Combined Dataset Research Articles

Population Pharmacokinetics and Dosing Simulations for Aripiprazole 2-Month Ready-to-Use Long-Acting Injectable in Adult Patients With Schizophrenia or Bipolar I Disorder.

A ready-to-use (RTU) long-acting injectable (LAI) formulation of aripiprazole monohydrate for administration once every 2 months, available in 960 mg (Ari 2MRTU 960) or 720 mg doses, has been developed for the treatment of schizophrenia or bipolar I disorder. A previously developed and validated population pharmacokinetic model for characterizing aripiprazole plasma concentrations following administration of oral aripiprazole or aripiprazole once-monthly (AOM) intramuscular injection was expanded to include the RTU LAI formulation of aripiprazole (Ari RTU LAI). Overall, 8899aripiprazole pharmacokinetic samples from 1191 adults from 10 clinical trials were included in the final combined analysis data set. Aripiprazole plasma concentration-time profiles were simulated for various Ari RTU LAI initiation and maintenance scenarios in 1000 virtual patients. Diagnostic plots demonstrated that the final population pharmacokinetic model, which incorporated data for oral aripiprazole, AOM, and Ari RTU LAI, adequately described aripiprazole concentrations following Ari RTU LAI administration. Absorption of Ari RTU LAI was modeled by a parallel zero-order and lagged first-order process. Simulations across multiple scenarios were performed to inform dosing recommendations, including various treatment initiation regimens for a 2-monthly formulation of Ari RTU LAI in patients with or without prior stabilization on oral aripiprazole, and for patients switching from AOM. Additional simulations accounted for missed/delayed doses, cytochrome (CYP) 2D6 metabolizer status, and concomitant use of CYP2D6 or CYP3A4 inhibitors. Overall, simulations across a variety of scenarios demonstrated an Ari RTU LAI pharmacokinetic exposure profile that was comparable to AOM, with a longer dosing interval.

It is a "small world": Relations between performance on five spatial tasks and five mathematical tasks in undergraduate students.

One of the most robust relations in cognition is that between spatial and mathematical reasoning. One important question is whether this relation is domain general or if specific relations exist between performance on different types of spatial tasks and performance on different types of mathematical tasks. In this study, we explore unique relations between performance on five spatial tasks and five mathematical tasks. An exploratory factor analysis conducted on Data Set 1 (N = 391) yielded a two-factor model, one spatial factor and one mathematical factor with significant cross-domain factor loadings. The general two-factor model structure was replicated in a confirmatory factor analysis conducted in a separate data set (N = 364) but the strength of the factor loadings differed by task. Multidimensional scaling and network-based analyses conducted on the combined data sets reveal one spatial cluster, with a central node and one more tightly interconnected mathematical cluster. Both clusters were interconnected via the math task assessing geometry and spatial sense. The unique links identified with the network-based analysis are representative of a "small-world network." These results have theoretical implications for our understanding of the spatial-mathematical relation and practical implications for our understanding of the limitations of transfer between spatial training paradigms and mathematical tasks. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

First Report of Powdery Mildew on Viburnum chinshanense Caused by Erysiphe pseudoviburni in China.

Viburnum chinshanense, a deciduous shrub in the family Caprifoliaceae, is a dominant tree distributed mainly in the North-Central and South-Central regions of China (Zhu et al. 2023). Because of its lush white flowers and vibrant red fruits, V. chinshanense is used widely as ornamental tree in China. In May 2022, severe powdery mildew symptoms were observed on V. chinshanense on the Huaxi Campus of Guizhou Normal University, Guiyang, China. The incidence was approximately 75% among 80 V. chinshanense plants observed. White mycelia were present on both adaxial and abaxial leaf sides, but not on fruits, petioles, or stems. Infected leaves showed slight chlorosis and twisting. The mycelia were amphigenous, forming small-to-large patches, often sparse on the upper leaf surface, but mostly confluent on the lower leaf surface. Hyphae were hyaline, 4-7 μm wide. Hyphal appressoria were lobed to multilobed, in opposite pairs or solitary. Conidiophores were erect, straight, or somewhat flexuous, 60-130 µm long (n = 30). Foot cells were subcylindrical to slightly curved-sinuous at the base, 20-40 × 6-10 µm (n = 30) in size, followed by 1-3 shorter cells. Conidia formed singly, occasionally two to three in a chain. Conidia were ellipsoid to ovoid, cylindrical, and 24-40 × 16-20 µm (n = 50). No fibrosin bodies were observed on the conidia. Chasmothecia were subglobose, 56-115 µm in diameter. The appendages were 35-70 µm long. Based on these morphological characteristics, the powdery mildew fungus was identified as Erysiphe pseudoviburni (Bradshaw et al. 2020). To confirm the identification, the ribosomal DNA internal transcribed spacer (ITS) and the ribosomal large subunit (LSU) region were amplified and sequenced using the ITS1/ITS4 primer pair (White et al. 1990) and the NL1/NL4 primer pair (Ziemiecki et al. 1990), respectively. The obtained 643-bp ITS sequence (GenBank accession no. ON729292) had 99.84% identity with E. pseudoviburni strains KUS-F27310 (MN431595) and MUMH0001 (LC009904). The obtained 593-bp LSU sequence (ON729293) had 99.83% identity with E. pseudoviburni (LC009904 and MN431595). Based on the phylogenetic analysis of the combined ITS and LSU dataset (Bradshaw et al. 2020), the isolate (GZVD-1) was grouped in a clade with the E. pseudoviburni strains KUS-F27319, KUS-F27310, and MUMH0001. To fulfill Koch's postulates, leaves of three healthy potted V. chinshanense plants were inoculated by gently pressing with diseased leaves. Non-contact plants were used as controls. All plants were incubated in a greenhouse at 25 ± 2°C, 80% relative humidity. Similar powdery mildew symptoms were observed on the inoculated plants 12 days after inoculation, whereas the control plants remained symptomless. The reisolated fungus from the inoculated plants was morphologically identical to that on originally diseased plants. ITS and LSU sequences of the reisolated fungus showed 100% identity with ON729292 and ON729293, respectively. E. pseudoviburni has previously been reported to infect some Viburnum species, including V. sieboldii in Japan (Takamatsu et al. 2015) and V. odoratissimum in South Korea (Bradshaw et al. 2020). To the best of our knowledge, this is the first report of powdery mildew caused by E. pseudoviburni on V. chinshanense in China. This work expands the known host range of E. pseudoviburni in the Viburnum genus.

First Report of Botryosphaeria dothidea Causing Postharvest Fruit Rot of Plum in China.

The Nai plum (Prunus salicina var. cordata cv. Younai) holds significance as an important deciduous fruit crop in China. In July 2023, symptoms of postharvest fruit rot were observed on Nai plum with a 10% disease incidence of harvested fruits in three supermarkets, located in Nanchang City, Jiangxi Province, China. Infected fruits displayed brown, circular lesions, accompanied by a transition in the surrounding peel color from cyan to red. To investigate the causal agent, small sections (3 to 4 mm2) from the periphery of ten infected fruits were subjected to surface sterilization using 75% ethanol for 30 seconds. Following sterilization, the samples were rinsed three times with sterilized distilled water, air-dried, and aseptically placed on potato dextrose agar (PDA) at 25 ℃ for 3 days. Isolated colonies were subcultured by hyphal tiptransfer. Ten of the resulting 12 fungal isolates showed similar morphological characteristics. The colonies exhibited an initial white hue, gradually transitioning to gray, and featured short and thick aerial hyphae with an irregular colony margin. Microscopic examination revealed conidiogenous cells that were hyaline, aseptate, and narrowly fusiform. The conidia were measured 11.0 to 15.6 × 3.2 to 4.9 µm (x̅ = 13.5 ± 1.4 × 4.0 ± 0.4 µm, n = 30), and were hyaline and subcylindrical. The morphological characteristics were in accordance with those of the Botryosphaeria species (Crous et al. 2006). To identify the strain, two representative isolates, JFRL03-1792 and JFRL03-1793, were selected for further characterization. Amplification of nucleotide sequences from three regions (ITS, TEF1-a and TUB2) was conducted using the primer sets ITS5/ITS4, EF1-728F/EF1-986R, and BT2A/BT2B, respectively (Guo et al. 2023). The resulting sequences were deposited in GenBank under the accession numbers: OR418373 and OR418374 for ITS; OR424405 and OR424405 for TEF1-a; OR424411 and OR424412 for TUB2. A BLASTN homology search of the obtained sequences revealed a high similarity of 99%-100% to the ITS (AY236949, 511/513 nucleotides), TEF1-a (AY236898, 282/282 nucleotides), and TUB2 (AY236927, 431/431 nucleotides) sequences of Botryosphaeria dothidea CWM8000 (ex-type). Maximum likelihood analyses were performed for the combined ITS, TEF1-a, and TUB2 dataset using Phylosuite V1.2.2 (Zhang et al. 2020). The resulting phylogenetic tree indicated that the two representative isolates were clustered together with Botryosphaeria dothidea in a clade with 95% bootstrap support. Based on the comprehensive assessment of morphological and molecular data, the two isolates were conclusively identified as B. dothidea. To confirm pathogenicity, six healthy Nai plum fruits were surface sterilized with 75% ethanol and were subsequently wounded with a sterile needle. A 5-mm-diameter mycelial plug of the isolate JFRL03-1792, cultured on PDA at 25 ℃ for three days, was applied to the wound. Another set of six fruits was inoculated with sterile agar plugs as control. Following incubation in a climatic chamber at 25 ℃ and 80% relative humidity, the fruits were examined after 5 days. The experiment was repeated twice. The fruits inoculated with B. dothidea displayed typical rot symptoms, while the control fruits remained asymptomatic. In adherence to Koch's postulates, the fungus was successfully re-isolated from the inoculated fruits and confirmed as B. dothidea through morphological and molecular analysis. B. dothidea has previously been reported causing fruit rot on kiwifruit, winter jujube, and apple (Tang et al. 2012; Zhou et al. 2015; Marsberg et al. 2017; Xu et al. 2023). In addition, B. dothidea also reported causing Botryosphaeria canker disease on plum (Lin et al. 1994). But to our knowledge, this is the first documentation of B. dothidea causing postharvest fruit rot on plum in China. This discovery imparts critical insights into the management of this high-risk disease affecting plum in China.

First Report ofLasiodiplodia hormozganensisCausing Leaf Spot Disease onAreca catechuin China.

The areca palm (Areca catechu L.) is one of the significant cash crops in Hainan Province (China), and a valuable tropical medicinal plant (Cao et al. 2020). In September 2020, spots were found on about 80% of the area of the leaves in a 1,000-acre plantation of areca palms in Haikou City, Hainan Province, and the average incidence was 25%. Initially, Elliptical or irregular dark brown spots appeared on the leaves, with an average size of about 1.5 cm2. With the further expansion of the disease, the spot turned light brown in the center with dark brown edges and a prominent yellow halo. Later stage of the disease, the spots became grayish-white in the center, with obvious whorls, on which many small black spots (pycnidia) were scattered. Eventually the leaves dried out. Ten leaves with typical symptoms were collected from the field. Lesion marginal tissues (5×5 mm2) were surfaced sterilized in 75% ethanol for 20 s, followed by 4 min in 1% NaClO, rinsed 3 times with sterile water, plated on PDA and incubated at 28 ℃. A fungus was isolated with a 98% isolation rate. This strain was named HNAC-5. Subcultures were 80 mm in diameter, white, villous, and neatly edged, after two days of incubation at 28 ℃ in dark. Pycnidia were solitary or clustered in stromata, with orifices that oozed black liquid. Conidiogenous cells were colorless and short cylindrical. Conidia unicellular, initially hyaline, aseptate, ellipsoid to ovoid with granular content, becoming pigmented, 1-septate with longitudinal striations, and measuring 20-31×10-13 μm (n=100). These morphological characteristics were similar to Lasiodiplodia spp. (Abdollahzadeh et al. 2010). The internal transcribed spacer region of rDNA, β-tubulin gene, and translation elongation gene were amplified using ITS1/ITS4, Bt2a/Bt2b, and EF1-728F/EF1-986R primers, respectively (Alves et al. 2008; Glass and Donaldson 1995; White et al. 1990). The resulting sequences were deposited in GenBank under accession numbers OR272043, OR282568, and OR282567. BLAST analysis showed that the three sequences of HNAC-5 were more than 99% similar to strain CBS 124709 of L. hormozganensis. Phylogenetic analysis was performed using the maximum likelihood method based on the three-gene combined dataset with MEGA 7.0 software. The results indicated that HNAC-5 was grouped in the same clade as otherL. hormozganensis Abdollahzadeh, Zare & A.J.L. Phillips. Pathogenicity test was carried out on 15 healthy leaves by in vivo inoculation. Ten leaves were pricked with a sterile needle and divided into group 1 and 2. The remaining five uninjured leaves were group 3. Group 1 and 3 were inoculated with 5-mm-diameter mycelial plugs obtained from 3-day cultures, and group 2 treated with PDA plugs served as controls. Fifteen leaves were cultured at 28°C and 100% relative humidity. After 5 days, leaves of group 1 showed symptoms of the disease and on the tenth day showed the same symptoms as the initial onset of the disease in the field, while leaves of Group 2 and 3 showed no symptoms. Pathogenicity tests were conducted three times with the same results. L. hormozganensiswas re-isolated from the inoculated symptomatic leaves, thus, Koch's postulates were confirmed. In China, L. hormozganensis has been reported to cause Bougainvillea spectabilis Willd. branch blight disease (Li et al. 2015), and Scaevola taccada (Gaertn.) Roxb. leaf spot disease (Zhang et al. 2020). To our knowledge, this is the first report of L. hormozganensiscausing leaf spot disease onA. catechuin China.

Lipopolysaccharide Regulates the Macrophage RNA-Binding Proteome.

RNA-protein interactions within cellular signaling pathways have significant modulatory effects on RNA binding proteins' (RBPs') effector functions. During the innate immune response, specific RNA-protein interactions have been reported as a regulatory layer of post-transcriptional control. We investigated changes in the RNA-bound proteome of immortalized mouse macrophages (IMM) following treatment with lipopolysaccharide (LPS). Stable isotope labeling by amino acids in cell culture (SILAC) of cells followed by unbiased purification of RNP complexes at two time points after LPS stimulation and bottom-up proteomic analysis by LC-MS/MS resulted in a set of significantly affected RBPs. Global RNA sequencing and LFQ proteomics were used to characterize the correlation of transcript and protein abundance changes in response to LPS at different time points with changes in protein-RNA binding. Il1α, MARCKS, and ACOD1 were noted as RBP candidates involved in innate immune signaling. The binding sites of the RBP and RNA conjugates at amino acid resolution were investigated by digesting the cross-linked oligonucleotide from peptides remaining after elution using Nuclease P1. The combined data sets provide directions for further studies of innate immune signaling regulation by RBP interactions with different classes of RNA.

First Report of Postharvest Fruit Rot Caused by Neofusicoccum parvum on Prunus salicina (Nai Plum) in China.

Nai plum (Prunus salicina var. cordata cv. Younai) is one of the most popular fruit crop in South China. In July 2023, a fruit rot of nai plum with about 5 % disease incidence was observed in a fruit market of Changsha city, Hunan Province, China. Initially, small, brown lesions appeared randomly on the fruit surface, with disease progression, the lesions gradually expanded and developed into soft rot. To isolate possible fungi from rotten fruits, small pieces (2 × 2 mm) from the periphery of 10 infected fruits were surface-sterilized using 70% ethanol for 10 s, rinsed three times in sterile distilled water, air dried, and then placed onto potato dextrose agar (PDA) plates and incubated at 28℃ for three days. Emerging colonies were subcultured by hyphal tiptransfer on fresh PDA. A total of ten isolates with similar morphology were obtained. Fungal colonies were initially white, gradually turning gray and eventually becoming black, and aerial hyphae were dense and fluffy. Conidia were hyaline, single celled, ellipsoidal to fusiform, and range from 12.7 to 20.0 μm long (avg. 16.9 ± 2.39 μm) × 5.3 to 7.3 μm wide (avg. 6.3 ± 0.82 μm). These morphological characteristics of these isolates matched those of Neofusicoccum parvum (Phillips et al. 2013). To future confirmation of the identify, the internal transcribed spacer (ITS) region, translation elongation factor 1-alpha (TEF1-a), and beta-tubulin TUB2) genes of two representative isolates (JXNP1 and JXNP2) were amplified and sequenced using primer sets ITS5/ITS4 (White et al. 1990), EF1-728F/EF1-986R (Carbone and Kohn 1999; Phillips et al. 2013), and BT2A/BT2B (Glass and Donaldson 1995), respectively. The sequences of both isolates were deposited in GenBank for the ITS (accession nos. OR899331 and OR899332), TEF1-a gene (accession nos. OR909890 and OR909891) and TUB2 gene (accession nos. OR909892 and OR909893). BLAST analysis showed 99-100% identity with the ex-type strain of N. parvum (CMW9081) for ITS, TEF1-a and TUB2. A maximum likelihood phylogenetic tree was constructed using IQtree web server based on combined ITS, TEF1-a and TUB2 data set. The phylogenetic tree revealed that two isolates clustered with N. parvum in a clade with 90% bootstrap support. Based on morphological and molecular data analysis, the isolates were identified as N. parvum. To confirm the pathogenicity, five healthy nai plum fruits were wounded by using a sterile needle after surface sterilization with 75% ethanol, then a 5-mm-diameter mycelial disc of isolate JXNP1 was taped to the wound, the control fruits were taped with sterile agar plugs. All fruits were incubated at 25 ℃ with 80% humidity. After five days, typical naturally occurring fruit rot symptoms appeared on the fruits which inoculated with N. parvum, whereas control fruits remained asymptomatic. To fulfill Koch's postulates, the pathogen was re-isolated from the inoculated fruits and comfirmed as N. parvum by morphological and molecular analysis. Previous studies reported that N. parvum caused fruit rot on various common fruits in China, including loquat, kiwifruit and citrus (Lei et al. 2013; Zhai et al. 2019; Zhou et al. 2013). To our knowledge, this is the first report of N. parvum causing postharvest fruit rot on nai plum in China. This finding provides critical insights for the management of the high-risk disease on plum in China.

Individual patient data meta-analysis of the effects of fluoxetine on functional outcomes after acute stroke.

Three large randomized controlled trials of fluoxetine for stroke recovery have been performed. We performed an individual patient data meta-analysis (IPDM) on the combined data. Fixed effects meta-analyses were performed on the combined data set, for the primary outcome (modified Rankin scale (mRS) at 6 months), and secondary outcomes common to the individual trials. As a sensitivity analysis, summary statistics from each trial were created and combined. The three trials recruited a combined total of 5907 people (mean age 69.5 years (SD 12.3), 2256 (38%) females, 2-15 days post-stroke) from Australia, New Zealand, United Kingdom, Sweden, and Vietnam; and randomized them to fluoxetine 20 mg daily or matching placebo for 6 months. Data on 5833 (98.75%) were available at 6 months. The adjusted ordinal comparison of mRS was similar in the two groups (common OR 0.96, 95% CI 0.87 to 1.05, p = 0.37). There were no statistically significant interactions between the minimization variables (baseline probability of being alive and independent at 6 months, time to treatment, motor deficit, or aphasia) and pre-specified subgroups (including age, pathological type, inability to assess mood, proxy or patient consent, baseline depression, country). Fluoxetine increased seizure risk (2.64% vs 1.8%, p = 0.03), falls with injury (6.26% vs 4.51%, p = 0.03), fractures (3.15% vs 1.39%, p < 0.0001) and hyponatremia (1.22% vs 0.61%, p = 0.01) but reduced new depression (10.05% vs 13.42%, p < 0.0001). At 12 months, there was no difference in adjusted mRS (n = 5760; common OR 0.98, 95% CI 0.89 to 1.07). Sensitivity analyses gave the same results. Fluoxetine 20 mg daily for 6 months did not improve functional recovery. It increased seizures, falls with injury, and bone fractures but reduced depression frequency at 6 months.

No relations between executive functions and dimensional models of psychopathology or is time the missing link?

Impaired executive functions (EF) have been found within various mental disorders (e.g., attention deficit hyperactivity disorder, autism spectrum disorder, schizophrenia spectrum disorders) as described in DSM-5. However, although impaired EF has been observed within several categories of mental disorders, empirical research on direct relations between EF and broader dimension of psychopathology is still scarce. Therefore, in the current investigation we examined relations between three EF performance tasks and self-reported dimensions of psychopathology (i.e., the internalizing, externalizing, and thought disorder spectra) in a combined dataset of patients with a broad range of mental disorders (N = 440). Despite previously reported results that indicate impaired EF in several categories of mental disorders, in this study no direct relations were found between EF performance tasks and self-reported broader dimensions of psychopathology. These results indicate that relations between EF and psychopathology could be more complex and non-linear in nature. We evaluate the need for integration of EF and dimensional models of psychopathology and reflect on EF as a possible transdiagnostic factor of psychopathology.

Prognostic value of mitophagy gene PINK1 in triple-negative breast cancer

Mitochondrial autophagy plays a crucial role in the development, progression, and treatment of triple-negative breast cancer (TNBC). A total of 43 genes related to mitochondria were obtained from the scientific literature in Pubmed. To assess the expression of these genes, they were categorized into high and low-scoring groups using the ssGSEA algorithm. Additionally, the infiltration of immune cells in the combined dataset was evaluated using the CIBERSORTx algorithm. To analyze the expression of the selected genes, one-way Cox regression analysis, along with clinical staging variables, was employed. A multifactorial Cox regression model was constructed, and a forest plot was generated to assess the predictive power of the model on the actual outcomes. The accuracy of the model was confirmed by validating the expression of the PINK1 gene and its model through immunohistochemistry. TNBC cancer was categorized into two molecular subtypes (cluster1 and cluster2) based on the MRGs. Finally, a prognostic model was developed using the PINK1 gene, which demonstrated a considerable degree of accuracy. The validity of the PINK1 gene and its model was confirmed through immunohistochemistry, indirectly indicating that PINK1 might serve as a potential therapeutic target and prognostic biomarker for TNBC.

Macitentan in Pulmonary Arterial Hypertension Associated with Connective Tissue Disease (CTD-PAH): Real-World Evidence from the Combined OPUS/OrPHeUS Dataset.

Data on real-world clinical practice and outcomes of patients with pulmonary arterial hypertension associated with connective tissue disease (CTD-PAH) are scarce. The OPUS/OrPHeUS studies enrolled patients newly initiating macitentan, including those with CTD-PAH. This analysis describes patient characteristics, treatment patterns, outcomes, and safety profiles of patients with CTD-PAH newly initiating macitentan in the US using the OPUS/OrPHeUS combined dataset. OPUS was a prospective, US, multicenter, long-term, observational drug registry (April 2014-June 2020). OrPHeUS was a retrospective, US, multicenter medical chart review (October 2013-March 2017). The characteristics, treatment patterns, safety, and outcomes during macitentan treatment of patients with CTD-PAH and its subgroups systemic sclerosis (SSc-PAH), systemic lupus erythematosus (SLE-PAH), and mixed CTD (MCTD-PAH) were descriptively compared to patients with idiopathic/heritable PAH (I/HPAH). The combined OPUS/OrPHeUS population included 2498 patients with I/HPAH and 1192 patients with CTD-PAH (708 SSc-PAH; 159 SLE-PAH; 124 MCTD-PAH, and 201 other CTD-PAH etiologies). At macitentan initiation for patients with I/HPAH and CTD-PAH, respectively: 61.2 and 69.3% were in World Health Organization functional class (WHO FC) III/IV; median 6-min walk distance was 289 and 279m; and 58.1 and 65.2% received macitentan as combination therapy. During follow-up, for patients with I/HPAH and CTD-PAH, respectively: median duration of macitentan exposure observed was 14.0 and 15.8months; 79.0 and 83.0% experienced an adverse event; Kaplan-Meier estimates (95% confidence limits [CL]) of patients free from all-cause hospitalization at 1year were 60.3% (58.1, 62.4) and 59.3% (56.1, 62.3); and Kaplan-Meier estimates (95% CL) of survival at 1year were 90.5% (89.1, 91.7) and 90.6% (88.6, 92.3). Macitentan was used in clinical practice in patients with CTD-PAH and its subgroups, including as combination therapy. The safety and tolerability profile of macitentan in patients with CTD-PAH was comparable to that of patients with I/HPAH. OPsumit® Users Registry (OPUS): NCT02126943; Opsumit® Historical Users cohort (OrPHeUS): NCT03197688; www. gov Graphical abstract available for this article.

Re-Identification of Aspergillus Subgenus Nidulantes Strains and Description of Three Unrecorded Species From Korea

ABSTRACT: Aspergillus subgenus Nidulantes with nine section forms the second largest subgenus of the fungi that comes under the genus Aspergillus. Species in this group of fungi are important as they are reported to play several important roles in the environment including influencing air quality in confined spaces, food spoilage, production of mycotoxins as well as in human pathogenicity. In the present study, 53 strains of Aspergillus subgenus Nidulantes (section: Nidulantes & Usti) isolated from Korea and preserved at the Korean Agricultural Culture Collection (KACC) were subjected to re-identification by using a combined dataset of partial β-tubulin (BenA), Calmodulin (CaM) gene sequences as well as their morphological data. We confirmed 14 species from 53 isolates in Korea. Of them, eleven species were reported in Korea previously (A. amoenus, A. baeticus, A. calidoustus, A. creber, A. insuetus, A. jensenii, A. nidulans, A. protuberus, A. sydowii, A. tabacinus and A. unguis), and three species (A. griseoaurantiacus, A. puulaauensis and A. sublatus) were previously unreported from Korea. We detailed the characteristic features of these three species, that remain unexplored in Korea.

Measuring the Queen Bee Phenomenon in technically efficient firms: implications from Southeast Asian manufacturers

This study examines the “Queen Bee Phenomenon,” that is, Southeast Asian manufacturers having female CEOs and owners. In addition, the buffering effect of female CEOs and owners on manufacturers seeking higher technical efficiencies is also examined in this research. This study uses the fractional regression and two-limit Tobit regression models to examine a combined set of cross-sectional data from surveys conducted by the World Bank, consisting of 3471 manufacturers in Southeast Asia, including those in Thailand, the Philippines, Indonesia, Malaysia, and Vietnam. Our results find that the “Queen Bee Phenomenon” does not exist in Southeast Asian manufacturing enterprises. Furthermore, manufacturers with higher technical efficiency levels are likely to hire fewer female workers; nevertheless, if female CEOs and owners run these technically efficient firms, hiring more female workers can be noticed. This research demonstrates that globalization through FDI and exports may promote female labor force participation among Southeast Asian enterprises and those seeking greater technical efficiencies.

Phylogenetic position of Vanda coelestis (Rchb.f.) Motes (Orchidaceae; Aeridinae): evidence from complete plastome and combined traditional sequences

The taxonomic status of Vanda coelestis (Rchb.f.) Motes remains a matter of discussion. So far, molecular systematic work has not been used to investigate. Here, we conducted the phylogenetic analyses using two datasets, the complete plastome and a combination of traditional molecular sequences (nrITS, matK, psbA-trnH, and trnL-trnF). Plastid-based phylogenetic trees indicated that this species was deeply embedded within the genus Vanda. In the analysis based on combined traditional sequences dataset, this species was further supported as sister to V. vietnamica with strong support.

Novel Diagnostic Biomarker BST2 Identified by Integrated Transcriptomics Promotes the Development of Endometriosis via the TNF-α/NF-κB Signaling Pathway.

Endometriosis (EMS) is a common gynecological condition with apparent heterogeneity, lack of diagnostic markers, and unclear pathogenesis. A series of bioinformatics methods were employed to explore EMS's pathological mechanisms and potential biomarkers by analyzing the combined datasets of EMS (GSE7305, GSE7307, GSE58198, E-MTAB-694), which included 34 normal, 127 eutopic, and 46 ectopic endometrium samples. Then, wet-laboratory experiments (including Western blot, qRT-PCR, and Immunohistochemistry, Immunofluorescence, CCK-8, EdU, Wound healing, Transwell, and Adhesion assays) were applied to examine the biomarkers' expression and function in primary endometrial stromal cells. Bioinformatic analysis indicated that the core pathogenesis of EMS was dysregulated immune-inflammation and tissue remolding processes. Among the upregulated DEGs, BST2 was screened as a potential diagnostic biomarker in EMS, which associated with the revised American Fertility Society (r-AFS) stage and immune-inflammation processes of EMS. Moreover, BST2's overexpression was affirmed in the RNA and protein levels in EMS tissues. In vitro experiments demonstrated that TNF-α promoted the expression of BST2 in ESCs. And BST2 knockdown inhibited migration, invasion, adhesion, and inflammation except for the proliferation of ESCs, probably via the TNF-α/NF-κB pathway. Through a combination of wet and dry studies, we concluded that the core pathogenesis of endometriosis was dysregulated immune-inflammation and tissue remolding, and BST2 might be a potential diagnostic and therapeutic target in endometriosis.

COVID-Net L2C-ULTRA: An Explainable Linear-Convex Ultrasound Augmentation Learning Framework to Improve COVID-19 Assessment and Monitoring.

While no longer a public health emergency of international concern, COVID-19 remains an established and ongoing global health threat. As the global population continues to face significant negative impacts of the pandemic, there has been an increased usage of point-of-care ultrasound (POCUS) imaging as a low-cost, portable, and effective modality of choice in the COVID-19 clinical workflow. A major barrier to the widespread adoption of POCUS in the COVID-19 clinical workflow is the scarcity of expert clinicians who can interpret POCUS examinations, leading to considerable interest in artificial intelligence-driven clinical decision support systems to tackle this challenge. A major challenge to building deep neural networks for COVID-19 screening using POCUS is the heterogeneity in the types of probes used to capture ultrasound images (e.g., convex vs. linear probes), which can lead to very different visual appearances. In this study, we propose an analytic framework for COVID-19 assessment able to consume ultrasound images captured by linear and convex probes. We analyze the impact of leveraging extended linear-convex ultrasound augmentation learning on producing enhanced deep neural networks for COVID-19 assessment, where we conduct data augmentation on convex probe data alongside linear probe data that have been transformed to better resemble convex probe data. The proposed explainable framework, called COVID-Net L2C-ULTRA, employs an efficient deep columnar anti-aliased convolutional neural network designed via a machine-driven design exploration strategy. Our experimental results confirm that the proposed extended linear-convex ultrasound augmentation learning significantly increases performance, with a gain of 3.9% in test accuracy and 3.2% in AUC, 10.9% in recall, and 4.4% in precision. The proposed method also demonstrates a much more effective utilization of linear probe images through a 5.1% performance improvement in recall when such images are added to the training dataset, while all other methods show a decrease in recall when trained on the combined linear-convex dataset. We further verify the validity of the model by assessing what the network considers to be the critical regions of an image with our contribution clinician.

Microsatellite Content in 397 Nuclear Exons and Their Flanking Regions in the Fern Family Ophioglossaceae.

Microsatellites or SSRs are small tandem repeats that are 1-6 bp long. They are usually highly polymorphic and form important portions of genomes. They have been extensively analyzed in humans, animals and model plants; however, information from non-flowering plants is generally lacking. Here, we examined 29 samples of Ophioglossaceae ferns, mainly from the genera Botrychium and Sceptridium. We analyzed the SSR distribution, density and composition in almost 400 nuclear exons and their flanking regions. We detected 45 SSRs in exons and 1475 SSRs in the flanking regions. In the exons, only di-, tri- and tetranucleotides were found, and all of them were 12 bp long. The annotation of the exons containing SSRs showed that they were related to various processes, such as metabolism, catalysis, transportation or plant growth. The flanking regions contained SSRs from all categories, with the most numerous being dinucleotides, followed by tetranucleotides. More than one-third of all the SSRs in the flanking regions were 12 bp long. The SSR densities in the exons were very low, ranging from 0 to 0.07 SSRs/kb, while those in the flanking regions ranged from 0.24 to 0.81 SSRs/kb; and those in the combined dataset ranged from 0.2 to 0.81 SSRs/kb. The majority of the detected SSRs in the flanking regions were polymorphic and present at the same loci across two or more samples but differing in the number of repeats. The SSRs detected here may serve as a basis for further population genetic, phylogenetic or evolutionary genetic studies, as well as for further studies focusing on SSRs in the genomes and their roles in adaptation, evolution and diseases.

Refinement of microplate boundaries assisted by integrated gravity analysis: Application to the Caribbean Sea

Under the long-term influence of subduction, collision and strike-slip faults, the Caribbean Sea and its surroundings have evolved complex topography and terranes, making it an excellent site to study the tectonic of microplates. However, some microplate boundaries of this area are still controversial or unclear. Here we employed the widely-used satellite-derived gravity dataset in combination with previous findings to conduct a detailed re-interpretation of tectonic boundaries. A newly proposed product of normalized multi-edge-attributes (PNMEA) with upward-continued free-air gravity anomalies (FGA) is used to constrain deep large-scale boundaries (i.e., oceanic trenches, deformed belts and fault systems). The residual crustal gravity anomalies (RCGA) obtained based on wavelet multi-scale decomposition further reveal density variations within the crust domain. The Tilt angle (TA) of FGA highlights fault strikes and patterns in the near-surface. Consequently, we refine the possible boundaries of microplates within the northern Caribbean boundary zone and the Nicaraguan Rise, and analyze the contact relationships among microplates. The results suggest a triple junction among the Gonave, Hispaniola and Septentrional microplates exists in the Windward Passage, and a zigzag low RCGA in the Mona Passage separates the Hispaniola and Puerto Rico microplates. In addition, the north and south Nicaraguan rises are inclined to be unaffiliated implied by the differences in multiple physical properties. We thus conclude that an integrated analytical approach involving potential-field edge detection and RCGA can provide additional constraints for identification of tectonic or microplate boundaries. Deep-shallow coupling and lithosphere-scale cooling differences may provide new perspectives to explain the complexity of temporal-spatial configuration due to multiple microplate interactions.

Variation in the Pedersen Conductance Near Jupiter's Main Emission Aurora: Comparison of Hubble Space Telescope and Galileo Measurements

AbstractWe present the first large‐scale statistical survey of the Jovian main emission (ME) to map auroral properties from their ionospheric locations out into the equatorial plane of the magnetosphere, where they are compared directly to in‐situ spacecraft measurements. We use magnetosphere‐ionosphere (MI) coupling theory to calculate currents from the auroral brightness as measured with the Hubble Space Telescope and from plasma flow speeds measured in‐situ with the Galileo spacecraft. The effective Pedersen conductance of the ionosphere remains a free parameter in this comparison. We calculate the Pedersen conductance from the combined data sets, and find it ranges from mho overall with averages of mho in the north and mho in the south. Considering the HST‐derived field‐aligned currents per radian of azimuth only, we find values of MA rad−1 and MA rad−1 in the north and south, respectively, in general agreement with previous results. Taking the currents and effective Pedersen conductance together, we find that the average ME intensity and plasma flow speed in the middle magnetosphere (10–30 RJ) are broadly consistent with one another under MI coupling theory. We find evidence for peaks in the distribution of near dawn, then again near 12 and 14 hr magnetic local time (MLT). This variation in Pedersen conductance with MLT may indicate the importance of conductance in modulating MLT‐ and local‐time‐asymmetries in the ME, including the apparent subcorotation of some auroral features within the ME.

Atrophy network mapping of clinical subtypes and main symptoms in frontotemporal dementia.

Frontotemporal Dementia (FTD) is a disease of high heterogeneity, apathy and disinhibition present in all subtypes of FTD and imposes a significant burden on families/society. Traditional neuroimaging analysis has limitations in elucidating the network localization due to individual clinical and neuroanatomical variability. The study aims to identify the atrophy network map associated with different FTD clinical subtypes and determine the specific localization of the network for apathy and disinhibition. Eighty FTD patients [45 behavioral variant FTD (bvFTD) and 35 semantic variant progressive primary aphasia (svPPA)] and 58 healthy controls (HCs) at Xuanwu Hospital were enrolled as Dataset 1; 112 FTD patients including 50 bvFTD, 32 svPPA, and 30 non-fluent variant PPA (nfvPPA) cases, and 110 HCs from Frontotemporal Lobar Degeneration Neuroimaging Initiative (FTLDNI) dataset were included as Dataset 2. Initially, single-subject atrophy maps were defined by comparing cortical thickness in each FTD patient versus HCs. Next, the network of brain regions functionally connected to each FTD patient's location of atrophy was determined using seed-based functional connectivity in a large (n = 1000) normative connectome. Finally, we used atrophy network mapping to define clinical subtype-specific network (45 bvFTD, 35 svPPA and 58 HCs in Dataset 1; 50 bvFTD, 32 svPPA, 30 nfvPPA and 110 HCs in Dataset 2) and symptom-specific networks [combined dataset 1 and 2, apathy without depression Vs non-apathy without depression (80:26), disinhibition Vs non-disinhibition (88:68)]. We compare the result with matched symptom networks derived from patients with focal brain lesions or conjunction analysis. Through the analysis of two datasets, we identified heterogeneity in atrophy patterns among FTD patients. However, these atrophy patterns are connected to a common brain network. The primary regions affected by atrophy in FTD included the frontal and temporal lobes, particularly the anterior temporal lobe. bvFTD connects to frontal and temporal cortical areas, svPPA mainly impacts the anterior temporal region, and nfvPPA targets the inferior frontal gyrus and precentral cortex regions. The apathy-specific network was localized in the orbital frontal cortex and ventral striatum, while the disinhibition-specific network was localized in the bilateral orbital frontal gyrus and right temporal lobe. Apathy and disinhibition atrophy networks resemble known motivational and criminal lesion networks respectively. A significant correlation was found between the apathy/disinhibition scores and functional connectivity between atrophy maps and the peak of the networks. This study localizes the common network of clinical subtypes and main symptoms in FTD, guiding future FTD neuromodulation interventions.