Effect of a 3-Month Single-Drug Approach Using Rivaroxaban for Symptomatic Proximal Deep Vein Thrombosis.

Background: Factor Xa inhibitors, such as rivaroxaban, are increasing the convenience of treatment for deep vein thrombosis (DVT). Limited evidence exists regarding clot evaluation at 3 months after treatment for DVT. Methods and Results: We retrospectively analyzed the clinical course of symptomatic proximal DVT in patients who received 3 months of anticoagulation treatment at our hospital. Patients treated with the rivaroxaban single-drug approach were classified as group A (n=42). Patients treated with unfractionated heparin (UFH) or subcutaneous fondaparinux followed by vitamin K antagonist comprised group B (n=60) as an historical cohort. The quantitative ultrasound thrombosis (QUT) score was used to quantify clot burden before and after treatment. No significant differences were observed in patient characteristics between the groups. Serum D-dimer levels in both groups significantly improved after treatment. Clot volume assessed using QUT also reduced significantly in both groups. The QUT score in groups A and B improved from 7.5 [4.8, 12.0] to 3.0 [1.8, 5.0; P=0.000] and 7.0 [4.0, 9.8] to 3.0 [2.0, 5.0; P=0.000], respectively. The change in QUT (∆QUT) was significantly greater in group A compared with group B (-4.5 [-8.25, -2.0] vs. -2.0 [-6.0, 0.0]; P=0.005). Conclusions: We were able to demonstrate the effectiveness of DVT treatment using rivaroxaban over a period of 3 months from onset, in terms of clot regression evaluated using the QUT score.

Intraspecific divergence in a coastal plant, Euphorbia jolkinii, at a major biogeographic boundary in East Asia.

PREMISE: Quaternary climatic fluctuations and long-distance seed dispersal across the sea are critical factors affecting the distribution of coastal plants, but the spatiotemporal nature of population expansion and distribution change of East Asian coastal plants during this period are rarely examined. To explore this process, we investigated the genome-wide phylogenetic patterns of Euphorbia jolkinii Boiss. (Euphorbiaceae), which grows widely on littoral areas of Japan, Korea, and Taiwan. METHODS: We used plastome sequences and genome-wide single nucleotide polymorphisms in samples across the species range to reveal phylogeographic patterns and spatiotemporal distributional changes. We conducted ecological niche modeling for the present and the last glacial maximum (LGM). RESULTS: Genetic differentiation was observed between the northern and southern populations of E. jolkinii, separated by the major biogeographic boundary, the Tokara Gap. These two groups of populations differentiated during the glacial period and subsequently intermingled in the intermorainic areas of the central Ryukyu Islands after the LGM. Ecological niche models suggested that the potential range of E. jolkinii was restricted to southern Kyushu; however, it was widespread in the southern Ryukyu Islands and Taiwan during the LGM. CONCLUSIONS: This study provides evidence of genetic differentiation among coastal plant populations separated by the prominent biogeographical boundary. Although coastal plants are typically expected to maintain population connectivity through sea-drifted seed dispersal, our findings suggest that genetic differences may arise because of a combination of limited gene flow and changes in climate during the glacial period.

Salvia guidongensis sp. nov.: unraveling a critical evolutionary link in East Asian Salvia from Central China integrating morphology, phylogeny, and plastid genomics.

Introduction: Salvia L., representing the largest genus within the mint family, is noted for its global distribution of approximately 1000 species, with East Asia, and particularly China, recognized as a critical center of diversity for the genus. Methods: Our research was conducted through extensive fieldwork in Guidong County, Hunan Province, China, where we identified a previously undescribed species of Salvia. The identification process involved detailed morphological observations, phylogenetic analyses, and plastid genomics. Results: The newly discovered species, Salvia guidongensis, exhibits unique characteristics not commonly observed in the East Asian lineage of Salvia, including dual floral colors within natural populations-either pale purple or pale yellow. Morphologically, while it shares similarities with members of sect. Glutinaria, S. guidongensis is distinct in its floral morphology, stature, and specific foliar traits. Phylogenetic analysis places S. guidongensis in a unique clade within the East Asian lineage of Salvia, suggesting it may serve as an important evolutionary link. Additionally, we explored the plastome features of S. guidongensis, comparing them with those of closely related species. Discussion: The discovery of S. guidongensis not only entriches the taxonomic tapestry of Salvia but also provides critical insights into the biogeography and evolutionary pathways of the genus in East Asia. By integrating morphological and molecular data, we validate the novel status of S. guidongensis and highlight its significance in bridging taxonomic and evolutionary gaps within Sect. Glutinaria of Salvia.

Corrigendum: Effect of balloon pulmonary angioplasty on cardio-ankle vascular index and biventricular remodeling in patients with chronic thromboembolic pulmonary hypertension.

[This corrects the article DOI: 10.3389/fcvm.2023.1325846.].

Double migration of the endangered Tricyrtis formosana (Liliaceae) in Japan.

The Ryukyu Islands of Japan are a biodiversity hotspot due to geographical and historical factors. Tricyrtis formosana is a perennial herbaceous plant that commonly found in Taiwan. But only a few populations have been identified in a limited habitat on Iriomote Island, while populations of unknown origin occur near human settlements in an area on the main island of Okinawa. To better understand these populations of the phylogenetic uniqueness and intrinsic vulnerability, we conducted comparative analyses including (1) phylogeny and population structure with MIG-seq data, (2) photosynthesis-related traits of plants grown under common conditions and (3) transcriptome analysis to detect deleterious variations. Results revealed that T. formosana was split into two clades by the congeners and that Iriomote and Okinawa populations independently derived from ancestral Taiwanese populations in each clade. Photosynthetic efficiency was lowest in the Iriomote population, followed by Okinawa and Taiwan. Transcriptome analysis showed that the Iriomote population accumulated more deleterious variations, suggesting intrinsic vulnerability. These results indicate that each T. formosana population in Japan is phylogenetically unique and has been independently dispersed from Taiwan, and that the Iriomote population presents a high conservation difficulty with a unique photosynthesis-related characteristic and a larger amount of deleterious variations.

Resurgence of human metapneumovirus infection and influenza after three seasons of inactivity in the post-COVID-19 era in Hokkaido, Japan, 2022-2023.

Following the coronavirus disease 2019 (COVID-19) outbreak in February 2020, incidences of various infectious diseases decreased notably in Hokkaido Prefecture, Japan. However, Japan began gradually easing COVID-19 infection control measures in 2022. Here, we conducted a survey of children hospitalized with human metapneumovirus (hMPV), influenza A and B, and respiratory syncytial virus infections in 18 hospitals across Hokkaido Prefecture, Japan, spanning from July 2019 to June 2023. From March 2020 to June 2022 (28 months), only 13 patients were hospitalized with hMPV, and two patients had influenza A. However, in October to November 2022, there was a re-emergence of hMPV infections, with a maximum of 27 hospitalizations per week. From July 2022 to June 2023 (12 months), the number of hMPV-related hospitalizations dramatically increased to 317 patients, with the majority aged 3-6 years (38.2%, [121/317]). Influenza A also showed an increase from December 2022, with a peak of 13 hospitalizations per week in March 2023, considerably fewer than the pre-COVID-19 outbreak in December 2019, when rates reached 45 hospitalizations per week. These findings suggest the possibility of observing more resurgences in infectious diseases in Japan after 2023 if infection control measures continue to be relaxed. Caution is needed in managing potential outbreaks.

Effect of balloon pulmonary angioplasty on cardio-ankle vascular index and biventricular remodeling in patients with chronic thromboembolic pulmonary hypertension.

Background: Chronic thromboembolic pulmonary hypertension (CTEPH) is caused by organized pulmonary thrombi, and pulmonary endarterectomy is the only curative treatment. Since balloon pulmonary angioplasty (BPA) has become an established therapeutic option for inoperable CTEPH, prognosis has improved. Recent reports suggest that arterial stiffness evaluated using the cardio-ankle vascular index (CAVI) may play an important role in the cardio-vascular interaction in CTEPH; however, the details remain unclear. This study aimed to clarify the role of CAVI in CTEPH through hemodynamic changes and ventricular remodeling after BPA. Methods and results: A total of 23 patients with CTEPH who had undergone BPA were enrolled in this study. The mean pulmonary artery pressure (mPAP) and CAVI significantly decreased after BPA [mPAP, 34 (26-45) mmHg to 20 (19-24) mmHg, p < 0.0001; CAVI, 9.4 (8.0-10.3) to 8.3 (7.5-9.6), p = 0.004]. The echocardiographic right ventricle was significantly decreased, and the left ventricular volume was significantly increased after BPA, indicating significant biventricular remodeling after BPA. Changes in CAVI (ΔCAVI) significantly correlated with changes in mPAP (r = 0.45, p = 0.03). Additionally, ΔCAVI was significantly correlated with changes in both right ventricular area and left ventricular volume. Conclusions: Arterial stiffness, evaluated using the CAVI, improved after BPA. Changes in CAVI were significantly correlated with changes in pulmonary arterial pressure and biventricular remodeling. CAVI may play an important role in cardiovascular interactions in patients with CTEPH.

Development and characterization of expressed sequence tag-simple sequence repeat markers for Anaphalis margaritacea var. yedoensis (Asteraceae).

RNA-sequencing was used to develop 16 microsatellite markers for the pearly everlasting, Anaphalis margaritacea var. yedoensis (Franch. et Sav.) Ohwi (Asteraceae), which inhabits gravel bars throughout the Japanese archipelago. The mean number of alleles for these 16 markers in two populations in the Hokkaido and Shizuoka Prefectures, was 3.5 and 4.0, respectively, while the mean expected heterozygosity was 0.525 and 0.560, respectively, with a significant genetic differentiation between the two populations. All markers could also be amplified in two conspecific taxa, A. margaritacea var. margaritacea and var. angustifolia, whereas 11 of the 16 markers were amplifiable in two congeneric species, A. sinica and A. alpicola. These newly developed microsatellite markers will support understanding of population genetics and mating systems in A. margaritacea var. yedoensis, and several will potentially be of use in similar studies in other Anaphalis species.

Changing Patterns of Infectious Diseases Among Hospitalized Children in Hokkaido, Japan, in the Post-COVID-19 Era, July 2019 to June 2022.

BACKGROUND: Many reports have reported a reduction in respiratory infectious diseases and infectious gastroenteritis immediately after the coronavirus disease 2019 (COVID-19) pandemic, but data continuing into 2022 are very limited. We sought to understand the current situation of various infectious diseases among children in Japan as of July 2022 to improve public health in the post-COVID-19 era. METHODS: We collected data on children hospitalized with infectious diseases in 18 hospitals in Japan from July 2019 to June 2022. RESULTS: In total, 3417 patients were hospitalized during the study period. Respiratory syncytial virus decreased drastically after COVID-19 spread in early 2020, and few patients were hospitalized for it from April 2020 to March 2021. However, an unexpected out-of-season re-emergence of respiratory syncytial virus was observed in August 2021 (50 patients per week), particularly prominent among older children 3-6 years old. A large epidemic of delayed norovirus gastroenteritis was observed in April 2021, suggesting that the nonpharmaceutical interventions for COVID-19 are less effective against norovirus. However, influenza, human metapneumovirus, Mycoplasma pneumoniae , and rotavirus gastroenteritis were rarely seen for more than 2 years. CONCLUSIONS: The incidence patterns of various infectious diseases in Japan have changed markedly since the beginning of the COVID-19 pandemic to the present. The epidemic pattern in the post-COVID-19 era is unpredictable and will require continued careful surveillance.

Plastome-based backbone phylogeny of East Asian Phedimus (Subgenus Aizoon: Crassulaceae), with special emphasis on Korean endemics.

Although the monophyly of Phedimus has been strongly demonstrated, the species relationships among approximately 20 species of Phedimus have been difficult to determine because of the uniformity of their floral characteristics and extreme variation of their vegetative characters, often accompanied by high polyploid and aneuploid series and diverse habitats. In this study, we assembled 15 complete chloroplast genomes of Phedimus species from East Asia and generated a plastome-based backbone phylogeny of the subgenus Aizoon. As a proxy for nuclear phylogeny, we reconstructed the nuclear ribosomal DNA internal transcribed spacer (nrDNA ITS) phylogeny independently. The 15 plastomes of subg. Aizoon were highly conserved in structure and organization; hence, the complete plastome phylogeny fully resolved the species relationships with strong support. We found that P. aizoon and P. kamtschaticus were polyphyletic and morphologically distinct or ambiguous species, and they most likely evolved from the two species complex. The crown age of subg. Aizoon was estimated to be 27 Ma, suggesting its origin to be in the late Oligocene; however, the major lineages were diversified during the Miocene. The two Korean endemics, P. takesimensis and P. zokuriensis, were inferred to have originated recently during the Pleistocene, whereas the other endemic, P. latiovalifolium, originated in the late Miocene. Several mutation hotspots and seven positively selected chloroplast genes were identified in the subg. Aizoon.

Urothelial Carcinoma With Pulmonary Tumor Thrombotic Microangiopathy After Chemotherapy for Hodgkin Lymphoma.

Treatment-related second malignancies (SMs) remain a major concern in long-term survivors of Hodgkin lymphoma (HL). In this report, the autopsy findings of a patient with HL, who was in complete remission after chemotherapy but expired of pulmonary tumor thrombotic microangiopathy (PTTM) caused by urothelial carcinoma of the renal pelvis (UCRP), were described. A 78-year-old Japanese man with a history of classical HL developed irreversible heart failure about 2.5 years after chemotherapy. The patient expired shortly after being admitted due to ineffective treatment for heart failure. However, the cause of death was not determined. The patient's autopsy findings revealed UCRP in the left kidney, as well as infiltration around the inferior vena cava and lungs, but no HL recurrence. The primary causes of mortality were respiratory and heart failure due to PTTM. Therefore, it is essential to consider the risk of SMs and search for them in patients with HL after chemotherapy.

The complete chloroplast genome sequence of Thalictrum aquilegiifolium var. sibiricum (Ranunculaceae).

Thalictrum aquilegiifolium (Ranunculaceae) is widely distributed in the Eurasian Continent and Japan and comprises some intraspecific taxa. We report here the complete chloroplast genome of T. aquilegiifolium var. sibiricum. The plastome of T. aquilegiifolium var. sibiricum is 156,074 bp in length, containing large (85,457 bp) and small (17,642 bp) single-copy regions which are separated by a pair of inverted repeats (26,487 bp each). The genome consists of 119 genes, including 88 protein-coding, four ribosomal RNA genes, and 27 transfer RNA genes. Our phylogenetic analysis revealed that Thalictrum species formed a highly supported clade, indicating that these species are monophyletic.

The complete chloroplast genome of a coastal plant, Euphorbia jolkinii (Euphorbiaceae).

The complete chloroplast genome sequence of a coastal plant, Euphorbia jolkinii Boiss. (Euphorbiaceae), was determined. The chloroplast genome was 162,854 bp in length, consisting of a large single copy region (90,726 bp), a small single copy region (18,422 bp), and two inverted repeats (26,853 bp). The chloroplast genome contained 115 genes, consisting of 80 unique protein-coding genes, 30 unique tRNA genes, four unique rRNA genes, and one pseudogene, rps16. GC content of the whole chloroplast genome was 35.6%. The phylogenetic analysis showed a close relationship between E. jolkinii and E. pekinensis Rupr. The sequence data would provide useful information to understand the evolutionary process of E. jolkinii.

The complete chloroplast genome sequence of Anaphalis margaritacea var. yedoensis (Asteraceae) and phylogenetic relationships within Gnaphalieae.

Anaphalis margaritacea var. yedoensis is a perennial herb adapted to the severe environment of pebbled river banks, where it is frequently found. In this study, we determined the complete chloroplast genome of A. margaritacea var. yedoensis and uncovered its phylogenetic relationships with other members of Gnaphalieae. The total chloroplast genome size of A. margaritaceae var. yedoensis is 153,231 bp, with a large single-copy region (LSC) of 84,981 bp, a small single-copy region (SSC) of 18,481 bp and a pair of inverted repeat (IR) regions of 24,885 bp. A total of 136 genes were annotated, including 39 tRNA genes, 8 rRNA genes, and 89 protein-coding genes. Phylogenetic analysis showed that A. margaritacea var. yedoensis and another Anaphalis species, A. sinica, do not form a monophyletic group, supporting previous phylogenetic studies using some specific regions of cpDNA that showed the genus Anaphalis is non-monophyletic.

Sp7 Transgenic Mice with a Markedly Impaired Lacunocanalicular Network Induced Sost and Reduced Bone Mass by Unloading.

The relationship of lacunocanalicular network structure and mechanoresponse has not been well studied. The lacunocanalicular structures differed in the compression and tension sides, in the regions, and in genders in wild-type femoral cortical bone. The overexpression of Sp7 in osteoblasts resulted in thin and porous cortical bone with increased osteoclasts and apoptotic osteocytes, and the number of canaliculi was half of that in the wild-type mice, leading to a markedly impaired lacunocanalicular network. To investigate the response to unloading, we performed tail suspension. Unloading reduced trabecular and cortical bone in the Sp7 transgenic mice due to reduced bone formation. Sost-positive osteocytes increased by unloading on the compression side, but not on the tension side of cortical bone in the wild-type femurs. However, these differential responses were lost in the Sp7 transgenic femurs. Serum Sost increased in the Sp7 transgenic mice, but not in the wild-type mice. Unloading reduced the Col1a1 and Bglap/Bglap2 expression in the Sp7 transgenic mice but not the wild-type mice. Thus, Sp7 transgenic mice with the impaired lacunocanalicular network induced Sost expression by unloading but lost the differential regulation in the compression and tension sides, and the mice failed to restore bone formation during unloading, implicating the relationship of lacunocanalicular network structure and the regulation of bone formation in mechanoresponse.

Plastome phylogenomics of Allaeanthus, Broussonetia and Malaisia (Dorstenieae, Moraceae) and the origin of B. × kazinoki.

Species of Broussonetia have been essential in the development of papermaking technology. In Japan and Korea, a hybrid between B. monoica and B. papyrifera (= B. × kazinoki) known as kozo and daknamu is still the major source of raw materials for making traditional paper washi and hanji, respectively. Despite their cultural and practical significance, however, the origin and taxonomy of kozo and daknamu remain controversial. Additionally, the long-held generic concept of Broussonetia s.l., which included Sect. Allaeanthus and Sect. Broussonetia, was challenged as phylogenetic analyses showed Malaisia is sister to the latter section. To re-examine the taxonomic proposition that recognizes Allaeanthus, Broussonetia, and Malaisia (i.e., Broussonetia alliance), plastome and nuclear ribosomal DNA (nrDNA) sequences of six species of the alliance were assembled. Characterized by the canonical quadripartite structure, genome alignments and contents of the six plastomes (160,121-162,594 bp) are highly conserved, except for the pseudogenization and/or loss of the rpl22 gene. Relationships of the Broussonetia alliance are identical between plastome and nrDNA trees, supporting the maintenance of Malaisia and the resurrection of Allaeanthus. The phylogenomic relationships also indicate that the monoecy in B. monoica is a derived state, possibly resulting from hybridization between the dioecious B. kaempferi (♀) and B. papyrifera (♂). Based on the hypervariable ndhF-rpl32 intergenic spacer selected by sliding window analysis, phylogeographic analysis indicates that B. monoica is the sole maternal parent of B. × kazinoki and that daknamu carries multiple haplotypes, while only one haplotype was detected in kozo. Because hybridizations between B. monoica and B. papyrifera are unidirectional and have occurred rarely in nature, our data suggest that daknamu might have originated via deliberate hybrid breeding selected for making hanji in Korea. On the contrary, kozo appears to have a single origin and the possibility of a Korean origin cannot be ruled out.

Neonatal suppurative parotitis: Case reports and literature review.

BACKGROUND: Neonatal suppurative parotitis is a rare disease, characterized mainly by unilateral parotid swelling with erythema and tenderness, and often purulent discharge from the Stensen's duct into the oral cavity. Only 44 cases were reported in the English literature between 1970 and 2013. METHODS: A MEDLINE search was conducted using the terms acute, neonatal, newborn, suppurative, bacterial, purulent, parotitis, parotid swelling, and parotid abscess, limited to the English-language literature starting from 2011. We reviewed all reported cases, together with two more managed cases in our hospital. We also describe the magnetic resonance imaging findings of the early stage of this disease. RESULTS: We identified 26 new cases since 2011. The total number of patients reviewed was 72, including our patients. The infection was unilateral in 83% of patients, and 67% of the affected patients were males. The serum amylase levels were generally not elevated despite marked parotid swelling. Of the causative agents of this disease, 65% were Staphylococcus aureus, of which 19% were methicillin-resistant S. aureus. As the rate of cesarean section was high in patients with this disease, it was considered a risk factor. The diffusion-weighted magnetic resonance images showed multiple punctate hyperintensity regions with reduced apparent diffusion coefficient, suggesting microabscess formation in the affected gland. CONCLUSIONS: Acute suppurative parotitis should be considered in cases of swelling and tenderness in the parotid gland during the neonatal period. Multiple punctate hyperintensities in the parotid gland on the diffusion-weighted images may indicate a retrograde bacterial infection from the Stensen's duct.

Probing the Biogenesis of Polysaccharide Granules in Algal Cells at Sub-Organellar Resolution via Raman Microscopy with Stable Isotope Labeling.

Phototrophs assimilate CO2 into organic compounds that accumulate in storage organelles. Elucidation of the carbon dynamics of storage organelles could enhance the production efficiency of valuable compounds and facilitate the screening of strains with high photosynthetic activity. To comprehensively elucidate the carbon dynamics of these organelles, the intraorganellar distribution of the carbon atoms that accumulate at specific time periods should be probed. In this study, the biosynthesis of polysaccharides in storage organelles was spatiotemporally probed via stimulated Raman scattering (SRS) microscopy using a stable isotope (13C) as the tracking probe. Paramylon granules (a storage organelle of ß-1,3-glucan) accumulated in a unicellular photosynthetic alga, Euglena gracilis, were investigated as a model organelle. The carbon source of the culture medium was switched from NaH12CO3 to NaH13CO3 during the production of the paramylon granules; this resulted in the distribution of the 12C and 13C constituents in the granules, so that the biosynthetic process could be tracked. Taking advantage of high-resolution SRS imaging and label switching, the localization of the 12C and 13C constituents inside a single paramylon granule could be visualized in three dimensions, thus revealing the growth process of paramylon granules. We propose that this method can be used for comprehensive elucidation of the dynamic activities of storage organelles.

Increased Arterial Stiffness in Chronic Thromboembolic Pulmonary Hypertension Was Improved with Riociguat and Balloon Pulmonary Angioplasty: A Case Report.

BACKGROUND: The role of arterial stiffness in the pathophysiology of chronic thromboembolic pulmonary hypertension (CTEPH) is unclear. The cardio-ankle vascular index (CAVI) is a novel arterial stiffness index reflecting stiffness of the arterial tree from the origin of the aorta to the ankle, independent from blood pressure at the time of measurement. CAVI reflects functional stiffness, due to smooth muscle cell contraction or relaxation, and organic stiffness, due to atherosclerosis. Here, we report the case of a patient with an increased CAVI due to CTEPH and the improvement after riociguat administration and balloon pulmonary angioplasty (BPA). CASE PRESENTATION: A 65-year-old man suffered from dyspnea on exertion, and he was diagnosed with distal CTEPH. The mean pulmonary artery pressure (mPAP) was 51 mmHg, and the initial CAVI was 10.0, which is high for patient's age. In addition to right ventricular dysfunction, left ventricular dysfunction was observed as reduced global longitudinal strain (GLS-LV). After riociguat administration, CAVI decreased to 9.1 and GLS-LV improved from -10.3% to -17.3%, although pulmonary hypertension remained (mPAP 41 mmHg). Subsequently, a total of five BPA sessions were performed. Six months after the final BPA, mPAP decreased to 19 mmHg and GLS-LV improved to 19.3%. The patient was symptom free and his 6-minute walk distance improved from 322 m to 510 m. CAVI markedly decreased to 5.8, which is extremely low for his age. CONCLUSION: These observations suggested that arterial stiffness as measured by CAVI was increased in CTEPH, potentially deteriorating cardiac function because of enhanced afterload. The mechanism of the increase of CAVI in this case of CTEPH was obscure; however, riociguat administration and BPA might improve the pathophysiology of CTEPH partly by decreasing CAVI.