Proteogenomics of Non-smoking Lung Cancer in East Asia Delineates Molecular Signatures of Pathogenesis and Progression.

Lung cancer in East Asia is characterized by a high percentage of never-smokers, early onset and predominant EGFR mutations. To illuminate the molecular phenotype of this demographically distinct disease, we performed a deep comprehensive proteogenomic study on a prospectively collected cohort in Taiwan, representing early stage, predominantly female, non-smoking lung adenocarcinoma. Integrated genomic, proteomic, and phosphoproteomic analysis delineated the demographically distinct molecular attributes and hallmarks of tumor progression. Mutational signature analysis revealed age- and gender-related mutagenesis mechanisms, characterized by high prevalence of APOBEC mutational signature in younger females and over-representation of environmental carcinogen-like mutational signatures in older females. A proteomics-informed classification distinguished the clinical characteristics of early stage patients with EGFR mutations. Furthermore, integrated protein network analysis revealed the cellular remodeling underpinning clinical trajectories and nominated candidate biomarkers for patient stratification and therapeutic intervention. This multi-omic molecular architecture may help develop strategies for management of early stage never-smoker lung adenocarcinoma.

Flap endonuclease Rad27 cleaves the RNA of R-loop structures to suppress telomere recombination.

The long non-coding telomeric RNA transcript TERRA, in the form of an RNA-DNA duplex, regulates telomere recombination. In a screen for nucleases that affects telomere recombination, mutations in DNA2, EXO1, MRE11 and SAE2 cause severe delay in type II survivor formation, indicating that type II telomere recombination is mediated through a mechanism similar to repairing double-strand breaks. On the other hand, mutation in RAD27 results in early formation of type II recombination, suggesting that RAD27 acts as a negative regulator in telomere recombination. RAD27 encodes a flap endonuclease that plays a role in DNA metabolism, including replication, repair and recombination. We demonstrate that Rad27 suppresses the accumulation of the TERRA-associated R-loop and selectively cleaves TERRA of R-loop and double-flapped structures in vitro. Moreover, we show that Rad27 negatively regulates single-stranded C-rich telomeric DNA circles (C-circles) in telomerase-deficient cells, revealing a close correlation between R-loop and C-circles during telomere recombination. These results demonstrate that Rad27 participates in telomere recombination by cleaving TERRA in the context of an R-loop or flapped RNA-DNA duplex, providing mechanistic insight into how Rad27 maintains chromosome stability by restricting the accumulation of the R-loop structure within the genome.

Soybean steroids improve crop abiotic stress tolerance and increase yield.

Sterols have long been associated with diverse fields, such as cancer treatment, drug development, and plant growth; however, their underlying mechanisms and functions remain enigmatic. Here, we unveil a critical role played by a GmNF-YC9-mediated CCAAT-box transcription complex in modulating the steroid metabolism pathway within soybeans. Specifically, this complex directly activates squalene monooxygenase (GmSQE1), which is a rate-limiting enzyme in steroid synthesis. Our findings demonstrate that overexpression of either GmNF-YC9 or GmSQE1 significantly enhances soybean stress tolerance, while the inhibition of SQE weakens this tolerance. Field experiments conducted over two seasons further reveal increased yields per plant in both GmNF-YC9 and GmSQE1 overexpressing plants under drought stress conditions. This enhanced stress tolerance is attributed to the reduction of abiotic stress-induced cell oxidative damage. Transcriptome and metabolome analyses shed light on the upregulation of multiple sterol compounds, including fucosterol and soyasaponin II, in GmNF-YC9 and GmSQE1 overexpressing soybean plants under stress conditions. Intriguingly, the application of soybean steroids, including fucosterol and soyasaponin II, significantly improves drought tolerance in soybean, wheat, foxtail millet, and maize. These findings underscore the pivotal role of soybean steroids in countering oxidative stress in plants and offer a new research strategy for enhancing crop stress tolerance and quality from gene regulation to chemical intervention.

Morphology and Alignment Transition of Hexabenzocoronene (HBC) Mesogen Films by Bar Coating: Effect of Coating Speed.

Films of the discotic liquid crystalline hexabenzocoronene (HBC) derivative, HBC-1,3,5-Ph-C12, were prepared on the quartz substrate by the bar-coating method. Depending on the coating speed, regularly spaced stripes or continuous films were observed. In the former case, columns of the HBC derivatives align more along the stripes, which are perpendicular to the coating direction, whereas in the latter case, columns of the HBC derivatives in the film align more along the coating direction. These distinctive structures are confirmed via polarized optical microscopy (POM), polarized UV-vis spectroscopy, and grazing incidence small-angle X-ray scattering measurements.

Comparation of 5 ml and 10 ml Negative Pressures with Wet-suction Techniques for EUS-FNA of Solid Lesions: A Single-center Randomized Controlled Trial.

BACKGROUND AND OBJECTIVES: The negative pressure selectable for the wet-suction technique remains uncertain. The aim was to investigate the quality of sampling and diagnostic accuracy with solid lesions by 5 mL and 10 mL negative pressure with wet-suction techniques. METHODS: This is a single-center, crossover, randomized controlled trial conducted with a random sampling technique. In all, 160 patients consecutively undergoing EUS-FNA for solid lesions were randomized in a ratio of 1:1 into 2 groups, the 5 mL and 10 mL negative pressure wet-suction group. The main outcome was to compare the sample quality between the 2 groups. The secondary outcome was to compare the histologic and cytologic diagnostic accuracy of solid lesions. RESULTS: Pancreatic (n=129) and nonpancreatic (n=27) lesions from 156 lesions were examined. The sample quality concluding cellularity, adequacy, integrity, and blood contamination were comparable between the 2 groups. However, in subgroup analysis, we found 19G FNA provided more integrity of specimen in 5 mL than in 10 mL group (100% vs. 82.9%, P=0.025). In contrast, this benefit was not noteworthy in the 22G FNA subgroup. And there was no statistically significant in histologic (87.82% vs. 87.18%, P=1.000) and cytologic (78.85% vs. 80.77%, P=0.778) accuracy between 5 mL and 10 mL groups. CONCLUSION: When using the wet-suction technique, 5 mL and 10 mL negative pressure offer equivalent sample quality and diagnostic accuracy. However, the 19G FNA can obtain better sample quality with 5 mL negative pressure than 10 mL negative pressure.

Clinimetric Properties of the "FIND-NEEDS" to Screen Geriatric Conditions.

INTRODUCTION: Comprehensive geriatric assessment (CGA) is used to thoroughly assess and identify complex healthcare problems among older adults. However, administration of CGA is time-consuming and labor intensive. A simple screening tool with the mnemonic "FIND-NEEDS" was developed to quickly identify common geriatric conditions. The present study was to evaluate the clinimetric properties of the FIND-NEEDS. METHODS: The participants comprised first-visiting older adults aged 65 years and above (and who were able to communicate by themselves or with the help of a caregiver) who were assessed (October to December, 2021) using the FIND-NEEDS and CGA at geriatric outpatient clinics of a tertiary, referred medical center. The FIND-NEEDS was examined for its criterion-related validity and compared with the CGA results. Two types of scoring (summed score and binary score) of FIND-NEEDS and CGA were analyzed using Spearman correlation, sensitivity and specificity, and area under receiver operating characteristic curve (AUC). RESULTS: The mean age of the 114 outpatients was 78.3 ± 7.6 years, and 79 (69.3%) were female. The internal consistency was excellent when using all FIND-NEEDS items, and was acceptable when using domain scores. Exploratory factor analysis showed that most of the FIND-NEEDS domain scores had factor loadings higher than 0.3. Intercorrelations of binary scores between domains of FIND-NEEDS and CGA showed most domains were moderately correlated. The overall correlation of summed scores between FIND-NEEDS and CGA was high. The FIND-NEEDS summed score was moderately correlated with CGA score (r = 0.494; p < 0.001), and the binary score showed excellent correlation (r = 0.944; p < 0.001). When using the CGA score as the gold standard, the FIND-NEEDS showed excellent AUC (0.950), sensitivity (1.00), and specificity (0.90). DISCUSSION/CONCLUSION: The present study demonstrated that the FIND-NEEDS had acceptable clinimetric properties to screen for geriatric problems among older adults. Further in-depth assessment and care plan can then be conducted afterwards.

Effects of an integrated ambulatory care program on healthcare utilization and costs in older patients with multimorbidity: a propensity score-matched cohort study.

BACKGROUND: Population aging has increased the prevalence of multimorbidity, jeopardizing the sustainability and efficiency of healthcare systems. This study aimed to evaluate the effects of an integrated ambulatory care program (IACP) on healthcare utilization and costs among older patients with multimorbidity while accounting for the confounding effects of frailty. METHODS: A retrospective cohort study using propensity matching including patients aged 65 or older with two or more chronic conditions attending the outpatient clinic at our hospital between June 1 and December 31, 2019, was conducted. Exposure was defined as receipt of IACP care. Patients not undergoing the IACP comprised the unexposed group and were matched at a ratio of 1:4 to patients undergoing the IACP group according to sex, age, Charlson Comorbidity Index score, multimorbidity frailty index score, and number of outpatient visits within 6 months before the index date. Outcomes were changes in healthcare utilization and related costs between 6 months before and after receiving IACP care. Multivariate regression analyses were used for data analysis and the Generalized Estimation Equation method was used to fit the regression models. RESULTS: A total of 166 (IACP) and 664 (non-exposed) patients were analyzed. The mean participant baseline ages were 77.15 ± 7.77 (IACP) and 77.28 ± 7.90 years (unexposed). In univariate analyses, the IACP group demonstrated greater reductions than the unexposed group in the frequency of outpatient visits (-3.16 vs. -1.36, p < 0.001), number of physicians visited (-0.99 vs. -0.17, p < 0.001), diagnostic fees (-1300 New Taiwan Dollar [NTD] vs. -520 NTD, p < 0.001), drug prescription fees (-250 NTD vs. -70 NTD, p < 0.001), and examination fees (-1620 NTD vs. -700 NTD, p = 0.014). Multivariate analyses demonstrated that patients in the IACP group experienced significant reduction in the frequency of outpatient visits (95% CI: -0.357 to -0.181, p < 0.001), number of physicians visited (95% CI: -0.334 to -0.199, p < 0.001), and overall outpatient costs (95% CI: -0.082 to -0.011, p = 0.01). However, emergency department utilization, hospitalization, and costs did not differ significantly. CONCLUSIONS: Expanding IACPs may help patients with multimorbidity reduce their use of outpatient clinics at the 6-month follow-up, reduce care fragmentation, and promote sustainability of the healthcare system.

microRNA-3037 targeting CYP6CY2 confers imidacloprid resistance to Sitobion miscanthi (Takahashi).

The wheat aphid Sitobion miscanthi is a dominant and destructive pest in agricultural production. Insecticides are the main substances used for effective control of wheat aphids. However, their extensive application has caused severe resistance of wheat aphids to some insecticides; therefore, exploring resistance mechanisms is essential for wheat aphid management. In the present study, CYP6CY2, a new P450 gene, was isolated and overexpressed in the imidacloprid-resistant strain (SM-R) compared to the imidacloprid-susceptible strain (SM-S). The increased sensitivity of S. miscanthi to imidacloprid after knockdown of CYP6CY2 indicates that it could be associated with imidacloprid resistance. Subsequently, the posttranscriptional regulation of CYP6CY2 in the 3' UTR by miR-3037 was confirmed, and CYP6CY2 participated in imidacloprid resistance. This finding is critical for determining the role of P450 in relation to the resistance of S. miscanthi to imidacloprid. It is of great significance to understand this regulatory mechanism of P450 expression in the resistance of S. miscanthi to neonicotinoids.

Frailty in Older Adults with Dengue Fever.

Background and objectives: Dengue is one of the most common epidemic infections around the world. Dengue infections in older adults are related to an atypical presentation and a high mortality. Frailty is associated with poor recovery from hospitalization due to infection. However, few studies describe frailty and functional decline after dengue infection. The current case series study aims to investigate the baseline frailty status, functional decline, and time to recovery in older adults after dengue infection. Method: We studied seven patients with post-dengue frailty who had been admitted to the geriatric ward in one tertiary medical center in Taiwan during the 2023 dengue fever outbreak. Result: The mean age was 82 years old. The clinical frailty scale worsened from a mean of 4.7 at baseline to 6.3 at dengue diagnosis. The mean Katz Index of independence in activities of daily living decreased from 10.6 at baseline to 4.7 with dengue, and it recovered to 6.7 one month after discharge. Conclusions: Our preliminary data suggest that there is indeed an increase in frailty in older adults due to dengue. Post-dengue frailty and functional decline might be profound and persistent. Acute geriatric care intervention rehabilitation for frailty after dengue may benefit this population.

Boundary-Rich Carbon-Based Electrocatalysts with Manganese(II)-Coordinated Active Environment for Selective Synthesis of Hydrogen Peroxide.

Coordinated manganese (Mn) electrocatalysts owing to their electronic structure flexibility, non-toxic and earth abundant features are promising for electrocatalytic reactions. However, achieving selective hydrogen peroxide (H2 O2 ) production through two electron oxygen reduction (2e-ORR) is a challenge on Mn-centered catalysts. Targeting this goal, we report on the creation of a secondary Mn(II)-coordinated active environment with reactant enrichment effect on boundary-rich porous carbon-based electrocatalysts, which facilitates the selective and rapid synthesis of H2 O2 through 2e-ORR. The catalysts exhibit nearly 100 % Faradaic efficiency and H2 O2 productivity up to 15.1 mol gcat -1 h-1 at 0.1 V versus reversible hydrogen electrode, representing the record high activity for Mn-based electrocatalyst in H2 O2 electrosynthesis. Mechanistic studies reveal that the epoxide and hydroxyl groups surrounding Mn(II) centers improve spin state by modifying electronic properties and charge transfer, thus tailoring the adsorption strength of *OOH intermediate. Multiscale simulations reveal that the high-curvature boundaries facilitate oxygen (O2 ) adsorption and result in local O2 enrichment due to the enhanced interaction between carbon surface and O2 . These merits together ensure the efficient formation of H2 O2 with high local concentration, which can directly boost the tandem reaction of hydrolysis of benzonitrile to benzamide with nearly 100 % conversion rate and exclusive benzamide selectivity.

Sparse-view synchrotron X-ray tomographic reconstruction with learning-based sinogram synthesis.

Synchrotron radiation can be used as a light source in X-ray microscopy to acquire a high-resolution image of a microscale object for tomography. However, numerous projections must be captured for a high-quality tomographic image to be reconstructed; thus, image acquisition is time consuming. Such dense imaging is not only expensive and time consuming but also results in the target receiving a large dose of radiation. To resolve these problems, sparse acquisition techniques have been proposed; however, the generated images often have many artefacts and are noisy. In this study, a deep-learning-based approach is proposed for the tomographic reconstruction of sparse-view projections that are acquired with a synchrotron light source; this approach proceeds as follows. A convolutional neural network (CNN) is used to first interpolate sparse X-ray projections and then synthesize a sufficiently large set of images to produce a sinogram. After the sinogram is constructed, a second CNN is used for error correction. In experiments, this method successfully produced high-quality tomography images from sparse-view projections for two data sets comprising Drosophila and mouse tomography images. However, the initial results for the smaller mouse data set were poor; therefore, transfer learning was used to apply the Drosophila model to the mouse data set, greatly improving the quality of the reconstructed sinogram. The method could be used to achieve high-quality tomography while reducing the radiation dose to imaging subjects and the imaging time and cost.

Domain-specific Physical Activity and the Risk of All-cause Mortality Among Middle-aged and Older Adults in Taiwan: A Prospective Cohort Study.

BACKGROUND: The impact of meeting leisure-time physical activity (LTPA) recommendations and household physical activity (HPA) on all-cause mortality in the Taiwanese population is unclear. We aimed to investigate the relationship between sufficient LTPA and all-cause mortality in middle-aged and older Taiwanese adults and the role of HPA in those with insufficient LTPA. METHODS: This nationwide prospective cohort study included 4,960 participants aged ≥50 years from the Taiwan Longitudinal Study in Aging (TLSA) survey. Physical activity patterns were assessed in 2003 and then followed up until 2015 for mortality through the National Death Registration Record. Cox proportional hazards regression was conducted to evaluate hazard ratios (HRs) and 95% confidence intervals (CIs) for all-cause mortality. RESULTS: Of the 4,960 participants, 1,712 died of all-cause mortality. Compared to those who had insufficient LTPA, participants who engaged in sufficient LTPA showed a significantly lower risk of all-cause mortality (HR = 0.84, 95% CI, 0.73-0.97). For those with insufficient LTPA, HPA also had a significantly reduced risk of all-cause mortality (HR = 0.85, 95% CI, 0.75-0.96) among general population. Similar associations were observed in subsequent sensitivity analyses. The subgroup analysis showed that the relationship between HPA and reduced mortality risk was only found in the women with insufficient LTPA group. CONCLUSION: This study confirmed that sufficient LTPA is associated with a lower risk of all-cause mortality. If sufficient LTPA cannot be performed, additional HPA is related to lower mortality.

Effectiveness of outpatient geriatric evaluation and management intervention on survival and nursing home admission: a systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: The benefit of inpatient comprehensive geriatric assessment on patient survival and function has been demonstrated among frail older patients. However, the influence of outpatient geriatric evaluation and management (GEM) on clinical outcomes remains debated. This study aimed to update the research evidence detailing the effect of outpatient GEM on survival and nursing-home admission through a comparison with conventional care. METHODS: Cochrane Library, EMBASE, and MEDLINE databases were searched up to January 29th, 2022, to identify randomized controlled trials (RCTs) including older people over age 55 that compared outpatient GEM with conventional care on mortality (primary outcome) and nursing-home admission (secondary outcome) during a follow-up period of 12 to 36 months. RESULTS: Nineteen reports from 11 studies that recruited 7,993 participants (mean age 70-83) were included. Overall, outpatient GEM significantly reduced mortality (risk ratio (RR) = 0.87, 95% confidence interval (CI) = 0.77-0.99, I2 = 12%). For the subgroup analysis categorized by different follow-up periods, its prognostic benefit was only disclosed for 24-month mortality (RR = 0.68, 95% CI = 0.51-0.91, I2 = 0%), but not for 12- or 15 to 18-month mortality. Furthermore, outpatient GEM had significantly trivial effects on nursing-home admission during the follow-up period of 12 or 24 months (RR = 0.91, 95% CI = 0.74-1.12, I2 = 0%). CONCLUSIONS: Outpatient GEM led by a geriatrician with a multidisciplinary team improved overall survival, specifically during the 24-month follow-up period. This trivial effect was demonstrated in rates of nursing-home admission. Future research on outpatient GEM involving a larger cohort is warranted to corroborate our findings.

Enhanced Optical Response of SnS/SnS2 Layered Heterostructure.

The SnS/SnS2 heterostructure was fabricated by the chemical vapor deposition method. The crystal structure properties of SnS2 and SnS were characterized by X-ray diffraction (XRD) pattern, Raman spectroscopy, and field emission scanning electron microscopy (FESEM). The frequency dependence photoconductivity explores its carrier kinetic decay process. The SnS/SnS2 heterostructure shows that the ratio of short time constant decay process reaches 0.729 with a time constant of 4.3 × 10-4 s. The power-dependent photoresponsivity investigates the mechanism of electron-hole pair recombination. The results indicate that the photoresponsivity of the SnS/SnS2 heterostructure has been increased to 7.31 × 10-3 A/W, representing a significant enhancement of approximately 7 times that of the individual films. The results show the optical response speed has been improved by using the SnS/SnS2 heterostructure. These results indicate an application potential of the layered SnS/SnS2 heterostructure for photodetection. This research provides valuable insights into the preparation of the heterostructure composed of SnS and SnS2, and presents an approach for designing high-performance photodetection devices.

Machine learning approaches to predict the apparent rate constants for aqueous organic compounds by ferrate.

The apparent second-order rate constant with hexavalent ferrate (Fe(VI)) (kFe(VI)) is a key indicator to evaluate the removal efficiency of a molecule by Fe(VI) oxidation. kFe(VI) is often determined by experiment, but such measurements can hardly catch up with the rapid growth of organic compounds (OCs). To address this issue, in this study, a total of 437 experimental second-order kFe(VI) rate constants at a range of conditions (pH and temperature) were used to train four machine learning (ML) algorithms (lasso regression (LR), ridge regression (RR), extreme gradient boosting (XGBoost), and the light gradient boosting machine (LightGBM)). Using the Morgan fingerprint (MF)) of a range of organic compounds (OCs) as the input, the performance of the four algorithms was comprehensively compared with respect to the coefficient of determination (R2) and root-mean-square error (RMSE). It is shown that the RR, XGBoost, and LightGBM models displayed generally acceptable performance kFe(VI) (R2test > 0.7). In addition, the shapely additive explanation (SHAP) and feature importance methods were employed to interpret the XGBoost/LightGBM and RR models, respectively. The results showed that the XGBoost/LightGBM and RR models suggestd pH as the most important predictor and the tree-based models elucidate how electron-donating and electron-withdrawing groups influence the reactivity of the Fe(VI) species. In addition, the RR model share eight common features, including pH, with the two tree-based models. This work provides a fast and acceptable method for predicting kFe(VI) values and can help researchers better understand the degradation behavior of OCs by Fe(VI) oxidation from the perspective of molecular structure.

Encouraging teacher participation in Professional Learning Communities: exploring the Facilitating or restricting factors that Influence collaborative activities.

With the ease of using information technology tools, the explosive growth of smartphone applications (apps), and the rise of learning communities on social media, the acceptance of learning communities has become one of the most significant challenges for higher education institutions in Taiwan. In order to better understand teachers' collaborative performance inlearning communities, this study employs the cognitive dimension (opportunism) andinternal tension dimension (e.g. rising expectation, relationship burden) as restrictive factors; on the other hand, it uses emotional support, sense of belonging, and interpersonal altruism as facilitating factors; and community interaction, relationship performance, and collaborative performance as endrogenous factors. With a cross-sectional survey method and a quantitative approach, this study further dives into the collaborative performance of professional learning communities. A total of 157 teachers (87 male and 70 female) were surveyed, and a structural equation modeling approach was used. It was found that social media learning communities have done better than previous courses of field learning in unrestraining learning styles and increasing the breadth of knowledge. Facilitating and restrictive factors led to the rearrangement of the entire knowledge contribution process, enabling new configurations of individuals, members, and community. Moreover, community interactions are important drivers of relationship and collaboration performance supported by empirical data. The findings offer guidelines for policymakers and educators who evaluate teachers' collaborative performance and relationship performance to promote teaching efficiency and effectiveness by incorporating cyberethics in educational activities.

Mitogen-activated protein kinase TaMPK3 suppresses ABA response by destabilising TaPYL4 receptor in wheat.

Abscisic acid (ABA) receptors are considered as the targeted manipulation of ABA sensitivity and water productivity in plants. Regulation of their stability or activity will directly affect ABA signalling. Mitogen-activated protein kinase (MAPK) cascades link multiple environmental and plant developmental cues. However, the molecular mechanism of ABA signalling and MAPK cascade interaction remains largely elusive. TaMPK3 overexpression decreases drought tolerance and wheat sensitivity to ABA, significantly weakening ABA's inhibitory effects on growth. Under drought stress, overexpression lines show lower survival rates, shoot fresh weight and proline content, but higher malondialdehyde levels at seedling stage, as well as decreased grain width and 1000 grain weight in both glasshouse and field conditions at the adult stage. TaMPK3-RNAi increases drought tolerance. TaMPK3 interaction with TaPYL4 leads to decreased TaPYL4 levels by promoting its ubiquitin-mediated degradation, whereas ABA treatment diminishes TaMPK3-TaPYL interactions. In addition, the expression of ABA signalling proteins is impaired in TaMPK3-overexpressing wheat plants under ABA treatment. The MPK3-PYL interaction module was found to be conserved across monocots and dicots. Our results suggest that the MPK3-PYL module could serve as a negative regulatory mechanism for balancing appropriate drought stress response with normal plant growth signalling in wheat.

Need for aligning the definition and reporting of cytokine release syndrome (CRS) in immuno-oncology clinical trials.

As cancer immunotherapies continue to expand across all areas of oncology, it is imperative to establish a standardized approach for defining and capturing clinically important toxicities, such as cytokine release syndrome (CRS). In this paper, we provide considerations for categorizing the variety of adverse events that may accompany CRS and for recognizing that presentations of CRS may differ among various immunotherapies (e.g., monoclonal antibodies, CAR T cell therapies and T cell engagers, which can include bispecific antibodies and other constructs). The goals of this paper are to ensure accurate and consistent identification of CRS in patients receiving immunotherapies in clinical studies to aid in reporting; enable more precise evaluation of the therapeutic risk-benefit profile and cross-study analyses; support evidence-based monitoring and management of important toxicities related to cancer immunotherapies; and improve patient care and outcomes. These efforts will become more important as the number and variety of molecular targets for immunotherapies broaden and as therapies with novel mechanisms continue to be developed.

Elevated tau and ß-amyloid in the serum of fibromyalgia patients.

OBJECTIVE: Fibromyalgia (FM) is a chronic widespread pain syndrome. Although its mechanism remains relatively unknown, accelerated neurodegeneration in the brain has been reported in patients with FM. Sleep disturbance can increase the risk of neurocognitive disorders, which are associated with tau and beta-amyloid (Aß) protein accumulation. We hypothesize neurodegeneration in patients with FM may be associated with sleep disturbance. METHODS: In this case-control study, we analyzed serum tau and Aß levels and their association with symptom profiles for patients with FM, by recruiting 22 patients with FM and 22 age-matched healthy participants. The visual analog scale, Fibromyalgia Impact Questionnaire, pressure pain threshold test, Pittsburgh Sleep Quality Index (PSQI), Beck Depression Inventory-II, Beck Anxiety Inventory, and serum tau and beta-amyloid-42 (Aß-42) levels were recorded. The Mann-Whitney test was conducted to compare questionnaire and protein level results between the groups. Pearson correlation test was conducted to investigate the correlation of questionnaire scores with tau and Aß-42 levels in patients with FM. The significance level was set at P < .05. RESULTS: Serum tau and Aß-42 levels were significantly higher in patients with FM than in controls. A positive correlation between serum tau levels and PSQI scores was observed in patients with FM (r = 0.476, P = .025). We found that only sleep disturbance in patients with FM was significantly associated with higher serum tau levels among all symptom scores. CONCLUSIONS: We suggest sleep disturbance may play a vital role in the pathomechanism of accelerated neurodegeneration in FM.

Fear of falling as a potential complication of Ramsay Hunt syndrome in older adults: a case report.

BACKGROUND: Fear of falling (FOF) is a common and major health concern in older adults. The consequences of FOF include reduced physical performance, social activity, and health-related quality of life. Ramsay Hunt syndrome (RHS) is a herpes zoster-related facial nerve dysfunction accompanied by an erythematous vesicular rash on the ear or mouth that may complicate ipsilateral facial paralysis and otalgia, vertigo, tinnitus, hearing loss, and meningoencephalitis. However, repeated falls and subsequent FOF due to RHS have not been reported in older adults. CASE PRESENTATION: A 65-year-old woman diagnosed with RHS experienced repeated falls during hospital admission and after discharge. Despite recovery of balance and no subsequent falls, the patient presented with persistent FOF at the geriatric outpatient follow-up visit 1 year after the RHS episode. The fear sensation impaired the patient's instrumental daily activities and was confirmed by documentation of serial comprehensive geriatric assessments, especially the Timed Up and Go test scores. CONCLUSIONS: RHS may cause repeated falls and FOF, leading to impairment in daily activities and psychosocial function in older adults. Therefore, clinicians should be mindful of falls and FOF when caring for older patients with RHS and should develop multidimensional strategies for fall prevention and FOF.