Do patients with nephrotic syndrome have an increased risk of osteoporosis? A nationwide population-based retrospective cohort study in Taiwan.

OBJECTIVES: To evaluate whether nephrotic syndrome (NS) and further corticosteroid (CS) use increase the risk of osteoporosis in Asian population during the period January 2000-December 2010. DESIGN: Nationwide population-based retrospective cohort study. SETTING: All healthcare facilities in Taiwan. PARTICIPANTS: A total of 28 772 individuals were enrolled. INTERVENTIONS: 26 614 individuals with newly diagnosed NS between 2000 and 2010 were identified and included in out study. 26 614 individuals with no NS diagnosis prior to the index date were age matched as controls. Diagnosis of osteoporosis prior to the diagnosis of NS or the same index date was identified, age, sex and NS-associated comorbidities were adjusted. PRIMARY OUTCOME MEASURE: To identify risk differences in developing osteoporosis among patients with a medical history of NS. RESULTS: After adjusting for covariates, osteoporosis risk was found to be 3.279 times greater in the NS cohort than in the non-NS cohort, when measured over 11 years after NS diagnosis. Stratification revealed that age older than 18 years, congestive heart failure, hyperlipidaemia, chronic kidney disease, liver cirrhosis and NS-related disease including diabetes mellitus, hepatitis B infection, hepatitis C infection, lymphoma and hypothyroidism, increased the risk of osteoporosis in the NS cohort, compared with the non-NS cohort. Additionally, osteoporosis risk was significantly higher in NS patients with CS use (adjusted HR (aHR)=3.397). The risk of osteoporosis in NS patients was positively associated with risk of hip and vertebral fracture (aHR=2.130 and 2.268, respectively). A significant association exists between NS and subsequent risk for osteoporosis. CONCLUSION: NS patients, particularly those treated with CS, should be evaluated for subsequent risk of osteoporosis.

Calcineurin inhibitor effects on kidney electrolyte handling and blood pressure: tacrolimus versus voclosporin.

BACKGROUND AND HYPOTHESIS: Calcineurin inhibitors affect kidney electrolyte handling and blood pressure through an effect on the distal tubule. The second generation calcineurin inhibitor voclosporin causes hypomagnesemia and hypercalciuria less often than tacrolimus. This suggests different effects on the distal tubule, but this has not yet been investigated experimentally. METHODS: Rats were treated with voclosporin, tacrolimus or vehicle for 28 days. Dosing was based on a pilot experiment to achieve clinically therapeutic concentrations. Drug effects were assessed by electrolyte handling at day 18 and 28, thiazide testing at day 20, telemetric blood pressure recordings, and analysis of mRNA and protein levels of distal tubular transporters at day 28. RESULTS: Compared to vehicle, tacrolimus but not voclosporin significantly increased the fractional excretions of calcium (>4-fold), magnesium and chloride (both 1.5-fold) and caused hypomagnesemia. Tacrolimus but not voclosporin significantly reduced distal tubular transporters at mRNA and/or protein level, including the sodium-chloride cotransporter, transient receptor melastatin 6, transient receptor potential vanilloid 5, cyclin M2, sodium-calcium exchanger and calbindin-D28K. Tacrolimus but not voclosporin reduced the mRNA level and urinary excretion of epidermal growth factor. The saluretic response to hydrochlorothiazide at day 20 was similar in the voclosporin and vehicle groups, whereas it was lower in the tacrolimus group. The phosphorylated form of the sodium-chloride cotransporter was significantly higher at day 28 in rats treated with voclosporin than in those treated with tacrolimus. Tacrolimus transiently increased blood pressure, whereas voclosporin caused a gradual but persistent increase in blood pressure which was further characterized by high renin, normal aldosterone, and low endothelin-1. CONCLUSIONS: In contrast to tacrolimus, voclosporin does not cause hypercalciuria and hypomagnesemia, but similarly causes hypertension. Our data reveal differences between the distal tubular effects of tacrolimus and voclosporin and provide a pathophysiological basis for the clinically observed differences between the two calcineurin inhibitors.

Complete chloroplast genome of Angelica hirsutiflora Liu et al. 1961 (Apiaceae).

Angelica hirsutiflora Liu et al.1961, is a perennial herb in the Apiaceae family that is endemic to Taiwan. In this study, the complete circular chloroplast genome of A. hirsutiflora was reconstructed and annotated using Illumina sequencing. The size of the chloroplast genome is 154,266 bp, consisting of two inverted repeats (IRs, 25,075 bp) separated by a large single-copy region (LSC, 86,569 bp) and a small single-copy region (SSC, 17,547 bp). The GC content of the chloroplast genome is 37.6%. There are 114 different genes in the chloroplast genome of A. hirsutiflora, including 80 protein-coding genes, 30 tRNA genes and four rRNA genes. A maximum-likelihood phylogenetic analysis showed that A. hirsutiflora forms a distinct clade, and separated from other species within the genus Angelica. This study provided insights into the evolutionary relationships among different species of Angelica.

Linking tonic and phasic pupil responses to P300 amplitude in an emotional face-word Stroop task.

The locus coeruleus-norepinephrine (LC-NE) system, which regulates arousal levels, is important for cognitive control, including emotional conflict resolution. Additionally, the LC-NE system is implicated in P300 generation. If the P300 is mediated by the LC-NE system, and considering the established correlations between LC activity and pupil dilation, P300 amplitude should correlate with task-evoked (phasic) pupil dilation on a trial-by-trial basis. However, prior studies, predominantly utilizing oddball-type paradigms, have not demonstrated correlations between concurrently recorded task-evoked pupil dilation and P300 responses. Using a recently developed emotional face-word Stroop task that links pupil dilation to the LC-NE system, here, we examined both intra- and inter-individual correlations between task-evoked pupil dilation and P300 amplitude. We found that lower accuracy, slower reaction times, and larger task-evoked pupil dilation were obtained in the incongruent compared to the congruent condition. Furthermore, we observed intra-individual correlations between task-evoked pupil dilation and P300 amplitude, with larger pupil dilation correlating with a greater P300 amplitude. In contrast, pupil dilation did not exhibit consistent correlations with N450 and N170 amplitudes. Baseline (tonic) pupil size also showed correlations with P300 and N170 amplitudes, with smaller pupil size corresponding to larger amplitude. Moreover, inter-individual differences in task-evoked pupil dilation between the congruent and incongruent conditions correlated with differences in reaction time and P300 amplitude, though these effects only approached significance. To summarize, our study provides evidence for a connection between task-evoked pupil dilation and P300 amplitude at the single-trial level, suggesting the involvement of the LC-NE system in P300 generation.

Chronic kidney disease increases the susceptibility to negative effects of low and high potassium intake.

BACKGROUND AND HYPOTHESIS: Dietary potassium (K+) has emerged as a modifiable factor for cardiovascular and kidney health in the general population, but its role in people with chronic kidney disease (CKD) is unclear. Here, we hypothesize that CKD increases the susceptibility to negative effects of low and high K+ diets. METHODS: We compared the effects of low, normal, or high KChloride (KCl) diets and a high KCitrate diet for four weeks in male rats with normal kidney function and in male rats with CKD using the 5/6th nephrectomy model (5/6Nx). RESULTS: Compared to rats with normal kidney function, 5/6Nx rats on the low KCl diet developed more severe extracellular and intracellular hypokalemia and more severe kidney injury, characterized by nephromegaly, infiltration of T-cells and macrophages, decreased eGFR and increased albuminuria. The high KCl diet caused hyperkalemia, hyperaldosteronism, hyperchloremic metabolic acidosis and severe hypertension in 5/6Nx but not in sham rats. The high KCitrate diet caused hypochloremic metabolic alkalosis but attenuated hypertension despite higher abundance of the phosphorylated sodium chloride cotransporter (pNCC) and similar levels of plasma aldosterone and epithelial sodium channel (ENaC) abundance. All 5/6Nx groups had more collagen deposition than the sham groups and this effect was most pronounced in the high KCitrate group. Plasma aldosterone correlated strongly with kidney collagen deposition. CONCLUSIONS: CKD increases the susceptibility to negative effects of low and high K+ diets in male rats, although the injury patterns are different. The low K+ diet caused inflammation, nephromegaly and kidney function decline, whereas the high K+ diet caused hypertension, hyperaldosteronism and kidney fibrosis. High KCitrate attenuated the hypertensive but not the pro-fibrotic effect of high KCl, which may be attributable to K+-induced aldosterone secretion. Our data suggest that especially in people with CKD it is important to identify the optimal threshold of dietary K+ intake.

A holo-spectral EEG analysis provides an early detection of cognitive decline and predicts the progression to Alzheimer's disease.

Aims: Our aim was to differentiate patients with mild cognitive impairment (MCI) and Alzheimer's disease (AD) from cognitively normal (CN) individuals and predict the progression from MCI to AD within a 3-year longitudinal follow-up. A newly developed Holo-Hilbert Spectral Analysis (HHSA) was applied to resting state EEG (rsEEG), and features were extracted and subjected to machine learning algorithms. Methods: A total of 205 participants were recruited from three hospitals, with CN (n = 51, MMSE > 26), MCI (n = 42, CDR = 0.5, MMSE ≥ 25), AD1 (n = 61, CDR = 1, MMSE < 25), AD2 (n = 35, CDR = 2, MMSE < 16), and AD3 (n = 16, CDR = 3, MMSE < 16). rsEEG was also acquired from all subjects. Seventy-two MCI patients (CDR = 0.5) were longitudinally followed up with two rsEEG recordings within 3 years and further subdivided into an MCI-stable group (MCI-S, n = 36) and an MCI-converted group (MCI-C, n = 36). The HHSA was then applied to the rsEEG data, and features were extracted and subjected to machine-learning algorithms. Results: (a) At the group level analysis, the HHSA contrast of MCI and different stages of AD showed augmented amplitude modulation (AM) power of lower-frequency oscillations (LFO; delta and theta bands) with attenuated AM power of higher-frequency oscillations (HFO; beta and gamma bands) compared with cognitively normal elderly controls. The alpha frequency oscillation showed augmented AM power across MCI to AD1 with a reverse trend at AD2. (b) At the individual level of cross-sectional analysis, implementation of machine learning algorithms discriminated between groups with good sensitivity (Sen) and specificity (Spec) as follows: CN elderly vs. MCI: 0.82 (Sen)/0.80 (Spec), CN vs. AD1: 0.94 (Sen)/0.80 (Spec), CN vs. AD2: 0.93 (Sen)/0.90 (Spec), and CN vs. AD3: 0.75 (Sen)/1.00 (Spec). (c) In the longitudinal MCI follow-up, the initial contrasted HHSA between MCI-S and MCI-C groups showed significantly attenuated AM power of alpha and beta band oscillations. (d) At the individual level analysis of longitudinal MCI groups, deploying machine learning algorithms with the best seven features resulted in a sensitivity of 0.9 by the support vector machine (SVM) classifier, with a specificity of 0.8 yielded by the decision tree classifier. Conclusion: Integrating HHSA into EEG signals and machine learning algorithms can differentiate between CN and MCI as well as also predict AD progression at the MCI stage.

The association between working memory precision and the nonlinear dynamics of frontal and parieto-occipital EEG activity.

Electrophysiological working memory (WM) research shows brain areas communicate via macroscopic oscillations across frequency bands, generating nonlinear amplitude modulation (AM) in the signal. Traditionally, AM is expressed as the coupling strength between the signal and a prespecified modulator at a lower frequency. Therefore, the idea of AM and coupling cannot be studied separately. In this study, 33 participants completed a color recall task while their brain activity was recorded through EEG. The AM of the EEG data was extracted using the Holo-Hilbert spectral analysis (HHSA), an adaptive method based on the Hilbert-Huang transforms. The results showed that WM load modulated parieto-occipital alpha/beta power suppression. Furthermore, individuals with higher frontal theta power and lower parieto-occipital alpha/beta power exhibited superior WM precision. In addition, the AM of parieto-occipital alpha/beta power predicted WM precision after presenting a target-defining probe array. The phase-amplitude coupling (PAC) between the frontal theta phase and parieto-occipital alpha/beta AM increased with WM load while processing incoming stimuli, but the PAC itself did not predict the subsequent recall performance. These results suggest frontal and parieto-occipital regions communicate through theta-alpha/beta PAC. However, the overall recall precision depends on the alpha/beta AM following the onset of the retro cue.

Why Do Bystanders Become Cyberbullies? The Effect of Perceived Reasonableness of Online Messages on Bystanders' Aggressive Tendency and Its Underlying Mechanism.

The objectives of this study were to examine the influence of bystanders' perceived reasonableness of online messages on their aggressive tendency toward victims and to examine the mediating role of bystanders' attribution of responsibility to victims on their aggressive tendency toward the victims. Our study involved two parts: In Study 1, 295 Taiwanese undergraduates were recruited, and questionnaires were distributed to them to measure their perceived reasonableness of cyberbullying attacks. In Study 2, a total of 78 university students were recruited. The participants' perceived reasonableness of cyberbullying attacks was reduced through experimental manipulation. Subsequently, they were randomly assigned to a group with relatively low reasonableness or a control group. The results of both studies revealed that the participants' aggressive tendency toward the victim was influenced by their perceived reasonableness of cyberbully messages. The relation between perceived reasonableness and aggressive tendency was mediated by the participants' attribution of responsibility to the victim.

Resting State Dynamics in People with Varying Degrees of Anxiety and Mindfulness: A Nonlinear and Nonstationary Perspective.

Anxiety and mindfulness are two inversely linked traits shown to be involved in various physiological domains. The current study used resting state electroencephalography (EEG) to explore differences between people with low mindfulness-high anxiety (LMHA) (n = 29) and high mindfulness-low anxiety (HMLA) (n = 27). The resting EEG was collected for a total of 6 min, with a randomized sequence of eyes closed and eyes opened conditions. Two advanced EEG analysis methods, Holo-Hilbert Spectral Analysis and Holo-Hilbert cross-frequency phase clustering (HHCFPC) were employed to estimate the power-based amplitude modulation of carrier frequencies, and cross-frequency coupling between low and high frequencies, respectively. The presence of higher oscillation power across the delta and theta frequencies in the LMHA group than the HMLA group might have been due to the similarity between the resting state and situations of uncertainty, which reportedly triggers motivational and emotional arousal. Although these two groups were formed based on their trait anxiety and trait mindfulness scores, it was anxiety that was found to be significant predictor of the EEG power, not mindfulness. It led us to conclude that it might be anxiety, not mindfulness, which might have contributed to higher electrophysiological arousal. Additionally, a higher δ-ß and δ-γ CFC in LMHA suggested greater local-global neural integration, consequently a greater functional association between cortex and limbic system than in the HMLA group. The present cross-sectional study may guide future longitudinal studies on anxiety aiming with interventions such as mindfulness to characterize the individuals based on their resting state physiology.

Identification of actionable targets for breast cancer intervention using a diversity outbred mouse model.

HER2-targeted therapy has improved breast cancer survival, but treatment resistance and disease prevention remain major challenges. Genes that enable HER2/Neu oncogenesis are the next intervention targets. A bioinformatics discovery platform of HER2/Neu-expressing Diversity Outbred (DO) F1 Mice was established to identify cancer-enabling genes. Quantitative Trait Loci (QTL) associated with onset ages and growth rates of spontaneous mammary tumors were sought. Twenty-six genes in 3 QTL contain sequence variations unique to the genetic backgrounds that are linked to aggressive tumors and 21 genes are associated with human breast cancer survival. Concurrent identification of TSC22D3, a transcription factor, and its target gene LILRB4, a myeloid cell checkpoint receptor, suggests an immune axis for regulation, or intervention, of disease. We also investigated TIEG1 gene that impedes tumor immunity but suppresses tumor growth. Although not an actionable target, TIEG1 study revealed genetic regulation of tumor progression, forming the basis of the genetics-based discovery platform.

Exploring the quality markers and mechanism of Bushen Huoxue Prescription in prevention and treatment of diabetic retinopathy based on Chinmedomics strategy.

ETHNOPHARMACOLOGICAL RELEVANCE: Chinese herbal medicines have complex chemical composition; therefore, revealing the effective substances of Chinese herbal medicine becomes a prerequisite for scientific elucidation of the mechanism of action of Bushen Huoxue Prescription (BHP) against diabetic retinopathy (DR) and the development of new drugs. AIM OF THE STUDY: The Chinmedomics technique was used to evaluate the pharmacodynamic ingredients and mechanism of action of BHP against DR rats. MATERIALS AND METHODS: The overall physiological condition of the rats, including body weight, blood glucose, inflammatory factor levels, histological staining, and urine metabolic profile were examined to evaluate the model and its effects. The chemical composition of BHP in vivo and ex vivo was fully analyzed utilizing UPLC-Q-Exactive Orbitrap MS in conjunction with TCM serum pharmacochemistry. Finally, correlation analysis between biomarkers, and serum migration components was used to identify Quality markers (Q-markers) that were significantly associated with effectiveness. RESULTS: The UPLC-Q-Exactive Orbitrap MS platform was used to identify a total of 29 chemicals in serum, 17 of which were highly linked with effectiveness and can be potentially employed as pharmacodynamic substances for BHP against DR. In addition, 14 biomarkers related to galactose metabolism, starch and sucrose metabolism, pantothenate and CoA biosynthesis, glycine, serine, and threonine metabolism were identified. These pathways reveal that DR may be inextricably linked to levels of oxidative stress and inflammation in the organism. Finally, five active ingredients were identified as potential Q-markers of BHP against DR, namely ajugol, protocatechuic acid, tanshinone IIA, panaxatriol and puerarin. CONCLUSION: This study successfully clarified the efficacy and Q-markers of BHP through the Chinmedomics strategy, which is of great significance in determining the quality standards of BHP.

Amplitude modulating frequency overrides carrier frequency in tACS-induced phosphene percept.

The amplitude modulated (AM) neural oscillation is an essential feature of neural dynamics to coordinate distant brain areas. The AM transcranial alternating current stimulation (tACS) has recently been adopted to examine various cognitive functions, but its neural mechanism remains unclear. The current study utilized the phosphene phenomenon to investigate whether, in an AM-tACS, the AM frequency could modulate or even override the carrier frequency in phosphene percept. We measured the phosphene threshold and the perceived flash rate/pattern from 12 human subjects (four females, aged from 20-44 years old) under tACS that paired carrier waves (10, 14, 18, 22 Hz) with different envelope conditions (0, 2, 4 Hz) over the mid-occipital and left facial areas. We also examined the phosphene source by adopting a high-density stimulation montage. Our results revealed that (1) phosphene threshold was higher for AM-tACS than sinusoidal tACS and demonstrated different carrier frequency functions in two stimulation montages. (2) AM-tACS slowed down the phosphene flashing and abolished the relation between the carrier frequency and flash percept in sinusoidal tACS. This effect was independent of the intensity change of the stimulation. (3) Left facial stimulation elicited phosphene in the upper-left visual field, while occipital stimulation elicited equally distributed phosphene. (4) The near-eye electrodermal activity (EDA) measured under the threshold-level occipital tACS was greater than the lowest power sufficient to elicit retinal phosphene. Our results show that AM frequency may override the carrier frequency and determine the perceived flashing frequency of AM-tACS-induced phosphene.

Genetic Approach for Joint Transmission Grouping in Next-Generation Cellular Networks.

Coordinated multipoint joint transmission (JT) is one of the critical downlink transmission technologies to improve network throughput. However, multiple cells in a JT group should have the same user data to transmit simultaneously, resulting in a considerable backhaul burden. Even when cells are already equipped with caches in fifth-generation networks, JT groups, without effectively utilizing the caching data, still cause unnecessary backhaul data traffic. In this article, we investigate the JT grouping problem with the consideration of caches at cells. Then, we propose a genetic approach to solve the above problem with the objective of minimizing the amount of backhaul data traffic subject to the data-rate requirement of each user. The simulation results show that our proposed generic algorithm can significantly decrease the backhaul bandwidth consumption compared to the two baselines.

Complete chloroplast genome and phylogenetic analysis of Bupleurum kaoi Liu, Chao, and Chuang, 1977: an endemic species in Taiwan.

Bupleurum kaoi Liu, Chao, and Chuang is an endemic and endangered herb in Taiwan. In this study, the complete circular chloroplast genome of B. kaoi was reconstructed and annotated using Illumina sequencing. The genome size of B. kaoi is 155,938 bp, including a pair of inverted repeat regions (IRs: 26308 bp), separated by a large single-copy (LSC) region of 85,784 bp and a small single-copy (SSC) region of 17,538 bp. The GC content of the chloroplast genome is 37.6%. There are 113 different genes in the chloroplast genome of B. kaoi, including 79 protein-coding genes, 30 tRNA genes, and four rRNA genes. A maximum-likelihood phylogenetic analysis showed that Bupleurum species is the monophyletic group, and B. kaoi belongs to subgenus Bupleurum and is closely related to B. scorzonerifolium.

Demographic history and population genetic structure of Anisakis pegreffii in the cutlassfish Trichiurus japonicus along the coast of mainland China and Taiwan.

Studying the genetic diversity of nematode parasite populations is crucial to gaining insight into parasite infection dynamics and informing parasite phylogeography. Anisakiasis is a zoonotic disease caused by the consumption of infectious third-stage larvae (L3) of Anisakis spp. carried by marine fish. In the present study, a total of 206 mitochondrial DNA sequences (cytochrome c oxidase 2, cox2) were used to study the genetic diversity, genetic structure, and historical demography of twelve A. pegreffii populations from Trichiurus japonicas along the coast of mainland China and Taiwan. Two distinct evolutionary lineages of A. pegreffii and no significant genealogical structures corresponding to sampling localities suggested that isolation in the marginal seas shaped their patterns of phylogeographic distribution along the coast of mainland China and Taiwan during glaciation with lower sea levels. Furthermore, pairwise FST values and AMOVA did not indicate any significant genetic differentiation among groups with no relation to the geographic area, which might be attributed to fewer barriers to gene flow as well as large population sizes. The results of the neutrality test, mismatch distribution, and Bayesian skyline plot analyses showed that entire population underwent population expansion during the late Pleistocene. Analysis of the demographic history revealed that A. pegreffii underwent historical lineage diversification and admixture due to secondary contact based on ABC analysis. The present research represents the first definitive population structure and demographic history across sampling locations of A. pegreffii along the coast of mainland China and Taiwan.

Late capsular blockage syndrome: Clinical and anterior segment optical coherence tomography characteristics.

BACKGROUND: Late capsular blockage syndrome (CBS) is a rare phenomenon which is found after cataract surgery. The mechanism, anterior segment optical coherence tomography (OCT) presentation, and clinical characteristics are not well studied. METHODS: We studied patients who developed late CBS in Taipei Veterans General Hospital from 2012 to 2019. Age, sex, systemic disease, ocular disease, interval between cataract surgery and CBS, axial length, type of intraocular lens implanted, grading of posterior capsular opacity, refraction, visual acuity, and anterior segment OCT findings were documented. Patients are categorized into two groups according to anterior segment OCT findings. All patients underwent Nd:YAG laser capsulotomy and were prescribed a low-dose topical steroid for 7 days. Postcapsulotomy refraction and visual acuity were recorded. All the clinical data were compared in the two groups. RESULTS: This study included 18 eyes with late CBS. Patients' median age was 80 (range, 54-92) years. The mean duration between cataract surgery and CBS diagnosis was 80.28 (range 15-136) months. According to anterior segment OCT findings, we subcategorized the patients into two groups: gravel appearance (n = 7) and milky (n = 11) appearance. After laser capsulotomy, mean visual acuity improved 0.18 ± 0.10 on the LogMAR. A significant myopic shift in refraction after laser capsulotomy was noted in the gravel appearance group compared to the milky appearance group ( p = 0.027). No patient developed complications or needed further treatment for CBS during the median follow-up of 14.5 months (range 1-84 months). CONCLUSION: High-resolution anterior segment OCT is useful for analyzing patients with late CBS. Our study implies that the two types of CBS presentation indicate different causes of late CBS formation, as well as distinct clinical presentation and postlaser capsulotomy refractive outcome. In addition, YAG laser capsulotomy is a safe late CBS treatment modality.

Evaluating the Different Stages of Parkinson's Disease Using Electroencephalography With Holo-Hilbert Spectral Analysis.

Electroencephalography (EEG) can reveal the abnormalities of dopaminergic subcortico-cortical circuits in patients with Parkinson's disease (PD). However, conventional time-frequency analysis of EEG signals cannot fully reveal the non-linear processes of neural activities and interactions. A novel Holo-Hilbert Spectral Analysis (HHSA) was applied to reveal non-linear features of resting state EEG in 99 PD patients and 59 healthy controls (HCs). PD patients demonstrated a reduction of ß bands in frontal and central regions, and reduction of γ bands in central, parietal, and temporal regions. Compared with early-stage PD patients, late-stage PD patients demonstrated reduction of ß bands in the posterior central region, and increased θ and δ2 bands in the left parietal region. θ and ß bands in all brain regions were positively correlated with Hamilton depression rating scale scores. Machine learning algorithms using three prioritized HHSA features demonstrated "Bag" with the best accuracy of 0.90, followed by "LogitBoost" with an accuracy of 0.89. Our findings strengthen the application of HHSA to reveal high-dimensional frequency features in EEG signals of PD patients. The EEG characteristics extracted by HHSA are important markers for the identification of depression severity and diagnosis of PD.

Management of Delayed Complications of Hydrogel Scleral Buckles.

(1) Background: hydrogel scleral buckles (HSB)-related complications can happen decades after implantation, although this material has been retrieved for a long time. Due to its fragile texture, ensuring the complete removal of this material and avoiding complications are challenging. Incomplete removal, iatrogenic complication, recurrent retinal detachment, and infection could occur. (2) Methods: chart review of patients who developed delayed HSB-related complications and received removal of HSB in Taipei Veterans General Hospital from 2004 to 2021. The presenting symptoms, prior diagnosis before referral, clinical findings, image features, surgical technique, operative findings, and outcome were analyzed. Detailed surgical procedure and tips for removal were demonstrated in the study. (3) Results: a total of eleven patients were identified. The presenting symptoms include limitations to extraocular movement (ten eyes, 90.9%), ocular redness (eight eyes, 72.7%), ocular fullness (eight eyes, 72.7%), pain (six eyes, 54.5%), and exposed ocular foreign body (five eyes, 45.5%). Of note, six patients (54.5%) have monocular glaucoma and four of them have intractable high intraocular pressure. All patients underwent surgeries to smoothly remove swollen HSB via transcutaneous or transconjunctival approach. Most symptoms improved after surgery and no cases developed surgical-related complications. (4) Conclusions: although HSB have been off the market for decades, delayed complications are still emerging. Clinicians should remain alert for potential complications for patients with prior HSB surgeries. Early diagnosis and meticulous management can help to safely remove the expanded HSB and reduce the associated complications.

Time-frequency analysis of pupil size modulated by global luminance, arousal, and saccade preparation signals using Hilbert-Huang transform.

Pupil size changes constantly and is mainly determined by global luminance signals. In addition, the pupil responds to various cognitive and arousal processes, with larger pupil dilation observed in higher levels of cognitive or arousal processing. Although these task-evoked pupillary responses are extensively used in the pupil research, pupil analysis focusing on the frequency domain, particularly in the context of arousal and cognitive modulations, is less established. Fourier Transform method (FFT) has been used to understand the modulation of task difficulty on pupil oscillations. However, physiological signals are often characterized as non-linear and non-stationary waves, and the conventional spectral analytical method with linearity presumption is less appropriate to reveal modulation dynamics between time and frequency. Here, we used Hilbert-Huang Transform (HHT) to examine the time-frequency modulations on pupil size regulated by arousal, cognitive, and global luminance signals. Consistent with previous research, using FFT, higher spectral densities were obtained with lower luminance background. Moreover, higher spectral densities were found in the high emotional arousal condition. With HHT, we further demonstrated temporal changes on amplitude spectrum and inter-trial phase coherence (ITPC) in each intrinsic mode function (IMF), with stronger amplitudes in higher IMFs (i.e., low frequencies). Moreover, although global luminance, arousal and saccade preparation modulated pupil oscillatory responses, the modulation pattern in different IMFs was different. Together, our results demonstrated dynamics between the time and frequency domain on pupil oscillatory responses, highlighting the importance of examining the time-frequency interactions in the context of various pupil modulations.

Nephron mass determines the excretion rate of urinary extracellular vesicles.

Urinary extracellular vesicles (uEVs) are emerging as non-invasive biomarkers for various kidney diseases, but it is unknown how differences in nephron mass impact uEV excretion. To address this, uEV excretion was measured before and after human kidney donor nephrectomy and rat nephrectomy. In male and female donors, uEVs were quantified in cell-free spot and 24-h urine samples using nanoparticle tracking analysis (NTA), EVQuant, and CD9-time-resolved fluorescence immunoassay. Female donors had significantly lower total kidney volume (TKV) and excreted 49% fewer uEVs than male donors. uEV excretion correlated positively with estimated glomerular filtration rate (eGFR), creatinine clearance, and TKV (R's between 0.6 and 0.7). uEV excretion rate could also be predicted from spot urines after multiplying spot uEV/creatinine by 24-h urine creatinine. Donor nephrectomy reduced eGFR by 36% ± 10%, but the excretion of uEVs by only 16% (CD9+ uEVs -37%, CD9- uEVs no decrease). Donor nephrectomy increased the podocyte marker WT-1 and the proximal tubule markers NHE3, NaPi-IIa, and cubilin in uEVs two- to four-fold when correcting for the nephrectomy. In rats, the changes in GFR and kidney weight correlated with the changes in uEV excretion rate (R = 0.46 and 0.60, P < 0.01). Furthermore, the estimated degree of hypertrophy matched the change in uEV excretion rate (1.4- to 1.5-fold after uninephrectomy and four-fold after 5/6th nephrectomy). Taken together, our data show that uEV excretion depends on nephron mass, and that nephrectomy reduces uEV excretion less than expected based on nephron loss due to compensatory hypertrophy. The major implication of our findings is that a measure for nephron mass or uEV excretion rate should be included when comparing uEV biomarkers between individuals.