[Research progress of PD-L1 in inflammatory lung diseases].

Programmed death-ligand 1 (PD-L1) is important in maintaining central and peripheral immune tolerance in normal tissues, mediating tumor immune escape and keeping the balance between anti- and pro-inflammatory responses. Inflammation plays an important role in inflammatory lung diseases. This article reviews the research progress and potential clinical value of PD-L1 in inflammatory lung diseases, including acute lung injury, chronic obstructive pulmonary disease, asthma and idiopathic pulmonary fibrosis.

An effective strategy for assembling the sex-limited chromosome.

BACKGROUND: Most currently available reference genomes lack the sequence map of sex-limited (such as Y and W) chromosomes, which results in incomplete assemblies that hinder further research on sex chromosomes. Recent advancements in long-read sequencing and population sequencing have provided the opportunity to assemble sex-limited chromosomes without the traditional complicated experimental efforts. FINDINGS: We introduce the first computational method, Sorting long Reads of Y or other sex-limited chromosome (SRY), which achieves improved assembly results compared to flow sorting. Specifically, SRY outperforms in the heterochromatic region and demonstrates comparable performance in other regions. Furthermore, SRY enhances the capabilities of the hybrid assembly software, resulting in improved continuity and accuracy. CONCLUSIONS: Our method enables true complete genome assembly and facilitates downstream research of sex-limited chromosomes.

Causal link between gut microbiota and osteoporosis analyzed via Mendelian randomization.

OBJECTIVE: Osteoporosis (OP) is closely associated with gut microbiota (GM), yet the nature of their causal relationship remains elusive. Therefore, this study aims to reverse causality between GM and OP by using population cohorts and two-sample MR (TSMR) analysis. MATERIALS AND METHODS: In this study, we conducted an extensive genome-wide association study (GWAS) using publicly accessible summary statistics data for GM and OP. Employing rigorous criteria (p < 1*e-5), we identified independent genetic loci that exhibited significant associations with GM relative abundances as instrumental variables (IVs). A causal evaluation was primarily carried out using the inverse variance-weighted (IVW) method, supplemented by additional analyses such as MR-Egger, weighted median, simple mode, and weighted mode. RESULTS: We unveiled that increased abundances of the family Pasteurellaceae, order Pasteurellales, and genus Ruminococcaceae UCG004 were linked to an increased risk of OP. Conversely, the family Oxalobacteraceae, unknown family id.1000006161, genus Lachnospiraceae NK4A136 group, unknown genus id.1000006162, and order NB1n were associated with a reduced risk of OP. To ensure the reliability of our findings, we conducted quality assessments through Cochrane's Q test and a leave-one-out analysis. Furthermore, the stability and consistency of the results were confirmed by the MR-Egger intercept test, Mendelian randomization pleiotropy residual sum and outlier (MR-PRESSO) global test, and sensitivity analysis (p > 0.05). Our study reveals the causal relationships between 211 GM taxa and OP, pinpointing specific GM taxa associated with the risk of OP. This research sheds light on the genetic mechanisms that underlie GM-mediated OP and opens up promising avenues for identifying valuable biomarkers and potential therapeutic targets in future OP research. CONCLUSIONS: This study establishes a substantial GM-OP link with specific taxa being identified, offering biomarkers for early detection, tailored interventions, and improved patient education. These findings enhance OP diagnosis, prevention, and treatment, promising more effective, individualized care and inspiring future research.

High-Resolution Laminar Identification in Macaque Primary Visual Cortex Using Neuropixels Probes.

Laminar electrode arrays allow simultaneous recording of activity of many cortical neurons and assignment to correct layers using current source density (CSD) analyses. Electrode arrays with 100-micron contact spacing can estimate borders between layer 4 versus superficial or deep layers, but in macaque primary visual cortex (V1) there are far more layers, such as 4A which is only 50-100 microns thick. Neuropixels electrode arrays have 20-micron spacing, and thus could potentially discern thinner layers and more precisely identify laminar borders. Here we show that CSD signals lack the spatial resolution required to take advantage of high density Neuropixels arrays and describe the development of approaches based on higher resolution electrical signals and analyses, including spike waveforms and spatial spread, unit density, high-frequency action potential (AP) power spectrum, temporal power change, and coherence spectrum, that afford far higher resolution of laminar distinctions, including the ability to precisely detect the borders of even the thinnest layers of V1.

Exotic Dark Matter Search with the Majorana Demonstrator.

With excellent energy resolution and ultralow-level radiogenic backgrounds, the high-purity germanium detectors in the Majorana Demonstrator enable searches for several classes of exotic dark matter (DM) models. In this work, we report new experimental limits on keV-scale sterile neutrino DM via the transition magnetic moment from conversion to active neutrinos ν_{s}→ν_{a}. We report new limits on fermionic dark matter absorption (χ+A→ν+A) and sub-GeV DM-nucleus 3→2 scattering (χ+χ+A→ϕ+A), and new exclusion limits for bosonic dark matter (axionlike particles and dark photons). These searches utilize the (1-100)-keV low-energy region of a 37.5-kg y exposure collected by the Demonstrator between May 2016 and November 2019 using a set of ^{76}Ge-enriched detectors whose surface exposure time was carefully controlled, resulting in extremely low levels of cosmogenic activation.

[Physical activity and its influencing factors in patients with diabetes mellitus: a comparative study between China and the United Kingdom].

Objective: To compare the differences in low-level physical activity (PA) and related influencing factors in patients with diabetes mellitus in China and the United Kingdom (UK). Methods: Using baseline survey data from the China Kadoorie Biobank and the UK Biobank, we analyzed the association between diabetes mellitus and low-level PA using logistic regression, with the participants' self-reported whether they had diabetes mellitus as the independent variable, and low-level PA as the dependent variable. Results: We included 509 254 Chinese adults and 359 763 British adults in the analysis. After adjusting for multiple factors, we found that both Chinese and British patients with diabetes mellitus were at elevated risk for low-level PA, with corresponding ORs (95%CIs) of 1.15 (1.12-1.19) and 1.37 (1.32-1.41), respectively. Patients with diabetes mellitus with longer disease duration and poorer glycemic control were at greater risk of having low-level of PA. Female, rural-distributed, employed, never-smoking Chinese diabetics, and male, urban-distributed, retired/unemployed, quit-smoking British diabetics were more likely to have low-level PA. Conclusions: Chinese and British patients with diabetes mellitus were more likely to have low-level PA compared with the general population, but the risk of low-level PA for patients in both countries varied by population characteristics. Therefore, PA guidelines and intervention measures should be based on the characteristics of individuals in the target countries and regions, which could improve PA levels among patients with diabetes mellitus.

[Efficacy of 0.05% cyclosporine A combined with vitamin A palmitate in the treatment of meibomian gland dysfunction-related dry eye].

Objective: To evaluate the efficacy of 0.05% cyclosporine A eye drops combined with vitamin A palmitate eye gel in the treatment of dry eye associated with meibomian gland dysfunction (MGD). Methods: A single-center, prospective, randomized, parallel controlled trial design was used to include patients diagnosed with MGD-associated dry eye. The patients were randomly divided into three groups and administered with medications binocularly for 12 weeks. The CsA+VA group was given 0.05% cyclosporine A eye drops twice a day and vitamin A palmitate eye gel three times a day. The CsA+HA group was given 0.05% cyclosporine A eye drops twice a day and 0.1% sodium hyaluronate eye drops three times a day. The HA group was given 0.1% sodium hyaluronate eye drops 3 times a day. The OSDI score, tear meniscus height, fluorescein tear break-up time, Schirmer Ⅰ test (without anesthesia), tear film lipid layer thickness, meibomian gland morphology and function examination, and corneal fluorescein sodium staining score were evaluated at baseline, 4, 8, and 12 weeks after the initiation of the treatment, respectively. Results: A total of 120 patients with MGD-related dry eye met the enrollment criteria, but 10 patients were lost to follow-up; 110 patients were finally included for observation, including 36 patients in the CsA+VA group, 38 in the CsA+HA group and 36 in the HA group. The OSDI score, tear meniscus height, fluorescein tear break-up time and meibomian gland secretion of the 3 groups were significantly improved. At the 12th week of the treatment, the differences of the CsA+VA group [25.45±15.11, (0.30±0.13) mm, (3.72±1.40) s, (5.03±2.52) points] and the CsA+HA group [26.98±16.89, (0.27±0.10) mm, (4.34±1.76) s, (5.11±2.39) points] from the HA group [24.57±11.26, (0.24±0.06) mm, (3.18±1.11) s, (9.11±3.34) points] were statistically significant (P<0.05). Compared with the CsA+HA group [(68.39±26.66) nm], the tear film lipid layer thickness in the CsA+VA group [(72.61±23.65) nm] was significantly increased (P<0.05). In the CsA+VA group, the meibomian gland secretion characters and discharge capacity among patients with severe abnormalities [(6.28±2.59) and (5.89±2.77) points at the 12th week of treatment], moderate abnormalities [(4.27±2.02) and (4.64±2.02) points at the 12th week of treatment] and mild abnormalities [(2.80±0.84) and (2.60±0.55) points at the 12th week of treatment] were significantly different (P<0.05). Conclusion: 0.05% cyclosporine A combined with vitamin A palmitate can significantly improve the symptoms and signs of patients with MGD-related dry eye, especially the tear film lipid layer thickness and the meibomian gland secretion characters and discharge capacity in severe cases.

[Epidemiological characteristics of severe fever with thrombocytopenia syndrome in China, 2018-2021].

Objective: To understand the epidemiological characteristics and incidence trend of severe fever with thrombocytopenia syndrome (SFTS) in China. Methods: The incidence data of SFTS in China from 2018 to 2021 were collected from Chinese Disease Prevention and Control Information System for a statistical and descriptive epidemiological analysis by using software such as Excel 2016, Joinpoint 5.0.2, SPSS 26.0, and GraphPad Prism 8.0, especially, the SFTS cases reported monthly by key provinces were analyzed. Results: From 2018 to 2021, a total of 8 835 SFTS cases were reported in 25 provinces and the annual incidence showed an upward trend. The distribution of SFTS cases showed clustering, but the cases were mainly sporadic ones. The cases began to increase in March, mainly occurred during April to October (96.79%,8 551/8 835), and peaked during May to July. The cases were mainly distributed in middle-aged and old farmers, and slight more cases were women. The average case fatality rate was 5.38%, which varied greatly with areas. The case fatality rate tended to increase with age. Conclusion: From 2018 to 2021, the epidemiological characteristics of SFTS in China remained stable, but the number of reported cases gradually increased and the distribution showed an expanding trend, to which close attention should be paid.

[Mutation characteristics of angioimmunoblastic T-cell lymphoma: an analysis of 75 cases].

Objective: To investigate the characteristics of gene mutations in angioimmunoblastic T-cell lymphoma (AITL). Methods: Seventy-five AITL cases diagnosed at the Department of Pathology, Ruijin Hospital Affiliated to Shanghai Jiaotong University School of Medicine, Shanghai, China from June 2021 to June 2023 were included. Their formalin-fixed and paraffin-embedded or fresh tissues were subject to targeted next generation sequencing (NGS). The sequencing data was collected, and the distribution and type of gene mutations were analyzed. Results: 492 potential driver mutations were identified in 74 out of the 84 genes. Targeted sequencing data for the 75 AITL patients showed that the genes with mutation frequencies of ≥10% were TET2 (89.3%), RHOA (57.3%), IDH2 (37.3%), DNMT3A (36.0%), KMT2C (21.3%), PLCG1 (12.0%), and KDM6B (10.7%). There were significant co-occurrence relationships between TET2 and RHOA, TET2 and IDH2, and RHOA and IDH2 gene mutations (P<0.05), respectively, while TET2 and KDM6B gene mutations were mutually exclusive (P<0.05). Conclusions: The study reveals the mutational characteristics of AITL patients using NGS technology, which would provide insights for molecular diagnosis and targeted therapy of AITL.

[Exploring the factors affecting music-related quality of life in post-lingual deaf adults with cochlear implants].

Objective: To observe the feelings of listening to music and the importance of music in the daily life of post-lingual deaf adults with cochlear implants, and to explore the relevant influencing factors. Methods: This was a cross-sectional survey study. From January 2021 to August 2021,the Music-Related Quality of Life Scale was used to evaluate the music needs and music experiences of 63 post-lingual deaf adults who met the inclusion criteria, including 27 males and 36 females, aged (40.7±12.3) years, at the time of surgery (36.8±13.1) years, and with a preoperative hearing aid ineffective time of (3.9±5.8) years. Indicators analyzed included age, duration of ineffective preoperative hearing aid wear, preoperative music preference, duration of postoperative cochlear implant use, current hearing aid modality, and auditory rehabilitation outcomes. Whether the six factors mentioned above constituted an influence on the subjects' music listening was investigated using SPSS 25.0 statistical software. Results: All of the observations in the scale were correlated with a single factor. The two sub-dimensions of music experience section were related to the effect of auditory rehabilitation. In the importance section, the effect of auditory rehabilitation was the influential factor of the dimension of "participation importance", and the preoperative enjoyment of music was the relevant influential factor of the dimension of "perceived importance". There was a significant difference between the groups when they were grouped by the above factors (P value<0.05), while there was no statistically significance between the groups when they were grouped by other factors (P value>0.05). Conclusions: Post-lingual deaf adults show the need and attempt to listen to music after cochlear implantation. The effectiveness of auditory rehabilitation and the degree of music preference preoperatively are two important factors that influence music listening in implant recipients. Once the level of auditory communication has been restored to a certain degree, it is important to pay more attention to the needs of music for implant recipients and train them in time, especially for those with music preferences preoperatively.

Artificial intelligence model GPT4 narrowly fails simulated radiological protection exam.

This study assesses the efficacy of Generative Pre-Trained Transformers (GPT) published by OpenAI in the specialised domains of radiological protection and health physics. Utilising a set of 1064 surrogate questions designed to mimic a health physics certification exam, we evaluated the models' ability to accurately respond to questions across five knowledge domains. Our results indicated that neither model met the 67% passing threshold, with GPT-3.5 achieving a 45.3% weighted average and GPT-4 attaining 61.7%. Despite GPT-4's significant parameter increase and multimodal capabilities, it demonstrated superior performance in all categories yet still fell short of a passing score. The study's methodology involved a simple, standardised prompting strategy without employing prompt engineering or in-context learning, which are known to potentially enhance performance. The analysis revealed that GPT-3.5 formatted answers more correctly, despite GPT-4's higher overall accuracy. The findings suggest that while GPT-3.5 and GPT-4 show promise in handling domain-specific content, their application in the field of radiological protection should be approached with caution, emphasising the need for human oversight and verification.

Bronchial embolisation for infected pulmonary artery pseudoaneurysms causing haemoptysis.

AIM: To report the authors' experience of bronchial artery embolisation (BAE) in a series of patients to control haemoptysis associated with infected pulmonary artery pseudoaneurysms (PAPs). MATERIALS AND METHODS: All patients who underwent BAE based on computed tomography angiography (CTA) findings indicative of haemoptysis between February 2019 and September 2022 at Xiangyang Central Hospital were identified. Charts of patients with haemoptysis and infectious PAPs were reviewed retrospectively. Data were collected data on age, sex, underlying pathology, source pulmonary artery of the PAP, association with cavitary lesions or consolidation, systemic angiography findings, technical and clinical success, and follow-up. RESULTS: Seventeen PAPs were treated in 16 patients, with a mean age of 60.3 years (range: 37-82 years). The most common underlying cause was tuberculosis (15/16, 93.8%). Imaging by CTA did not identify the source pulmonary artery for 15 (88.2%) PAPs; all were associated with cavitary lesions or consolidation. All PAPs were visualised on systemic angiography. The technical and clinical success rates were both 87.5%. Two patients who experienced a recurrence of haemoptysis during follow-up underwent repeat CTA, which confirmed the elimination of the previous PAP. CONCLUSION: BAE may be a valuable technique to control haemoptysis associated with infectious PAPs that are visualised on systemic angiography. A possible contributing factor is PAPs arising from very small pulmonary arteries.

Incidence and risk factors for subsequent infections among rectal carriers with carbapenem-resistant Klebsiella pneumoniae: a systematic review and meta-analysis.

BACKGROUND: Carbapenem-resistant Klebsiella pneumoniae (CRKp) is a major pathogen causing nosocomial infections with a high mortality and poor prognosis. Gastrointestinal carriage has been acknowledged as the primary reservoir of CRKp infections. AIM: To explore the incidence and risk factors associated with CRKp infection following colonization. METHODS: The PubMed, Web of Science, and Cochrane Library databases were searched for relevant articles published between December 1998 and June 2023. Pooled estimates with a 95% confidence interval (CI) were calculated for the incidence rate, whereas pooled odds ratios (ORs) were calculated for the risk factors for which the OR was reported in three or more studies. FINDINGS: Fourteen studies were included in the review with 5483 patients for the assessment of incidence, whereas seven of these studies with 2170 patients were included for the analysis of risk factors. In the meta-analysis, the incidence of CRKp infections after colonization was 23.2% (17.9-28.5). Additionally, three independent risk factors for subsequent CRKp infections were identified as admission to the intensive care unit (ICU) (2.59; 95% CI: 1.64-4.11), invasive procedures (2.53; 95% CI: 1.59-4.03), and multi-site colonization (6.24; 95% CI: 2.38-16.33). CONCLUSION: This review reveals the incidence of CRKp infections in rectal carriers in different countries, emphasizing the role of rectal colonization with CRKp as an important source of nosocomial infections. Significantly, the risk factors indicated in this review can assist clinicians in identifying CRKp carriers with an elevated risk of subsequent infections, thereby enabling further measures to be taken to prevent nosocomial infections.

Anthropogenic, biogenic, and photochemical influences on surface formaldehyde and its significant decadal (2006-2017) decrease in the Lewiston-Clarkston valley of the northwestern United States.

Formaldehyde (HCHO) is a key carcinogen and plays an important role in atmospheric chemistry. Both field measurements and Positive Matrix Factorization (PMF) modeling have been employed to investigate the concentrations and sources of HCHO in the Lewiston-Clarkston (LC) valley of the mountainous northwestern U.S. Different instruments were deployed to measure surface formaldehyde and other related compounds in July of 2016 and 2017. The measurements reveal that the average HCHO concentrations have significantly decreased to 2-5 ppb in the LC valley in comparison to its levels (10-20 ppb) observed in July 2006. This discovery with surface measurements deserves attention given that satellite retrievals showed an increasing long-term trend from 2005 to 2014 in total vertical column density of HCHO in the region, suggesting that satellite instruments may not adequately resolve small valleys in the mountainous region. Our PMF modeling identified four major sources of HCHO in the valley: (1) emissions from a local paper mill, (2) secondary formation and background, (3) biogenic sources, and (4) traffic. This study reveals that the emissions from the paper mill cause high HCHO spikes (6-19 ppb) in the early morning. It is found that biogenic volatile organic compounds (VOCs) in the area are influenced by national forests surrounding the region (e.g., Nez Perce-Clearwater, Umatilla, Wallowa-Whitman, and Idaho Panhandle National Forests). The results provide useful information for developing strategies to control HCHO levels and have implications for future HCHO studies in atmospheric chemistry, which affects secondary aerosols and ozone formation.

[Regulatory mechanisms and clinical significance of circadian disruption in intensive care unit patients].

Organisms adapt to the circadian changes in the external environment by regulating various life activity processes and establishing regular circadian cycles. A growing number of studies indicate that there is an extensive association between circadian disruption and critical illness, and circadian disruption is a pathological syndrome influencing the clinical outcome of critically ill patients. As a result of the disease itself, the ICU environment and medical interventions, critically ill patients often experience severe circadian disruption, which leads to aberrations in a wide range of physiological and behavioral functions of the organism, and finally exacerbates disease progression. In this paper, we reviewed the regulatory mechanisms of biological circadian rhythms, the causes and consequences of circadian disruption in critically ill patients, the assessment of circadian disruption, and strategies to restore circadian homeostasis to assist in the comprehensive treatment of critically ill patients.

Constraints on the Decay of

^{180m}Ta is a rare nuclear isomer whose decay has never been observed. Its remarkably long lifetime surpasses the half-lives of all other known ß and electron capture decays due to the large K-spin differences and small energy differences between the isomeric and lower-energy states. Detecting its decay presents a significant experimental challenge but could shed light on neutrino-induced nucleosynthesis mechanisms, the nature of dark matter, and K-spin violation. For this study, we repurposed the Majorana Demonstrator, an experimental search for the neutrinoless double-beta decay of ^{76}Ge using an array of high-purity germanium detectors, to search for the decay of ^{180m}Ta. More than 17 kg, the largest amount of tantalum metal ever used for such a search, was installed within the ultralow-background detector array. In this Letter, we present results from the first year of Ta data taking and provide an updated limit for the ^{180m}Ta half-life on the different decay channels. With new limits up to 1.5×10^{19} yr, we improved existing limits by 1-2 orders of magnitude which are the most sensitive searches for a single ß and electron capture decay ever achieved. Over all channels, the decay can be excluded for T_{1/2}<0.29×10^{18} yr.

Can Optical Surface Imaging Replace Non-coplanar Cone-beam Computed Tomography for Non-coplanar Set-up Verification in Single-isocentre Non-coplanar Stereotactic Radiosurgery and Hypofractionated Stereotactic Radiotherapy for Single and Multiple Brain Metastases?

AIMS: To conduct a direct comparison regarding the non-coplanar positioning accuracy between the optical surface imaging system Catalyst HDTM and non-coplanar cone-beam computed tomography (NC-CBCT) in intracranial single-isocentre non-coplanar stereotactic radiosurgery (SRS) and hypofractionated stereotactic radiotherapy (HSRT). MATERIALS AND METHODS: Twenty patients with between one and five brain metastases who underwent single-isocentre non-coplanar volumetric modulated arc therapy (NC-VMAT) SRS or HSRT were enrolled in this study. For each non-zero couch angle, both Catalyst HDTM and NC-CBCT were used for set-up verification prior to beam delivery. The set-up error reported by Catalyst HDTM was compared with the set-up error derived from NC-CBCT, which was defined as the gold standard. Additionally, the dose delivery accuracy of each non-coplanar field after using Catalyst HDTM and NC-CBCT for set-up correction was measured with SRS MapCHECKTM. RESULTS: The median set-up error differences (absolute values) between the two positioning methods were 0.30 mm, 0.40 mm, 0.50 mm, 0.15°, 0.10° and 0.10° in the vertical, longitudinal, lateral, yaw, pitch and roll directions, respectively. The largest absolute set-up error differences regarding translation and rotation were 1.5 mm and 1.1°, which occurred in the longitudinal and yaw directions, respectively. Only 35.71% of the pairs of measurements were within the tolerance of 0.5 mm and 0.5° simultaneously. In addition, the non-coplanar field with NC-CBCT correction yielded a higher gamma passing rate than that with Catalyst HDTM correction (P < 0.05), especially for evaluation criteria of 1%/1 mm with a median increase of 12.8%. CONCLUSIONS: Catalyst HDTM may not replace NC-CBCT for non-coplanar set-up corrections in single-isocentre NC-VMAT SRS and HSRT for single and multiple brain metastases. The potential role of Catalyst HDTM in intracranial SRS/HSRT needs to be further studied in the future.