New insights on hidradenitis suppurativa phenotypes and treatment response: An exploratory automated analysis of the SUNSHINE and SUNRISE trials.

BACKGROUND: Defining hidradenitis suppurativa (HS) subtypes was previously limited by small sample sizes and poor interrater reliability; no study has investigated subtype treatment responses. The objective of this analysis was to characterize HS clusters in adult patients with moderate to severe HS and evaluate secukinumab treatment responses between clusters. METHODS: Clusters were identified via an unsupervised machine learning clustering analysis using baseline data from the randomized, placebo-controlled SUNSHINE (NCT03713619) and SUNRISE (NCT03713632) phase 3 trials. To assess treatment responses, patients received secukinumab every 2 (SECQ2W) or 4 weeks (SECQ4W) or placebo, for 16 weeks, after which, placebo patients randomly switched to SECQ2W/SECQ4W, and SECQ2W/SECQ4W patients maintained their original treatment, until week 52. Baseline outcomes included patient characteristics, disease characteristics and severity, HS-associated comorbidities and previous treatment exposures. Treatment response was assessed via the HS clinical response (HiSCR), abscess and inflammatory nodule (AN) count, flares and NRS30 (skin pain). RESULTS: Based on baseline data, three clusters were identified from 1084 patients (Cluster 1: 54.1%, Cluster 2: 17.8%, Cluster 3: 28.1%). Cluster 1 was predominantly female (65.4%) and was characterized by milder HS. Cluster 2 had more patients from the Asia Pacific, Middle East and Africa region (58.5%) and was characterized by moderate HS. Cluster 3 had the highest rates of previous exposure to biologics (45.9%) and prior HS-related surgeries (47.5%) and was characterized by severe HS. SECQ2W and SECQ4W demonstrated efficacy versus placebo in all clusters at week 16; SECQ2W and SECQ4W efficacy was maintained to week 52. SECQ2W treatment showed a trend for greater efficacy versus SECQ4W in Cluster 3 through week 52. CONCLUSIONS: Three HS clusters were identified. Secukinumab demonstrated benefit over placebo in all clusters. However, patients with more severe disease may take longer to respond and more frequent secukinumab dosing may be required for these patients. TRIAL REGISTRATION: SUNSHINE (NCT03713619) and SUNRISE (NCT03713632).

Retrospective, observational study of different medication regimens and outcome in children with cough variant asthma.

OBJECTIVE: This retrospective longitudinal cohort study aimed to explore the best therapeutic regimen and treatment duration of cough variant asthma (CVA) in children. METHODS: A total of 314 children with CVA were divided into receive inhaled corticosteroids (ICS) combined with long-acting beta2-agonist (LABA) group, ICS combined with leukotriene receptor antagonists (LTRA) group, ICS monotherapy group and LTRA monotherapy group. All clinical data were statistically analyzed. Logistic regression model was used to compare the advantages and disadvantages of different treatment schemes at each follow-up time point and the best treatment scheme. The Cox proportional hazard regression model based on inverse probability weighting was used to compare the effects of different medication regimens on adverse outcomes with asthma recurrence or progression as the end point. RESULTS: (1) After comprehensive analysis, ICS + LABA group was the preferred control regimen for CVA within 8 weeks. After 8 weeks of diagnosis, the efficacy of ICS group or LTRA group was comparable to that of ICS + LABA group and ICS + LTRA group. (2) The ICS + LABA group showed a significant improvement in cough at an early stage, particularly at 4 weeks; the symptoms of ICS + LTRA and ICS groups were significantly improved at 36 weeks. The LTRA group alone showed significant improvement at 20 weeks. CONCLUSION: ICS + LABA, ICS + LTRA, ICS alone and LTRA alone can effectively treat CVA. ICS + LABA could improve the symptoms most quickly within 8 weeks after CVA diagnosis, followed by ICS + LATR group. After 8 weeks, it can be reduced to ICS alone to control CVA for at least 36 weeks based on the remission of symptoms in children.

Tissue/Organ Adaptable Bioelectronic Silk-Based Implants.

Implantable bioelectronic devices, designed for both monitoring and modulating living organisms, require functional and biological adaptability. Pure silk is innovatively employed, which is known for its excellent biocompatibility, to engineer water-triggered, geometrically reconfigurable membranes, on which functions can be integrated by Micro Electro Mechanical System (MEMS) techniques and specially functionalized silk. These devices can undergo programmed shape deformations within 10 min once triggered by water, and thus establishing stable bioelectronic interfaces with natively fitted geometries. As a testament to the applicability of this approach, a twining peripheral nerve electrode is designed, fabricated, and rigorously tested, demonstrating its efficacy in nerve modulation while ensuring biocompatibility for successful implantation.

Through-polymer, via technology-enabled, flexible, lightweight, and integrated devices for implantable neural probes.

In implantable electrophysiological recording systems, the headstage typically comprises neural probes that interface with brain tissue and integrated circuit chips for signal processing. While advancements in MEMS and CMOS technology have significantly improved these components, their interconnection still relies on conventional printed circuit boards and sophisticated adapters. This conventional approach adds considerable weight and volume to the package, especially for high channel count systems. To address this issue, we developed a through-polymer via (TPV) method inspired by the through-silicon via (TSV) technique in advanced three-dimensional packaging. This innovation enables the vertical integration of flexible probes, amplifier chips, and PCBs, realizing a flexible, lightweight, and integrated device (FLID). The total weight of the FLIDis only 25% that of its conventional counterparts relying on adapters, which significantly increased the activity levels of animals wearing the FLIDs to nearly match the levels of control animals without implants. Furthermore, by incorporating a platinum-iridium alloy as the top layer material for electrical contact, the FLID realizes exceptional electrical performance, enabling in vivo measurements of both local field potentials and individual neuron action potentials. These findings showcase the potential of FLIDs in scaling up implantable neural recording systems and mark a significant advancement in the field of neurotechnology.

Chemically modified microRNA delivery via DNA tetrahedral frameworks for dental pulp regeneration.

Dental pulp regeneration is a promising strategy for addressing tooth disorders. Incorporating this strategy involves the fundamental challenge of establishing functional vascular networks using dental pulp stem cells (DPSCs) to support tissue regeneration. Current therapeutic approaches lack efficient and stable methods for activating DPSCs. In the study, we used a chemically modified microRNA (miRNA)-loaded tetrahedral-framework nucleic acid nanostructure to promote DPSC-mediated angiogenesis and dental pulp regeneration. Incorporating chemically modified miR-126-3p into tetrahedral DNA nanostructures (miR@TDNs) represents a notable advancement in the stability and efficacy of miRNA delivery into DPSCs. These nanostructures enhanced DPSC proliferation, migration, and upregulated angiogenesis-related genes, enhancing their paracrine signaling effects on endothelial cells. This enhanced effect was substantiated by improvements in endothelial cell tube formation, migration, and gene expression. Moreover, in vivo investigations employing matrigel plug assays and ectopic dental pulp transplantation confirmed the potential of miR@TDNs in promoting angiogenesis and facilitating dental pulp regeneration. Our findings demonstrated the potential of chemically modified miRNA-loaded nucleic acid nanostructures in enhancing DPSC-mediated angiogenesis and supporting dental pulp regeneration. These results highlighted the promising role of chemically modified nucleic acid-based delivery systems as therapeutic agents in regenerative dentistry and tissue engineering.

Ultraflexible PEDOT:PSS/IrOx-Modified Electrodes: Applications in Behavioral Modulation and Neural Signal Recording in Mice.

Recent advancements in neural probe technology have become pivotal in both neuroscience research and the clinical management of neurological disorders. State-of-the-art developments have led to the advent of multichannel, high-density bidirectional neural interfaces that are adept at both recording and modulating neuronal activity within the central nervous system. Despite this progress, extant bidirectional probes designed for simultaneous recording and stimulation are beset with limitations, including elicitation of inflammatory responses and insufficient charge injection capacity. In this paper, we delineate the design and application of an innovative ultraflexible bidirectional neural probe engineered from polyimide. This probe is distinguished by its ability to facilitate high-resolution recordings and precise stimulation control in deep brain regions. Electrodes enhanced with a PEDOT:PSS/IrOx composite exhibit a substantial increase in charge storage capacity, escalating from 0.14 ± 0.01 mC/cm2 to an impressive 24.75 ± 0.18 mC/cm2. This augmentation significantly bolsters the electrodes' charge transfer efficacy. In tandem, we observed a notable reduction in electrode impedance, from 3.47 ± 1.77 MΩ to a mere 41.88 ± 4.04 kΩ, while the phase angle exhibited a positive shift from -72.61 ± 1.84° to -34.17 ± 0.42°. To substantiate the electrodes' functional prowess, we conducted in vivo experiments, where the probes were surgically implanted into the bilateral motor cortex of mice. These experiments involved the synchronous recording and meticulous analysis of neural signal fluctuations during stimulation and an assessment of the probes' proficiency in modulating directional turning behaviors in the subjects. The empirical evidence corroborates that targeted stimulation within the bilateral motor cortex of mice can modulate the intensity of neural signals in the stimulated locale, enabling the directional control of the mice's turning behavior to the contralateral side of the stimulation site.

Light exposure and its applications in human health.

Light exposure has been proven to have a significant impact on human health. As a result, researchers are increasingly exploring its potential benefits and drawbacks. With advancements in understanding light and the manufacturing of light sources, modern health lighting has become widely utilized in daily life and plays a critical role in the prevention and treatment of various illnesses. The use of light in healthcare is a global trend, with many countries actively promoting the development and application of relevant scientific research and medical technology. This field has gained worldwide attention and support from scientists and doctors alike. In this review, we examine the application of lighting in human health and recent breakthroughs in light exposure related to pathology, therapeutic strategies, molecular changes, and more. Finally, we also discuss potential future developments and areas of application.

Single-Nucleotide-Specific Lipidic Nanoflares for Precise and Visible Detection of KRAS Mutations via Toehold-Initiated Self-Priming DNA Polymerization.

Accurate identification of single-nucleotide mutations in circulating tumor DNA (ctDNA) is critical for cancer surveillance and cell biology research. However, achieving precise and sensitive detection of ctDNAs in complex physiological environments remains challenging due to their low expression and interference from numerous homologous species. This study introduces single-nucleotide-specific lipidic nanoflares designed for the precise and visible detection of ctDNA via toehold-initiated self-priming DNA polymerization (TPP). This system can be assembled from only a single cholesterol-conjugated multifunctional molecular beacon (MMB) via hydrophobicity-mediated aggregation. This results in a compact, high-density, and nick-hidden arrangement of MMBs on the surface of lipidic micelles, thereby enhancing their biostability and localized concentrations. The assay commences with the binding of frequently mutated regions of ctDNA to the MMB toehold domain. This domain is the proximal holding point for initiating the TPP-based strand-displacement reaction, which is the key step in enabling the discrimination of single-base mutations. We successfully detected a single-base mutation in ctDNA (KRAS G12D) in its wild-type gene (KRAS WT), which is one of the most frequently mutated ctDNAs. Notably, coexisting homologous species did not interfere with signal transduction, and small differences in these variations can be visualized by fluorescence imaging. The limit of detection was as low as 10 amol, with the system functioning well in physiological media. In particular, this system allowed us to resolve genetic mutations in the KRAS gene in colorectal cancer, suggesting its high potential in clinical diagnosis and personalized medicine.

New strategies for confirmatory testing of secondary hypotheses on combined data from multiple trials.

BACKGROUND: Pivotal evidence of efficacy of a new drug is typically generated by (at least) two clinical trials which independently provide statistically significant and mutually corroborating evidence of efficacy based on a primary endpoint. In this situation, showing drug effects on clinically important secondary objectives can be demanding in terms of sample size requirements. Statistically efficient methods to power for such endpoints while controlling the Type I error are needed. METHODS: We review existing strategies for establishing claims on important but sample size-intense secondary endpoints. We present new strategies based on combined data from two independent, identically designed and concurrent trials, controlling the Type I error at the submission level. We explain the methodology and provide three case studies. RESULTS: Different strategies have been used for establishing secondary claims. One new strategy, involving a protocol planned analysis of combined data across trials, and controlling the Type I error at the submission level, is particularly efficient. It has already been successfully used in support of label claims. Regulatory views on this strategy differ. CONCLUSIONS: Inference on combined data across trials is a useful approach for generating pivotal evidence of efficacy for important but sample size-intense secondary endpoints. It requires careful preparation and regulatory discussion.

From Short Circuit to Completed Circuit: Conductive Hydrogel Facilitating Oral Wound Healing.

The primary challenges posed by oral mucosal diseases are their high incidence and the difficulty in managing symptoms. Inspired by the ability of bioelectricity to activate cells, accelerate metabolism, and enhance immunity, a conductive polyacrylamide/sodium alginate crosslinked hydrogel composite containing reduced graphene oxide (PAA-SA@rGO) is developed. This composite possesses antibacterial, anti-inflammatory, and antioxidant properties, serving as a bridge to turn the "short circuit" of the injured site into a "completed circuit," thereby prompting fibroblasts in proximity to the wound site to secrete growth factors and expedite tissue regeneration. Simultaneously, the PAA-SA@rGO hydrogel effectively seals wounds to form a barrier, exhibits antibacterial and anti-inflammatory properties, and prevents foreign bacterial invasion. As the electric field of the wound is rebuilt and repaired by the PAA-SA@rGO hydrogel, a 5 × 5 mm2 wound in the full-thickness buccal mucosa of rats can be expeditiously mended within mere 7 days. The theoretical calculations indicate that the PAA-SA@rGO hydrogel can aggregate and express SOX2, PITX1, and PITX2 at the wound site, which has a promoting effect on rapid wound healing. Importantly, this PAA-SA@rGO hydrogel has a fast curative effect and only needs to be applied for the first three days, which significantly improves patient satisfaction during treatment.

CFATransUnet: Channel-wise cross fusion attention and transformer for 2D medical image segmentation.

Medical image segmentation faces current challenges in effectively extracting and fusing long-distance and local semantic information, as well as mitigating or eliminating semantic gaps during the encoding and decoding process. To alleviate the above two problems, we propose a new U-shaped network structure, called CFATransUnet, with Transformer and CNN blocks as the backbone network, equipped with Channel-wise Cross Fusion Attention and Transformer (CCFAT) module, containing Channel-wise Cross Fusion Transformer (CCFT) and Channel-wise Cross Fusion Attention (CCFA). Specifically, we use a Transformer and CNN blocks to construct the encoder and decoder for adequate extraction and fusion of long-range and local semantic features. The CCFT module utilizes the self-attention mechanism to reintegrate semantic information from different stages into cross-level global features to reduce the semantic asymmetry between features at different levels. The CCFA module adaptively acquires the importance of each feature channel based on a global perspective in a network learning manner, enhancing effective information grasping and suppressing non-important features to mitigate semantic gaps. The combination of CCFT and CCFA can guide the effective fusion of different levels of features more powerfully with a global perspective. The consistent architecture of the encoder and decoder also alleviates the semantic gap. Experimental results suggest that the proposed CFATransUnet achieves state-of-the-art performance on four datasets. The code is available at https://github.com/CPU0808066/CFATransUnet.

Knowledge, psychological impacts, and protective behaviours during the first wave of the COVID-19 pandemic among Chinese residents in Canada with dependent school-age children: a cross-sectional online study.

BACKGROUND: The purpose of this study was to describe the knowledge, protective behaviours, and psychological impact of COVID-19 on Chinese residents in Canada, as the emotional and behavioural impacts of the pandemic have not been intensively studied amongst these populations. It was important to determine whether having dependent school-age children (DSAC) aged 16 or under was associated with adverse psychological impacts amongst the Chinese residents living in the country. METHODS: In April 2020, 757 eligible participants were recruited through a snowball sampling to complete an online survey related to the COVID-19 pandemic. Psychological, behavioural, and sociodemographic variables were collected and first analyzed using descriptive and univariate statistics. Multiple logistic regression analyses were performed to further confirm the observed significant associations in bivariate analyses for selected psychological outcome variables. RESULTS: Seven hundred forty-two participants who responded to the "dependent school-age children" question were included in the analysis. Most of them identified as females (65.8%) and 77.2% included receiving a university degree or higher. There were no significant differences in COVID-19 knowledge between those living with or without DSAC. However, participants with DSAC were more likely to perceive themselves as being at greater risk of contracting COVID-19 (p = .023); therefore, having a higher chance of adopting protective behaviours (e.g., hand washing, sanitizing frequently or disinfecting work and living spaces (p < .05), elevated risks of depression (p = .007), and stress (p = .010), compared to those without DSAC. CONCLUSIONS: Predominantly, the Chinese residents in Canada with dependent school-age children were more likely to report the negative psychological impacts of the pandemic. These findings warrant further investigations that may contribute to informing key stakeholders about the identification and implementation of policies and interventions to support the needs of parents with young children, during and after the pandemic.

PDK4-dependent hypercatabolism and lactate production of senescent cells promotes cancer malignancy.

Senescent cells remain metabolically active, but their metabolic landscape and resulting implications remain underexplored. Here, we report upregulation of pyruvate dehydrogenase kinase 4 (PDK4) upon senescence, particularly in some stromal cell lines. Senescent cells display a PDK4-dependent increase in aerobic glycolysis and enhanced lactate production but maintain mitochondrial respiration and redox activity, thus adopting a special form of metabolic reprogramming. Medium from PDK4+ stromal cells promotes the malignancy of recipient cancer cells in vitro, whereas inhibition of PDK4 causes tumor regression in vivo. We find that lactate promotes reactive oxygen species production via NOX1 to drive the senescence-associated secretory phenotype, whereas PDK4 suppression reduces DNA damage severity and restrains the senescence-associated secretory phenotype. In preclinical trials, PDK4 inhibition alleviates physical dysfunction and prevents age-associated frailty. Together, our study confirms the hypercatabolic nature of senescent cells and reveals a metabolic link between cellular senescence, lactate production, and possibly, age-related pathologies, including but not limited to cancer.

Severe problem of macrolides resistance to common pathogens in China.

With the widespread use of macrolide antibiotics in China, common pathogens causing children's infections, such as Streptococcus pneumoniae, Streptococcus (including Group A streptococcus, Group B streptococcus), Staphylococcus aureus, Bordetella pertussis, and Mycoplasma pneumoniae, have shown varying degrees of drug resistance. In order to provide such problem and related evidence for rational use of antibiotics in clinic, we reviewed the drug resistance of common bacteria to macrolides in children recent 20 years.

Epidemiological characteristics of common respiratory infectious diseases in children before and during the COVID-19 epidemic.

Background: Since the outbreak of coronavirus disease 2019 (COVID-19), public's awareness of infection prevention and control has increased overall, and various prevention and control measures have been adopted. These measures may also have a certain impact on the occurrence of other infectious diseases. Therefore, we collected information on children with several respiratory infectious diseases in Jinan Children's Hospital in China from 2016 to 2022 and analyzed their changes. Method: We collected data on age, sex and number of cases of pertussis, measles, scarlet fever, pulmonary tuberculosis, mumps and influenza, which were diagnosed by clinical and laboratory criteria, from 1 January 2016 to 31 December 2022 in Jinan Children's Hospital in Jinan, Shandong Province, China. Data on the number of people affected by these diseases in China from the Chinese Center for Disease Control and Prevention were compared. Then, we processed the data by using WPS Excel 2019 and SPSS. Results: A total of 12,225 cases were included in this study in Jinan Children's Hospital, which consisted of 3,688 cases of pertussis (2,200 cases before COVID-19 and 1,488 during COVID-19), 680 cases of measles (650 cases before COVID-19 and 30 during COVID-19), 4,688 cases of scarlet fever (4,001 cases before COVID-19 and 687 during COVID-19), 114 cases of tuberculosis (86 cases before COVID-19 and 28 during COVID-19), 449 cases of mumps (340 cases before COVID-19 and 109 during COVID-19) and 2,606 cases of influenza (1,051 cases before COVID-19 and 1,555 during COVID-19). The numbers of children in the hospital with pertussis, measles, scarlet fever, mumps and influenza decreased substantially during COVID-19 in 2020-2022 compared with numbers in 2016-2019, while numbers of patients in China with all six respiratory infectious diseases, including pulmonary tuberculosis, declined during the pandemic. A rebound of pertussis, scarlet fever and influenza was observed in 2021 and 2022. Conclusions: The study found that viral pathogens such as those causing measles, mumps and influenza all decreased during the pandemic, after which influenza rebounded. Infection diseases caused by bacteria such as scarlet fever and pertussis also decreased during COVID-19, and then a rebound occurred. However, tuberculosis stayed relatively constant.

A mosquito mouthpart-like bionic neural probe.

Advancements in microscale electrode technology have revolutionized the field of neuroscience and clinical applications by offering high temporal and spatial resolution of recording and stimulation. Flexible neural probes, with their mechanical compliance to brain tissue, have been shown to be superior to rigid devices in terms of stability and longevity in chronic recordings. Shuttle devices are commonly used to assist flexible probe implantation; however, the protective membrane of the brain still makes penetration difficult. Hidden damage to brain vessels during implantation is a significant risk. Inspired by the anatomy of the mosquito mouthparts, we present a biomimetic neuroprobe system that integrates high-sensitivity sensors with a high-fidelity multichannel flexible electrode array. This customizable system achieves distributed and minimally invasive implantation across brain regions. Most importantly, the system's nonvisual monitoring capability provides an early warning detection for intracranial soft tissues, such as vessels, reducing the potential for injury during implantation. The neural probe system demonstrates exceptional sensitivity and adaptability to environmental stimuli, as well as outstanding performance in postoperative and chronic recordings. These findings suggest that our biomimetic neural-probe device offers promising potential for future applications in neuroscience and brain-machine interfaces. A mosquito mouthpart-like bionic neural probe consisting of a highly sensitive tactile sensor module, a flexible microelectrode array, and implanted modules that mimic the structure of mosquito mouthparts. The system enables distributed implantation of electrode arrays across multiple brain regions while making the implantation minimally invasive and avoiding additional dural removal. The tactile sensor array can monitor the implantation process to achieve early warning of vascular damage. The excellent postoperative short-term recording performance and long-term neural activity tracking ability demonstrate that the system is a promising tool in the field of brain-computer interfaces.

Is the incident of once chronic obstructive pulmonary disease related admission a high risk for readmission in the future?

Background: Although it is known that a history of acute exacerbation of chronic obstructive pulmonary disease (AECOPD) is the most important predictor of future risk of AECOPD and readmission to hospitals, there is no scientific evidence that an event of only one chronic obstructive pulmonary disease (COPD)-related admission is a high risk of future readmission. We retrospectively analyzed the association of an incident of one COPD-related admission with future readmission risk. Methods: This is a retrospective study. The data of AECOPD-related admissions and readmissions during 5 years were obtained and analyzed for the admission frequencies of patients with AECOPD and an association of the admission history with a future readmission risk. Results: The admission frequency of patients with frequent admission (3 or more admissions within 5 years) was 4.1 times that of those with non-frequent admission (0.95 vs. 0.23 times per person per year). In each calendar year during the 5-year study period, most patients (88.2%) were hospitalized only once, and 11.8% had two or more admissions. Nevertheless, their average number of admissions in each calendar year was 3.3 times that of those who only had one admission each year (3.33 vs. 1.00 times per person per year). More importantly, the positive predictive value for future readmission due to AECOPD was only 14.8% in those who had one admission in the previous year. The patients with the greater readmission risk were those with two or more admissions due to AECOPD in the previous year [crude odds ratio (OR): 4.10, 95% confidence interval (CI): 1.24-13.58 and 7.51, 95% CI: 3.81-16.68]. Conclusions: There is a subtype of frequent admission due to AECOPD, and it can be distinguished by having three or more admissions in the past 5 years or two or more admissions in the previous year. Nevertheless, an incident of admission once a year is not a good predictor of future readmission.