A new species and some new distribution records of the genus Apatetica Westwood from China (Coleoptera, Staphylinidae, Apateticinae).

Five species of Apatetica Westwood, 1848 from China are recorded and illustrated: Apateticaangusticollis sp. nov. from Sichuan, A.confusa Assing, 2018 from Yunnan, A.intermedia Cameron, 1930 from Sichuan, A.laevicollis Fauvel, 1904 from Guangdong and Guangxi, and A.sikkimi Fauvel, 1895 from Xizang. The last four are new to China. The new species is described, and a photograph of a living specimen is presented. Apateticaintermedia and A.sikkimi are redescribed and diagnosed. A key to Chinese species of the genus is provided.

Efficacy of Biologic Therapies for Eosinophilic Otitis Media: A Systematic Review and Meta-analysis.

Eosinophilic otitis media, first reported in Japan, is a viscous, intractable otitis media often linked to bronchial asthma and chronic rhinosinusitis, characterized by highly viscous middle ear effusion. Its pathological mechanism remains unclear and the condition occasionally does not respond to steroids. It is now recognized as a rare type 2 inflammatory disease and should be treated specifically to enhance quality of life. This systematic review and meta-analysis evaluated the efficacies of biologic treatments. We searched PubMed, SCOPUS, Embase, Web of Science, and Cochrane databases up to September 2023. We retrieved ear examination findings, otitis media-related and symptom scores, air-bone gaps and hearing thresholds, serum eosinophil, and immunoglobulin E (IgE) levels before and after biologic treatments. Biologics treatment significantly improved subjective otitis media-related scores, compared with control group (standard mean difference (SMD) -1.62; 95% confidence interval (CI) [-2.24; -1.01], I2=54%). Additionally, the serum eosinophil counts and IgE levels significantly decreased (SMD -1.40; 95% CI [-1.99; -0.81], I 2=0%) after 6-12 months of biologic treatments, but the hearing thresholds did not significantly change. There were no significant differences between groups treated with dupilumab and groups treated with other biologics. Biologics treatment for eosinophilic otitis media significantly improved subjective otitis media-related scores and decreased serum eosinophil and IgE levels, but no significant changes in hearing threshold. More randomized cohort studies are needed to confirm the efficacies of biologics in patients with refractory eosinophilic otitis media.

Triaxial-mechanical and permeability properties of coal body under varying CO2 pressures.

The sequestration of CO2 in coal seams has become an effective way to curb greenhouse-gas emissions. Coal mechanics and permeability properties are key factors affecting the safe sequestration of CO2 in coal seams, and both are significantly affected by the CO2 injection pressure. In this study, triaxial compression-permeability tests were conducted on coal under varying CO2 and limited confining pressures using a measurement system to determine the coupled mechanical properties and adsorption permeability of coal. The effects of CO2 pressure on the mechanical properties and evolution of coal permeability were investigated. A three-dimensional statistical damage constitutive model of coal that considers CO2 adsorption damage was established. The results showed that the stress-strain curve of the coal was divided into four stages. During the first two stages, the amplitudes of the permeability changes were small, whereas at the peak stress point, a permeability "jump" phenomenon occurred, after which an increase in stress resulted in a slower amplitude increase in permeability. The CO2 pressure had an evident damage-deterioration effect on the mechanical properties of the coal samples, and the primary failure characteristic was shearing damage. The higher the CO2 pressure, the higher the degree of internal fragmentation and fracture network complexity of the coal body. During the triaxial compression-permeability experiment, the normalized permeability of the coal samples tended to increase slowly, followed by a rapid increase and back to a slow increase. However, with increasing CO2 pressure, the initial permeability of the coal samples decreased, whereas the normalized permeability increased sharply. The rationality and accuracy of the constitutive model were verified by comparing the established constitutive model and test stress-strain curves of the coal samples. The results of this study can provide theoretical references for CO2 geological storage and facilitate the selection of appropriate CO2 injection pressures.

Genotype of dengue virus serotype 1 in relation to severe dengue in Guangzhou, China.

Guangzhou has been the city most affected by the dengue virus (DENV) in China, with a predominance of DENV serotype 1 (DENV-1). Viral factors such as dengue serotype and genotype are associated with severe dengue (SD). However, none of the studies have investigated the relationship between DENV-1 genotypes and SD. To understand the association between DENV-1 genotypes and SD, the clinical manifestations of patients infected with different genotypes were investigated. A total of 122 patients with confirmed DENV-1 genotype infection were recruited for this study. The clinical manifestations, laboratory tests, and levels of inflammatory mediator factors were statistically analyzed to investigate the characteristics of clinical manifestations and immune response on the DENV-1 genotype. In the case of DENV-1 infection, the incidence of SD with genotype V infection was significantly higher than that with genotype I infection. Meanwhile, patients infected with genotype V were more common in ostealgia and bleeding significantly. In addition, levels of inflammatory mediator factors including IFN-γ, TNF-α, IL-10, and soluble vascular cell adhesion molecule 1 were higher in patients with SD infected with genotype V. Meanwhile, the concentrations of regulated upon activation normal T-cell expressed and secreted and growth-related gene alpha were lower in patients with SD infected with genotype V. The higher incidence of SD in patients infected with DENV-1 genotype V may be attributed to elevated cytokines and adhesion molecules, along with decreased chemokines.

An immunophenotype-coupled transcriptomic atlas of human hematopoietic progenitors.

Analysis of the human hematopoietic progenitor compartment is being transformed by single-cell multimodal approaches. Cellular indexing of transcriptomes and epitopes by sequencing (CITE-seq) enables coupled surface protein and transcriptome profiling, thereby revealing genomic programs underlying progenitor states. To perform CITE-seq systematically on primary human bone marrow cells, we used titrations with 266 CITE-seq antibodies (antibody-derived tags) and machine learning to optimize a panel of 132 antibodies. Multimodal analysis resolved >80 stem, progenitor, immune, stromal and transitional cells defined by distinctive surface markers and transcriptomes. This dataset enables flow cytometry solutions for in silico-predicted cell states and identifies dozens of cell surface markers consistently detected across donors spanning race and sex. Finally, aligning annotations from this atlas, we nominate normal marrow equivalents for acute myeloid leukemia stem cell populations that differ in clinical response. This atlas serves as an advanced digital resource for hematopoietic progenitor analyses in human health and disease.

Higher mortality and longer length of stay in hospitalized patients with newly diagnosed diabetes.

AIMS: We investigated the association between diabetes status at admission and in-hospital outcomes in all hospitalized patients, regardless of the reason for admission. METHODS: All individuals aged 20 years or older who were admitted to Yongin Severance Hospital between March 2020 and February 2022 were included in study. Subjects were categorized into three groups: non-DM, known DM, and newly diagnosed DM, based on medical history, anti-diabetic medications use, and laboratory test. Hospitalization-related outcomes, including in-hospital mortality and length of hospital stay, were compared between groups. RESULTS: 33,166 participants were enrolled. At hospitalization, 6,572 (19.8 %) subjects were classified as known DM, and another 2,634 (7.9 %) subjects were classified as newly diagnosed DM. In-hospital mortality was highest in newly diagnosed DM (HR 1.89, 95% CI 1.58-2.26, p < 0.001) followed by known DM (HR 1.41, 95% CI 1.18-1.69, p < 0.001) compared to non-DM. Length of hospital stay was significantly longer in newly diagnosed DM (median [IQR] 9.0 [5.0-18.0],days) than known DM (median [IQR] 5.0 [3.0-10.0],days)(p < 0.001) and non-DM (median [IQR] 4.0 [2.0-7.0],days). After adjusting for multiple covariates, newly diagnosed diabetes was independently associated with increased in-hospital mortality (p < 0.001). CONCLUSIONS: Diabetes status at admission was closely linked to hospitalization-related outcomes. Notably, individuals with newly diagnosed diabetes demonstrated a higher risk of in-hospital mortality and a prolonged length of hospital stay.

Robust Chemical Synthesis of "Difficult Peptides" via 2-Hydroxyphenol-pseudoproline (ψ2-hydroxyphenolpro) Modifications.

The challenging preparation of "difficult peptides" has always hindered the development of peptide-active pharmaceutical ingredients. Pseudoproline (ψpro) building blocks have been proven effective and powerful tools for the synthesis of "difficult peptides". In this paper, we efficiently prepared a set of novel 2-(oxazolidin-2-yl)phenol compounds as proline surrogates (2-hydroxyphenol-pseudoprolines, ψ2-hydroxyphenolpro) and applied it in the synthesis of many well-known "difficult peptides", including human thymosin α1, amylin, and ß-amyloid (1-42) (Aß42).

Synthesis and antimicrobial studies of cadasides analogues via on-resin esterification.

A series of cadasides analogues have been prepared via a combination of solid-phase peptide synthesis and solution-phase cyclization. Primary structure-activity relationship studies of cadasides have also been established and revealed the critical roles of unnatural amino acid residues, which will facilitate the further development of cadasides analogues with improved antimicrobial activities.

Huoxue Tongluo decoction combined with acupuncture in the treatment of lumbar disc herniation and its effect on JOA and VAS scores.

BACKGROUND: Lumbar disc herniation (LDH) is a common clinical disease of the skeletal system, and its prevalence has been on a rise. OBJECTIVE: To evaluate the efficacy of Huoxue Tongluo decoction plus acupuncture in the treatment of lumbar disc herniation and its effectiveness in improving the functional recovery of the patients' affected joints and mitigating their pain. METHODS: In this prospective study, 110 patients with lumbar disc herniation enrolled in our Hospital from June 2019 to June 2021 were collected and randomized to receive either conventional treatment (control group) or Huoxue Tongluo Decoction plus acupuncture (study group). RESULTS: Huoxue Tongluo Decoction plus acupuncture resulted in more rapid mitigation of lower extremity symptoms and lumbar symptoms versus conventional treatment (P< 0.05). Patients receiving traditional Chinese medicine (TCM) showed milder inflammatory responses than those with conventional medication, as evidenced by the lower serum concentrations of tumor necrosis factor-α (TNF-α), interleukin (IL)-6, and high-sensitivity C-reactive protein (hs-CRP) (P< 0.05). After treatment, the study group had higher Japanese Orthopedic Association (JOA) scores and lower visual analogue scale (VAS) scores than the control group (P< 0.05), suggesting that the combination of the herbal decoction and acupuncture provided better functional recovery of the affected joints and pain mitigation for the patients. Furthermore, the lower Pittsburgh sleep quality index (PSQI) scores in patients in the study group indicated better sleep quality of patients after TCM intervention than after conventional treatment (P< 0.05). Huoxue Tongluo Decoction plus acupuncture was associated with a significantly higher efficacy (94.55%) versus conventional treatment (80%) (P< 0.05). CONCLUSIONS: Huoxue Tongluo Decoction combined with acupuncture significantly offers a viable treatment alternative for lumbar disc herniation with promising treatment outcomes, mitigates patients' limb pain, and improves their lumbar function and sleep quality. Further trials are, however, required prior to general application in clinical practice.

Single-cell m6A mapping in vivo using picoMeRIP-seq.

Current N6-methyladenosine (m6A) mapping methods need large amounts of RNA or are limited to cultured cells. Through optimized sample recovery and signal-to-noise ratio, we developed picogram-scale m6A RNA immunoprecipitation and sequencing (picoMeRIP-seq) for studying m6A in vivo in single cells and scarce cell types using standard laboratory equipment. We benchmark m6A mapping on titrations of poly(A) RNA and embryonic stem cells and in single zebrafish zygotes, mouse oocytes and embryos.

Pembrolizumab for Patients with Relapsed or Refractory Extranodal NK/T-Cell Lymphoma in Korea / Journal of the Korean Cancer Association, 대한암학회지

Purpose@#Programmed death-1 blockade with pembrolizumab has shown promising activity in relapsed/refractory (R/R) extranodal natural killer/T-cell lymphoma (NKTCL), but studies are limited, with small patient numbers. @*Materials and Methods@#Thirteen institutes involved with the Consortium for Improving Survival of Lymphoma, a Korean lymphoma study group, collected the clinical data of 59 patients treated with pembrolizumab as salvage therapy between 2016 and 2022. @*Results@#The median age of the patients was 60 years (range, 22 to 87 years), and 76.3% had advanced Ann Abor stage disease. Pembrolizumab was given to 35.6%, 40.7%, and 23.7% of the patients as second-, third-, and fourth- or higher-line chemotherapy, respectively. The overall response rate was 40.7%, with 28.8% having complete response. The estimated 2-year progression-free survival (PFS) and overall survival rates for all patients were 21.5% and 28.7%, respectively; for responders, the rates were 53.0% and 60.7%, respectively. Although not statistically significant, Eastern Cooperative Oncology Group performance status ≥ 2 (hazard ratio [HR], 1.91; 95% confidence interval [95% CI], 0.93 to 3.94; p=0.078) and stage III or IV disease (HR, 2.59; 95% CI, 0.96 to 6.96; p=0.060) were associated with a trend toward shorter PFS in multivariate analysis. Grade 3 or 4 adverse events (AEs) were noted in 12 patients (20.3%); neutropenia (10.2%), fatigue (6.8%), and pneumonitis (5.1%) were most common AEs. @*Conclusion@#In conclusion, while pembrolizumab had a modest effect on patients with R/R NKTCL, it may be a useful salvage therapy for patients with localized disease and good performance status.

SoUth Korean study to PrEvent cognitive impaiRment and protect BRAIN health through Multidomain interventions via facE-to-facE and video communication plaTforms in mild cognitive impairment (SUPERBRAIN-MEET): Protocol for a Multicenter Randomized Controlled Trial

Background@#and Purpose: The SoUth Korea study to PrEvent cognitive impaiRment and protect BRAIN health through lifestyle intervention (SUPERBRAIN) proved the feasibility of multidomain intervention for elderly people. One-quarter of the Korean population over 65 years of age has mild cognitive impairment (MCI). Digital health interventions may be costeffective and have fewer spatial constraints. We aim to examine the efficacy of a multidomain intervention through both face-to-face interactions and video communication platforms using a tablet personal computer (PC) application in MCI. @*Methods@#Three hundred participants aged 60–85 years, with MCI and at least one modifiable dementia risk factor, will be recruited from 17 centers and randomly assigned in a 1:1 ratio to the multidomain intervention and the waiting-list control groups. Participants will receive the 24-week intervention through the tablet PC SUPERBRAIN application, which encompasses the following five elements: managing metabolic and vascular risk factors, cognitive training,physical exercise, nutritional guidance, and boosting motivation. Participants will attend the interventions at a facility every 1–2 weeks. They will also engage in one or two self-administered cognitive training sessions utilizing the tablet PC application at home each week. They will participate in twice or thrice weekly online exercise sessions at home via the ZOOM platform. The primary outcome will be the change in the total scale index score of the Repeatable Battery for the Assessment of Neuropsychological Status from baseline to study end. @*Conclusions@#This study will inform the effectiveness of a comprehensive multidomain intervention utilizing digital technologies in MCI.

Hyperammonemic Encephalopathy Caused by the c.386+5G>A Mutation in OTC Gene in a Young Adult Woman

Noncirrhotic hyperammonemia as a cause of acute confusion remains diagnostic challenge. Deficiency of ornithine transcarbamylase (OTC) is the urea cycle disorder, inborn errors caused by a defect of the enzymes in the urea cycle, leading to an accumulation of ammonia mainly in newborn. There were very few cases, in which OTC deficiency result in hyperammonemia in adulthood. Herein, we report a young adult woman of hyperammonemic encephalopathy with OTC deficiency, diagnosed by high blood ammonia, glutamine and low plasma levels of citrulline. Next generation sequencing showed the c.386+5G>A mutation of the OTC gene.

Surgical management of giant adrenal myelolipoma using a modified Makuuchi incision: a case report / 고신대학교의과대학학술지

Giant adrenal myelolipomas are rare, benign, and hormonally inactive tumors. We present the case of a 53-year-old man with a 19-cm retroperitoneal mass, initially suspected to be a retroperitoneal liposarcoma, angiomyolipoma, or adrenal myelolipoma. After conducting endocrine assessments, which were within normal ranges, we decided to perform surgical excision using a modified Makuuchi incision. The tumor was successfully removed, and the final pathological examination confirmed the diagnosis of adrenal myelolipoma. The patient was discharged with no complications and remained without disease recurrence or distant metastasis as of 1 year postoperatively. In conclusion, giant myelolipomas are rare and cause symptoms owing to their large size. Surgical removal is recommended for large or symptomatic myelolipomas. The modified Makuuchi incision allows efficient and safe tumor removal in open surgery for giant myelolipomas.

Bering: joint cell segmentation and annotation for spatial transcriptomics with transferred graph embeddings.

Single-cell spatial transcriptomics such as in-situ hybridization or sequencing technologies can provide subcellular resolution that enables the identification of individual cell identities, locations, and a deep understanding of subcellular mechanisms. However, accurate segmentation and annotation that allows individual cell boundaries to be determined remains a major challenge that limits all the above and downstream insights. Current machine learning methods heavily rely on nuclei or cell body staining, resulting in the significant loss of both transcriptome depth and the limited ability to learn latent representations of spatial colocalization relationships. Here, we propose Bering, a graph deep learning model that leverages transcript colocalization relationships for joint noise-aware cell segmentation and molecular annotation in 2D and 3D spatial transcriptomics data. Graph embeddings for the cell annotation are transferred as a component of multi-modal input for cell segmentation, which is employed to enrich gene relationships throughout the process. To evaluate performance, we benchmarked Bering with state-of-the-art methods and observed significant improvement in cell segmentation accuracies and numbers of detected transcripts across various spatial technologies and tissues. To streamline segmentation processes, we constructed expansive pre-trained models, which yield high segmentation accuracy in new data through transfer learning and self-distillation, demonstrating the generalizability of Bering.

Spatiotemporal variability and environmental effects of greenhouse gases, nutrients, and dissolved carbons in an ice-covered reservoir.

Ice cover restructures the distribution of substances in ice and underlying water and poses non-negligible environmental effects. This study aimed to clarify the spatiotemporal variability and environmental effects of methane (CH4), nitrous oxide (N2O), total nitrogen (TN), total phosphorus (TP), dissolved organic carbon (DOC), and dissolved inorganic carbon (DIC) in ice and water columns during different ice-covered periods. We surveyed the ice-growth, ice-stability, and ice-melt periods in an ice-covered reservoir located in Northeast China. The results showed that underlying water (CH4: 1218.9 ± 2678.9 nmol L-1 and N2O: 19.3 ± 7.3 nmol L-1) and ice (CH4: 535.2 ± 2373.1 nmol L-1 and N2O: 9.9 ± 1.5 nmol L-1) were sources of atmospheric greenhouse gases. N2O concentrations were the highest in the bottom water of the reservoir while CH4 accumulated the most below the ice in the riverine zone. These can be attributed to differences in the solubilities and relative molecular masses of the two gases. Higher concentrations of N2O, TN, TP, DOC, and DIC were recorded in the underlying water than those in the ice due to the preferential redistribution of these substances in the aqueous phase during ice formation. Additionally, we distinguished between bubble and no-bubble areas in the riverine zone and found that the higher CH4 concentrations in the underlying water than those in the ice were due to CH4 bubbles. In addition, we reviewed various substances in ice-water systems and found that the substances in ice-water systems can be divided into solute exclusion and particle entrapment, which are attributed to differences between dissolved and particulate states. These findings are important for a comprehensive understanding of substances dynamics during ice-covered periods.

Objective Assessment of Visual Field Defects Caused by Optic Chiasm and Its Posterior Visual Pathway Injury.

OBJECTIVES: To investigate the characteristics and objective assessment method of visual field defects caused by optic chiasm and its posterior visual pathway injury. METHODS: Typical cases of visual field defects caused by injuries to the optic chiasm, optic tracts, optic radiations, and visual cortex were selected. Visual field examinations, visual evoked potential (VEP) and multifocal visual evolved potential (mfVEP) measurements, craniocerebral CT/MRI, and retinal optical coherence tomography (OCT) were performed, respectively, and the aforementioned visual electrophysiological and neuroimaging indicators were analyzed comprehensively. RESULTS: The electrophysiological manifestations of visual field defects caused by optic chiasm injuries were bitemporal hemianopsia mfVEP abnormalities. The visual field defects caused by optic tract, optic radiation, and visual cortex injuries were all manifested homonymous hemianopsia mfVEP abnormalities contralateral to the lesion. Mild relative afferent pupil disorder (RAPD) and characteristic optic nerve atrophy were observed in hemianopsia patients with optic tract injuries, but not in patients with optic radiation or visual cortex injuries. Neuroimaging could provide morphological evidence of damages to the optic chiasm and its posterior visual pathway. CONCLUSIONS: Visual field defects caused by optic chiasm, optic tract, optic radiation, and visual cortex injuries have their respective characteristics. The combined application of mfVEP and static visual field measurements, in combination with neuroimaging, can maximize the assessment of the location and degree of visual pathway damage, providing an effective scheme for the identification of such injuries.

Guided construction of single cell reference for human and mouse lung.

Accurate cell type identification is a key and rate-limiting step in single-cell data analysis. Single-cell references with comprehensive cell types, reproducible and functionally validated cell identities, and common nomenclatures are much needed by the research community for automated cell type annotation, data integration, and data sharing. Here, we develop a computational pipeline utilizing the LungMAP CellCards as a dictionary to consolidate single-cell transcriptomic datasets of 104 human lungs and 17 mouse lung samples to construct LungMAP single-cell reference (CellRef) for both normal human and mouse lungs. CellRefs define 48 human and 40 mouse lung cell types catalogued from diverse anatomic locations and developmental time points. We demonstrate the accuracy and stability of LungMAP CellRefs and their utility for automated cell type annotation of both normal and diseased lungs using multiple independent methods and testing data. We develop user-friendly web interfaces for easy access and maximal utilization of the LungMAP CellRefs.

Schizophrenia-associated NRXN1 deletions induce developmental-timing- and cell-type-specific vulnerabilities in human brain organoids.

De novo mutations and copy number deletions in NRXN1 (2p16.3) pose a significant risk for schizophrenia (SCZ). It is unclear how NRXN1 deletions impact cortical development in a cell type-specific manner and disease background modulates these phenotypes. Here, we leveraged human pluripotent stem cell-derived forebrain organoid models carrying NRXN1 heterozygous deletions in isogenic and SCZ patient genetic backgrounds and conducted single-cell transcriptomic analysis over the course of brain organoid development from 3 weeks to 3.5 months. Intriguingly, while both deletions similarly impacted molecular pathways associated with ubiquitin-proteasome system, alternative splicing, and synaptic signaling in maturing glutamatergic and GABAergic neurons, SCZ-NRXN1 deletions specifically perturbed developmental trajectories of early neural progenitors and accumulated disease-specific transcriptomic signatures. Using calcium imaging, we found that both deletions led to long-lasting changes in spontaneous and synchronous neuronal networks, implicating synaptic dysfunction. Our study reveals developmental-timing- and cell-type-dependent actions of NRXN1 deletions in unique genetic contexts.