous penetration of the tested caffeine permeation and vascular absorption, which is one of the key metrics for systemic drug exposure evaluation., (© 2024 IOP Publishing Ltd.)