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Objective: To describe the characteristics of COVID-19 patients with pneumothorax and pneumomediastinum (PTX/PM) and their association with patient outcomes. Patients and methods: Adults admitted to five Mayo Clinic hospitals with COVID-19 between 03/2020–01/2022 were evaluated. PTX/PM was defined by imaging. Descriptive analyses and a matched (age, sex, admission month, COVID-19 severity) cohort comparison was performed. Hospital mortality, length of stay (LOS), and predisposing factors were assessed. Results: Among 6663 patients, 197 had PTX/PM (3 %) (75 PM, 40 PTX, 82 both). The median age was 59, with 71 % males. Exposure to invasive and non-invasive mechanical ventilation and high-flow nasal cannula before PTX/PM were 42 %, 17 %, and 20 %, respectively. Among isolated PTX and PM/PTX patients 70 % and 53.7 % underwent an intervention, respectively, while 96 % of the PM-only group was followed conservatively.A total of 171 patients with PTX/PM were compared to 171 matched controls. PTX/PM patients had more underlying lung disease (40.9 vs. 23.4 %, p

Abstract Background Mycetoma is a chronic disease affecting the skin and subcutaneous tissue endemic in the tropical and subtropical regions. Several bacteria and fungi can cause mycetoma, but fungal mycetoma (eumycetoma) is challenging because the treatment requires a combination of a long-term antifungal agent and surgery. Although the transmission route has not yet been elucidated, infection from the soil is a leading hypothesis. However, there are few soil investigation studies, and the geographical distribution of mycetoma pathogens is not well documented. Here, we used multiplex real-time PCR technology to identify three fungal species from soil samples. Methods In total, 64 DNA samples were extracted from soil collected in seven villages in an endemic area in Sennar State, Sudan, in 2019. Primers and fluorescent probes specifically targeting the ribosomal DNA of Madurella mycetomatis, Falciformispora senegalensis, and F. tompkinsii were designed. Results Multiplex real-time PCR was performed and identified the major pathogen, M. mycetomatis that existed in most sites (95%). In addition, two other pathogens were identified from some sites. This is the first report on the use of this technique for identifying the eumycetoma causative microorganisms. Conclusions This study demonstrated that soil DNA investigation can elucidate the risk area of mycetoma-causative agents. The results will contribute to the design of prevention measures, and further large-scale studies may be effective in understanding the natural habitats of mycetoma pathogens.

The atmospheric deposition of iron (Fe) promotes primary production in the surface ocean, which results in the enhanced uptake of carbon dioxide into surface seawater. Given that microorganisms in seawater utilize dissolved Fe (d-Fe) as a nutrient, the bioavailability of Fe in aerosol particles depends on its solubility. However, the factors controlling fractional Fe solubility (Fesol %) in aerosol particles have not been fully understood. This study performed annual observations of the total and dissolved metal concentrations in size-fractionated (seven fractions) aerosol particles at Higashi-Hiroshima, Japan. The feasibility of the molar concentration ratio of d-Fe relative to dissolved Al ([d-Fe] / [d-Al]) as an indicator of sources of d-Fe in aerosol particles was investigated because this ratio is likely dependent on the emission sources of Fe (e.g., mineral dust, fly ash, and anthropogenic Fe oxides) and their dissolution processes (proton- and ligand-promoted dissolutions). Approximately 70 % of the total Fe in total suspended particulates (TSPs) was present in coarse aerosol particles, whereas about 70 % of d-Fe in TSPs was mainly found in fine aerosol particles. The average Fesol % in fine aerosol particles (11.4 ± 7.0 %) was higher than that of coarse aerosol particles (2.19 ± 2.27 %). In addition, the average ratio of [d-Fe] / [d-Al] in coarse aerosol particles (0.408 ± 0.168) was lower than that in fine aerosol particles (1.15 ± 0.80). The range of [d-Fe] / [d-Al] ratios in the coarse aerosol particles (0.121–0.927) was similar to that obtained by proton-promoted dissolution of mineral dust (0.1–1.0), which indicates that the d-Fe in coarse aerosol particles was derived from mineral dust. The [d-Fe] / [d-Al] ratios of fine aerosol particles ranged from 0.386 to 4.67, and [d-Fe] / [d-Al] ratios greater than 1.50 cannot be explained by proton- and ligand-promoted dissolutions (1.00 < [d-Fe] / [d-Al] < 1.50). The [d-Fe] / [d-Al] ratio correlated with the enrichment factor of Fe in fine aerosol particles (r: 0.505), which indicates that anthropogenic Fe with a high [d-Fe] / [d-Al] ratio was the source of d-Fe in fine aerosol particles. The high [d-Fe] / [d-Al] ratio was attributed to anthropogenic Fe oxides emitted from high-temperature combustions. Finally, the fraction of anthropogenic Fe oxides to d-Fe in TSPs was calculated based on the [d-Fe] / [d-Al] ratio of aerosols and their emission source samples. As a result, the fraction of anthropogenic Fe oxides to d-Fe in TSPs varied from 1.48 % to 80.7 %. A high fraction was observed in summer when air masses originated from industrial regions in Japan. By contrast, approximately 10 % of d-Fe in the TSPs collected in spring and during Asian dust events was derived from anthropogenic Fe oxides when air masses were frequently transported from East Asia to the Pacific Ocean. Thus, mineral dust was the dominant source of d-Fe in Asian outflow to the Pacific Ocean.

Abstract Changes in the thermal structure of lake ecosystems have been documented as a response to climate change, but the dynamics of biomass distribution, which fundamentally determines species conservation, has been less studied. An interdisciplinary approach was used to demonstrate the influence of climate‐driven changes on the environmental DNA (eDNA) distribution of two species (Gymnogobius isaza and Palaemon paucidens) in Lake Biwa, the largest monomictic lake in Japan. In field surveys in 2016–2017 (full water circulation) and 2019 (partial water circulation), eDNA concentrations of these species were measured for 43 and 47 samples, respectively, collected from the lake bottom. The correlative relationship was investigated between species' eDNA concentrations and environmental variables. The species–environment relationship was then applied to species' eDNA distributions under existing and future environments calculated by a lake ecosystem model. Based on differences in the estimated eDNA distributions, we suggest that different species respond differently to climate change. The distribution of G. isaza will expand in the future if full water circulation occurs, although it appears to be independent of water circulation at present. Partial water circulation enlarges the distribution area of P. paucidens, but its eDNA concentrations will be low in the future, regardless of the extent of water circulation. These results indicate that species such as P. paucidens, which is now abundant but vulnerable to climate change, require special attention. Furthermore, our study emphasizes the potential application of interdisciplinary methodologies for improved species conservation.

Atmospheric deposition is one of the main sources of dissolved iron (Fe) in the ocean surfaces. Atmospheric processes are recognized as controlling fractional Fe solubility (Fesol%) in marine aerosol particles. However, the impact of these processes on Fesol% remains unclear. One of the reasons for this is the lack of field observations focusing on the relationship between Fesol% and Fe species in marine aerosol particles. In particular, the effects of organic ligands on Fesol% have not been thoroughly investigated in observational studies. In this study, Fe species in size-fractionated aerosol particles in the Pacific Ocean were determined using X-ray absorption fine structure (XAFS) spectroscopy. The internal mixing states of Fe and organic carbon were investigated using scanning transmission X-ray microscopy (STXM). The effects of atmospheric processes on Fesol% in marine aerosol particles were investigated based on the speciation results. Iron in size-fractionated aerosol particles was mainly derived from mineral dust, regardless of aerosol diameter, because the enrichment factor of Fe was almost 1 in both coarse (PM>1.3) and fine aerosol particles (PM1.3). Approximately 80 % of the total Fe (insoluble + labile Fe) was present in PM>1.3, whereas labile Fe was mainly present in PM1.3. The Fesol% in PM>1.3 was not significantly increased (2.56±2.53 %, 0.00 %–8.50 %, n=20) by the atmospheric processes because mineral dust was not acidified beyond the buffer capacity of calcite. In contrast, mineral dust in PM1.3 was acidified beyond the buffer capacity of calcite. As a result, Fesol% in PM1.3 (0.202 %–64.7 %, n=10) was an order of magnitude higher than that in PM>1.3. The PM1.3 contained ferric organic complexes with humic-like substances (Fe(III)-HULIS, but not Fe-oxalate complexes), and the abundance correlated with Fesol%. Iron(III)-HULIS was formed during transport in the Pacific Ocean because Fe(III)-HULIS was not found in aerosol particles in Beijing and Japan. The pH estimations of mineral dust in PM1.3 established that Fe was solubilized by proton-promoted dissolution under highly acidic conditions (pH < 3.0), whereas Fe(III)-HULIS was stabilized under moderately acidic conditions (pH 3.0–6.0). Since the observed labile Fe concentration could not be reproduced by proton-promoted dissolution under moderately acidic conditions, the pH of mineral dust increased after proton-promoted dissolution. The cloud process in the marine atmosphere increases the mineral dust pH because the dust particles are covered with organic carbon and Na. The precipitation of ferrihydrite was suppressed by Fe(III)-HULIS owing to its high water solubility. Thus, the organic complexation of Fe with HULIS plays a significant role in the stabilization of Fe that was initially solubilized by proton-promoted dissolution.

Biodiversity monitoring is important for the conservation of natural ecosystems in general, but particularly for amphibians, whose populations are pronouncedly declining. However, amphibians’ ecological traits (e.g. nocturnal or aquatic) often prevent their precise monitoring. Environmental DNA (eDNA) metabarcoding – analysis of extra-organismal DNA released into the environment – allows the easy and effective monitoring of the biodiversity of aquatic organisms. Here, we developed and tested the utility of original PCR primer sets. First, we conducted in vitro PCR amplification tests with universal primer candidates using total DNA extracted from amphibian tissues. Five primer sets successfully amplified the target DNA fragments (partial 16S rRNA gene fragments of 160–311 bp) from all 16 taxa tested (from the three living amphibian orders Anura, Caudata and Gymnophiona). Next, we investigated the taxonomic resolution retrieved using each primer set. The results revealed that the universal primer set “Amph16S” had the highest resolution amongst the tested sets. Finally, we applied Amph16S to the water samples collected in the field and evaluated its detection capability by comparing the species detected using eDNA and physical survey (capture-based sampling and visual survey) in multiple agricultural ecosystems across Japan (160 sites in 10 areas). The eDNA metabarcoding with Amph16S detected twice as many species as the physical surveys (16 vs. 8 species, respectively), indicating the effectiveness of Amph16S in biodiversity monitoring and ecological research for amphibian communities.

The source apportionment of aerosol iron (Fe), including natural and combustion Fe, is an important issue because aerosol Fe can enhance oceanic primary production in the surface ocean. Based on our previous finding that combustion Fe emitted by evaporation processes has Fe isotope ratios (δ56Fe) that are approximately 4 ‰ lower than those of natural Fe, this study aimed to distinguish aerosol Fe sources over the northwestern Pacific using two size-fractionated marine aerosols. The δ56Fe values of fine and coarse particles from the eastern or northern Pacific were found to be similar to each other, ranging from 0.0 ‰ to 0.4 ‰. Most of them were close to the crustal average, suggesting the dominance of natural Fe. On the other hand, particles from the direction of East Asia demonstrated lower δ56Fe values in fine particles (−0.5 ‰ to −2.2 ‰) than in coarse particles (on average −0.02 ± 0.12 ‰). The correlations between the δ56Fe values and the enrichment factors of lead and vanadium suggested that the low δ56Fe values obtained were due to the presence of combustion Fe. The δ56Fe values of the soluble component of fine particles in this region were lower than the total, indicating the preferential dissolution of combustion Fe. In addition, we found a negative correlation between the δ56Fe value and the fractional Fe solubility in air masses from the direction of East Asia. These results suggest that the presence of combustion Fe is an important factor in controlling the fractional Fe solubility in air masses from the direction of East Asia, whereas other factors are more important in the other areas. By assuming typical δ56Fe values for combustion and natural Fe, the contribution of combustion Fe to the total (acid-digested) Fe in aerosols was estimated to reach up to 50 % of fine and 21 % of bulk (coarse + fine) particles in air masses from the direction of East Asia, whereas its contribution was small in the other areas. The contribution of combustion Fe to the soluble Fe component estimated for one sample was approximately twice as large as the total, indicating the importance of combustion Fe as a soluble Fe source despite lower emissions than the natural. These isotope-based estimates were compared with those estimated using an atmospheric chemical transport model (IMPACT), in which the fractions of combustion Fe in fine particles, especially in air masses from the direction of East Asia, were consistent with each other. In contrast, the model estimated a relatively large contribution from combustion Fe in coarse particles, probably because of the different characteristics of combustion Fe that are included in the model calculation and the isotope-based estimation. This highlights the importance of observational data on δ56Fe for size-fractionated aerosols to scale the combustion Fe emission by the model. The average deposition fluxes of soluble Fe to the surface ocean were 1.4 and 2.9 nmol m−2 d−1 from combustion and natural aerosols, respectively, in air masses from the direction of East Asia, which suggests that combustion Fe could be an important Fe source to the surface seawater among other Fe sources. Distinguishing Fe sources using the δ56Fe values of marine aerosols and seawater is anticipated to lead to a more quantitative understanding of the Fe cycle in the atmosphere and surface ocean.

Abstract Environmental DNA (eDNA) can be a powerful tool for detecting the distribution and abundance of target species. This study aimed to test the longevity of eDNA in marine sediment through a tank experiment and to use this information to reconstruct past faunal occurrence. In the tank experiment, juvenile jack mackerel (Trachurus japonicus) were kept in flow-through tanks with marine sediment for two weeks. Water and sediment samples from the tanks were collected after the removal of fish. In the field trial, sediment cores were collected in Moune Bay, northeast Japan, where unusual blooms of jellyfish (Aurelia sp.) occurred after a tsunami. The samples were analyzed by layers to detect the eDNA of jellyfish. The tank experiment revealed that after fish were removed, eDNA was not present in the water the next day, or subsequently, whereas eDNA was detectable in the sediment for 12 months. In the sediment core samples, jellyfish eDNA was detected at high concentrations above the layer with the highest content of polycyclic aromatic hydrocarbons, reflecting tsunami-induced oil spills. Thus, marine sediment eDNA preserves a record of target species for at least one year and can be used to reconstruct past faunal occurrence.

No abstract available. Article truncated after 150 words. A 58-year-old woman with a history of orthotopic heart transplant, performed for Adriamycin-induced cardiomyopathy, treated with mycophenolate and tacrolimus, presented for routine interval follow up. The patient’s past medical history was significant for follicular thyroid carcinoma treated with total thyroidectomy and bilateral breast carcinoma in remission as well as hypothyroidism and type II diabetes mellitus. In addition to tacrolimus and mycophenolate, the patient’s medications included aspirin, insulin, itraconazole (for anti-fungal prophylaxis), levothyroxine, prednisone (tapering since transplant), and valganciclovir. The patient recently complained of rhinorrhea and cough productive of brown-tinged sputum, improving over the previous 2 weeks; she denied fever, chills, shortness of breath, night sweats chest pain, or gastrointestinal symptoms. Physical examination showed the patient to be afebrile with normal heart and respiratory rates and blood pressure. Her room air oxygen saturation was 99%. The patient’s complete blood count and serum chemistries showed largely normal values, with the white blood …

Abstract Alien ant species (Formicidae, Hymenoptera) cause serious damage worldwide. Early detection of invasion and rapid management are significant for controlling these species. However, these attempts are sometimes hindered by the need for direct detection techniques, such as capture, visual observation, or morphological identification. In this study, we demonstrated that environmental DNA (eDNA) analysis can be used as a monitoring tool for alien ants using Linepithema humile (Argentine ant), one of the most invasive ants, as a model species. We designed a new real-time PCR assay specific to L. humile and successfully detected eDNA from the surface soil. The reliability of eDNA analysis was substantiated by comparing eDNA detection results with traditional survey results. Additionally, we examined the relationship between eDNA concentration and distance from nests and trails. Our results support the effectiveness of eDNA for alien ant monitoring and suggest that this new method could improve our ability to detect invasive ant species.

Mycetoma is a tropical disease caused by several fungi and bacteria present in the soil. Fungal mycetoma and eumycetoma are especially challenging to treat; therefore, prevention, early diagnosis, and early treatment are important, but it is also necessary to understand the geographic distribution of these pathogenic fungi. In this study, we used DNA metabarcoding methodology to identify fungal species from soil samples. Soil sampling was implemented at seven villages in an endemic area of Sennar State in Sudan in 2019, and ten sampling sites were selected in each village according to land-use conditions. In total, 70 soil samples were collected from ground surfaces, and DNA in the soil was extracted with a combined method of alkaline DNA extraction and a commercial soil DNA extraction kit. The region for universal primers was selected to be the ribosomal internal transcribed spacer one region for metabarcoding. After the second PCR for DNA library preparation, the amplicon-based DNA analysis was performed using next-generation sequencing with two sets of universal primers. A total of twelve mycetoma-causative fungal species were identified, including the prime agent, Madurella mycetomatis, and additional pathogens, Falciformispora senegalensis and Falciformispora tompkinsii, in 53 soil samples. This study demonstrated that soil DNA metabarcoding can elucidate the presence of multiple mycetoma-causative fungi, which may contribute to accurate diagnosis for patient treatment and geographical mapping.

Objective: To assess the contribution and safety of bronchoscopic cryobiopsy vs traditional forceps biopsy used in clinical practice for diagnosing diffuse parenchymal lung disease (DPLD). Patients and Methods: We identified 271 patients who underwent bronchoscopic biopsy for DPLD at Mayo Clinic, MN (June 1, 2013, through September 30, 2017). Medical records were reviewed including prebiopsy clinical and radiographic impressions. Diagnostic yield was assessed in terms of a specific histologic pattern resulting in a diagnosis when combined with the clinical-radiologic context. Clinical utility was defined as a biopsy result deemed useful in patient management. Results: The cohort included 120 cryobiopsy and 151 forceps biopsy cases with mean age 61±14 years and 143 (53%) men. Diagnostic yield (55% vs 41%; odds ratio [OR], 1.73; 95% CI, 1.07 to 2.83; P=.026) and clinical utility (60% vs 40%; OR, 2.21; 95% CI, 1.36 to 3.63; P=.001) were higher for the cryobiopsy group, and the association remained after control for prebiopsy clinical impressions (OR, 2.21; 95% CI, 1.22 to 4.08; P=.010 and OR, 3.23; 95% CI, 1.76 to 6.10; P

Abstract Aqueous environmental DNA (eDNA) analysis has been applied to the monitoring of various ecosystems and taxa, and the characteristics of aqueous eDNA have been previously studied. In contrast, although sedimentary eDNA has been used to restore past information, the characteristics of sedimentary eDNA are not well understood. In this study, we compared the properties of sedimentary and aqueous eDNA of macro‐organisms. First, to clarify the preservation ability of sediments, we compared the difference in decay rates between aqueous and sedimentary eDNA using samples collected from a biotope (an artificial pond prepared with concrete). Next, to clarify the biological information retained in sedimentary eDNA both qualitatively and quantitatively, we compared eDNA concentrations between sediment and water samples collected simultaneously from a lake, and the fish species detected by eDNA metabarcoding were also compared. The results demonstrated the following: (a) the decay rate (decreased eDNA copy number divided by the initial eDNA copy number per unit time) of sedimentary eDNA (0.00033 ± 0.000049 [mean ± SE]/hr) was lower than that of aqueous eDNA (0.01863 ± 0.0011/hr); (b) sedimentary eDNA concentration of the mitochondrial marker of three fish species was higher than aqueous eDNA concentration for the same sample weight (12.5–1,456.9 times); and (c) the species composition obtained by metabarcoding was not significantly different between sediment and water; however, considering the lower decay rate of sedimentary eDNA, using both sample types may provide more comprehensive information of species distribution. Thus, sedimentary eDNA analysis will expand future biomonitoring and ecological studies by providing a difference in timescale.

Abstract Environmental DNA (eDNA) analysis has seen rapid development in the last decade, as a novel biodiversity monitoring method. Previous studies have evaluated optimal strategies, at several experimental steps of eDNA metabarcoding, for the simultaneous detection of fish species. However, optimal sampling strategies, especially the season and the location of water sampling, have not been evaluated thoroughly. To identify optimal sampling seasons and locations, we performed sampling monthly or at two‐monthly intervals throughout the year in three dam reservoirs. Water samples were collected from 15 and nine locations in the Miharu and Okawa dam reservoirs in Fukushima Prefecture, respectively, and five locations in the Sugo dam reservoir in Hyogo Prefecture, Japan. One liter of water was filtered with glass‐fiber filters, and eDNA was extracted. By performing MiFish metabarcoding, we successfully detected a total of 21, 24, and 22 fish species in Miharu, Okawa, and Sugo reservoirs, respectively. From these results, the eDNA metabarcoding method had a similar level of performance compared to conventional long‐term data. Furthermore, it was found to be effective in evaluating entire fish communities. The number of species detected by eDNA survey peaked in May in Miharu and Okawa reservoirs, and in March and June in Sugo reservoir, which corresponds with the breeding seasons of many of fish species inhabiting the reservoirs. In addition, the number of detected species was significantly higher in shore, compared to offshore samples in the Miharu reservoir, and a similar tendency was found in the other two reservoirs. Based on these results, we can conclude that the efficiency of species detection by eDNA metabarcoding could be maximized by collecting water from shore locations during the breeding seasons of the inhabiting fish. These results will contribute in the determination of sampling seasons and locations for fish fauna survey via eDNA metabarcoding, in the future.

Abstract Monitoring reproductive migration is essential for the conservation of anadromous species. Shishamo smelt (Spirinchus lanceolatus) is endemic to Hokkaido, the northernmost large island in Japan. S. lanceolatus is an anadromous species that is known to migrate into rivers for a very short period in early winter. While this species has a special value for local fisheries, the catch amount has drastically declined in the last few decades. Information about S. lanceolatus reproductive migration dynamics is limited, which prevents them from being efficiently managed as a resource. In this study, we used environmental DNA (eDNA) methods as a noninvasive molecular tool for estimating presence/absence and abundance/biomass of S. lanceolatus during their migration into rivers. We developed a species‐specific qPCR system for S. lanceolatus, examining (a) temporal variation in S. lanceolatus eDNA concentrations compared with catch data gathered by traditional methods and (b) variability of migratory patterns among river systems. In a core river for their spawning migration, we consistently detected S. lanceolatus eDNA throughout the spawning season, and the temporal distribution of eDNA concentration was consistent with that of the number of migrating S. lanceolatus estimated by catch survey data. In addition, we were able to detect S. lanceolatus eDNA even from rivers without any official record of their migration. Among rivers with eDNA detection, the relative eDNA concentrations varied, indicating that the population biomass differs largely among the river populations. Our study suggests that eDNA detection systems are useful for tracking reproductive migration of S. lanceolatus at fine spatio‐temporal scales.

Preventing mosquito-borne infectious diseases requires that vector mosquitoes are monitored and controlled. Targeting immature mosquitoes (eggs, larvae, and pupae), which have less mobility than adults, is an effective management approach. However, conducting these surveys is often difficult due to the limitations of morphological classification and survey costs. The application of environmental DNA (eDNA) analysis can solve these issues because it allows easy estimation of species distribution and morphology-independent species identification. Although a few previous studies have reported mosquito eDNA detection, there is a gap in knowledge regarding the dynamics related to the persistence of immature mosquito eDNA. We used Culex pipiens pallens, a vector of West Nile fever, as a model species. First, we developed a species-specific detection assay and confirmed its specificity using in silico and in vitro tests. Next, we conducted laboratory experiments using breeding tanks. Water samples were collected at each developmental stage. In addition, water samples were collected daily until the seventh day after emergence from the pupae. We quantified eDNA using real-time PCR with the developed assay to investigate the dynamics of mosquito eDNA. The specificity of the developed assay was confirmed by in silico and in vitro tests. Mosquito eDNA was detected at all developmental stages and detected up to seven days after emergence of pupae. In particular, high concentrations of eDNA were detected immediately after hatching from eggs and after emergence from pupae. Highly frequent positive eDNA signals were continuously detected between egg hatching and pupa hatching. Mosquito eDNA was detected immediately after the eggs were introduced, and eDNA-positive detections continued until pupae emergence, suggesting that eDNA analysis is useful for monitoring mosquito larvae. In the future, monitoring immature mosquitoes using eDNA analysis will contribute to prevent mosquito-borne infectious diseases.

Smart agriculture is recommended for labor-saving, refinement and high quality production of rice cultivation with safety and security. The Terrestrial laser measurement has the advantage of acquiring 3D point cloud information with high accuracy and high density, but there is a disadvantage that it becomes difficult to measure the base of rice plant when paddy rice grew. In this study, the 3D point cloud information obtained by terrestrial laser measurement was used to three-dimensionally measure the growth state in the field corresponding to the growing period in time series. The growth characteristics of the whole field as a community were extracted as a representative value of mean growth. Then we attempted extraction of individual differences in growth and growth unevenness, as the deviation from the mean value of the field in terms of the growth characteristics of each strain focused on the individual plants. it is difficult to observe the root of the rice during the growing period, it was used for analyzing the growth quantity as the growth difference height for each growing period by obtaining the difference of the elevation value of the rice at the early stage of growth and at each stage of growing. The spatial variation in the growth quantity of the whole field area and the local area was calculated, the range of the deviation for evaluating the mean variation and the growth abnormality was examined, and the setting of the threshold for evaluating the growth normal and abnormality was examined.

This case highlights the importance of recognizing any new soft tissue abnormalities in cancer patients with an indwelling pleural catheter (IPC) or who has had an IPC. This report also describes the first case of catheter tract metastasis (CTM) due to renal cell carcinoma (RCC) and the second case of CTM post‐IPC removal.

Water sampling and filtration of environmental DNA (eDNA) analysis have been performed by several different methods, and each method may yield a different species composition or eDNA concentration. Here, we investigated the eDNA of seawater samples directly collected by SCUBA to compare two widely used filtration methods: open filtration with a glass filter (GF/F) and enclosed filtration (Sterivex). We referred to biomass based on visual observation data collected simultaneously to clarify the difference between organism groups. Water samples were collected at two points in the Sea of Japan in May, September and December 2018. The respective samples were filtered through GF/F and Sterivex for eDNA extraction. We quantified the eDNA concentration of five fish and two cnidarian species by quantitative polymerase chain reaction (qPCR) using species-specific primers/probe sets. A strong correlation of eDNA concentration was obtained between GF/F and Sterivex; the intercepts and slopes of the linear regression lines were slightly different in fish and jellyfish. The amount of eDNA detected using the GF/F filtration method was higher than that detected using Sterivex when the eDNA concentration was high; the opposite trend was observed when the eDNA concentration was relatively low. The concentration of eDNA correlated with visually estimated biomass; eDNA concentration per biomass in jellyfish was approximately 700 times greater than that in fish. We conclude that GF/F provides an advantage in collecting a large amount of eDNA, whereas Sterivex offers superior eDNA sensitivity. Both filtration methods are effective in estimating the spatiotemporal biomass size of target marine species.

Abstract Background Many survivors of the Great East Japan Earthquake that occurred in 2011 were at risk of deteriorating health, especially elderly people living in disaster-stricken areas. The objectives of this prospective study were: a) to clarify the different lifestyle and psychosocial factors associated with frailty by sex among the non-disabled elderly survivors, and b) to describe the differences in characteristics stratified by the degree of disaster-related housing damage. Methods We followed 2261 Japanese survivors aged ≥65 years (45.3% male; mean age, 71.7 years) without disability or frailty who completed a self-administered questionnaire at baseline. All participants completed a baseline questionnaire in 2011 and at least one identical follow-up questionnaire between 2012 and 2015 regarding lifestyle (smoking status, alcohol intake, physical activity, sedentary lifestyle, and dietary intake) and psychosocial factors (self-rated health, standard of living, psychological distress, and social networks). Frailty was defined as a score of ≥5 on the Kihon Checklist, which is used by the Japanese government to certify the need for long-term care insurance. Adjusted odds ratios and 95% confidence intervals with frailty as the dichotomous dependent variable and health factors as the independent variables were calculated using a multilevel model for repeated measures by sex, followed by stratification analyses by the degree of housing damage. Results Over the 4-year study period, 510 participants (22.6%) developed frailty. In the post-disaster setting, many of the psychosocial factors remained more prevalent 4 years later among survivors with extensive housing damage. The presence of risk factors regarding the development of frailty differed by the degree of housing damage. Among men, psychological distress, in parallel with a poor social network, was related to frailty among only the participants with extensive housing damage and those living in temporary housing, whereas among women, worsening psychological distress was associated only with no damage and no displaced survivors. Among women with extensive damage and displacement, health outcomes such as overweight and diabetes and poor social networks were strongly related to frailty. Conclusions Lifestyle and psychosocial factors associated with the risk of frailty differ by sex and the degree of housing damage.

Introduction: Bronchopleural fistula (BPF) is a feared complication of pulmonary resection. Fistula plugs (FP) have been described as an adequate treatment in anorectal disease. We describe our early experience placing an FP in the treatment of BPF. Materials and methods: We retrospectively reviewed 5 patients for whom a FP was placed for BPF at our institution. Demographic data, initial perioperative information, method and technique of FP placement, and success is reported. Results: Five patients (4 male, 1 female) with a median age of 63 years (range, 57–76 years) underwent 6 FP placements for BPF. Two patients were post-pneumonectomy and 3 patients post-lobectomy. The median time to presentation following surgery was 118 days (range 22–218). Upon bronchoscopic or operative re-evaluation, 3 patients had successful cessation of their air leak at 0, 1 and 4 days. Two of three patients subsequently underwent a thoracic muscle flap placement to augment healing. One patient had a persistent air leak despite 2 separate FP placements. The air leak stopped with endobronchial valves (EBV) which were deployed proximal to the FP, 9 days after placement of the FP. Another patient had a successful muscle flap placed 80 days after FP placement. There were no complications associated with the FP. Three of five patients were deemed successfully treated with FP placement alone. Conclusion: In patients with a postoperative BPF and pleural window, placement of a FP had a modest success rate and can be considered as a treatment modality option for BPF. Keywords: Bronchopleural fistula, Fistula plug, Persistent air leak, Prolong air leak

Introduction: Central airway obstruction (CAO) often requires repeated interventional procedures which offer variable efficacy, a time-limited effect, and have inherent limitations. Paclitaxel has been used to prevent restenosis in blood vessels. The literature describing the use of paclitaxel to prevent recurrent airway stenosis is limited. We sought to describe our experience using a paclitaxel-coated balloon (PCB) for CAO. Material and methods: We performed a retrospective review of all patients who underwent PCB airway dilation. We collected: basic demographics, details of the CAO, details of the bronchoscopes used, PCB size, PCB dilation pressure, duration of PCB inflation, concurrent non-PCB interventions, estimated pre- and post-PCB CAO luminal diameter, follow up bronchoscopy date and luminal diameter, and spirometry results. Results: PCB dilation was performed in 10 cases on 5 patients. Eight PCB dilations were performed for CAO related to distal airway stent stenosis. Concurrent non-PCB interventions were performed with 6 PCB dilations. Nine cases documented improvements and 1 was unchanged immediately post-PCB dilation. Median luminal diameter pre-PCB dilation was 2 mm. Immediately post-PCB dilation, the median change in luminal diameter was 2 mm. Follow up bronchoscopy information was available for 9 cases. For these 9 cases, luminal diameter was unchanged in 5 and worse in 4 when compared to immediate post-PCB dilation. Conclusion: PCB dilation in benign CAO produced a modest effect in this cohort of challenging airways. Larger prospective studies are needed to assess how a PCB would perform when compared to a non-drug coated balloon. Keywords: Paclitaxel balloon dilation, Central airway obstruction, Balloon dilation, Airway stenosis, Airway stricture

No abstract available. Article truncated after 150 words. A 37-year-old woman complaining of chest pain and cough underwent resection of a mediastinal foregut duplication cyst complicated by a 10-day hospitalization with a prolonged air leak. Seven years later, she presented with worsening cough and shortness of breath, complaining of similar symptoms intermittently in the 7 years between her surgery and presentation. Chest CT showed a hyperattenuating lesion obstructing the medial basal segmental airways, with bronchoscopy revealing suture and a pledget obstructing the medial basal segmental right lower lobe bronchus. The pledget and suture were successfully removed. Repeat bronchoscopy several months later showed no residual airway foreign body, although medial basal subsegmental bronchial stenosis prevented advancement of the bronchoscope distally; this finding correlated with the CT impression of airway stenosis or occlusion in this region on the follow up CT. Bronchogenic cysts result from abnormal lung budding and development of the ventral foregut during the first trimester (1). Many …

Background. The FilmArray Respiratory Panel (FARP) (BioFire Diagnostics, Inc.) is a multiplex, polymerase chain reaction (PCR) technique that can detect 17 respiratory viruses and 3 bacterial targets in a single reaction. Immunocompromised hosts (ICH) with respiratory illnesses often undergo bronchoscopy with bronchoalveolar lavage (BAL). This prospective study aimed to evaluate the yield and concordance of NP and BAL FARP testing when performed on the same patient concurrently. Methods. From February to December 2016, 125 patients (100 ICH and 25 non-ICH) were enrolled. NP swabs and BAL samples were sent for FARP testing. Results. The yield of the BAL FARP among ICH and non-ICH was 24% (24/100) and 8% (2/25), respectively. The yield of positive NP swabs in ICH was 27% (27/100) versus 4% (1/25) in non-ICH. The majority of patients (89%; 111/125) had concordant results between NP and BAL specimens. Of the 24 ICH patients who had a positive BAL FARP, the majority (79%) had the same pathogen detected from the NP swab. Conclusion. The FARP may be useful in the ICH. Given the high concordance, in patients whom a pathogen is identified on the NP FARP, a FARP performed on BAL will likely yield the same result. However, if the NP FARP is negative, performing the test on a BAL sample may have an incremental yield.

Objective. To determine whether results of the nasopharyngeal FilmArray respiratory panel (NP-FARP) influenced antibiotic decisions. Methods. We reviewed the medical records of nonintensive care unit (ICU) inpatients that had an NP-FARP performed at our institution between June 2013 and June 2014. The inpatient records were reviewed 48 hours after the NP-FARP for the following data: demographic information; NP-FARP, serum procalcitonin, and methicillin-resistant Staphylococcus aureus nasal swab (MRSA NS) results; antibiotics prior and post-48 hours of the NP-FARP result; and the current immunosuppression status. Clinical outcome data were not obtained. Patients were categorized into those who had a positive (+) or a negative (−) NP-FARP. We further subdivided these two categories into groups A, B, and C based on the antibiotic modifications 48 hours after their NP-FARP result. Group A included patients who were never initiated on antimicrobial therapy. Patients whose antibiotics were discontinued or deescalated were placed in group B. Patients with antibiotic escalation or continuation without change constituted group C. We compared and analyzed groups A, B, and C in the (+) and (−) NP-FARP cohorts. Results. A total of 545 patients were included. There were 143 (26%) patients with positive and 402 (74%) patients with negative NP-FARPs. Comparison of groups A, B, and C between those with a (+) and (−) NP-FARP were as follows: (+) A and (−) A, 28/143 (20%) and 84/402 (21%); (+) B and (−) B, 59/143 (41%) and 147/402 (37%); and (+) C and (−) C, 56/143 (39%) and 171/402 (43%), respectively. We found no statistically significant differences between groups (+) A versus (−) A, (+) B versus (−) B, and (+) C versus (−) C with respect to age, gender, MRSA NS result, procalcitonin result, or concurrent immunosuppression. Conclusion. In non-ICU inpatients, NP-FARP alone or in combination with procalcitonin or MRSA NS did not influence antibiotic decisions during the study period.

To study the effect of ultrafiltration on the radiocarbon ages of relatively poorly preserved bones in Japan, we analyzed the 14C dates of high-molecular-weight (HMW) gelatin samples and compared them with those of other extracted organic fractions, unfiltered gelatin samples extracted from NaOH-treated or NaOH-untreated collagen, and XAD-purified hydrolysates of animal fossil bones (~4600 BP; gelatin yield of 2-4%) from the Awazu underwater archaeological site, Shiga, Japan. NaOH-treated, unfiltered gelatins and XAD-purified hydrolysates showed statistically similar 14C ages to those of HMW gelatins. The 14C ages of the HMW gelatins were the oldest and similar to those of wood collected from the same layer as the bones, and the NaOH-treated, unfiltered gelatins gave 14C ages within the acceptable margins of error; therefore, ultrafiltration was effective for accurate 14C dating, while NaOH-treated gelatin without ultrafiltration was also sufficient to obtain accurate 14C dates on the animal bones. The 14C ages of human skeletons (Ø750 BP; gelatin yield of 2-11%) from 5 individuals excavated from an archaeological site in Yuigahama, Kamakura, Japan, showed statistically the same 14C ages as NaOHtreated, unfiltered gelatins and HMW gelatins within the margins of error, although HMW gelatins were likely to give slightly older ages than unfiltered gelatin with a yield of less than Ø3%. These results indicate that unfiltered gelatins extracted from fossil bones of gelatin yield more than Ø3% can produce accurate 14C ages without the need for ultrafiltration. Ten bone fragments from 3 humans showed the same 14C ages for each individual, suggesting that any bone part from an individual can be used to obtain a representative age. The 14C ages of tooth enamels of 2 individuals were 35 and 70 yr older than their bone ages. Death dates obtained from these age gaps agreed with those determined by morphology. [ABSTRACT FROM AUTHOR]

In plant genomes, there exist discrete regions rich in CpG dinucleotides, namely CpG clusters. In rice, most of these CpG clusters are associated with genes. Rice genes are grouped into one of the five classes according to the position of an associated CpG cluster. Among them, class 1 genes, which harbor a CpG cluster at the 5'-terminus, share similarities with human genes having CpG islands. In the present study, by analyzing plant genome sequence data, primarily from rice, we investigated the chromosomal distribution of genes of each class, mainly class 1 genes. Class 1 genes were not uniformly distributed across the rice genome, but were clustered into discrete chromosomal segments. EST-based analysis of the distribution of expressed genes indicates that this segmental distribution of class 1 genes caused a preferential distribution of expressed genes within class 1 gene-rich segments. We then compared the methylation status of genes of each class to examine the possibility that differential DNA methylation, if any, is relevant to the observed differential expression level of genes inside and outside the class 1 segments. The difference in the methylation level between these genes was revealed to be fairly small, which does not support the above-mentioned possibility. [ABSTRACT FROM AUTHOR]

Background and Objectives: All 4 previous nationwide surveys of multiple sclerosis (MS) in Japan were conducted before the discovery of anti-aquaporin-4 (AQP4) antibodies; thus, neuromyelitis optica spectrum disorder (NMOSD) was included in MS, as optic-spinal MS. We aimed to clarify the epidemiologic features and trends of MS and NMOSD in Japan separately using a fifth nationwide survey., Methods: The primary survey, in which a questionnaire was sent to 3,799 selected departments (including neurology/internal medicine, pediatrics, and ophthalmology), explored the estimated number and prevalence of patients with MS or NMOSD in 2017, and the secondary survey collected detailed characteristics of the patients using a second questionnaire., Results: The response rates for the primary and secondary surveys were 60.1% and 53.9%, respectively. The estimated total number of patients with MS or NMOSD was 24,800, 2.5-fold higher than that in the fourth survey in 2003. The crude prevalence was 19.6 per 100,000 patients (14.2 for MS and 5.4 for NMOSD), compared with 7.7 per 100,000 patients in the fourth survey. Patients with MS showed milder disability (median Expanded Disability Status Scale [EDSS] score: 2.0 [interquartile range 1.0-4.5] vs 2.5 [1.0-6.0]), decreased secondary progression (8.5% vs 15.2%), and increased usage of disease-modifying drugs (63.7% vs 37.2%) compared with those with conventional MS in the fourth survey. The proportions of oligoclonal bands and Barkhof criteria fulfillment on MRI, which are features of classical MS, increased with advancing year of birth. Patients with NMOSD also showed less disability and shorter disease duration than patients with optic-spinal MS in the fourth survey (EDSS score: 3.5 [2.0-5.5] vs 3.8 [2.0-6.0]; disease duration: 8.0 [3.9-14.8] vs 10.0 [5.0-16.0]). Among patients with NMOSD, disability was exacerbated by a history of longitudinally extensive spinal cord lesions and anti-AQP4 antibody positivity, which both decreased with advancing year of birth., Discussion: The prevalences of MS (particularly with classical features) and NMOSD have been increasing in Japan, suggesting the contribution of environmental factors. However, disabilities in patients with MS and NMOSD have been mitigated. Extensive usage of various disease-modifying drugs could be a factor contributing to this disability mitigation in MS.

The cell cycle is driven by cyclin-dependent kinases (Cdks). The decision whether the cell cycle proceeds is made during G1 phase, when Cdk4/6 functions. Cyclin-dependent kinase inhibitor 2 (Cdkn2) is a specific inhibitor of Cdk4/6, and their interaction depends on D84 in Cdkn2 and R24/31 in Cdk4/6. This knowledge is based mainly on studies in mammalian cells. Here, we comprehensively analyzed Cdk4/6 and Cdkn2 in invertebrates and found that Cdk4/6 was present in most of the investigated phyla, but the distribution of Cdkn2 was rather uneven among and within the phyla. The positive charge of R24/R31 in Cdk4/6 was conserved in all analyzed species in phyla with Cdkn2. The presence of Cdkn2 and the conservation of the positive charge were statistically correlated. We also found that Cdkn2 has been tightly linked to Fas associated factor 1 (Faf1) during evolution. We discuss potential interactions between Cdkn2 and Cdk4/6 in evolution and the possible cause of the strong conservation of the microsynteny., (© 2024 The Author(s). Genes to Cells published by Molecular Biology Society of Japan and John Wiley & Sons Australia, Ltd.)

Brain-derived neurotrophic factor (BDNF) is expressed in the white adipose tissues (WATs), and the expression increases during high-fat diet (HFD) feeding, implicating its role in obesity. Here, we focused on BDNF expression in epididymal WAT (eWAT), a visceral adipose tissue, in mice. During 2 weeks of HFD feeding, Bdnf mRNA expression in eWAT slightly increased, but a robust increase was observed after 8 weeks of HFD feeding. This upregulation of Bdnf mRNA was correlated with significant induction of hypoxia-inducible factor 1α (Hif1α) and platelet-derived growth factor subunit B (Pdgfb) mRNA in eWAT following 8 weeks of HFD feeding. Furthermore, the increased expression of the M1 macrophage markers was strongly correlated with the elevation of Bdnf mRNA in the eWAT. Notably, 8 weeks of HFD feeding significantly elevated Tnfα mRNA expression in eWAT, while no such induction was observed in inguinal WAT (iWAT). In contrast, the expression of Adipoq (adiponectin), implicated in improved insulin sensitivity and anti-inflammatory effects, was significantly upregulated in iWAT, but not in eWAT. Thus, our study may show the role of BDNF in eWAT in obesity models, potentially contributing to the pathological state of visceral adipose tissues., (© 2024 Molecular Biology Society of Japan and John Wiley & Sons Australia, Ltd.)

The relation between Body Mass Index (BMI) and adverse outcomes after endovascular therapy (EVT) for patients with lower extremity artery disease (LEAD) remains incompletely understood. From April 2010 to March 2020, 199 consecutive patients who underwent EVT for LEAD were retrospectively analyzed. The patients were divided into three groups based on BMI; underweight < 18.5 kg/m 2 , normal weight ≥ 18.5 and < 25.0 kg/m 2 , and overweight ≥ 25.0 kg/m 2 . The endpoint of this study was a composite of all-cause mortality, major amputation, and major bleeding. Patients who were underweight often exhibited anemia (53.3 vs. 22.3 vs. 15.4%, respectively; p = 0.001) and severe chronic kidney disease (50.0 vs. 30.8 vs. 20.5%, respectively; p = 0.03). Furthermore, these patients had higher incidences of Trans-Atlantic Inter-Society Consensus class C or D lesions (40.0 vs. 20.0 vs. 10.3%, respectively; p = 0.01). During the median follow-up duration of 3.6 years (interquartile range: 1.2 to 6.7 years), there were 73 incidents of the composite endpoint. When the overweight group was assigned as the reference group, the adjusted hazard ratios for the composite endpoint for the underweight and normal weight patients were 3.67 (95% confidence interval [CI] 1.39-10.83, p = 0.008) and 2.35 (95% CI 1.06-6.23, p = 0.03), respectively. Kaplan-Meier curve demonstrated that the freedom from the composite endpoint for underweight, normal weight, and overweight patients was 41.6%, 60.0%, 83.8%, respectively (p < 0.001). These results suggest that there was an inverse association between BMI and adverse outcomes composed of mortality, limb amputation, and bleeding in patients with LEAD undergoing EVT., (© 2024. The Author(s) under exclusive licence to Japanese Association of Cardiovascular Intervention and Therapeutics.)

In the present work, we addressed the relationship between parental leave policies and social norms. Using a pre-registered, cross-national approach, we examined the relationship between parental leave policies and the perception of social norms for the gender division of childcare. In this study, 19,259 students (11,924 women) from 48 countries indicated the degree to which they believe childcare is (descriptive norm) and should be (prescriptive norm) equally divided among mothers and fathers. Policies were primarily operationalized as the existence of parental leave options in the respective country. The descriptive and prescriptive norms of equal division of childcare were stronger when parental leave was available in a country - also when controlling for potential confounding variables. Moreover, analyses of time since policy change suggested that policy change may initially affect prescriptive norms and then descriptive norms at a later point. However, due to the cross-sectional nature of the data, drawing causal inferences is difficult., (© 2024 British Psychological Society.)

Background: In atrial fibrillation (AF) management, understanding left atrial (LA) substrate is crucial. While both electroanatomic mapping (EAM) and late gadolinium enhancement magnetic resonance imaging (LGE-MRI) are accepted methods for assessing the atrial substrate and are associated with ablation outcome, recent findings have highlighted discrepancies between low-voltage areas (LVAs) in EAM and LGE areas., Objective: The purpose of this study was to explore the relationship between LGE regions and unipolar and bipolar LVAs using multipolar high-density mapping., Methods: Twenty patients scheduled for AF ablation underwent preablation LGE-MRI. LA segmentation was conducted using a deep learning approach, which subsequently generated a 3-dimensional mesh integrating the LGE data. High-density EAM was performed in sinus rhythm for each patient. The electroanatomic map and LGE-MRI mesh were coregistered. LVAs were defined using cutoffs of 0.5 mV for bipolar voltage and 2.5 mV for unipolar voltage. The correspondence between LGE areas and LVAs in the LA was analyzed using confusion matrices and performance metrics., Results: A considerable 87.3% of LGE regions overlapped with unipolar LVAs, compared with only 16.2% overlap observed with bipolar LVAs. Across all performance metrics, unipolar LVAs outperformed bipolar LVAs in identifying LGE areas (precision: 78.6% vs 61.1%; sensitivity: 87.3% vs 16.2%; F 1 score: 81.3% vs 26.0%; accuracy: 74.0% vs 35.3%)., Conclusion: Our findings demonstrate that unipolar LVAs strongly correlate with LGE regions. These findings support the integration of unipolar mapping alongside bipolar mapping into clinical practice. This would offer a nuanced approach to diagnose and manage AF by revealing critical insights into the complex architecture of the atrial substrate., Competing Interests: Disclosures The authors have no conflicts of interest to disclose., (Copyright © 2024 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Changes in local cerebral blood flow (CBF) are a major cause of transient neurological events (TNEs) after revascularization for moyamoya disease (MMD); however, the influence of preoperative collateral pathway development on TNEs has not yet been investigated. This study included 28 hemispheres from 28 consecutive patients with MMD who underwent surgical revascularization, including a superficial temporal artery (STA) to middle cerebral artery (MCA) bypass, between January 2014 and March 2022. The collateralization pathways included the anterior communicating artery (AcomA) collaterals, posterior communicating artery (PcomA) collaterals, transdural collaterals, posterior pericallosal anastomosis, lenticulostriate anastomosis, thalamic anastomosis, and choroidal anastomosis. These collateral pathways were analyzed to identify predictive factors significantly associated with TNEs. TNEs were observed in 11 (39.3%) hemispheres. The development of posterior pericallosal anastomosis and choroidal anastomosis was a significant independent predictor of the occurrence of TNEs after bypass surgery for MMD (P = 0.01, OR 26.9, 95% CI 1.50-480.0; P = 0.002, OR 47.6, 95% CI 2.65-856.6). The development of choroidal and posterior pericallosal anastomosis could be reliable preoperative predictors of TNEs after bypass surgery for MMD. Our results provide useful information for future studies aimed at clarifying the mechanisms underlying TNEs., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Intervention for severe aortic stenosis (AS) has dramatically progressed since the introduction of transcatheter aortic valve replacement (TAVR). Decades ago, controversies existed regarding comparing clinical outcomes between TAVR and surgical aortic valve replacement (SAVR) in various risk profiles. Recently, we discussed the durability of transcatheter heart valves and their lifetime management after aortic valve replacement (AVR). Regarding the management of AS, we discuss the appropriate timing of intervention for severe aortic stenosis, especially in asymptomatic patients. In spite of dramatic progression of intervention for AS, there are no established medications available to prevent or slow the progression of AS at present. Basic research and genome studies have suggested several targets associated with the progression of aortic valve calcification. Randomized controlled trials evaluating the efficacy of medications to prevent AS progression are ongoing, which might lead to new strategies for AS management. In this review, we summarize the current management of AS and the drugs expected to prevent the progression of AS.

Background: Incidence of ischemic stroke increased after natural disasters. Therefore, it is important to establish a means of identifying high-risk populations for incident stroke. We performed a prospective cohort study to examine whether these three cardiovascular disease-related miRNAs (miR-126, miR-197, and miR-223) are associated with incident stroke among elderly survivors of the Great East Japan Earthquake., Method: This cohort study was conducted using the data of 1192 survivors of the Great East Japan Earthquake over 60-years old who underwent a health check-up in December 2011. We followed up participants to record stroke cases until the end of 2016. We measured serum miRNAs by quantitative real-time polymerase chain reaction. HRs for incident stroke were estimated by Cox proportional hazard regression analyses., Result: The serum miR-197 level was significantly associated with the incident stroke; the HR per one standard deviation change in the miR-197 level was 1.65 (95% confidence interval: 1.19 - 2.30). In contrast, the levels of miR-126 and miR-223 were not associated with the incident stroke., Conclusion: We found that a higher miR-197 level is associated with an increased risk of incident stroke; thus, miR-197 is expected to be useful as a predictive biomarker.

Aims: This study aimed to evaluate the long-term results of Japan Maternal Emergency Life-Saving (J-MELS) simulation training on obstetric healthcare providers, over a 12-month follow-up period., Methods: A total of 273 trainees from 17 J-MELS Basic courses conducted between August 2021 and October 2023 were included. The trainees' responses to the pre- and post-tests, questionnaires, and self-reports on the usefulness of the J-MELS scenarios in actual clinical settings at 1, 6, and 12 months after the training were analyzed. Multivariate logistic regression analysis was also conducted to identify the factors influencing knowledge retention., Results: We found an overall improvement in clinical knowledge acquisition after J-MELS training and a significant retention of this improvement at least until 12 months later. However, these scores gradually declined over. Trainees reported increased usefulness of J-MELS scenarios in actual clinical practice at 1, 6, and 12 months after training, particularly in managing obstetric emergencies such as atonic postpartum hemorrhage. Knowledge retention was influenced by several specific factors, such as years of clinical experience, affiliated institutions, qualifications, and especially pre-test scores., Conclusion: Our longitudinal follow-up study demonstrated, for the first time, the long-term results of J-MELS simulation training using post-tests and self-report data. Our findings provide valuable insight into the impact of J-MELS simulation training on maternal emergency care. By elucidating the factors influencing knowledge retention and practical utility, the findings offer actionable recommendations for optimizing training strategies and improving maternal outcomes in actual clinical practice., (© 2024 Japan Society of Obstetrics and Gynecology.)

Cells regularly repair numerous mutations. However, the effect of CRISPR/Cas9-induced dsDNA breaks on the repair processes of naturally occurring genome-wide mutations is unclear. In this study, we used TSCE5 cells with the heterozygous thymidine kinase genotype (TK +/- ) to examine these effects. We strategically inserted the target sites for guide RNA (gRNA)/Cas9 and I-SceI into the functional allele and designed the experiment such that deletions of > 81 bp or base substitutions within exon five disrupted the TK gene, resulting in a TK -/- genotype. TSCE5 cells in the resting state exhibited 16 genome-wide mutations that affected cellular functions. After gRNA/Cas9 editing, these cells produced 859 mutations, including 67 high-impact variants that severely affected cellular functions under standard culture conditions. Mutation profile analysis indicated a significant accumulation of C to A substitutions, underscoring the widespread induction of characteristic mutations by gRNA/Cas9. In contrast, gRNA/Cas9-edited cells under conditions of S∼G2/M arrest and cyclin-dependent kinase 1 inhibition showed only five mutations. Transcriptomic analysis revealed the downregulation of DNA replication genes and upregulation of alternative DNA repair genes, such as zinc finger protein 384 (ZNF384) and dual specificity phosphatase, under S∼G2/M conditions. Additionally, activation of nucleotide and base excision repair gene, including O-6-methylguanine-DNA methyltransferase and xeroderma pigmentosum complementation group C, was observed. This study highlights the profound impact of CRISPR/Cas9 editing on genome-wide mutation processes and underscores the emergence of novel DNA repair pathways. Finally, our findings provide significant insights into the maintenance of genome integrity during genome editing., Competing Interests: Conflicts of interest The authors declare that they have no conflicts of interest with the contents of this article., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Anemia, a common comorbidity in older patients with heart failure (HF) and atrial fibrillation (AF), is associated with an increased risk of adverse events. This study evaluated the prognostic effects of longitudinal changes in anemia status on clinical outcomes in patients with AF., Methods and Results: We prospectively evaluated data of 1,388 patients with AF from the Hokuriku-Plus AF Registry (1,010 men; mean [±SD] age 72.3±9.7 years) and recorded the incidence of death, HF, thromboembolism, and major bleeding. Of these patients, the 1,233 for whom hemoglobin levels were available at baseline and at the 1-year follow-up were further evaluated. Patients were categorized into 3 groups based on longitudinal changes in 1-year anemia status: Group 1, AF without anemia; Group 2, AF with improved anemia; and Group 3, AF with sustained or new-onset anemia. Over the 1-5 years of follow up, the incidences of death, HF, thromboembolism, and major bleeding were significantly higher among patients with than without anemia. In addition, the incidence of death or HF was significantly higher in Group 3 than in Groups 1 and 2. Multivariate analysis revealed no anemia or improvement in anemia in 1 year as an independent predictor for a favorable prognosis for cardiovascular death and HF., Conclusions: Recovery from anemia may be associated with a favorable clinical course of AF.

Background: Although targeting atrial fibrillation (AF) drivers and substrates has been used as an effective adjunctive ablation strategy for patients with persistent AF (PsAF), it can result in iatrogenic scar-related atrial tachycardia (iAT) requiring additional ablation. Personalized atrial digital twins (DTs) have been used preprocedurally to devise ablation targeting that eliminate the fibrotic substrate arrhythmogenic propensity and could potentially be used to predict and prevent postablation iAT., Objectives: In this study, the authors sought to explore possible alternative configurations of ablation lesions that could prevent iAT occurrence with the use of biatrial DTs of prospectively enrolled PsAF patients., Methods: Biatrial DTs were generated from late gadolinium enhancement-magnetic resonance images of 37 consecutive PsAF patients, and the fibrotic substrate locations in the DT capable of sustaining reentries were determined. These locations were ablated in DTs by representing a single compound region of ablation with normal power (SSA), and postablation iAT occurrence was determined. At locations of iAT, ablation at the same DT target was repeated, but applying multiple lesions of reduced-strength (MRA) instead of SSA., Results: Eighty-three locations in the fibrotic substrates of 28 personalized biatrial DTs were capable of sustaining reentries and were thus targeted for SSA ablation. Of these ablations, 45 resulted in iAT. Repeating the ablation at these targets with MRA instead of SSA resulted in the prevention of iAT occurrence at 15 locations (18% reduction in the rate of iAT occurrence)., Conclusions: Personalized atrial DTs enable preprocedure prediction of iAT occurrence after ablation in the fibrotic substrate. It also suggests MRA could be a potential strategy for preventing postablation AT., Competing Interests: Funding Support and Author Disclosures This work was supported by funding from National Institutes of Health grants U01-HL141074 (Dr Trayanova), R01HL166759 (Drs Trayanova., Kholmovski, and Spragg), and R01HL142496 (Dr Trayanova). The authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2024 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Purpose: Non-functioning pituitary adenomas (NFPAs) are often associated with hyperprolactinemia, which is known as the "stalk effect". However, the relationships between hyperprolactinemia and the radiographic characteristics of the tumor that affects the pituitary stalk have not been well characterized. We aimed to identify the differences in the clinical and radiographic characteristics of patients with NFPA, with and without hyperprolactinemia., Methods: We enrolled 107 patients with NFPA and allocated them to hyperprolactinemia and non-hyperprolactinemia groups using two different cut-off values: (1) the upper limit of the normal reference range, adjusted for sex and menopausal status, and (2) the upper quartile across the cohort, and compared their clinical and radiographic characteristics. These analyses were conducted to clarify the relationship between the "stalk effect" and the postoperative change in antidiuretic hormone secretion., Results: The specific radiographic characteristics of the patients included the presence of a cystic or hemorrhagic tumor and the presence of pituitary stalk deviation, which were more frequent in the patients with hyperprolactinemia. Interestingly, the incidence of postoperative transient diabetes insipidus was statistically significantly higher in the hyperprolactinemia group (≥40 ng/mL) and in the group with radiologic evidence of stalk deviation, which were shown to be independent risk factors on multivariate analysis., Conclusion: The presence of a "stalk effect" was associated with a higher risk of postoperative transient diabetes insipidus, reflecting perioperative pituitary stalk dysfunction following NFPA surgery, especially in patients with serum prolactin concentrations ≥40 ng/mL and radiologic evidence of stalk deviation., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

With the rapid growth of inland aquaculture worldwide, side effects such as the discharge of nutrients and antibiotics pose a threat to the global environments. A sustainable future for aquaculture requires an effective management system, including the early detection of disease through the monitoring of specific biomarkers in aquaculture tanks. To this end, we investigated whether fish feces in aquaculture tanks could be used for non-invasive health monitoring using ayu ( Plecoglossus altivelis ) infected with Flavobacterium psychrophilum , which causes bacterial cold-water disease worldwide. Feces that were subsequently produced in the tanks were used for metagenomic and metabolomic analyses. The relative abundances of the genera Cypionkella (0.6% ± 1.0%, 0.1% ± 0.2%), Klebsiella (11.2% ± 10.0%, 6.2% ± 5.9%), and F. psychrophilum (0.5% ± 1.0%, 0.0% ± 0.0%) were significantly higher in the feces of the infection challenge test tanks than in those of the control tanks. The abundances of cortisol, glucose, and acetate in the feces of the infection challenge test tanks were 2.4, 2.4, and 1.3 times higher, respectively, than those of the control tanks. Metagenome analysis suggested that acetate was produced by microbes such as Cypionkella . The abundances of indicated microbes or metabolites increased after day 4 of infection at the earliest, and were thus considered possible biomarkers. Our results suggest that feces produced in aquaculture tanks can potentially be used for non-invasive and holistic monitoring of fish diseases in aquaculture systems., Importance: The aquaculture industry is rapidly growing, yet sustainability remains a challenge. One crucial task is to reduce losses due to diseases. Monitoring fish health and detecting diseases early are key to establishing sustainable aquaculture. Using metagenomic and metabolomic analyses, we found that feces of ayu infected with Flavobacterium psychrophilum contain various specific biomarkers that increased 4 days post-challenge, at the earliest. Our findings are the first step in establishing a novel, non-invasive, and holistic monitoring method for fish diseases in aquaculture systems, especially in ayu, which is an important freshwater fish species in Asia, promoting a sustainable future., Competing Interests: The authors declare no conflict of interest.

Aquaculture contributes to the sustainable development of food security, marine resource conservation, and economy. Shifting aquaculture feed from fish meal and oil to terrestrial plant derivatives may result in cost savings. However, many carnivorous fish cannot be sustained on plant-derived materials, necessitating the need for the identification of important factors for farmed fish growth and the identification of whether components derived from terrestrial plants can be used in feed. Herein, we focused on the carnivorous fish leopard coral grouper ( P. leopardus ) to identify the essential growth factors and clarify their intake timing from feeds. Furthermore, we evaluated the functionality of starch, which are easily produced by terrestrial plants. Results reveal that carbohydrates, which are not considered essential for carnivorous fish, can be introduced as a major part of an artificial diet. The development of artificial feed using starch offers the possibility of increasing the growth of carnivorous fish in aquaculture.

The immunoproteasome subunit LMP7 (β5i)/LMP2 (β1i) dual blockade has been reported to suppress B cell differentiation and activation, suggesting that the dual inhibition of LMP7/LMP2 is a promising approach for treating autoimmune diseases. In contrast, the inhibition of the constitutive proteasome subunit β5c correlates with cytotoxicity against non-immune cells. Therefore, LMP7/LMP2 dual inhibitors with high selectivity over β5c may be desirable for treating autoimmune diseases. In this study, we present the optimization and discovery of α-amido boronic acids using cryo-electron microscopy (cryo-EM). The exploitation of structural differences between the proteasome subunits led to the identification of a highly selective LMP7/LMP2 dual inhibitor 19. Molecular dynamics simulation based on cryo-EM structures of the proteasome subunits complexed with 19 explained the inhibitory activity profile. In mice immunized with 4-hydroxy-3-nitrophenylacetyl conjugated to ovalbumin, results indicate that 19 is orally bioavailable and shows promise as potential treatment for autoimmune diseases., Competing Interests: Declaration of competing interest 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., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Objective To determine whether nutritional status is related to the incidence of thrombosis and mortality in patients with Coronavirus disease 2019 (COVID-19). Methods A total of 496 consecutive patients who were admitted and diagnosed with COVID-19 between April 2020 and March 2023 were retrospectively analyzed. The geriatric nutritional risk index (GNRI) on admission was calculated as follows: 14.89×serum albumin (g/dL) +41.7×body mass index/22. Patients were divided into two groups according to the median GNRI values. The endpoint of this study was a composite of in-hospital thrombotic events and mortality. Results The median GNRI value was 99.3. Patients in the low GNRI (≤99.3) group were older (75±21 vs. 51±20 years, p<0.001) and more likely to be female (55.6% vs. 41.1%, p<0.05). In addition, patients with a low GNRI often exhibited hypertension (43.5% vs. 28.2%, p<0.001) and had a history of cardiovascular disease (34.3% vs. 14.5%, p<0.001). Under these conditions, the median D-dimer levels on admission were significantly higher in patients with a low GNRI (0.90 μg/mL; IQR, 0.49-1.64 μg/mL) than those with high GNRI (0.36 μg/mL; IQR, 0.26-0.51 μg/mL, p<0.001). During hospitalization, the composite endpoint was observed in 32 patients. In the logistic regression analysis, a low GNRI was significantly associated with the composite endpoint adjusted using inverse probability of treatment weighting (odds ratio, 3.24; 95% confidence interval: 1.51-6.93, p<0.05). Conclusion Assessment of the GNRI provides useful information for predicting in-hospital thrombosis and mortality in COVID-19 patients.

Background: The 2022 Japan Atherosclerosis Society familial hypercholesterolemia (FH) clinical criteria were modified. In particular, the cutoff value of Achilles tendon thickness (ATT) on radiography was changed from ≥9 mm in both sexes to ≥8.0 mm in men and ≥7.5 mm in women., Methods: A total of 872 patients with FH were retrospectively reviewed. Patients were categorized by an ATT of <7.5/8.0 mm (group 1), ≥7.5/8.0 and <9.0 mm (group 2, new group with FH by ATT), and ≥9 mm (group 3)., Results: In total, 492 patients fell into in group 1, 102 in group 2, and 263 in group 3, and 14.0%, 55.9%, and 79.8% of patients in groups 1, 2, and 3, respectively, were positive for a FH mutation. Further, among patients with an LDL cholesterol >180 mg/dL, 37.3%, 77.3%, and 86.5% of patients had a FH mutation in groups 1, 2, and 3, respectively. The proportion of patients with protein-truncating mutation (3.8%, 16.7%, and 53.2%, respectively) differed significantly across groups 1 through 3, respectively. Interestingly, only a very small proportion of the patients in groups 2 and 3 had palpable xanthomas (3.0% and 14.4% respectively)., Conclusions: This study validates the new radiographic ATT criteria, since the vast majority of patients in the intermediate ATT category had true FH, as shown by positive genetic testing, whereas the old ATT criteria left them with just a deferred diagnosis of FH. In addition, use of physical examination alone for the presence of tendon xanthoma may lead to underdiagnosis of FH., (Copyright © 2024. Published by Elsevier Inc.)

We report a simple and atom-efficient method for the synthesis of bithiophene-fused isoquinolines by iridium-catalyzed [2 + 2 + 2] cycloaddition of bithiophene-linked diynes with nitriles. All three structural isomers of bithiophene-linked diynes underwent [2 + 2 + 2] cycloaddition, and the trend in the reactivity for cycloaddition was diyne 1 = diyne 3 > diyne 2 . Dibenzothiophene-linked diyne also reacted with nitriles to form a variety of cycloadducts. Cycloaddition of bithiophene-linked diynes with alkynes and an isocyanate formed naphthodithiophenes and a 2-pyridone derivative, respectively. Cycloadducts bearing a 2-aminopyridine moiety and benzothiophene rings showed intense fluorescence at around 530 nm and gave a fluorescence quantum yield of 0.44. Furthermore, quantum chemical calculations provided insight into the origin of the difference in reactivity of three bithiophene-linked diynes. The different reactivities of the three diynes 1-3 are believed to originate from the step where an iridacyclopentadiene reacts with a coordinated nitrile to form azairidabicyclo[3.2.0]heptatriene. HOMOs of iridacyclopentadiene play a decisive role in this step.

Atrial fibrillation (AF), the most common heart rhythm disorder, may cause stroke and heart failure. For patients with persistent AF with fibrosis proliferation, the standard AF treatment-pulmonary vein isolation-has poor outcomes, necessitating redo procedures, owing to insufficient understanding of what constitutes good targets in fibrotic substrates. Here we present a prospective clinical and personalized digital twin study that characterizes the arrhythmogenic properties of persistent AF substrates and uncovers locations possessing rotor-attracting capabilities. Among these, a portion needs to be ablated to render the substrate not inducible for rotors, but the rest (37%) lose rotor-attracting capabilities when another location is ablated. Leveraging digital twin mechanistic insights, we suggest ablation targets that eliminate arrhythmia propensity with minimum lesions while also minimizing the risk of iatrogenic tachycardia and AF recurrence. Our findings provide further evidence regarding the appropriate substrate ablation targets in persistent AF, opening the door for effective strategies to mitigate patients' AF burden.