Seminal plasma S100A8/A9 as a potential biomarker of genital tract inflammation.

ABSTRACT: Infections and inflammatory reactions in the male genital tract are the leading causes of male infertility with a prevalence of 6%-10%, primarily affecting testicular and epididymal function and ultimately compromising sperm quality. However, most infertile patients with genital infection/inflammation are asymptomatic and easily overlooked. Traditional indicators, including white blood cells, elastase, and other components in semen, can reflect inflammation of the genital tract, but there is still a lack of a uniform standard method of detection. Therefore, it is necessary to explore reliable markers in semen that reflect the inflammatory status of the genital tract. Using the experimental autoimmune orchitis (EAO) model to simulate noninfectious chronic orchitis, we successfully collected ejaculated seminal fluid from EAO rats using optimized electrical stimulation devices. Proteomic analysis was performed using isobaric tags for relative and absolute quantification (iTRAQ). Compared to the control group, 55 upregulated and 105 downregulated proteins were identified in seminal plasma samples from the EAO group. In a preliminary screening, the inflammation-related protein S100A8/A9 was upregulated. We further verified that S100A8/A9 was increased in seminal plasma and highly expressed in testicular macrophages of the EAO model. In patients with oligoasthenospermia and genital tract infections, we also found that S100A8/A9 levels were remarkably increased in seminal plasma and testicular macrophages. S100A8/A9 in semen may be a potential biomarker for chronic genital inflammation. Our study provides a new potential biomarker for early diagnosis and further understanding of male infertility caused by genital inflammation.

Efficacy and safety of stereotactic radiotherapy on elderly patients with stage I-II central non-small cell lung cancer.

Background: Many studies demonstrated the safety and efficacy of SBRT in the treatment of elderly patients with early-stage non-small cell lung cancer (NSCLC). However, those studies focused on patients with peripheral lung cancer. This study aimed to evaluate the clinical efficacy and toxicity of SBRT in elderly patients with stage I-II central NSCLC in single institution. Methods: From April 2009 to January 2020, a retrospective study was conducted on patients ≥ 65 years old with stage I-II NSCLC that was centrally localized and treated with SBRT at a single institution. Absolute C-reactive protein (CRP)/albumin ratio (CAR) and body mass index (BMI) recorded at pretreatment were analyzed. Endpoints included overall survival (OS), progression-free survival (PFS), cancer-specific death, noncancer-specific death, local progression (LP) and distant progression (DP). Results: Stereotactic body radiation treatment (SBRT) was administered to a total of 44 patients. The most common dose fractionation schedule was 60 Gy given in 5 fractions. The median PFS of the cohort was 31 months (95% CI, 19.47-42.53 months). The median OS of all patients was 69 months (95% CI, 33.8-104.2 months). The median time to noncancer-specific death was 54.5 months. The median time to cancer-specific death was 36 months. The cumulative incidences of cancer-specific death at 1 year, 5 years, and 10 years were 11.63% (95%CI, 4.2-23.23%), 42.99% (95%CI, 27.56-57.53%), and 65.94% (95%CI, 45.76-80.1%), respectively. pre-SBRT BMI of ≤ 22.77 (HR 4.60, 95% CI 1.84-11.51, P=0.001) and pre-SBRT CAR of ≤0.91 (HR 5.19, 95% CI 2.15-12.52, P<0.000) were significant predictors of higher OS on multivariable analysis. The median times to LP and DP were 10 months and 11 months, respectively. In terms of acute toxicity, grade 1 including cough (38.64%), radiation pneumonitis (29.55%), anemia (25%), and fatigue (20.45%) was often observed. There was no evidence of grade 4 or 5 acute toxicity. In terms of late toxicity, 2 patients developed grade 1 pulmonary fibrosis during follow-up. Conclusion: This study showed that SBRT can effectively control local tumor progression, and have acceptable toxicity for elderly patients with centrally located stage I-II NSCLC. Lower pre-SBRT BMI and lower pre-SBRT CAR were associated with a decreased risk of cancer-specific death.

Unveiling the Selectivity of Ru(II)-Catalyzed C-H Activation for Defluorinative Cyclization of 2-Arylbenzimidazole and Trifluoromethyl Diazo: A DFT Study.

The synthesis of monofluorinated heterocyclic compounds by C-H activation combined with defluorination is useful. Studies on the reaction mechanism and selectivity have shown that these processes play a positive role in promoting the development of monofluorinated reactions. Density functional theory (DFT) calculations were performed to investigate the mechanism and selectivity of Ru(II)-catalyzed 2-arylbenzimidazole with trifluoromethyl diazo. DFT calculations showed that C-H activation occurs through a concerted metalation/deprotonation (CMD) mechanism. After that, deprotonation and defluorinative cyclization are assisted by acetate and trifluoroethanol (TFE). Further mechanistic insights through noncovalent interaction (NCI) analysis were also obtained to elucidate the origin of the selectivity in the defluorination process.

Eco-friendly electronic food labels: Development and application of Ion-SSPB double network hydrogel.

Although various conductive hydrogels have been developed for sensing, ideal materials for meeting the safety and toughness requirements of food detection are still lacking. This study introduces Ion-SSPB, a conductive hydrogel fabricated from eco-friendly, food-grade materials such as corn starch (CS), sodium alginate (SA), polyvinyl alcohol (PVA) and bentonite (BT). It leverages a green manufacturing approach designed for application in electronic food sensors. The hydrogel is achieved through a double network strategy and salt immersion method, which endows it with tunable mechanical and rheological properties. A key innovation of Ion-SSPB is the incorporation of bentonite, which enhances its performance, including low swelling, freezing resistance, and minimal residual adhesion. The hydrogel with 4% (w/v) BT concentration (Ion-SSPB4%) is an effective medium for detecting impedance changes in mangoes, correlating with their ripening stages. The Ion-SSPB hydrogel represents a significant advancement in the field of electronic food labels, combining environmental sustainability with technical efficacy.

Reversible male contraception by targeted inhibition of serine/threonine kinase 33.

Men or mice with homozygous serine/threonine kinase 33 (STK33) mutations are sterile owing to defective sperm morphology and motility. To chemically evaluate STK33 for male contraception with STK33-specific inhibitors, we screened our multibillion-compound collection of DNA-encoded chemical libraries, uncovered potent STK33-specific inhibitors, determined the STK33 kinase domain structure bound with a truncated hit CDD-2211, and generated an optimized hit CDD-2807 that demonstrates nanomolar cellular potency (half-maximal inhibitory concentration = 9.2 nanomolar) and favorable metabolic stability. In mice, CDD-2807 exhibited no toxicity, efficiently crossed the blood-testis barrier, did not accumulate in brain, and induced a reversible contraceptive effect that phenocopied genetic STK33 perturbations without altering testis size. Thus, STK33 is a chemically validated, nonhormonal contraceptive target, and CDD-2807 is an effective tool compound.

The FAITHS2 Model Predicts Functional Disability in Patients With Acute Ischemic Stroke.

The present study aimed to develop a model to predict functional disability at 3 months in patients with acute ischemic stroke (AIS) (n = 5,406). The primary outcome was functional disability (modified Rankin Scale [mRS] >2) at 3 months. A prediction model including blood biomarkers was developed based on a multivariable logistic regression model, which was internally validated by the 100-time bootstrap method. A nomogram and a web-based calculator were developed for usage in clinical practice. At 3 months, 11% (638/5,406) of the patients had functional disability. Seven independent predictors of functional disability at 3 months were incorporated into the FAITHS2 model (fasting plasma glucose, age, interleukin-6, stroke history, National Institute of Health Stroke Scale [NIHSS] at admission, sex, and systolic blood pressure). The Area Under Curves (AUCs) were 0.814 (95% confidence interval [CI] 0.796-0.832) and 0.808 (95% CI 0.806-0.810), and the Brier scores were 0.088 ± 0.214 and 0.089 ± 0.003 for the derivation cohort and internal validation, respectively, showing optimal performance of the model. The FAITHS2 model has excellent potential to be a dependable application for individualized clinical decision making.

The function and application of edible fungal polysaccharides.

Edible fungi, commonly known as mushrooms, are precious medicinal and edible homologous gifts from nature to us. Edible fungal polysaccharides (EFPs) are a variety of bioactive macromolecular which isolated from fruiting bodies, mycelia or fermentation broths of edible or medicinal fungus. Increasing researches have confirmed that EFPs possess multiple biological activities both in vitro and in vivo settings, including antioxidant, antiviral, anti-inflammatory, immunomodulatory, anti-tumor, hypoglycemic, hypolipidemic, and regulating intestinal flora activities. As a result, they have emerged as a prominent focus in the healthcare, pharmaceutical, and cosmetic industries. Fungal EFPs have safe, non-toxic, biodegradable, and biocompatible properties with low immunogenicity, bioadhesion ability, and antibacterial activities, presenting diverse potential applications in the food industries, cosmetic, biomedical, packaging, and new materials. Moreover, varying raw materials, extraction, purification, chemical modification methods, and culture conditions can result in variances in the structure and biological activities of EFPs. The purpose of this review is to provide comprehensively and systematically organized information on the structure, modification, biological activities, and potential applications of EFPs to support their therapeutic effects and health functions. This review provides new insights and a theoretical basis for prospective investigations and advancements in EFPs in fields such as medicine, food, and new materials.

Effects of Fu's subcutaneous needling at myofascial trigger points on pain and lumbar mobility in patients with lumbar disc herniation： a randomized controlled trial. / ç­‹è†œè§¦å‘ç‚¹æµ®é’ˆæ²»ç–—å¯¹è °æ¤Žé—´ç›˜çªå‡ºç—‡æ‚£è€ ç–¼ç—›åŠè °éƒ¨æ´»åŠ¨åº¦å½±å“çš„éšæœºå¯¹ç §ç ”ç©¶.

OBJECTIVES: To explore the therapeutic effect of Fu's subcutaneous needling at myofascial trigger points (MTrPs) on pain, lumbar mobility and the quality of life in patients with lumbar disc herniation (LDH), so as to provide clinicians with new ideas and methods in treating LDH. METHODS: One hundred patients with LDH admitted to department of rehabilitation medicine of the affiliated hospital of Chengdu University of Traditional Chinese Medicine from January 2022 to January 2023 were collected as the subjects, and they were randomly divided into an observation group and a control group, 50 cases in each one. In the observation group, the spreading technique of Fu's subcutaneous needling was delivered at MTrP. In the control group, the routine acupuncture was applied to Shenshu (BL23), Weizhong (BL40) and MTrP. The treatment was given 3 times weekly, for 2 weeks in the two groups. The score of visual analogue scale (VAS) was evaluated before treatment, at the moment after the 1st treatment completion and after 2 weeks of treatment, separately, and the inclinometer was adopted to measure the range of motion (ROM) of the lumbar flexion, extension and lateral flexion. The numbers of MTrPs and their distribution were recorded before treatment and after the completion of a 2-week treatment in the two groups. Before treatment and in 4 weeks of follow-up, using SF-36 scale, the score of the quality of life was evaluated. The incidence of adverse effects was recorded. RESULTS: At the moment of the 1st treatment completion and after 2 weeks of treatment, VAS score and ROM of the lumbar region were significantly improved in comparison with those before treatment in the two groups and the improvement was superior in the observation group compared with the control group (P<0.05, P<0.01). After 2 weeks of treatment, the total number of MTrPs and the counts of MTrPs in each muscle zone were reduced when compared with those before treatment (P<0.05). In the observation group, the total number of MTrPs and numbers of MTrPs in the zones of quadratus lumborum, musculi multifidus and musculi iliocostalis lumborum decreased significantly when compared with the control group (P<0.05), while the difference was not significant in the numbers in the zone of musculi glutaeus medius between the two groups. In 4 weeks of follow-up, the scores of SF-36 scale were improved in comparison with those before treatment in each group and the result in the observation was better (P<0.05). No any adverse events occurred during treatment in the two groups. CONCLUSIONS: Fu's subcutaneous needling is effective for reducing the numbers of MTrPs and improving analgesia, ROM of the lumbar region, as well as the long-term quality of life in the patients with LDH.

SMARCA5 reprograms AKR1B1-mediated fructose metabolism to control leukemogenesis.

A significant variation in chromatin accessibility is an epigenetic feature of leukemia. The cause of this variation in leukemia, however, remains elusive. Here, we identify SMARCA5, a core ATPase of the imitation switch (ISWI) chromatin remodeling complex, as being responsible for aberrant chromatin accessibility in leukemia cells. We find that SMARCA5 is required to maintain aberrant chromatin accessibility for leukemogenesis and then promotes transcriptional activation of AKR1B1, an aldo/keto reductase, by recruiting transcription co-activator DDX5 and transcription factor SP1. Higher levels of AKR1B1 are associated with a poor prognosis in leukemia patients and promote leukemogenesis by reprogramming fructose metabolism. Moreover, pharmacological inhibition of AKR1B1 has been shown to have significant therapeutic effects in leukemia mice and leukemia patient cells. Thus, our findings link the aberrant chromatin state mediated by SMARCA5 to AKR1B1-mediated endogenous fructose metabolism reprogramming and shed light on the essential role of AKR1B1 in leukemogenesis, which may provide therapeutic strategies for leukemia.

Percent duration of heart rate acceleration within the respiratory cycle: A novel approach to assess heart rate asymmetry.

Accelerations and decelerations of heart rate are nonsymmetrical in the magnitude and number of beat-to-beat changes.The asymmetric features of heart rate variability are related to respiratory durations. To explore the link between respiration and heart rate asymmetry (HRA), we evaluated 14 seated, healthy young adults who breathed with nine combinations of inspiration duration (TI) and expiration duration (TE), chosen respectively from 2, 4, and 6 seconds. A 5-minute R-R interval (RRI) time series was obtained from each study period to construct an averaged pattern waveform relative to the respiratory cycle. We observed that the time interval between inspiration onset and RRI minimum progressively lengthened as TI and TE increased. The time interval between expiration onset and RRI maximum also lengthen when TE increased, but shortened when TI increased. Consequently, TI and TE had different effects on the acceleration time (AT; from RRI maximum to RRI minimum) and deceleration time (DT; from RRI minimum to RRI maximum). The percentage of AT within the respiratory cycle showed a strong correlation with traditional Guzik's (r = 0.862, P < 0.001) and Porta's (r = 0.878, P < 0.001) indexes of HRA assessed in a Poincaré plot analysis. These findings suggest that, in addition to considering the magnitude and number of beat-to-beat changes, HRA can also be assessed based on another aspect: the duration of consecutive changes. The stepwise link between the duration of heart rate change and respiratory duration provides insight into the mechanisms connecting respiration to HRA.

Use superb microvascular imaging to diagnose and predict metastatic cervical lymph nodes in patients with papillary thyroid carcinoma.

PURPOSE: Papillary thyroid carcinoma (PTC) with metastatic lymph nodes (LNs) is closely associated with disease recurrence. This study accessed the value of superb microvascular imaging (SMI) in the diagnosis and prediction of metastatic cervical LNs in patients with PTC. METHODS: A total of 183 cervical LNs (103 metastatic and 80 reactive) from 116 patients with PTC were analysed. Metastatic cervical LNs were confirmed by pathology or/and cytology; reactive cervical LNs were confirmed by pathology or clinical features. The characteristic of conventional ultrasound (US) was extracted using univariate and multivariate analyses. The diagnostic performance of US and SMI were compared using the area under the receiver operating curve (AUC) with corresponding sensitivity and specificity. A nomogram was developed to predict metastatic LNs in patients with PTC, based on multivariate analyses. RESULTS: L/S < 2, ill-defined border, absence of hilum, isoechoic or hyperechoic, heterogeneous internal echo, peripheral or mixed vascular pattern on color Doppler flow imaging (CDFI) and SMI, and a larger SMI vascular index appeared more frequently in metastatic LNs in the training datasets than in reactive LNs (P < 0.05). The diagnostic sensitivity, specificity and accuracy of SMI vs US are 94.4% and 87.3%, 79.3% and 69.3%, and 87.6% and 79.1%, respectively; SMI combined with US exhibited a higher AUC [0.926 (0.877-0.975)] than US only [0.829 (0.759-0.900)]. L/S < 2, peripheral or mixed vascular type on CDFI, and peripheral or mixed vascular types on SMI were independent predictors of metastatic LNs with PTC. The nomogram based on these three parameters exhibited excellent discrimination, with an AUC of 0.926. CONCLUSION: SMI was superior to US in diagnosing metastatic LNs in PTC. US combined with SMI significantly improved the diagnostic accuracy of metastatic cervical LNs with PTC. SMI is efficacious for differentiating and predicting metastatic cervical LNs.

A case report of classic galactosemia with a GALT gene variant and a literature review.

BACKGROUND: Galactosemia is an autosomal recessive disorder resulting from an enzyme defect in the galactose metabolic pathway. The most severe manifestation of classic galactosemia is caused by galactose-1-phosphate uridylyltransferase (GALT) deficiency, and this condition can be fatal during infancy if left untreated. It also may result in long-term complications in affected individuals. CASE PRESENTATION: This report describes a patient whose initial clinical symptoms were jaundice and liver dysfunction. The patient's liver and coagulation functions did not improve after multiple admissions and treatment with antibiotics, hepatoprotective and choleretic agents and blood transfusion. Genetic analysis revealed the presence of two variants in the GALT gene in the compound heterozygous state: c.377 + 2dup and c.368G > C (p.Arg123Pro). Currently, the variant locus (c.377 + 2dup) in the GALT gene has not been reported in the Human Gene Mutation Database (HGMD), while c.368G > C (p.Arg123Pro) has not been reported in the Genome Aggregation Database (GnomAD) nor the HGMD in East Asian population. We postulated that the two variants may contribute to the development of classical galactosemia. CONCLUSIONS: Applications of whole-exome sequencing to detect the two variants can improve the detection and early diagnosis of classical galactosemia and, more specifically, may identify individuals who are compound heterozygous with variants in the GALT gene. Variants in the GALT gene have a potential therapeutic significance for classical galactosemia.

Recent insights into breast milk microRNA: their role as functional regulators.

Breast milk (BM) is a primary biofluid that plays a crucial role in infant development and the regulation of the immune system. As a class of rich biomolecules in BM, microRNAs (miRNAs) are regarded as active factors contributing to infant growth and development. Surprisingly, these molecules exhibit resilience in harsh conditions, providing an opportunity for infants to absorb them. In addition, many studies have shown that miRNAs in breast milk, when absorbed into the gastrointestinal system, can act as a class of functional regulators to effectively regulate gene expression. Understanding the absorption pattern of BM miRNA may facilitate the creation of formula with a more optimal miRNA balance and pave the way for novel drug delivery techniques. In this review, we initially present evidence of BM miRNA absorption. Subsequently, we compile studies that integrate both in vivo and in vitro findings to illustrate the bioavailability and biodistribution of BM miRNAs post-absorption. In addition, we evaluate the strengths and weaknesses of previous studies and discuss potential variables contributing to discrepancies in their outcomes. This literature review indicates that miRNAs can be absorbed and act as regulatory agents.

Identification and validation of potential diagnostic signature and immune cell infiltration for HIRI based on cuproptosis-related genes through bioinformatics analysis and machine learning.

Background and aims: Cuproptosis has emerged as a significant contributor in the progression of various diseases. This study aimed to assess the potential impact of cuproptosis-related genes (CRGs) on the development of hepatic ischemia and reperfusion injury (HIRI). Methods: The datasets related to HIRI were sourced from the Gene Expression Omnibus database. The comparative analysis of differential gene expression involving CRGs was performed between HIRI and normal liver samples. Correlation analysis, function enrichment analyses, and protein-protein interactions were employed to understand the interactions and roles of these genes. Machine learning techniques were used to identify hub genes. Additionally, differences in immune cell infiltration between HIRI patients and controls were analyzed. Quantitative real-time PCR and western blotting were used to verify the expression of the hub genes. Results: Seventy-five HIRI and 80 control samples from three databases were included in the bioinformatics analysis. Three hub CRGs (NLRP3, ATP7B and NFE2L2) were identified using three machine learning models. Diagnostic accuracy was assessed using a receiver operating characteristic (ROC) curve for the hub genes, which yielded an area under the ROC curve (AUC) of 0.832. Remarkably, in the validation datasets GSE15480 and GSE228782, the three hub genes had AUC reached 0.904. Additional analyses, including nomograms, decision curves, and calibration curves, supported their predictive power for diagnosis. Enrichment analyses indicated the involvement of these genes in multiple pathways associated with HIRI progression. Comparative assessments using CIBERSORT and gene set enrichment analysis suggested elevated expression of these hub genes in activated dendritic cells, neutrophils, activated CD4 memory T cells, and activated mast cells in HIRI samples versus controls. A ceRNA network underscored a complex regulatory interplay among genes. The genes mRNA and protein levels were also verified in HIRI-affected mouse liver tissues. Conclusion: Our findings have provided a comprehensive understanding of the association between cuproptosis and HIRI, establishing a promising diagnostic pattern and identifying latent therapeutic targets for HIRI treatment. Additionally, our study offers novel insights to delve deeper into the underlying mechanisms of HIRI.

Safety, pharmacokinetics, and food-effect of pivmecillinam after single- and multiple-dose in healthy Chinese subjects: a phase I study.

Urinary tract infection (UTI) is one of the most prevalent bacterial infectious diseases worldwide. However, the resistance of urinary pathogens to other UTI antibiotics such as trimethoprim and trimethoprim/sulphamethoxazole increased. Pivmecillinam is a prodrug of mecillinam, which is effective for the treatment of urinary tract infections. The purpose of this study was to assess the safety, and pharmacokinetics of pivmecillinam and mecillinam after single- and multiple-dose oral administration of pivmecillinam tablets in healthy Chinese subjects. The study also investigated the profile of urinary excretion of mecillinam, as well as the effect of food and gender on the pharmacokinetics of pivmecillinam and mecillinam. This study was a single-center, open-label phase I study carried out in three groups. In total, 34 subjects were included in the study: group 1-food effect study with pivmecillinam 200 mg (n = 12); group 2-single- and multiple-dose study with pivmecillinam 400 mg (n = 12); group 3-single dose study with pivmecillinam 600 mg (n = 10). The plasma and urine concentrations of pivmecillinam and mecillinam were measured, and their pharmacokinetics were calculated. Treatment-emergent adverse events were evaluated and recorded in safety assessments for three groups. No severe adverse events were found in this study. After a single dose of pivmecillinam was taken orally, the maximum plasma concentration (Cmax) and the area under the concentration-time curve (AUC) of pivmecillinam increased in a dose-proportional manner, nor did mecillinam. Food had significant effects on Cmax and AUC0-t of pivmecillinam and Cmax of mecillinam. The mean cumulative percentage of urine excretion of mecillinam at 0 to 24 h ranged from 35.5 to 44.0%. Urinary cumulative excretion is relative to the drug dose, but the diet and multiple-dose administration did not affect the urinary cumulative excretion rate. The safety and pharmacokinetics of pivmecillinam and mecillinam after single- (200/400/600 mg) or multiple-dose (400 mg) administration were demonstrated in healthy Chinese subjects. Food affected the pharmacokinetics of pivmecillinam and mecillinam.

How to use one surface electromyography sensor to recognize six hand movements for a mechanical hand in real time: a method based on Morse code.

Surface electromyography (sEMG) signal is a kind of physiological signal reflecting muscle activity and muscle force. At present, the existing methods of recognizing human motion intention need more than two sensors to recognize more than two kinds of movements, the sensor pasting positions are special, and the hardware conditions for execution are high. In this work, a real-time motion intention recognition method based on Morse code is proposed and applied to the mechanical hand. The short-time and long-term muscle contraction signals collected by a single sEMG sensor were extracted and encoded with the Morse code method, and then the developed mapping method from Morse code to six hand movements were used to recognize hand movements. The average recognition accuracy of hand movements was 94.8704 ± 2.3556%, the average adjusting time was 34.89 s for all subjects, and the execution time of a single movement was 381 ms. The corresponding experiment video can be found in the attachment to show the experiment. The method proposed in this work is a method with one sensor to recognize six movements, low hardware conditions, high recognition accuracy, and insensitive to the difference of sensor pasting position.

Integrated and DC-powered superconducting microcomb.

Frequency combs, specialized laser sources emitting multiple equidistant frequency lines, have revolutionized science and technology with unprecedented precision and versatility. Recently, integrated frequency combs are emerging as scalable solutions for on-chip photonics. Here, we demonstrate a fully integrated superconducting microcomb that is easy to manufacture, simple to operate, and consumes ultra-low power. Our turnkey apparatus comprises a basic nonlinear superconducting device, a Josephson junction, directly coupled to a superconducting microstrip resonator. We showcase coherent comb generation through self-started mode-locking. Therefore, comb emission is initiated solely by activating a DC bias source, with power consumption as low as tens of picowatts. The resulting comb spectrum resides in the microwave domain and spans multiple octaves. The linewidths of all comb lines can be narrowed down to 1 Hz through a unique coherent injection-locking technique. Our work represents a critical step towards fully integrated microwave photonics and offers the potential for integrated quantum processors.

Unraveling transcriptomic signatures and dysregulated pathways in systemic lupus erythematosus across disease states.

OBJECTIVES: This study aims to elucidate the transcriptomic signatures and dysregulated pathways in patients with Systemic Lupus Erythematosus (SLE), with a particular focus on those persisting during disease remission. METHODS: We conducted bulk RNA-sequencing of peripheral blood mononuclear cells (PBMCs) from a well-defined cohort comprising 26 remission patients meeting the Low Lupus Disease Activity State (LLDAS) criteria, 76 patients experiencing disease flares, and 15 healthy controls. To elucidate immune signature changes associated with varying disease states, we performed extensive analyses, including the identification of differentially expressed genes and pathways, as well as the construction of protein-protein interaction networks. RESULTS: Several transcriptomic features recovered during remission compared to the active disease state, including down-regulation of plasma and cell cycle signatures, as well as up-regulation of lymphocytes. However, specific innate immune response signatures, such as the interferon (IFN) signature, and gene modules involved in chromatin structure modification, persisted across different disease states. Drug repurposing analysis revealed certain drug classes that can target these persistent signatures, potentially preventing disease relapse. CONCLUSION: Our comprehensive transcriptomic study revealed gene expression signatures for SLE in both active and remission states. The discovery of gene expression modules persisting in the remission stage may shed light on the underlying mechanisms of vulnerability to relapse in these patients, providing valuable insights for their treatment.

A Predefined Rule-Based Multi-Factor Risk Stratification Is Associated With Improved Outcomes at a Rural Primary Care Practice.

This study built a predefined rule-based risk stratification paradigm using 19 factors in a primary care setting that works with rural communities. The factors include medical and nonmedical variables. The nonmedical variables represent 3 demographic attributes and one other factor represents transportation availability. Medical variables represent major clinical variables such as blood pressure and BMI. Many risk stratification models are found in the literature but few integrate medical and nonmedical variables, and to our knowledge, no such model is designed specifically for rural communities. The data used in this study contain the associated variables of all medical visits in 2021. Data from 2022 were used to evaluate the model. After our risk stratification model and several interventions were adopted in 2022, the percentage of patients with high or medium risk of deteriorating health outcomes dropped from 34.9% to 24.4%, which is a reduction of 30%. The medium-complex patient population size, which had been 29% of all patients, decreased by about 4% to 5.7%. According to the analysis, the total risk score showed a strong correlation with 3 risk factors: dual diagnoses, the number of seen providers, and PHQ9 (0.63, 0.54, and 0.45 correlation coefficients, respectively).