In vitro and in vivo studies on exogenous polyamines and α-difluoromethylornithine to enhance bone formation and suppress osteoclast differentiation.

Exogenous polyamines, including putrescine (PUT), spermidine (SPD), and spermine (SPM), and the irreversible inhibitor of the rate-limiting enzyme ornithine decarboxylase (ODC) of polyamine biosynthesis, α-difluoromethylornithine (DFMO), are implicated as stimulants for bone formation. We demonstrate in this study the osteogenic potential of exogenous polyamines and DFMO in human osteoblasts (hOBs), murine monocyte cell line RAW 264.7, and an ovariectomized rat model. The effect of polyamines and DFMO on hOBs and RAW 264.7 cells was studied by analyzing gene expression, alkaline phosphatase (ALP) activity, tartrate-resistant acid phosphatase (TRAP) activity, and matrix mineralization. Ovariectomized rats were treated with polyamines and DFMO and analyzed by micro computed tomography (micro CT). The mRNA level of the early onset genes of osteogenic differentiation, Runt-related transcription factor 2 (Runx2) and ALP, was significantly elevated in hOBs under osteogenic conditions, while both ALP activity and matrix mineralization were enhanced by exogenous polyamines and DFMO. Under osteoclastogenic conditions, the gene expression of both receptor activator of nuclear factor-κB (RANK) and nuclear factor of activated T-cells, cytoplasmic 1 (NFATc1) was reduced, and TRAP activity was suppressed by exogenous polyamines and DFMO in RAW 264.7 cells. In an osteoporotic animal model of ovariectomized rats, SPM and DFMO were found to improve bone volume in rat femurs, while trabecular thickness was increased in all treatment groups. Results from this study provide in vitro and in vivo evidence indicating that polyamines and DFMO act as stimulants for bone formation, and their osteogenic effect may be associated with the suppression of osteoclastogenesis.

Incidence and co-infection with COVID-19 of dengue during the COVID-19 pandemic.

The co-infection of dengue and COVID-19 has been regarded as a public health issue for dengue-endemic countries during the COVID-19 pandemic. Travel restrictions might decrease the chance of mosquitoes biting and, thus, reduce the risk of dengue transmission. However, the spread of dengue was reported to increase with the policies of lockdowns and social distancing in specific areas due to delayed interventions in dengue transmission. Of cases experiencing dengue and COVID-19 co-infection, most recovered after receiving supportive care and/or steroid therapy. However, some episodes of severe or fatal diseases in specific individuals, such as pregnant women, have been reported, and the clinical course of this co-infection is unrecognized or unpredictable. Accordingly, it is crucial to promptly identify predictors of developing severe viral diseases among co-infection patients.

Prompt antimicrobial therapy and source control on survival and defervescence of adults with bacteraemia in the emergency department: the faster, the better.

BACKGROUND: Bacteraemia is a critical condition that generally leads to substantial morbidity and mortality. It is unclear whether delayed antimicrobial therapy (and/or source control) has a prognostic or defervescence effect on patients with source-control-required (ScR) or unrequired (ScU) bacteraemia. METHODS: The multicenter cohort included treatment-naïve adults with bacteraemia in the emergency department. Clinical information was retrospectively obtained and etiologic pathogens were prospectively restored to accurately determine the time-to-appropriate antibiotic (TtAa). The association between TtAa or time-to-source control (TtSc, for ScR bacteraemia) and 30-day crude mortality or delayed defervescence were respectively studied by adjusting independent determinants of mortality or delayed defervescence, recognised by a logistic regression model. RESULTS: Of the total 5477 patients, each hour of TtAa delay was associated with an average increase of 0.2% (adjusted odds ratio [AOR], 1.002; P < 0.001) and 0.3% (AOR 1.003; P < 0.001) in mortality rates for patients having ScU (3953 patients) and ScR (1524) bacteraemia, respectively. Notably, these AORs were augmented to 0.4% and 0.5% for critically ill individuals. For patients experiencing ScR bacteraemia, each hour of TtSc delay was significantly associated with an average increase of 0.31% and 0.33% in mortality rates for overall and critically ill individuals, respectively. For febrile patients, each additional hour of TtAa was significantly associated with an average 0.2% and 0.3% increase in the proportion of delayed defervescence for ScU (3085 patients) and ScR (1266) bacteraemia, respectively, and 0.5% and 0.9% for critically ill individuals. For 1266 febrile patients with ScR bacteraemia, each hour of TtSc delay respectively was significantly associated with an average increase of 0.3% and 0.4% in mortality rates for the overall population and those with critical illness. CONCLUSIONS: Regardless of the need for source control in cases of bacteraemia, there seems to be a significant association between the prompt administration of appropriate antimicrobials and both a favourable prognosis and rapid defervescence, particularly among critically ill patients. For ScR bacteraemia, delayed source control has been identified as a determinant of unfavourable prognosis and delayed defervescence. Moreover, this association with patient survival and the speed of defervescence appears to be augmented among critically ill patients.

Enhancement of NETosis by ACE2-cross-reactive anti-SARS-CoV-2 RBD antibodies in patients with COVID-19.

BACKGROUND: High levels of neutrophil extracellular trap (NET) formation or NETosis and autoantibodies are related to poor prognosis and disease severity of COVID-19 patients. Human angiotensin-converting enzyme 2 (ACE2) cross-reactive anti-severe acute respiratory syndrome coronavirus 2 spike protein receptor-binding domain (SARS-CoV-2 RBD) antibodies (CR Abs) have been reported as one of the sources of anti-ACE2 autoantibodies. However, the pathological implications of CR Abs in NET formation remain unknown. METHODS: In this study, we first assessed the presence of CR Abs in the sera of COVID-19 patients with different severity by serological analysis. Sera and purified IgG from CR Abs positive COVID-19 patients as well as a mouse monoclonal Ab (mAb 127) that can recognize both ACE2 and the RBD were tested for their influence on NETosis and the possible mechanisms involved were studied. RESULTS: An association between CR Abs levels and the severity of COVID-19 in 120 patients was found. The CR Abs-positive sera and IgG from severe COVID-19 patients and mAb 127 significantly activated human leukocytes and triggered NETosis, in the presence of RBD. This NETosis, triggered by the coexistence of CR Abs and RBD, activated thrombus-related cells but was abolished when the interaction between CR Abs and ACE2 or Fc receptors was disrupted. We also revealed that CR Abs-induced NETosis was suppressed in the presence of recombinant ACE2 or the Src family kinase inhibitor, dasatinib. Furthermore, we found that COVID-19 vaccination not only reduced COVID-19 severity but also prevented the production of CR Abs after SARS-CoV-2 infection. CONCLUSIONS: Our findings provide possible pathogenic effects of CR Abs in exacerbating COVID-19 by enhancing NETosis, highlighting ACE2 and dasatinib as potential treatments, and supporting the benefit of vaccination in reducing disease severity and CR Abs production in COVID-19 patients.

Identification of two new species and a new host record of Distoseptispora (Distoseptisporaceae, Distoseptisporales, Sordariomycetes) from terrestrial and freshwater habitats in Southern China.

During our investigation of saprophytic fungi in Guizhou and Hainan provinces, China, three hyphomycetes were collected from terrestrial and freshwater habitats. Based on morphological characteristics and phylogenetic analyses of combined ITS, LSU, tef1-α, and rpb2 sequence data, two new species are introduced: Distoseptisporahainanensis and D.lanceolatispora. Additionally, one known species, D.tectonae, previously unreported from Edgeworthiachrysantha, is newly reported. Detailed descriptions, illustrations, and a phylogenetic tree to show the two new species and the new host record of Distoseptispora are provided. In addition, a checklist of Distoseptispora species with their locations, lifestyles, habitats, and hosts is provided.

Low-Dose Versus Standard-Dose Alteplase in Bridging Therapy for Large Vessel Stroke: A Systematic Review and Meta-Analysis.

INTRODUCTION The efficacy and safety of low- and standard-dose alteplase for acute ischemic stroke (AIS) have not been consistently compared in previous studies. Nevertheless, the distinctions in the effects of low- and standard-dose alteplase, particularly within the context of bridging therapy (BT) for large vessel occlusion (LVO), warrant further exploration. This study compared clinical outcomes between BT with low- and standard-dose alteplase in patients with LVO-related AIS. METHODS We performed a search for randomized controlled trials and prospective or retrospective cohort studies investigating the clinical outcomes of BT in AIS in the PubMed, Embase, and Cochrane Library databases from inception to November 2022. The outcomes of interest were 90-day functional independence, successful recanalization, symptomatic intracerebral hemorrhage (sICH) and mortality; these outcomes were compared between patients who received BT with low- (primarily 0.6 mg/kg) and standard-dose alteplase (0.9 mg/kg). We used the standard-dose group as the reference and calculated the odds ratio (OR) and its 95% confidence interval (CI) from the raw numbers. Meta-analysis and ethnicity-based subgroup analysis (Asian and non-Asian) were performed. RESULTS Five observational studies, published after 2017 and including 408 patients, were included. The meta-analysis results demonstrated that compared with BT with standard-dose alteplase, BT with low-dose alteplase did not improve 90-day functional independence (odds ratio, [OR] 1.02; 95% confidence interval [CI], 0.58-1.80). Nevertheless, BT with low-dose alteplase was associated with a comparable successful recanalization rate (OR, 1.35; 95% CI, 0.68-2.67) and similar sICH incidence (OR 0.36; 95% CI, 0.10-1.36), and mortality (OR, 0.64; 95% CI, 0.27-1.54) compared with BT with standard-dose alteplase; however, the above three results were nonsignificant. In the ethnicity-based subgroup analyses, no differences were noted between Asian and non-Asian participants. CONCLUSIONS In patients with LVO-related AIS, BT with low- or standard-dose alteplase may provide similar efficacy, with no significant differences in sICH incidence and mortality. Additional well-designed prospective studies are required to confirm this result.

Phage transcriptional regulator X (PtrX)-mediated augmentation of toxin production and virulence in Clostridioides difficile strain R20291.

Clostridioides difficile is a Gram-positive, anaerobic, and spore-forming bacterial member of the human gut microbiome. The primary virulence factors of C. difficile are toxin A and toxin B. These toxins damage the cell cytoskeleton and cause various diseases, from diarrhea to severe pseudomembranous colitis. Evidence suggests that bacteriophages can regulate the expression of the pathogenicity locus (PaLoc) genes of C. difficile. We previously demonstrated that the genome of the C. difficile RT027 strain NCKUH-21 contains a prophage-like DNA sequence, which was found to be markedly similar to that of the φCD38-2 phage. In the present study, we investigated the mechanisms underlying the φNCKUH-21-mediated regulation of the pathogenicity and the PaLoc genes expression in the lysogenized C. difficile strain R20291. The carriage of φNCKUH-21 in R20291 cells substantially enhanced toxin production, bacterial motility, biofilm formation, and spore germination in vitro. Subsequent mouse studies revealed that the lysogenized R20291 strain caused a more severe infection than the wild-type strain. We screened three φNCKUH-21 genes encoding DNA-binding proteins to check their effects on PaLoc genes expression. The overexpression of NCKUH-21_03890, annotated as a transcriptional regulator (phage transcriptional regulator X, PtrX), considerably enhanced toxin production, biofilm formation, and bacterial motility of R20291. Transcriptome analysis further confirmed that the overexpression of ptrX led to the upregulation of the expression of toxin genes, flagellar genes, and csrA. In the ptrX-overexpressing R20291 strain, PtrX influenced the expression of flagellar genes and the sigma factor gene sigD, possibly through an increased flagellar phase ON configuration ratio.

A near-infrared fluorescent probe with a substantial Stokes shift designed for the detection and imaging of ß-galactosidase within living cells and animals.

ß-Galactosidase serves as a pivotal biomarker for both cancer and cellular aging. The advancement of fluorescent sensors for tracking ß-galactosidase activity is imperative in the realm of cancer diagnosis. We have designed a near-infrared fluorescent probe (PTA-gal) for the detection of ß-galactosidase in living systems with large Stokes shifts. PTA-gal exhibits remarkable sensitivity and selectivity in detecting ß-galactosidase, producing near-infrared fluorescent signals with a remarkably low detection limit (2.2 × 10-5 U/mL) and a high quantum yield (0.30). Moreover, PTA-gal demonstrates biocompatibility and can effectively detect ß-galactosidase in cancer cells as well as within living animals.

Validation of Model-Basis Transfer Learning for a Personalized Electroencephalogram-Based Emotion-Classification Model.

The electroencephalogram (EEG)-based affective brain-computer interface (aBCI) has attracted extensive attention in multidisciplinary fields in the past decade. However, the inherent variability of emotional responses recorded in EEG signals increases the vulnerability of pre-trained machine-learning models and impedes the applicability of aBCIs with real-life settings. To overcome the shortcomings associated with the limited personal data in affective modeling, this study proposes a model-basis transfer learning (TL) approach and verifies its feasibility to construct a personalized model using less emotion-annotated data in a longitudinal eight-day dataset comprising data on 10 subjects. By performing daily reliability testing, the proposed TL approach outperformed the subject-dependent counterpart (using limited data only) by ~6% in binary valence classification after recycling a compact set of the eight most transferable models from other subjects. These empirical findings practically contribute to progress in applying TL in realistic aBCI applications.Clinical Relevance- The proposed model-basis TL approach overcomes the shortcoming of inherent variability in EEG signals, supporting realistic aBCI applications.

[Evaluation of the effect of 3D printing resin splint based on the retention effect of orthodontic treatment in patients with periodontal disease].

PURPOSE: To investigate the difference in the retention effect of 3D printing resin splint and Hawley retainer combined with lingual retention wire in periodontal disease patients after orthodontic treatment. METHODS: Forty patients who finished orthodontic treatment for periodontal disease from January 2021 to February 2022 were selected and divided into experimental group and control group according to the random number table method, with 20 patients in each group. Patients in the experimental group used 3D printing resin splint for retention, while patients in the control group used Hawley retainer combined with a lingual retention wire for retention. The chair-side operation time of the retainers was recorded for both groups. The maxillary and mandibular cuspid width, molar width, overjet, overbite and irregularity index were measured at 1 month and 6 months after orthodontic treatment in both groups. Statistical analysis was performed with SPSS 12.0 software package. RESULTS: The mean time for chair-side manipulation of experimental group and control group was 8.23, 11.17 min, respectively. The difference between the two groups was statistically significant (P＜0.05) when comparing the width of the maxillary and mandibular cusps, the width of the molars, overjet, overbite and the irregularity index after 1 month and 6 months of wear of the retainers, which were significantly greater in the experimental group than in the control group at 6 months(P＜0.05). CONCLUSIONS: 3D printing resin splint, with short chair-side manipulation time, was more effective than Hawley retainer combined with a lingual retention wire, and the efficacy of both groups was otherwise generally consistent.

Electroencephalogram-Driven Machine-Learning Scenario for Assessing Impulse Control Disorder Comorbidity in Parkinson's Disease Using a Low-Cost, Custom LEGO-Like Headset.

Patients with Parkinson's disease (PD) may develop cognitive symptoms of impulse control disorders (ICDs) when chronically treated with dopamine agonist (DA) therapy for motor deficits. Motor and cognitive comorbidities critically increase the disability and mortality of the affected patients. This study proposes an electroencephalogram (EEG)-driven machine-learning scenario to automatically assess ICD comorbidity in PD. We employed a classic Go/NoGo task to appraise the capacity of cognitive and motoric inhibition with a low-cost, custom LEGO-like headset to record task-relevant EEG activity. Further, we optimized a support vector machine (SVM) and support vector regression (SVR) pipeline to learn discriminative EEG spectral signatures for the detection of ICD comorbidity and the estimation of ICD severity, respectively. With a dataset of 21 subjects with typical PD, 9 subjects with PD and ICD comorbidity (ICD), and 25 healthy controls (HC), the study results showed that the SVM pipeline differentiated subjects with ICD from subjects with PD with an accuracy of 66.3% and returned an around-chance accuracy of 53.3% for the classification of PD versus HC subjects without the comorbidity concern. Furthermore, the SVR pipeline yielded significantly higher severity scores for the ICD group than for the PD group and resembled the ICD vs. PD distinction according to the clinical questionnaire scores, which was barely replicated by random guessing. Without a commercial, high-precision EEG product, our demonstration may facilitate deploying a wearable computer-aided diagnosis system to assess the risk of DA-triggered cognitive comorbidity in patients with PD in their daily environment.

Exploring Spatio-Spectral Electroencephalogram Modulations of Imbuing Emotional Intent During Active Piano Playing.

Imbuing emotional intent serves as a crucial modulator of music improvisation during active musical instrument playing. However, most improvisation-related neural endeavors have been gained without considering the emotional context. This study attempts to exploit reproducible spatio-spectral electroencephalogram (EEG) oscillations of emotional intent using a data-driven independent component analysis framework in an ecological multiday piano playing experiment. Through the four-day 32-ch EEG dataset of 10 professional players, we showed that EEG patterns were substantially affected by both intra- and inter-individual variability underlying the emotional intent of the dichotomized valence (positive vs. negative) and arousal (high vs. low) categories. Less than half (3-4) of the 10 participants analogously exhibited day-reproducible ( ≥ three days) spectral modulations at the right frontal beta in response to the valence contrast as well as the frontal central gamma and the superior parietal alpha to the arousal counterpart. In particular, the frontal engagement facilitates a better understanding of the frontal cortex (e.g., dorsolateral prefrontal cortex and anterior cingulate cortex) and its role in intervening emotional processes and expressing spectral signatures that are relatively resistant to natural EEG variability. Such ecologically vivid EEG findings may lead to better understanding of the development of a brain-computer music interface infrastructure capable of guiding the training, performance, and appreciation for emotional improvisatory status or actuating music interaction via emotional context.

Predictive models for short-term mortality and length of hospital stay among adults with community-onset bacteraemia before and during the COVID-19 pandemic: application of early data dynamics.

BACKGROUND: The development of scoring systems to predict the short-term mortality and the length of hospital stay (LOS) in patients with bacteraemia is essential to improve the quality of care and reduce the occupancy variance in the hospital bed. METHODS: Adults hospitalised with community-onset bacteraemia in the coronavirus disease 2019 (COVID-19) and pre-COVID-19 eras were captured as the validation and derivation cohorts in the multicentre study, respectively. Model I incorporated all variables available on day 0, Model II incorporated all variables available on day 3, and Models III, IV, and V incorporated the variables that changed from day 0 to day 3. This study adopted the statistical and machine learning (ML) methods to jointly determine the prediction performance of these models in two study cohorts. RESULTS: A total of 3,639 (81.4%) and 834 (18.6%) patients were included in the derivation and validation cohorts, respectively. Model IV achieved the best performance in predicting 30-day mortality in both cohorts. The most frequently identified variables incorporated into Model IV were deteriorated consciousness from day 0 to day 3 and deteriorated respiration from day 0 to day 3. Model V achieved the best performance in predicting LOS in both cohorts. The most frequently identified variables in Model V were deteriorated consciousness from day 0 to day 3, a body temperature ≤ 36.0 °C or ≥ 39.0 °C on day 3, and a diagnosis of complicated bacteraemia. CONCLUSIONS: For hospitalised adults with community-onset bacteraemia, clinical variables that dynamically changed from day 0 to day 3 were crucial in predicting the short-term mortality and LOS.

Movement Artifact Suppression in Wearable Low-Density and Dry EEG Recordings Using Active Electrodes and Artifact Subspace Reconstruction.

Wearable low-density dry electroencephalogram (EEG) headsets facilitate multidisciplinary applications of brain-activity decoding and brain-triggered interaction for healthy people in real-world scenarios. However, movement artifacts pose a great challenge to their validity in users with naturalistic behaviors (i.e., without highly controlled settings in a laboratory). High-precision, high-density EEG instruments commonly embed an active electrode infrastructure and/or incorporate an auxiliary artifact subspace reconstruction (ASR) pipeline to handle movement artifact interferences. Existing endeavors motivate this study to explore the efficacy of both hardware and software solutions in low-density and dry EEG recordings against non-tethered settings, which are rarely found in the literature. Therefore, this study employed a LEGO-like electrode-holder assembly grid to coordinate three 3-channel system designs (with passive/active dry vs. passive wet electrodes). It also conducted a simultaneous EEG recording while performing an oddball task during treadmill walking, with speeds of 1 and 2 KPH. The quantitative metrics of pre-stimulus noise, signal-to-noise ratio, and inter-subject correlation from the collected event-related potentials of 18 subjects were assessed. Results indicate that while treating a passive-wet system as benchmark, only the active-electrode design more or less rectified movement artifacts for dry electrodes, whereas the ASR pipeline was substantially compromised by limited electrodes. These findings suggest that a lightweight, minimally obtrusive dry EEG headset should at least equip an active-electrode infrastructure to withstand realistic movement artifacts for potentially sustaining its validity and applicability in real-world scenarios.

Morphological and phylogenetic analyses reveal three new species and one new record of Tubeufia (Tubeufiales, Tubeufiaceae) from southern China.

During an investigation of helicosporous fungi in China, a total of seven helicosporous hyphomycetes were obtained from decaying wood in the southern region of the country. Based on phylogenetic analyses using a combined LSU, ITS, tef1α, and rpb2 sequence matrix, in conjunction with morphological comparisons, these taxa were classified within Tubeufia (Tubeufiaceae, Tubeufiales) and were recognized as three new species, viz. Tubeufiaguttulata, T.hainanensis, and T.muriformis, as well as one new distribution record, viz. T.cocois. Evidence for these new taxa and the new record, descriptions, illustrations, notes, and phylogenetic evidence are provided for the newly collected helicosporous species.

Morphological and Multi-Gene Phylogenetic Analyses Reveal Pseudotubeufia gen. nov. and Two New Species in Tubeufiaceae from China.

Three helicosporous hyphomycete collections representing two species were obtained from rotting wood found in freshwater and terrestrial habitats in the Guizhou and Guangxi Provinces, China. A new genus Pseudotubeufia (Tubeufiaceae, Tubeufiales), comprising Ps. hyalospora sp. nov. and Ps. laxispora sp. nov., was introduced with morphological characteristic and molecular data. In addition, the molecular evidence showed that Helicomyces sp. (G.M. 2020-09-19.1), H. roseus (CBS: 102.76), and the new genus Pseudotubeufia clustered together with high support based on a multi-gene (LSU, ITS, tef1α, and rpb2) phylogenetic analysis. Detailed descriptions, illustrations, and notes of the three new collections are provided.

Additions to the Genus Helicosporium (Tubeufiaceae, Tubeufiales) from China with an Identification Key for Helicosporium Taxa.

Helicosporous hyphomycetes is a group of filamentous fungi that shows promising application prospects in metabolizing bioactive natural compounds. During a study of helicosporous fungi in China, six new helicosporous taxa were collected and isolated from decaying wood in Guangxi Zhuang Autonomous Region, China. Morphological comparisons with multi-gene phylogenetic analyses revealed that these six taxa belong to Helicosporium (Tubeufiaceae, Tubeufiales), and they were recognized as three novel species and were named Helicosporium liuzhouense, H. multidentatum, and H. nanningense. Detailed descriptions and illustrations of the newly discovered taxa and comparisons with similar fungi are provided. In addition, a list and a key to accepted Helicosporium species are provided.

Two new fungal genera (Diaporthales) found on Dipterocarpaceae in Thailand.

Diaporthales is a species-rich order of fungi that includes endophytes, saprobes, and pathogens associated with forest plants and crops. They may also occur as parasites or secondary invaders of plant tissues injured or infected by other organisms or inhabit living animal and human tissues, as well as soil. Meanwhile, some severe pathogens wipe out large-scale cultivations of profitable crops, timber monocultures, and forests. Based on morphological and phylogenetic analyses of combined ITS, LSU, tef1-α, and rpb2 sequence data, generated using maximum likelihood (ML), maximum parsimony (MP), and MrBayes (BI), we introduce two new genera of Diaporthales found in Dipterocarpaceae in Thailand, namely Pulvinaticonidioma and Subellipsoidispora. Pulvinaticonidioma is characterized by solitary, subglobose, pycnidial, unilocular conidiomata with the internal layers convex and pulvinate at the base; hyaline, unbranched, septate conidiophores; hyaline, phialidic, cylindrical to ampulliform, determinate conidiogenous cells and hyaline, cylindrical, straight, unicellular, and aseptate conidia with obtuse ends. Subellipsoidispora has clavate to broadly fusoid, short pedicellate asci with an indistinct J- apical ring; biturbinate to subellipsoidal, hyaline to pale brown, smooth, guttulate ascospores that are 1-septate and slightly constricted at the septa. Detailed morphological and phylogenetic comparisons of these two new genera are provided in this study.