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Background: Thromboembolic events are a well-recognized cause of in-hospital deaths of patients with infectious diseases. However, thromboembolic events in patients with scrub typhus, caused by Orientia tsutsugamushi have rarely been reported. This study aimed to assess risk factors associated with thromboembolic events in patients with scrub typhus. Methods: All 93 scrub typhus patients' diagnoses were confirmed serologically or by positive nested polymerase chain reaction (PCR). The clinical and laboratory findings from 12 scrub typhus patients with thromboembolic events and 81 scrub typhus patients with nonthromboembolic events were retrospectively studied. To determine the factors implicated in thromboembolic events, we performed multivariate logistic regression analysis using the six independent factors identified by the univariate analysis. Findings: The mean age of the patients in the thromboembolic group was 76.4 years (median, 76 years), and in nonthromboembolic group it was 64.6 years (median, 65 years) (P<0·001). Thromboembolic events were observed in 12 patients. These events included acute coronary syndrome (n = 5), acute limb ischemia (n = 4), ischemic stroke (n = 1), deep vein thrombosis combined with pulmonary thromboembolism (n = 1), and left common iliac artery aneurysm with a thrombus (n = 1). According to multivariate analysis, the following four factors were significantly associated with the thromboembolic events: 1) treatment with rifampin (OR = 57.6; CI 1.2–2700.3), 2) Taguchi genotype (OR = 41.5, P = 0.028; CI 1.5–1154.6), 3) atrial fibrillation (OR = 9.4, P = 0.034; CI 1.2–74.0), and 4) age (OR = 1.1, P = 0.046; CI 1.0–1.3). Conclusions: Our study suggests that clinicians should be cautious when managing patients with scrub typhus to avoid the development of thromboembolic events, especially in patients with risk factors such as treatment with rifampin, Taguchi genotype, atrial fibrillation, and advanced age. Author summary: Scrub typhus, a disease caused by Orientia tsutsugamushi, is typically treated with antibiotics. It can sometimes lead to serious complications, including thromboembolic events. These events can be life-threatening but have been rarely reported due to under-suspicion in clinical practice, as their rarity often leads to them being overlooked. In this regard, our study suggests that clinicians should be cautious when managing patients with scrub typhus to prevent the development of thromboembolic events, especially in patients with risk factors such as treatment with rifampin, Taguchi genotype, atrial fibrillation, and advanced age. [ABSTRACT FROM AUTHOR]

A catalogue of neuronal cell types has often been called a ‘parts list’ of the brain1, and regarded as a prerequisite for understanding brain function2,3. In the optic lobe of Drosophila, rules of connectivity between cell types have already proven to be essential for understanding fly vision4,5. Here we analyse the fly connectome to complete the list of cell types intrinsic to the optic lobe, as well as the rules governing their connectivity. Most new cell types contain 10 to 100 cells, and integrate information over medium distances in the visual field. Some existing type families (Tm, Li, and LPi)6–10 at least double in number of types. A new serpentine medulla (Sm) interneuron family contains more types than any other. Three families of cross-neuropil types are revealed. The consistency of types is demonstrated by analysing the distances in high-dimensional feature space, and is further validated by algorithms that select small subsets of discriminative features. We use connectivity to hypothesize about the functional roles of cell types in motion, object and colour vision. Connectivity with ‘boundary types’ that straddle the optic lobe and central brain is also quantified. We showcase the advantages of connectomic cell typing: complete and unbiased sampling, a rich array of features based on connectivity and reduction of the connectome to a substantially simpler wiring diagram of cell types, with immediate relevance for brain function and development.An analysis of the Drosophila connectome yields all cell types intrinsic to the optic lobe, and their rules of connectivity. [ABSTRACT FROM AUTHOR]

Many animals use visual information to navigate1–4, but how such information is encoded and integrated by the navigation system remains incompletely understood. In Drosophila melanogaster, EPG neurons in the central complex compute the heading direction5 by integrating visual input from ER neurons6–12, which are part of the anterior visual pathway (AVP)10,13–16. Here we densely reconstruct all neurons in the AVP using electron-microscopy data17. The AVP comprises four neuropils, sequentially linked by three major classes of neurons: MeTu neurons10,14,15, which connect the medulla in the optic lobe to the small unit of the anterior optic tubercle (AOTUsu) in the central brain; TuBu neurons9,16, which connect the AOTUsu to the bulb neuropil; and ER neurons6–12, which connect the bulb to the EPG neurons. On the basis of morphologies, connectivity between neural classes and the locations of synapses, we identify distinct information channels that originate from four types of MeTu neurons, and we further divide these into ten subtypes according to the presynaptic connections in the medulla and the postsynaptic connections in the AOTUsu. Using the connectivity of the entire AVP and the dendritic fields of the MeTu neurons in the optic lobes, we infer potential visual features and the visual area from which any ER neuron receives input. We confirm some of these predictions physiologically. These results provide a strong foundation for understanding how distinct sensory features can be extracted and transformed across multiple processing stages to construct higher-order cognitive representations.Electron-microscopy data are used to reconstruct the neurons that make up the anterior visual pathway in the Drosophila brain, providing insight into how visual features are encoded to guide navigation. [ABSTRACT FROM AUTHOR]

This study aimed to evaluate the incidence of clinically significant intraocular inflammation (csIOI) after treatment with intravitreal injection (IVI) of brolucizumab and identify csIOI risk factors. We categorized 60,966 South Korean patients from a nationwide population-based cohort into 4 groups: groups 1 (Ranibizumab), 2 (Aflibercept), 3 (Brolucizumab), and 4 (switched to brolucizumab). We used the Kaplan–Meier method to estimate the cumulative incidence of csIOI in each group and calculated the hazard ratios (HRs) and 95% confidence intervals (CIs). We constructed a multivariate model using forward selection methods to identify risk factors for csIOI. The cumulative incidence of csIOI within 180 days of the index date in groups 1, 2, 3, and 4 was 0.36% (67/18,537), 0.49% (186/37,951), 3.47% (38/1,095), and 3.69% (125/3,383), respectively. Multivariate analysis revealed a significant increase in csIOI risk in groups 3 (HR 11.08, 95% CI 7.42–16.53, P < 0.001) and 4 (HR 10.40, 95% CI 7.67–14.09, P < 0.001). History of retinal vascular occlusion (HR 1.56, 95% CI 1.01–2.40, P = 0.043) significantly increased csIOI risk after brolucizumab IVI treatment; female sex (HR 0.78, 95% CI 0.64–0.96, p = 0.020) and diabetes (HR 0.72, 95% CI 0.58–0.90, p = 0.004) decreased the risk. csIOI incidence was higher after brolucizumab IVI treatment than after ranibizumab and aflibercept IVI treatment. Retinal vein occlusion history, female sex, and diabetes are associated with csIOI after brolucizumab IVI treatment. [ABSTRACT FROM AUTHOR]

Background: While numerous studies have been conducted on sudden sensorineural hearing loss (SSNHL), research on how treatment outcomes and prognosis vary by age remains insufficient. This study aims to investigate the differences in recovery rates among SSNHL patients divided by age groups. Methods: A retrospective study was conducted on 177 patients diagnosed with SSNHL from 2020 to 2023. The patients were categorized into four age groups: under 20, 30–40, 50–60, and over 70. Recovery rates and associated symptoms were compared across these groups. Results: Significant recovery rates were observed in all age groups except for those over 70 (p = 0.006, p = 0.003, p = 0.009). No significant differences were found in recovery rates based on gender (p > 0.75) or symptoms such as tinnitus, ear fullness, and dizziness (p > 0.05). Conclusions: The study revealed that younger and middle-aged adults showed statistically significant improvements in recovery rates, while the elderly exhibited relatively lower recovery rates. [ABSTRACT FROM AUTHOR]

Height is known to be a classically heritable trait controlled by complex polygenic factors. Numerous height-associated genetic variants across the genome have been identified so far. It is also a representative of externally visible characteristics (EVC) for predicting appearance in forensic science. When biological evidence at a crime scene is deficient in identifying an individual, the examination of forensic DNA phenotyping using some genetic variants could be considered. In this study, we aimed to predict 'height', a representative forensic phenotype, by using a small number of genetic variants when short tandem repeat (STR) analysis is hard with insufficient biological samples. Our results not only replicated previous genetic signals but also indicated an upward trend in polygenic score (PGS) with increasing height in the validation and replication stages for both genders. These results demonstrate that the established SNP sets in this study could be used for height estimation in the Korean population. Specifically, since the PGS model constructed in this study targets only a small number of SNPs, it contributes to enabling forensic DNA phenotyping even at crime scenes with a minimal amount of biological evidence. To the best of our knowledge, this was the first study to evaluate a PGS model for height estimation in the Korean population using GWAS signals. Our study offers insight into the polygenic effect of height in East Asians, incorporating genetic variants from non-Asian populations. [ABSTRACT FROM AUTHOR]

Background: No studies to date have compared audiologic characteristics in patients with continuous and intermittent tinnitus. The present study classified tinnitus patients into continuous and intermittent groups based on tinnitus duration and compared their audiologic characteristics. Methods: This study enrolled 604 patients with tinnitus from January 2019 to December 2022. Clinical manifestations, PTA results, the frequency and loudness of tinnitus, ABR, DPOAE, and TEOAE tests were compared in patients with continuous and intermittent tinnitus. Results: Of the 604 patients, 231 (38.2%) had continuous and 373 (61.8%) had intermittent tinnitus. There were no significant between-group differences in otologic symptoms, tinnitus onomatopoeia. PTA showed that hearing thresholds, except at 125 Hz, were significantly higher in patients with continuous rather than intermittent tinnitus. The loudness of tinnitus was significantly greater in patients with continuous rather than intermittent tinnitus. ABR tests showed that the absolute latency of wave V was significantly longer in continuous than in intermittent tinnitus. Signal-to-noise ratios on TEOAE tests were significantly lower in patients with continuous rather than intermittent tinnitus at all frequencies tested (1, 1.5, 2, 3, and 4 kHz). Response rates to sound stimuli at all frequencies, except for 1 kHz, were significantly lower on DPOAE tests in patients with continuous rather than intermittent tinnitus. Conclusions: Continuous tinnitus is more common in males, more persistent over time, and is associated with a higher rate of hearing loss. In contrast, intermittent tinnitus is more common in women, appears acutely, and is associated with a relatively lower rate of hearing loss. Based on the findings of the current paper, it seems that audiologic characteristics may differ between patients with continuous and intermittent tinnitus. [ABSTRACT FROM AUTHOR]

Simple Summary: Simple Summary: Nineteen geriatric dogs (aged 8–20 years) with chronic diseases, including myxomatous mitral valve disease, chronic kidney disease, intervertebral disk disease, cognitive dysfunction syndrome, degenerative joint disease, osteoarthritis, and progressive retinal atrophy, were included in this retrospective study. They were divided into two groups: a control group treated with adipose tissue-derived mesenchymal stem cells (MSCs) (n = 9) and a treatment group receiving MSCs derived from gonadal tissue (n = 10). MSC therapies were administered intravenously at monthly intervals, with multiple frequencies, using allogeneic MSCs. Safety was evaluated through short-term and long-term physical exams, blood tests, imaging studies, and the monitoring of adverse events. No clinical adverse effects were observed in the dogs treated with gonadal tissue-derived MSCs. Ensuring the safety of mesenchymal stem cell (MSC) therapy is a fundamental requirement in clinical practice. This study aimed to assess the safety of using gonadal tissue-derived MSCs (n = 10) compared to the commonly utilized adipose tissue-derived MSCs (n = 9) in geriatric dogs with chronic diseases. All participants received allogeneic MSC therapy, and no allergic reactions due to allogeneic cell immunogenicity were noted. Both groups showed no adverse changes in physical exams or hematological parameters before and after therapy. Importantly, there were no instances of tumor formation or growth post-treatment in either group. The findings demonstrated that dogs treated with gonadal tissue-derived MSCs experienced no clinical adverse effects. However, clinical adverse effects were reported in one case of adipose tissue-derived MSC therapy. Despite limitations in monitoring beyond one year and constraints due to a small and diverse patient group, this pioneering study validates the safe use of gonadal tissue-derived MSCs in aged companion animals. It underscores the potential of utilizing tissues from neutering procedures to advance regenerative medicine and expand cell banks and therapy options for companion animals. [ABSTRACT FROM AUTHOR]

Cutaneous leishmaniasis (CL) is a tropical disease endemic in many parts of the world. Characteristic clinical manifestations of CL include the formation of ulcerative skin lesions that can inflict life-long disability if left untreated. Although drugs are available, they are unaffordable and out of reach for individuals who need them the most. Developing a highly cost-efficient CL vaccine could address this problem but such a vaccine remains unavailable. Here, we developed a chimeric influenza virus-like particle expressing the Leishmania amazonensis promastigote surface antigen (LaPSA-VLP). LaPSA-VLPs were self-assembled in Spodoptera frugiperda insect cell lines using the baculovirus expression system. After characterizing the vaccines and confirming successful VLP assembly, BALB/c mice were immunized with these vaccines for efficacy assessment. Sera acquired from mice upon subcutaneous immunization with the LaPSA-VLP specifically interacted with the L. amazonensis soluble total antigens. LaPSA-VLP-immunized mice elicited significantly greater quantities of parasite-specific IgG from the spleens, popliteal lymph nodes, and footpads than unimmunized mice. LaPSA-VLP immunization also enhanced the proliferation of B cell populations in the spleens of mice and significantly lessened the CL symptoms, notably the footpad swelling and IFN-γ-mediated inflammatory response. Overall, immunizing mice with the LaPSA-VLPs prevented mice from developing severe CL symptoms, signifying their developmental potential. [ABSTRACT FROM AUTHOR]

Extracellular fluid (ECF) excess is common in patients with chronic kidney disease (CKD). This study (involving 284 patients with CKD) explored the association between choroidal vascularity index (CVI) and ECF excess. We categorised patients into three groups based on extracellular water/total body water: normal, mildly overhydrated, and severely overhydrated. The more severe ECF status was associated with a lower CVI after adjustment (B = − 0.902, p = 0.001). In non-diabetic patients, both vascular luminal (LA, p < 0.001) and stromal areas (SA, p = 0.003) were significantly reduced in patients with severe ECF excess compared to others, whereas diabetic patients showed no significant differences in LA (p = 0.96) and SA (p = 0.86) based on ECF excess status. These findings suggest that ECF status may influence CVI in patients with CKD, underscoring the need for further research to clarify its direct impact on choroidal changes. [ABSTRACT FROM AUTHOR]

Simple Summary: Extraskeletal osteosarcoma is an osteoid-producing neoplasm without primary bone involvement. Imaging findings of extraskeletal osteosarcoma are well described in human medicine; however, while there have been several case reports and studies of canine extraskeletal osteosarcoma addressed in veterinary medicine, there is limited information on the computed tomography findings of the disease. Therefore, the goal of the present case series was to investigate the computed tomography characteristics of extraskeletal osteosarcoma in dogs. The objective of the present case series was to investigate the various computed tomography findings of six dogs diagnosed with extraskeletal osteosarcoma (exOSA) at several locations. Among the tumors evaluated, four were subcutaneous, one was mammary, and one involved the intestinal tract. Intralesional mineralization was observed in all six dogs. Most of the tumors were moderately calcified, exhibited amorphous mineralization, and were heterogeneous on post-contrast imaging. Three of the tumors were peripherally enhanced, and regional lymphadenopathy was identified in two of the dogs, which was presumed to be metastatic. No lymph node calcification was reported. Although the presence of intralesional mineralization is not a pathognomonic finding, it was consistently identified in the present case series. Therefore, exOSA should be considered in the differential diagnosis when mineralization occurs in a mass unrelated to osseous structures. [ABSTRACT FROM AUTHOR]

Simple Summary: Chronic kidney disease (CKD) is common in old dogs and cats. Patients with CKD have impaired renal structures and decreased renal function. Because renal degeneration is generally irreversible, treatment of CKD is focused mainly on conserving the remaining renal function. In this study, we retrospectively evaluated the effects of oligo-fucoidan, fucoxanthin, and L-carnitine in canine CKD patients. The supplements were supplied for 6 months and showed a reno-protective effect, consistent with previous animal model studies. Based on our results, the combination of oligo-fucoidan, fucoxanthin, and L-carnitine has the potential to delay the progression of canine CKD and be used as an adjuvant therapy. Chronic kidney disease (CKD) commonly occurs in old dogs and cats. Oligo-fucoidan, fucoxanthin, and L-carnitine (OFL) compounds have a variety of reno-protective properties, including anti-inflammatory, anti-oxidative, and anti-fibrotic effects. Because their effects have not been investigated in naturally occurring canine CKD, we examined their reno-protective activities in dog patients with CKD. A total of 50 patients (OFL, n = 28; control, n = 22) were included in the analysis. A significant difference was identified in serum blood urea nitrogen and creatinine concentrations between the control and OFL groups at 6 months. No significant difference in electrolytes was found between the groups. A significant difference was identified in serum creatinine concentration between the control and OFL groups in azotemic (CKD IRIS stage 2–4) at 6 months. The OFL compounds showed a reno-protective effect, consistent with previous animal studies. The OFL combination can potentially delay the progression of canine CKD and be used as an adjuvant therapy. [ABSTRACT FROM AUTHOR]

Nitric oxide (NO) is an important molecule in cell communication that also plays an important role in many biological processes. Given the dual role of NO in nerve degeneration and regeneration after facial nerve injury, we sought to delve deeper into its role through a systematic literature review. A comprehensive review of the literature employing SCOPUS, PubMed, Cochrane Library, EMBASE, and Google Scholar databases was conducted to evaluate the induction and role of NO in neurodegeneration and regeneration after facial nerve injury. From the 20 papers ultimately reviewed, the central findings were that neuronal nitric oxide synthase(nNOS), endothelial nitric oxide synthase (eNOS), and induced nitric oxide synthase (iNOS) increased or decreased depending on the method of facial nerve damage, damaged area, harvested area, and animal age, and were correlated with degeneration and regeneration of the facial nerve. Research conducted on rats and mice demonstrated that NO, nNOS, eNOS, and iNOS play significant roles in nerve regeneration and degeneration. However, the relationship between nerve damage and NO could not be defined by a simple causal relationship. Instead, the involvement of NOS depends on the type of nerve cell, source of NO, timing, and location of expression, age of the target animal, and proximity of the damage location to the brainstem. Consequently, nNOS, eNOS, and iNOS expression levels and functions may vary significantly. [ABSTRACT FROM AUTHOR]

Molecular chaperones are highly conserved across evolution and play a crucial role in preserving protein homeostasis. The 60 kDa heat shock protein (HSP60), also referred to as chaperonin 60 (Cpn60), resides within mitochondria and is involved in maintaining the organelle's proteome integrity and homeostasis. The HSP60 family, encompassing Cpn60, plays diverse roles in cellular processes, including protein folding, cell signaling, and managing high-temperature stress. In prokaryotes, HSP60 is well understood as a GroEL/GroES complex, which forms a double-ring cavity and aids in protein folding. In eukaryotes, HSP60 is implicated in numerous biological functions, like facilitating the folding of native proteins and influencing disease and development processes. Notably, research highlights its critical involvement in sustaining oxidative stress and preserving mitochondrial integrity. HSP60 perturbation results in the loss of the mitochondria integrity and activates apoptosis. Currently, numerous clinical investigations are in progress to explore targeting HSP60 both in vivo and in vitro across various disease models. These studies aim to enhance our comprehension of disease mechanisms and potentially harness HSP60 as a therapeutic target for various conditions, including cancer, inflammatory disorders, and neurodegenerative diseases. This review delves into the diverse functions of HSP60 in regulating proteo-homeostasis, oxidative stress, ROS, apoptosis, and its implications in diseases like cancer and neurodegeneration. [ABSTRACT FROM AUTHOR]

We report a novel BPS jumping phenomenon of 5d N = 1 supersymmetric gauge theories whose brane configuration is equipped with an O7-plane. The study of the relation between O7+-plane and O7−-plane reveals that such BPS jumps take place when the Higgsing is triggered near the O7-plane upon a particular parameter tuning of the theories. We propose two types of gauge theories whose BPS spectra jump. One is the SU(2N + 8) gauge theory with a symmetric hypermultiplet converted to the SU(2N) gauge theory with an antisymmetric hypermultiplet. The other is pure SO(2N + 8) gauge theory jumping to pure Sp(N) gauge theory. We explicitly confirm our proposal through the (un)refined instanton partition functions. Furthermore, we discuss feasible generalizations involving an Op-plane for supersymmetric gauge theories of eight supercharges in four and three dimensions (p = 6, 5 respectively). [ABSTRACT FROM AUTHOR]

Facial nerve injury can cause significant functional impairment, impacting both the peripheral and central nervous systems. The present study evaluated changes in facial motor function, numbers of cholinergic neurons and microglia, and nNOS levels in the facial nucleus of the central nervous system (CNS) following peripheral facial nerve injury. Facial nerve function, as determined by eyeblink and whisker-movement reflexes, was evaluated at baseline and 1, 2, 3, 4, 8, and 12 weeks after inducing facial nerve injury through compression or axotomy. The expression of choline acetyltransferase (ChAT), ionized calcium-binding adaptor molecule 1 (Iba-1), and neuronal nitric oxide synthase (nNOS) in the facial nucleus of the CNS was analyzed 2, 4, and 12 weeks after peripheral facial nerve injury. Compression-induced facial nerve injury was found to lead to temporary facial motor impairment, whereas axotomy resulted in persistent impairment. Moreover, both compression and axotomy reduced ChAT expression and increased Iba-1 and nNOS expression in the facial nucleus, indicating upregulation of an inflammatory response and neurodegeneration. These results indicate that, compared with compression-induced injury, axotomy-induced facial nerve injury results in greater facial motor dysfunction and more persistent microglial and nitric oxide activation in the facial nucleus of the CNS. [ABSTRACT FROM AUTHOR]

The heat shock response is an evolutionarily conserved mechanism that protects cells or organisms from the harmful effects of various stressors such as heat, chemicals toxins, UV radiation, and oxidizing agents. The heat shock response triggers the expression of a specific set of genes and proteins known as heat shock genes/proteins or molecular chaperones, including HSP100, HSP90, HSP70, HSP60, and small HSPs. Heat shock proteins (HSPs) play a crucial role in thermotolerance and aiding in protecting cells from harmful insults of stressors. HSPs are involved in essential cellular functions such as protein folding, eliminating misfolded proteins, apoptosis, and modulating cell signaling. The stress response to various environmental insults has been extensively studied in organisms from prokaryotes to higher organisms. The responses of organisms to various environmental stressors rely on the intensity and threshold of the stress stimuli, which vary among organisms and cellular contexts. Studies on heat shock proteins have primarily focused on HSP70, HSP90, HSP60, small HSPs, and ubiquitin, along with their applications in human biology. The current review highlighted a comprehensive mechanism of heat shock response and explores the function of heat shock proteins in stress management, as well as their potential as therapeutic agents and diagnostic markers for various diseases. [ABSTRACT FROM AUTHOR]

Alopecia, a prevalent yet challenging condition with limited FDA-approved treatments which is accompanied by notable side effects, necessitates the exploration of natural alternatives. This study elucidated the hair growth properties of Gynostemma pentaphyllum leaf hydrodistillate (GPHD) both in vitro and in vivo. Furthermore, damulin B, a major component of GPHD, demonstrated hair growth-promoting properties in vitro. Beyond its established anti-diabetic, anti-obesity, and anti-inflammatory attributes, GPHD exhibited hair growth induction in mice parallel to minoxidil. Moreover, it upregulated the expression of autocrine factors associated with hair growth, including VEGF, IGF-1, KGF, and HGF. Biochemical assays revealed that minoxidil, GPHD, and damulin B induced hair growth via the Wnt/β-catenin pathway through AKT signaling, aligning with in vivo experiments demonstrating improved expression of growth factors. These findings suggest that GPHD and damulin B contribute to the hair growth-inducing properties of dermal papilla cells through the AKT/β-catenin signaling pathway. [ABSTRACT FROM AUTHOR]

We propose two novel methods for computing the superconformal index of 5d superconformal field theories that cannot be described by conventional Lagrangian descriptions under mass deformations. The first approach involves the use of Higgs branch flows from UV Lagrangian theories, guided by transitions in 5-brane webs in Type IIB string theory. The second method employs the relationship between O7+-plane and O7−-plane with eight D7-branes, which applies to particular non-Lagrangian theories realized by brane configurations involving an O7+-plane. As a concrete application of our method, we compute the superconformal indices for all known rank-1 non-Lagrangian theories, which we also use to identify flavor symmetries and their global forms at the conformal field theory (CFT) fixed points. [ABSTRACT FROM AUTHOR]

Background: Chronic right-ventricular (RV) pacing can worsen heart failure in patients with a low ejection fraction (EF), but little is known about pacing-induced cardiomyopathy (PICM) in patients with preserved EF. We aimed to investigate risk factors of PICM in these patients during long-term follow-up. Methods: The prospective registry at Chosun University Hospital, South Korea, included de novo patients with preserved EF undergoing transvenous permanent pacemaker (PPM) implantation for atrioventricular blockage from 2017 to 2021. Patients with EF ≥ 50% and expected ventricular pacing ≥ 40% were included. Composite outcomes were cardiac death (pump failure), hospitalization because of heart failure, PICM, and biventricular pacing (BVP) upgrade. Results: A total of 168 patients (69 men, 76.3 ± 10.4 years) were included. During three years of follow-up, one patient died, 14 were hospitalized, 16 suffered PICM, and two underwent BVP upgrade. PICM were associated with reduced global longitudinal strain (GLS), prolonged paced QRS duration (pQRSd) and diastolic variables (E/e', LAVI). Cox regression analysis identified pQRSd (hazard ratio [HR], 1.111; 95% confidence interval [CI], 1.011–1.222; P = 0.03) and reduced GLS (HR, 1.569; 95% CI, 1.163–2.118; P = 0.003) as independent predictors of PICM. GLS showed high predictive accuracy for PICM, with an area under the curve of 0.84 (95% CI 0.779–0.894; P < 0.001) [GLS –12.0, 62.5% sensitivity, and 86.1% specificity]. Conclusion: RV pacing increased the risk of PICM in patients with preserved EF. Reduced GLS and prolonged pQRSd could help identify individuals at high risk of PICM even with preserved EF. [ABSTRACT FROM AUTHOR]

This paper presents a computer-simulation-based design of an in-line, coaxial-to-circular waveguide adapter for converting the coaxial transverse electromagnetic (TEM) mode to the circular waveguide TE11 mode over more than a one-octave bandwidth. The proposed adapter consists of a coaxial-to-rectangular waveguide transformer employing a stepped-ridge converter and a rectangular-to-circular waveguide transformer employing a curved transition. The proposed adapter has been optimized using a commercial simulation tool. The dimensions of the designed adapter are given so that it can be verified by anyone who is interested. The designed adapter operates from 8.00 GHz to 22.95 GHz (2.87:1 bandwidth) with a reflection coefficient of less than −20 dB and a higher-order mode level of less than −25.0 dB. [ABSTRACT FROM AUTHOR]

Otitis media (OM) is a common cause of hearing loss in children that requires corrective surgery. Various studies have investigated the pathomechanisms and treatment of OM. Autophagy, an essential cellular recycling and elimination mechanism implicated in various diseases, is known to play an important role in the pathogenesis of OM. Here, we conducted a literature review on autophagy in OM, highlighting the relationship between expression patterns of autophagy-related factors and pathophysiological and clinical aspects of OM. We summarized the existing research results on the expression of autophagy-related factors in acute OM (AOM), OM with effusion (OME), chronic OM (COM) with cholesteatoma, and COM without cholesteatoma (CholeOM) in animals and humans. Autophagy-related factors are expressed in the middle ear mucosa or fluid of AOM, effusion of OME, granulation tissue of COM, and cholesteatoma of CholeOM. Among ATGs and other autophagy-related factors, the most extensively studied in relation to the pathogenesis of OM are mTOR, LC3II/I, PI3K, Beclin-1, FLIP, Akt, and Rubicon. Expression of autophagy-related factors is associated with AOM, OME, COM, and CholeOM. Inadequate expression of these factors or a decrease/increase in autophagy responses can result in OM, underscoring the critical role of ATGs and related factors in the pathogenesis of OM. [ABSTRACT FROM AUTHOR]

Objective The potential of using retinal images as a biomarker of cardiovascular disease (CVD) risk has gained significant attention, but regulatory approval of such artificial intelligence (AI) algorithms is lacking. In this regulated pivotal trial, we validated the efficacy of Reti-CVD, an AI-Software as a Medical Device (AI-SaMD), that utilizes retinal images to stratify CVD risk. Materials and Methods In this retrospective study, we used data from the Cardiovascular and Metabolic Diseases Etiology Research Center-High Risk (CMERC-HI) Cohort. Cox proportional hazard model was used to estimate hazard ratio (HR) trend across the 3-tier CVD risk groups (low-, moderate-, and high-risk) according to Reti-CVD in prediction of CVD events. The cardiac computed tomography-measured coronary artery calcium (CAC), carotid intima-media thickness (CIMT), and brachial-ankle pulse wave velocity (baPWV) were compared to Reti-CVD. Results A total of 1106 participants were included, with 33 (3.0%) participants experiencing CVD events over 5 years; the Reti-CVD-defined risk groups (low, moderate, and high) were significantly associated with increased CVD risk (HR trend, 2.02; 95% CI, 1.26-3.24). When all variables of Reti-CVD, CAC, CIMT, baPWV, and other traditional risk factors were incorporated into one Cox model, the Reti-CVD risk groups were only significantly associated with increased CVD risk (HR = 2.40 [0.82-7.03] in moderate risk and HR = 3.56 [1.34-9.51] in high risk using low-risk as a reference). Discussion This regulated pivotal study validated an AI-SaMD, retinal image-based, personalized CVD risk scoring system (Reti-CVD). Conclusion These results led the Korean regulatory body to authorize Reti-CVD. [ABSTRACT FROM AUTHOR]

This study aimed to examine comorbidity associations across age groups of inpatients with endocrine diseases as the primary diagnosis throughout the life cycle to develop an effective management strategy. Data were obtained from the Korean National Hospital Discharge In-depth Injury Survey (KNHDS) from 2006 to 2021, involving 68,515 discharged patients aged ≥ 19 years with a principal diagnosis of endocrine disease. A database was constructed for analysis, extracting general characteristics and comorbidities. Employing R version 4.2.3, the Chi-squared test and the Apriori algorithm of ARM (association rule mining) were used for analyzing general characteristics and comorbidity associations. There were more women (53.1%) than men (46.9%) (p < 0.001, with women (61.2 ± 17.2) having a higher average age than men (58.6 ± 58.6) (p < 0.001). Common comorbidities include unspecified diabetes mellitus; essential (primary) hypertension; unspecified diabetes mellitus; and other disorders of fluid, electrolyte, and acid-base balance. Notably, type 2 diabetes mellitus, disorders of lipoprotein metabolism and other lipidemia, polyneuropathy in diseases classified elsewhere, retinal disorders in diseases classified elsewhere, and essential (primary) hypertension prevail across all age groups. Association rules further highlight specific comorbidities appearing selectively in certain age groups. In conclusion, establishing a management strategy for comorbidities in patients with a primary diagnosis of an endocrine disorder is necessary. [ABSTRACT FROM AUTHOR]

Ketone bodies (KBs), such as acetoacetate and β-hydroxybutyrate, serve as crucial alternative energy sources during glucose deficiency. KBs, generated through ketogenesis in the liver, are metabolized into acetyl-CoA in extrahepatic tissues, entering the tricarboxylic acid cycle and electron transport chain for ATP production. Reduced glucose metabolism and mitochondrial dysfunction correlate with increased neuronal death and brain damage during cerebral ischemia and neurodegeneration. Both KBs and the ketogenic diet (KD) demonstrate neuroprotective effects by orchestrating various cellular processes through metabolic and signaling functions. They enhance mitochondrial function, mitigate oxidative stress and apoptosis, and regulate epigenetic and post-translational modifications of histones and non-histone proteins. Additionally, KBs and KD contribute to reducing neuroinflammation and modulating autophagy, neurotransmission systems, and gut microbiome. This review aims to explore the current understanding of the molecular mechanisms underpinning the neuroprotective effects of KBs and KD against brain damage in cerebral ischemia and neurodegenerative diseases, including Alzheimer's disease and Parkinson's disease. [ABSTRACT FROM AUTHOR]

Understanding the intrinsic properties of cathode active particles is required to understand how they depend on the charge transfer resistance at solid–liquid or solid‐solid interfaces. Depth‐of‐discharge (DOD)‐dependent charge transport occurs when lithium ions move from the bulk electrolyte to the cathode active particles. However, composite electrodes consist of unevenly distributed active material, conductive additives, and polymeric binder, which complicates the electron/ion conduction path; hence, estimating the DOD‐dependent charge transfer resistance is difficult. However, micro‐sized spherical cathode active particles can be arranged into a cylindrical cavity trap on a microelectrode to evaluate the interfacial behavior of LiNi0.8Co0.1Mn0.1O2 (NCM811) cathode active particles in liquid and solid electrolyte systems. The electrochemical parameters calculated from the resultant Tafel plot can encourage meaningful discussions and demonstrate the reliability of the measurement technique. [ABSTRACT FROM AUTHOR]

Background: Meningoencephalomyelitis of unknown etiology (MUE) is a comprehensive term for non-infectious inflammatory brain diseases of the central nervous system (CNS) caused by abnormal autoimmune responses. This study aims to compare the differences in survival and clinical response of MUE according to the adjuvant immunosuppressant use. Medical records of 82 dogs diagnosed with MUE were reviewed retrospectively. Results: The overall survival time was 769 days (range 14–2687 days). The median survival time for each adjunctive was: leflunomide 1035 days (range 126–2163 days), mycophenolate mofetil 865 days (range 39–2191 days), cyclosporin 441 days (range 11–2176 days), cytosine arabinoside 754 days (range 6–1898 days) and a combination of mycophenolate mofetil and cytosine arabinoside 132 days (range 23–1227 days). There was no significant difference in the incidence rate of adverse events according to the immunosuppressants, but moderate to severe anemia was confirmed in 3 patients (18.7%) in the leflunomide group. Conclusions: The survival time and response rate of MUE dogs differed depending on which adjunctive immunosuppressants were used. Leflunomide showed a long survival time and a relatively good response rate in dogs with MUE. However, a large-scale further study with standardized doses of immunosuppressants and supportive treatment and constant monitoring interval is needed. [ABSTRACT FROM AUTHOR]

Soft hydrated permeable surfaces of hydrogels exhibit unique lubrication behaviors, including frictional hysteresis found in tribo-rheometry measurements. A hydrogel lubrication model that describes the transient behavior was previously developed using the structure kinetics model in the field of rheology and rate-and-state friction model, where the friction change is described as a competition between buildup and breakdown rates. In this study, the model is further modified to include the effect of hydrophilicity of a countersurface. Ultraviolet (UV)/ozone treatment on an aluminum surface significantly removes organic materials, resulting in extremely hydrophilic surface. Friction response of a polyacrylamide hydrogel against untreated and UV/ozone-treated aluminum exhibited noteworthy difference in the trajectory of hysteresis. Model fits were conducted using the modified lubrication model on both hystereses, and the fitting parameters of both hystereses are compared with each other to identify a parameter addressing hydrophilicity. Based on the model fits, we suggest that the hydrophilicity of the countersurface initially prevents the adsorption on the hydrogel surface because it holds water better. However, once water goes out of the contact due to contact pressure, a stronger adsorption occurs, which increases friction and decreases the speed dependence of friction. [ABSTRACT FROM AUTHOR]

No matter what treatment is used after nerve transection, a complete cure is impossible, so basic and clinical research is underway to find a cure. As part of this research, autophagy is being investigated for its role in nerve regeneration. Here, we review the existing literature regarding the involvement and significance of autophagy in peripheral nerve injury and regeneration. A comprehensive literature review was conducted to assess the induction and role of autophagy in peripheral nerve injury and subsequent regeneration. Studies were included if they were prospective or retrospective investigations of autophagy and facial or peripheral nerves. Articles not mentioning autophagy or the facial or peripheral nerves, review articles, off-topic articles, and those not written in English were excluded. A total of 14 peripheral nerve studies that met these criteria, including 11 involving sciatic nerves, 2 involving facial nerves, and 1 involving the inferior alveolar nerve, were included in this review. Studies conducted on rats and mice have demonstrated activation of autophagy and expression of related factors in peripheral nerves with or without stimulation of autophagy-inducing factors such as rapamycin, curcumin, three-dimensional melatonin nerve scaffolds, CXCL12, resveratrol, nerve growth factor, lentinan, adipose-derived stem cells and melatonin, basic fibroblast growth factor, and epothilone B. Among the most studied of these factors in relation to degeneration and regeneration of facial and sciatic nerves are LC3II/I, PI3K, mTOR, Beclin-1, ATG3, ATG5, ATG7, ATG9, and ATG12. This analysis indicates that autophagy is involved in the process of nerve regeneration following facial and sciatic nerve damage. Inadequate autophagy induction or failure of autophagy responses can result in regeneration issues after peripheral nerve damage. Animal studies suggest that autophagy plays an important role in peripheral nerve degeneration and regeneration. [ABSTRACT FROM AUTHOR]

We construct Seiberg-Witten curves for 5d N = 1 gauge theories whose Type IIB 5-brane configuration involves an O7-plane and discuss an intriguing relation between theories with an O7+-plane and those with an O7−-plane and 8 D7-branes. We claim that 5-brane configurations with an O7+-plane can be effectively understood as 5-brane configurations with a set of an O7−-plane and eight D7-branes with some special tuning of their masses such that the D7-branes are frozen at the O7−-plane. We check this equivalence between SU(N) gauge theory with a symmetric hypermultiplet and SU(N) gauge theory with an antisymmetric with 8 fundamentals, and also between SO(2N) gauge theory and Sp(N) gauge theory with eight fundamentals. We also compute the Seiberg-Witten curves for non-Lagrangian theories with a symmetric hypermultiplet, which includes the local ℙ2 theory with an adjoint. [ABSTRACT FROM AUTHOR]

The gut microbiome is a diverse bacterial community in the human gastrointestinal tract that plays important roles in a variety of biological processes. Short-chain fatty acids (SCFA) are produced through fermentation of dietary fiber. Certain microbes in the gut are responsible for producing SCFAs such as acetate, propionate and butyrate. An imbalance in gut microbiome diversity can lead to metabolic disorders and inflammation-related diseases. Changes in SCFA levels and associated microbiota were observed in IBD, suggesting an association between SCFAs and disease. The gut microbiota and SCFAs affect reactive oxygen species (ROS) associated with IBD. Gut microbes and SCFAs are closely related to IBD, and it is important to study them further. [ABSTRACT FROM AUTHOR]

Schizophrenia, a severe mental illness affecting about 1% of the population, manifests during young adulthood, leading to abnormal mental function and behavior. Its multifactorial etiology involves genetic factors, experiences of adversity, infection, and gene–environment interactions. Emerging research indicates that maternal infection or stress during pregnancy may also increase schizophrenia risk in offspring. Recent research on the gut–brain axis highlights the gut microbiome's potential influence on central nervous system (CNS) function and mental health, including schizophrenia. The gut microbiota, located in the digestive system, has a significant role to play in human physiology, affecting immune system development, vitamin synthesis, and protection against pathogenic bacteria. Disruptions to the gut microbiota, caused by diet, medication use, environmental pollutants, and stress, may lead to imbalances with far-reaching effects on CNS function and mental health. Of interest are short-chain fatty acids (SCFAs), metabolic byproducts produced by gut microbes during fermentation. SCFAs can cross the blood–brain barrier, influencing CNS activity, including microglia and cytokine modulation. The dysregulation of neurotransmitters produced by gut microbes may contribute to CNS disorders, including schizophrenia. This review explores the potential relationship between SCFAs, the gut microbiome, and schizophrenia. Our aim is to deepen the understanding of the gut–brain axis in schizophrenia and to elucidate its implications for future research and therapeutic approaches. [ABSTRACT FROM AUTHOR]

The coronavirus disease 2019 (COVID-19) has been reported to affect vascular networks including the eye. However, evidence on the causal relationship between COVID-19 infection and retinal vascular occlusions remains limited. This study aimed to determine the change in retinal vascular occlusion incidence during COVID-19 era and whether severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection induces retinal vascular occlusion. Retinal vein occlusion (RVO) and retinal artery occlusion (RAO) incidences during 2018–2019 and 2020–July 2021 were compared, those in confirmed and suspected COVID-19 patients diagnosed from 2020 to January 2021 were calculated, and those in COVID-19 patients during 180 days prior and 180 days after diagnosis were assessed. Additionally, the standardized incidence ratio of RVOs in COVID-19 patients was analyzed. Incidence rates per 100,000 people/year of RVO during 2018–2019 and 2020–2021 was 102.0 and 98.8, respectively. RAO incidence rates during 2018–2019 and 2020–2021 were 11.7 and 12.0, respectively. In both confirmed and suspected COVID-19 patients, the incidence of RVO and RAO did not change significantly from 180 days before to after diagnosis in the adjusted model. RVO incidence slightly decreased while RAO incidence increased during the COVID-19 pandemic. SARS-CoV-2 infection did not significantly increase RVO or RAO incidence. [ABSTRACT FROM AUTHOR]

Simple Summary: Two species of Sympetrum, namely S. depressiusculum and S. frequens, have been documented in South Korea. However, the distinction between these two species and their identity within South Korean populations has been a longstanding point of contention. To solve this issue, morphology, two mitochondrial genes, and one nuclear region were analyzed for S. depressiusculum samples from The Netherlands and Russia and S. frequens samples from Japan, as well as samples of Sympetrum from South Korea. Further, available public sequence data for the two species were included. Morphology, sequence divergence, and phylogenetic results all consistently suggest that South Korean populations form a single species. Analyses of haplotype network and gene pool distribution patterns in a nuclear region conducted to better explain the current taxonomic implications indicated changes in the dominant gene pool from The Netherlands and Russia to South Korea and Japan. However, such divergence and subdivision could be explained within the context of within-species diversification patterns, suggesting that South Korean populations constitute one species, S. depressiusculum, by applying the senior name. In South Korea, both Sympetrum depressiusculum Sélys, 1841 (Odonata: Libellulidae), which is distributed throughout Europe and from Russia to the Korean Peninsula, and Sympetrum frequens Sélys, 1883, which is endemic to Japan, are recorded. However, the identity of South Korean populations and the validity of listing the two species have not yet been settled. In this study, we collected seventy-four individuals of Sympetrum species from South Korea (five localities), Russia, The Netherlands, and Japan. These samples were examined for morphology and sequenced for partial COI, 16S rRNA, and a nuclear internal spacer (ITS) region, after which these molecular data were combined with available public data from Russia, Japan, and The Netherlands. Major morphological characters that have been used to distinguish the two species and phylogenetic, network, and structure analyses all consistently suggest that South Korean populations form a single species. Consequently, it could be valid to treat South Korean populations as one species, S. depressiusculum, by applying the senior name. Nevertheless, the validity of maintaining each as an independent species in other countries may need additional study considering that our samples were focused more on South Korea and limited for Europe, Russia, and Japan. [ABSTRACT FROM AUTHOR]

Carbonized fibers with quantifiable mechanical properties were prepared from environmentally benign lyocell fibers (LFs) through sulfuric acid-catalyzed continuous thermostabilization and following carbonization. The pristine LF was decomposed into small molecules which can be evaporated at high temperatures during thermal treatment, leading to a low mass yield (~ 12 wt%) after carbonization. In contrast, the impregnated LF with sulfuric acid (ILF) underwent various chemical reactions at low temperatures, catalyzed in the presence of protons and water within the fiber. These catalyzed reactions encompassed not only thermal dissociation of glycosidic bonds, but also elimination reactions, the dehydration of decomposed products to 5-hydroxymethylfurfural, and its subsequent conversion. A series of chemical analyses revealed that linear cellulosic macromolecular chains were transformed into highly crosslinked network structures consisting of decomposed products. As a consequence of this chemical transformation, the mass yield of ILF increased by more than double compared to that of LF. In addition, the density of the carbonized ILF was higher than that of the carbonized LF, indicating that impregnation with sulfuric acid contributed to the development of carbon structures. Unlike the highly brittle carbonized LFs, the carbonized fibers derived from the thermostabilized ILFs exhibited superior tensile strength and modulus with values of 0.92 GPa and 41 GPa, respectively. [ABSTRACT FROM AUTHOR]

This article discusses a case study of a 68-year-old man with a history of hypertension and diabetes who presented with symptoms of bradycardia and complete atrioventricular block. Due to a malfunctioning electrophysiology system, the authors used modified bipolar chest leads for continuous electrographic recording during the procedure. They successfully achieved left bundle branch capture and implanted a dual-chamber pacemaker without complications. The study highlights the usefulness of modified chest leads as an alternative option for cardiac rhythm monitoring when an electrophysiological recording system is unavailable. [Extracted from the article]

Facial nerve palsy directly impacts the quality of life, with patients with facial nerve palsy showing increased rates of depression and limitations in social activities. Although facial nerve palsy is not life-threatening, it can devastate the emotional and social lives of affected individuals. Hence, improving the prognosis of patients with this condition is of vital importance. The prognosis of patients with facial nerve palsy is determined by the cause of the disease, the degree of damage, and the treatment provided. The facial nerve can be easily damaged by middle ear and temporal bone surgery, trauma or infection, and tumors of the peripheral facial nerve or tumors surrounding the nerve secondary to systemic disease. In addition, idiopathic, acquired immunodeficiency syndrome and autoimmune diseases may damage the facial nerve. The treatment used for facial paralysis depends on the cause. Treatment of facial nerve amputation injury varies depending on the degree of facial nerve damage, comorbidities, and duration of injury. Recently, interest has increased in Toll-like receptors (TLRs) related to innate immune responses, as these receptors are known to be related to nerve regeneration. In addition to innate immune cells, both neurons and glia of the central nervous system (CNS) and peripheral nervous system (PNS) express TLRs. A comprehensive literature review was conducted to assess the expression and role of TLRs in peripheral nerve injury and subsequent regeneration. Studies conducted on rats and mice have demonstrated the expression of TLR1–13. Among these, TLR2–5 and TLR7 have received the most research attention in relation to facial nerve degeneration and regeneration. TLR10, TLR11, and TLR13 increase during compression injury of the facial nerve, whereas during cutting injury, TLR1–5, TLR8, and TLR10–13 increase, indicating that these TLRs are involved in the degeneration and regeneration of the facial nerve following each type of injury. Inadequate TLR expression or absence of TLR responses can hinder regeneration after facial nerve damage. Animal studies suggest that TLRs play an important role in facial nerve degeneration and regeneration. [ABSTRACT FROM AUTHOR]

Tinnitus is one of the most common symptoms of sudden sensorineural hearing loss (SSNHL), with the incidence of tinnitus in patients with SSNHL ranging from 60% to 90%. Little is known, however, about the specific audiologic and hematologic factors that may be associated with the development of tinnitus. To better understand the relationship between tinnitus and SSNHL, the present study compared audiologic and hematologic factors in SSNHL patients with tinnitus and without tinnitus. The present study compared 120 patients with SSNHL with tinnitus and 59 patients with SSNHL without tinnitus at their initial examination. Their audiology and hematologic test results were analyzed, and hearing recovery was determined by comparing the hearing thresholds before and after treatment. 120 patients with tinnitus showed longer III and V latency in auditory brainstem response (ABR) tests, lower signal-to-noise ratios (SNR) at 2 kHz in transient evoked otoacoustic emissions (TEOAE) tests, and lower response rates at 2 kHz in distortion product otoacoustic emissions (DPOAE) tests of the affected ear (p < 0.05 each) than the 59 patients without tinnitus. However, there were no significant between-group differences in the mean hearing threshold and hearing recovery rate of the affected ear. Patients with tinnitus had significantly worse mean hearing thresholds and hearing thresholds at 4 kHz in the nonaffected ear. The percentages of monocytes and large unstained cells (%LUCs) were higher in the group without tinnitus (p < 0.05), although there were no significant between-group differences in inflammatory markers, such as neutrophil-to-lymphocyte ratio (NLR), monocyte-to-lymphocyte ratio (MLR) and platelet-to-lymphocyte ratio (PLR). Tinnitus accompanying SSNHL may be associated with baseline hearing level, as well as being an indicator of damage to outer hair cells and auditory nerves. Additional studies are needed to evaluate hematologic data in SSNHL patients with and without tinnitus. 背景和目的：耳鸣是突发性感觉神经性听力损失（SSNHL）最常见的症状之一。SSNHL 患者中, 耳鸣的发生率为 60% 至 90%。然而, 我们对可能与耳鸣的发生相关的特定听力学和血液学因素知之甚少。 为了更好地了解耳鸣和 SSNHL 之间的关系, 本研究比较了 有耳鸣和无耳鸣的SSNHL患者的听力学和血液学因素。 对象和方法：本研究在初次检查时比较了 120 名有耳鸣的 SSNHL 患者和 59 名无耳鸣的 SSNHL 患者。分析了他们的听力学和血液学测试结果, 通过比较治疗前和治疗后的听力阈值来确定听力恢复情况。 结果：与 59 名无耳鸣患者相比, 120 名耳鸣患者在听性脑干反应（ABR）测试中表现出较长的 III 和 V 潜伏期, 在瞬态诱发耳声发射 (TEOAE) 测试中 表现出较低的2kHz 时信噪比 (SNR), 在失真产物耳声发射 (DPOAE) 测试中受累耳表现出较低的 2kHz 时响应率（ p<0.05）。然而, 在受累耳的平均听力阈值和听力恢复率方面, 并没有出现重大的组间差异。耳鸣患者的未受累耳的平均听阈和 4kHz 听阈明显较差。 无耳鸣组的单核细胞和未染色大细胞 (%LUC) 的百分比较高（p<0.05）, 尽管在炎症标志物方面, 例如中性粒细胞与淋巴细胞比率 (NLR)、单核细胞与淋巴细胞比率(MLR) 和血小板与淋巴细胞比率 (PLR), 组间差异不显著, 。 结论：伴随 SSNHL 的耳鸣可能与基线听力水平相关, 而且还是外毛细胞和听觉神经受损的指标。 需要进一步的研究来评估有和没有耳鸣的 SSNHL 患者的血液学数据。 [ABSTRACT FROM AUTHOR]

Osteoporosis is a condition characterized by decreased bone mineral density (BMD) and reduced bone strength, leading to an increased risk of fractures. Here, to identify novel risk variants for susceptibility to osteoporosis-related traits, an exome-wide association study is performed with 6,485 exonic single nucleotide polymorphisms (SNPs) in 2,666 women of two Korean study cohorts. The rs2781 SNP in UBAP2 gene is suggestively associated with osteoporosis and BMD with p-values of 6.1 × 10−7 (odds ratio = 1.72) and 1.1 × 10−7 in the case-control and quantitative analyzes, respectively. Knockdown of Ubap2 in mouse cells decreases osteoblastogenesis and increases osteoclastogenesis, and knockdown of ubap2 in zebrafish reveals abnormal bone formation. Ubap2 expression is associated with E-cadherin (Cdh1) and Fra1 (Fosl1) expression in the osteclastogenesis-induced monocytes. UBAP2 mRNA levels are significantly reduced in bone marrow, but increased in peripheral blood, from women with osteoporosis compared to controls. UBAP2 protein level is correlated with the blood plasma level of the representative osteoporosis biomarker osteocalcin. These results suggest that UBAP2 has a critical role in bone homeostasis through the regulation of bone remodeling. The authors identify UBAP2 as a novel osteoporosis susceptibility gene by performing association studies focusing on coding regions of the genome, and report that it plays a role in bone homeostasis through the regulation of bone remodelling. [ABSTRACT FROM AUTHOR]

Despite the importance of preventing chronic kidney disease (CKD), predicting high-risk patients who require active intervention is challenging, especially in people with preserved kidney function. In this study, a predictive risk score for CKD (Reti-CKD score) was derived from a deep learning algorithm using retinal photographs. The performance of the Reti-CKD score was verified using two longitudinal cohorts of the UK Biobank and Korean Diabetic Cohort. Validation was done in people with preserved kidney function, excluding individuals with eGFR <90 mL/min/1.73 m2 or proteinuria at baseline. In the UK Biobank, 720/30,477 (2.4%) participants had CKD events during the 10.8-year follow-up period. In the Korean Diabetic Cohort, 206/5014 (4.1%) had CKD events during the 6.1-year follow-up period. When the validation cohorts were divided into quartiles of Reti-CKD score, the hazard ratios for CKD development were 3.68 (95% Confidence Interval [CI], 2.88–4.41) in the UK Biobank and 9.36 (5.26–16.67) in the Korean Diabetic Cohort in the highest quartile compared to the lowest. The Reti-CKD score, compared to eGFR based methods, showed a superior concordance index for predicting CKD incidence, with a delta of 0.020 (95% CI, 0.011–0.029) in the UK Biobank and 0.024 (95% CI, 0.002–0.046) in the Korean Diabetic Cohort. In people with preserved kidney function, the Reti-CKD score effectively stratifies future CKD risk with greater performance than conventional eGFR-based methods. [ABSTRACT FROM AUTHOR]

Various methods have been used to improve function and manage facial nerve injury. Although electrical stimulation therapy is frequently used to treat facial paralysis, its effects have been found to vary and no clear standards have been developed. The current review describes the results of preclinical and clinical studies evaluating the effectiveness of electrical stimulation therapy in promoting the recovery of a peripheral facial nerve injury. Evidence is presented showing the efficacy of electrical stimulation in promoting nerve regeneration after peripheral nerve injuries in both animal models and human patients. The ability of electrical stimulation to promote the recovery of facial paralysis was found to depend on the type of injury (compression or transection), the species of animal tested, the type of disease, the frequency and method of electrical stimulation, and the duration of the follow-up. Electrical stimulation, however, can also have potential negative outcomes, such as reinforcing synkinesis, including mistargeted axonal regrowth via inappropriate routes; excessive collateral axonal branching at the lesion site; and multiple innervations at neuromuscular junctions. Because of the inconsistencies among studies and the low quality of evidence, electrical stimulation therapy is not currently regarded as a primary treatment of facial paralysis in patients. However, understanding the effects of electrical stimulation, as determined in preclinical and clinical studies, is important for the potential validity of future research on electrical stimulation. [ABSTRACT FROM AUTHOR]

Crack propagation has been extensively spotlighted as a main reason for the degradation of secondary‐particle‐type active materials, including LiNixMnyCo1−x−yO2 (NMC). Numerous experimental analyses and 3D‐modeling‐based investigations have been conducted to unravel this complicated phenomenon, especially for nickel‐rich NMCs, which experience substantial crack propagation during high‐voltage, high‐temperature, or high‐depth‐of‐discharge operations. To fundamentally clarify this unavoidable degradation factor and permit its suppression, a digital‐twin‐guided electro–chemo–mechanical (ECM) model of a single few‐micrometer‐sized LiNi0.7Mn0.15Co0.15O2 (NMC711) particle is developed in this study using a 3D reconstruction technique. Because the digital twin technique replicates a real pore‐containing NMC711 secondary particle, this digital‐twin electrochemical model simulates voltage profiles even at 8C‐rate within an error of 0.48% by fitting two key parameters: diffusion coefficient and exchange current density. The digital‐twin‐based ECM model is developed based on the verified electrochemical parameters and mechanical properties such as lithium‐induced strain from axis lattice parameters and stress–strain curve measured by nanoindentation. Using this model, the electrochemical‐reaction‐induced mechanical properties including strain, stress, and strain energy density are also visualized in operando in a single NMC711 particle. Finally, the advanced operando ECM analysis allows for the diagnosis of crack formation, highlighting the effectiveness of this platform in elucidating crack formation in active materials. [ABSTRACT FROM AUTHOR]

Background: Left bundle branch area pacing (LBBAP) has emerged as a novel form of physiological pacing. However, few physicians have used stylet-driven pacing leads with a steerable delivery sheath for left fascicular bundle pacing. Case presentation: A 75-year-old man with a history of heart valve surgery and atrial fibrillation arrived at the emergency department complaining of exertional dyspnea and general weakness. Twelve-lead electrocardiography showed atrial fibrillation with regular RR intervals with escape beats of 41 beats per minutes, which suggested complete atrioventricular block. Two-dimensional echocardiography showed global hypokinesia and a huge atrium. Given the impaired left ventricular (LV) function and the deleterious effects of right ventricular apical pacing, conduction system pacing was attempted. Mapping of His bundle and left bundle potential using a steerable delivery sheath was attempted; however, it did not appear prominent. Several attempts to deploy the lead failed because the sheath was malpositioned such that the lead could not move perpendicularly. Reshaping the sheath allowed for an extended reach so that the pacing lead could be positioned inferior to the previously attempted site toward the apex, deep inside the septum, where the distal left septal fascicle was captured rather than the left bundle branch trunk. During the 6-month follow-up period, the patient was free of any symptoms. Capture threshold and sensing value were stable and follow-up echocardiography showed slightly improved LV function. Conclusions: Left fascicular bundle pacing may be an alternative strategy when conventional pacing using stylet-driven pacing leads with a steerable delivery sheath fails to capture the left branch bundle in patients with challenging anatomy. [ABSTRACT FROM AUTHOR]

Mass spectrometry (MS) based proteomics is widely used for biomarker discovery. However, often, most biomarker candidates from discovery are discarded during the validation processes. Such discrepancies between biomarker discovery and validation are caused by several factors, mainly due to the differences in analytical methodology and experimental conditions. Here, we generated a peptide library which allows discovery of biomarkers in the equal settings as the validation process, thereby making the transition from discovery to validation more robust and efficient. The peptide library initiated with a list of 3393 proteins detectable in the blood from public databases. For each protein, surrogate peptides favorable for detection in mass spectrometry was selected and synthesized. A total of 4683 synthesized peptides were spiked into neat serum and plasma samples to check their quantifiability in a 10 min liquid chromatography-MS/MS run time. This led to the PepQuant library, which is composed of 852 quantifiable peptides that cover 452 human blood proteins. Using the PepQuant library, we discovered 30 candidate biomarkers for breast cancer. Among the 30 candidates, nine biomarkers, FN1, VWF, PRG4, MMP9, CLU, PRDX6, PPBP, APOC1, and CHL1 were validated. By combining the quantification values of these markers, we generated a machine learning model predicting breast cancer, showing an average area under the curve of 0.9105 for the receiver operating characteristic curve. [ABSTRACT FROM AUTHOR]