Search

Exposure to nature has been linked to improved mental health. This raises an interesting question of whether incorporating natural features, such as bodies of water, into the built environment can also improve mental health. This study determined whether the presence or absence of bodies of water in leisure areas in the natural and built environment impacts people's direct attention, preference for certain types of landscapes, feelings of restorativeness when in those landscapes, and physiological indicators, such as heart rate and electromyographic readings. The study included 136 participants. The results showed that in their resting state, participants were substantially less physiologically stressed when they were in the presence of bodies of water in natural settings than in their absence in the built environment. However, when the built environment included bodies of water, people's heart rates were lower when viewing, feeling, and reporting on the atmosphere of these environments. The results showed that people can reduce tension and stress by spending time around bodies of water in the natural areas of leisure settings. Furthermore, natural environments, with or without bodies of water, can help alleviate direct attention fatigue and are preferred to the built environment. However, leisure areas in the built environment that incorporate bodies of water can generate positive emotions. Our study demonstrated that leisure areas with waterscapes in both built and natural environments may enhance physiological and psychological well-being. [ABSTRACT FROM AUTHOR]

This population-based study investigated the risk of having had prior herpes zoster within five years preceding a diagnosis of head and neck cancer. We conducted a case-control study that included 9,191 patients with a diagnosis of head and neck cancer in Taiwan's Longitudinal Health Insurance Database 2010 and 36,764 matched controls. We assessed the odds of patients with head and neck cancer having had a diagnosis of herpes zoster during the five years preceding head and neck cancer using multiple logistic regression analysis. The prevalence of prior herpes zoster among the total sample was 4.6%, 7.9% and 3.8% among patients with and without head and neck cancer, respectively (p < 0.001). The odds ratio of herpes zoster among the head and neck cancer- versus control group was 2.198 (95% CI = 2.001 ~ 2.415) after adjusting for sociodemographic characteristics and hypertension, diabetes, hyperlipidemia, tobacco use disorder, HPV infection, and alcohol dependence syndrome. Statistically significant excess odds were observed for all specific subtypes of head and neck cancer except for sinonasal cancer. Herpes zoster infection within the 5 years preceding a diagnosis of head and neck cancer may be a harbinger of developing head and neck cancer. [ABSTRACT FROM AUTHOR]

Purpose: Heterozygous STAT1 Gain-of-Function (GOF) mutations are the most common cause of chronic mucocutaneous candidiasis (CMC) among Inborn Errors of Immunity. Clinically, these mutations manifest as a broad spectrum of immune dysregulation, including autoimmune diseases, vascular disorders, and malignancies. The pathogenic mechanisms of immune dysregulation and its impact on immune cells are not yet fully understood. In treatment, JAK inhibitors have shown therapeutic effectiveness in some patients. Methods: We analyzed clinical presentations, cellular phenotypes, and functional impacts in five Taiwanese patients with STAT1 GOF. Results: We identified two novel GOF mutations in 5 patients from 2 Taiwanese families, presenting with symptoms of CMC, late-onset rosacea, and autoimmunity. The enhanced phosphorylation and delayed dephosphorylation were displayed by the patients' cells. There are alterations in both innate and adaptive immune cells, including expansion of CD38+HLADR +CD8+ T cells, a skewed activated Tfh cells toward Th1, reduction of memory, marginal zone and anergic B cells, all main functional dendritic cell lineages, and a reduction in classical monocyte. Baricitinib showed therapeutic effectiveness without side effects. Conclusion: Our study provides the first comprehensive clinical and molecular characteristics in STAT1 GOF patient in Taiwan and highlights the dysregulated T and B cells subsets which may hinge the autoimmunity in STAT1 GOF patients. It also demonstrated the therapeutic safety and efficacy of baricitinib in pediatric patient. Further research is needed to delineate how the aberrant STAT1 signaling lead to the changes in cellular populations as well as to better link to the clinical manifestations of the disease. [ABSTRACT FROM AUTHOR]

Purpose: Anti-granulocyte-macrophage colony-stimulating factor autoantibodies (anti-GM-CSF Abs) are implicated in the pathogenesis of Cryptococcus gattii (C. gattii) infection and pulmonary alveolar proteinosis (PAP). Their presence has also been noted in nocardiosis cases, particularly those with disseminated disease. This study delineates a case series characterizing clinical features and specificity of anti-GM-CSF Abs in nocardiosis patients. Methods: In this study, eight patients were recruited to determine the presence or absence of anti-GM-CSF Abs. In addition to the detailed description of the clinical course, we thoroughly investigated the autoantibodies regarding the characteristics, isotypes, subclasses, titers, and neutralizing capacities by utilizing the plasma samples from patients. Results: Of eight patients, five tested positive for anti-GM-CSF Abs, all with central nervous system (CNS) involvement; patients negative for these antibodies did not develop CNS nocardiosis. Distinct from previously documented cases, none of our patients with anti-GM-CSF Abs exhibited PAP symptoms. The titer and neutralizing activity of anti-GM-CSF Abs in our cohort did not significantly deviate from those found in C. gattii cryptococcosis and PAP patients. Uniquely, one individual (Patient 3) showed a minimal titer and neutralizing action of anti-GM-CSF Abs, with no relation to disease severity. Moreover, IgM autoantibodies were notably present in all CNS nocardiosis cases investigated. Conclusion: The presence of anti-GM-CSF Abs suggests an intrinsic immunodeficiency predisposing individuals toward CNS nocardiosis. The presence of anti-GM-CSF Abs helps to elucidate vulnerability to CNS nocardiosis, even with low titer of autoantibodies. Consequently, systematic screening for anti-GM-CSF Abs should be considered a crucial diagnostic step for nocardiosis patients. [ABSTRACT FROM AUTHOR]

Adolescence is a critical period during which youth develop and shape their behaviors. Because differences between youths are strongly connected to environmental factors, we aimed to elucidate possible pathways from home-school regulation and atmosphere to youths' prosocial and antisocial behaviors. Data were derived from the China Education Panel Survey. This study involved a total of 9291 students aged 14–15 years (4834 boys, 4457 girls). We used structural equation modeling (SEM) with LISREL 8.80 and Monte Carlo resampling with R to conduct the analysis strategy. In the home-school regulation, parental supervision on the one hand and teacher criticism on the other hand have direct positive and negative predictive effects on youths' prosocial behaviors, respectively, while their direct effects on antisocial behavior are the opposite; teachers praise does not directly affect adolescents' prosocial and antisocial behaviors. In the home-school atmosphere, family interaction and perceived good class climate directly positively affect youths' prosocial behaviors, while the direct effects of both on antisocial behavior are not significant. The SEM results reveal that academic self-efficacy and depressive symptoms may be underlying mediating mechanisms through which home-school regulation and atmosphere during adolescence affect students' prosocial and antisocial behaviors. Intervention programs targeting home-school supportive environments and prevention programs targeting positive emotion and self-awareness may yield benefits for proper social behavior in adolescents. For example, by enhancing the way and frequency of parent–child interaction, teachers and students jointly create a good class climate of care and friendship to strengthen a home-school supportive environment. Improve adolescents' positive emotions such as contentment, optimism, and hope to reduce the possibility of depression. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the clinical feasibility and tolerability of large volume subcutaneous delivery at different injection depths for lean and non-lean subjects. Methods: A single-center, randomized, subject-blinded, crossover study in 62 healthy subjects was conducted to evaluate delivery of a 10-cP solution containing hyaluronic acid. Subjects were separated into lean and non-lean cohort by SC thickness. A syringe pump was used to study the effect of different volumes (5, 12, 25 mL) of a viscous placebo solution and needle lengths (6, 9 and 12 mm) delivered at 0.5 mL/min. Results: Across all treatments, injection sites were observed to have negligible leakage, ~34 kPa of back pressure, and VAS of mild pain with higher pain from needle insertion than during injection. While mild to moderate erythema was the most frequently reported ISR and edema was most prominent for 25 mL injections, all ISRs were resolved within 4 hours post injection. Subjects were unbothered by ISRs across all treatments and rated them as low distress scores (average 1.0–1.5 out of 6). Conclusion: SC injection of 25 mL is feasible and tolerable using a low-pain formulation for abdomen injection irrespective of subcutaneous thickness and injection depths at a delivery rate of 0.5 mL/min. [ABSTRACT FROM AUTHOR]

This study aimed to identify the factors affecting hip−knee−ankle (HKA) angle following Oxford medial unicompartmental knee arthroplasty (MUKA). A retrospective analysis of 200 patients who underwent Oxford MUKA from June 2018 to October 2020 was conducted. Univariate and multivariate analyses were performed to investigate the impact of surgical and radiographic characteristics on the postoperative HKA angle. The mean HKA angle was 9.5 ± 4.3° before surgery and 3.6 ± 3.7° after surgery (p < 0.001). The postoperative HKA angle significantly correlated with the preoperative HKA angle, bearing size, tibial component alignment angle, and BMI (r = 0.71, p < 0.001; r = − 0.24, p = 0.001; r = 0.21, p = 0.004; r = − 0.18, p = 0.011). Multiple linear regression analysis revealed that the preoperative HKA angle (β = 0.68, p < 0.001), bearing size (β = − 0.31, p < 0.001), tibial component alignment angle (β = 0.14, p = 0.003), and BMI (β = − 0.09, p = 0.047) significantly affected the postoperative HKA angle. In conclusion, larger preoperative varus deformity, smaller bearing size, greater varus alignment of the tibial component, and lower BMI lead to greater postoperative varus alignment of the lower limb in Oxford MUKA. With this concept, surgeons can more accurately predict postoperative lower limb alignment and avoid malalignment in Oxford MUKA. [ABSTRACT FROM AUTHOR]

The growth of music streaming market is expected to be boosted by the rising use of smart devices and the streaming platforms in the forecast period. Music recommendation systems for groups have been intensively studied as the application scenario becomes more dynamic, where different kinds of group formulations lead to different levels of similarity in music tastes. This paper proposes a music recommendation framework to generate a Top-N list in high-similar, high-dissimilar, and regular groups. Additionally, we investigate the performance of the recommendation system in a wide range of aspects, including precision, ranking quality, and novelty. Based on the listening frequency of each user and for each track, implicit feedback is also derived from the track popularity. To prevent popularity bias, we combine track popularity and group popularity into latent factor models to improve the performance of the recommendation algorithm. As a result of our evaluation, we found that the proposed methods provided excellent recommendations regarding accuracy, diversity, and novelty. [ABSTRACT FROM AUTHOR]

Previous neuroscientific research has expounded on the fundamental role played by emotion during moral decision-making. Negative emotionality has been observed to exert a general inhibitory effect towards harmful behaviors against others. Nevertheless, the downregulation of negative affects at different levels of moral processing (e.g. impersonal versus personal moral dilemmas) alongside its possible interactions with other factors (e.g. perspective taking) hasn't been directly assessed; both of which can assist in predicting future moral decision-making. In the present research, we empirically test (Study 1, N = 41) whether downregulating negative emotionality through pharmacological interventions using lorazepam (a GABA receptor agonist), modulate the permissibility of harm to others –i.e. if participants find it more morally permissible to harm others when harm is unavoidable (inevitable harm moral dilemmas), than when it may be avoided (evitable harm moral dilemmas). Furthermore, using another sample (Study 2, N = 31), we assess whether lorazepam's effect is modulated by different perspective-taking conditions during a moral dilemma task –e.g. "is it morally permissible for you to [...]?" (1st person perspective), relative to "is it morally permissible for [x individual] to [...]?" (3rd person perspective)–, where the outcome of the different scenarios is controlled. The results of both studies converge, revealing an emotion-dependent, rather than an outcome-dependent, pharmacological modulation. Lorazepam only influenced interpersonal moral judgments when not modulated by the evitable/inevitable condition. Furthermore, there was a significant interaction between perspective-taking and drug administration, as lorazepam exerted a larger effect in modulating moral choices rather than moral judgements. [ABSTRACT FROM AUTHOR]

While Human Papillomavirus (HPV) particles have been detected in a small proportion of benign thyroid nodules or thyroid cancer cases, a role of HPV in these thyroid conditions has not been established. This study aims to investigate the association of HPV infection with thyroid cancer (TC) using a nationwide population-based study. We retrieved data for this case–control study from Taiwan's Longitudinal Health Insurance Database 2010. The study sample included 3062 patients with TC and 9186 propensity-scored matched controls. We employed multivariate logistic regression models to quantitatively evaluate the association of TC with HPV infections after taking age, sex, monthly income, geographic location and urbanization level of the patient's residence, diabetes, hypertension, and hyperlipidemia into considerations. Chi-squared test revealed that there was a significant difference in the prevalence of prior HPV infections between patients with TC and controls (15.3% vs. 7.6%, p < 0.001). The adjusted odds ratio of prior HPV infections for patients with TC was 2.199 (95% CI = 1.939–2.492) relative to controls. The adjusted ORs of prior HPV infections for patients with TC was similar for males and females. Our research suggests a significant link between HPV infection and the development of TC. [ABSTRACT FROM AUTHOR]

Flexor hallucis longus (FHL) transfer is an effective surgery in treating insertional Achilles tendinopathy (IAT). However, limited data exist regarding the post-surgery changes in the transferred FHL. The study aimed to compare the sequential changes and hypertrophy of FHL after isolated FHL transfer (FHLT). We retrospectively enrolled patients who underwent isolated FHLT for insertional Achilles pathology from 2015 to 2020 and divided them into two groups based on whether reattachment of the residue Achilles stump to the FHL was performed or not. We recorded demographic characteristics, MRI parameters, and functional outcome. We also analyzed the correlation between the collected data and FHL hypertrophy. Results revealed no significant differences in most MRI parameters of FHL and functional outcomes between the groups. However, the fat distribution within the FHL showed significant reduction and notable 20.2% hypertrophy after FHLT. Interestingly, the hypertrophy of the FHL was significantly more pronounced in the non-reattached group. Furthermore, we observed a positive correlation between the follow-up period and FHL hypertrophy. In conclusion, the FHL demonstrated significant enlargement over time following FHLT. The compensatory hypertrophy of the transferred FHL was particularly evident and the cumulative incidences of FHL enlargement over time were higher in the non-reattached groupcompared to reattached group. However, both reattachment and non-reattachment of Achilles stump on FHL transfer for insertional Achilles tendinopathy carried similar postoperative functional outcomes. [ABSTRACT FROM AUTHOR]

Protozoan parasites use cAMP signaling to precisely regulate the place and time of developmental differentiation, yet it is unclear how this signaling is initiated. Encystation of the intestinal parasite Giardia lamblia can be activated by multiple stimuli, which we hypothesize result in a common physiological change. We demonstrate that bile alters plasma membrane fluidity by reducing cholesterol-rich lipid microdomains, while alkaline pH enhances bile function. Through depletion of the cAMP producing enzyme Adenylate Cyclase 2 (AC2) and the use of a newly developed Giardia-specific cAMP sensor, we show that AC2 is necessary for encystation stimuli-induced cAMP upregulation and activation of downstream signaling. Conversely, over expression of AC2 or exogenous cAMP were sufficient to initiate encystation. Our findings indicate that encystation stimuli induce membrane reorganization, trigger AC2-dependent cAMP upregulation, and initiate encystation-specific gene expression, thereby advancing our understanding of a critical stage in the life cycle of a globally important parasite. Giardia lamblia is an established model for studying encystation. Shih et al show bile and alkaline pH induce changes in membrane ordering, upregulate cAMP, and initiate encystation gene expression. [ABSTRACT FROM AUTHOR]

Sugar-sweetened beverages (SSB) are previously reported to jeopardize maternal fetal health, most well-known for gestational diabetes, childhood obesity, and cognitive impairment. Although warnings and diet recommendations urge pregnant women to consume less SSB, there is no noticeable difference in their behavior. How and why reproductive women change their SSB consumption patterns were not investigated previously. Our study aims to investigate beverage consumption patterns and how these patterns change in pregnancy in the context of substance use disorder (SUD). We invited all pregnant women visiting the clinic to answer a structured 20-min questionnaire every trimester during the regular antennal visit. At the end of the study, 337 pregnant women aged over 20 participated. A total of 301 responses entered for final analysis, with a response rate of 89.3%. Our finding showed those with high DSM-5-TR scores reduced SSB intake after becoming pregnant, while those with mild or low DSM-5-TR scores increased SSB intake after becoming pregnant. The top 3 factors related to their SSB consumption were "use despite of known health hazard (n = 133)", "increased desire to drink (n = 88)", and "excessive time spent on seeking SSB (n = 85)". The least reported factors were in the domains of social impairment (ranging from n = 3 to n = 26), pharmacologic effects (i.e., tolerance (n = 24) and withdrawal (n = 70). When participants reduced SSB consumption after becoming pregnant, their choice of beverages largely shifted to sugarless beverage but not much plain water. The result provided new insights in deciphering pregnant women's psychomotor factors for SSB intake, which served as useful references for making clinical or even public health recommendations. [ABSTRACT FROM AUTHOR]

Introduction: Organophosphates (OPs) are a major public health problem worldwide due to ease of access and high toxicity lacking effective biomarkers and treatment. Cholinergic agents such as OPs and carbamates are responsible for many pesticide-related deaths. While the inhibition of AChE is thought to be the main mechanism of injury, there are other important pathways that contribute to the overall toxicity of OPs such as mitochondrial dysfunction. An existing gap in OP poisoning are biomarkers to gauge severity and prognosis. Cell-free DNA (cfDNA) are novel biomarkers that have gained increased attention as a sensitive biomarker of disease with novel use in acute poisoning. This study investigates alterations in cerebral mitochondrial function in a rodent model of chlorpyrifos poisoning with the use of cfDNA as a potential biomarker. Methods: Twenty rodents were divided into two groups: Control (n = 10) and Chlorpyrifos (n = 10). Chlorpyrifos was administered through the venous femoral line with a Harvard Apparatus 11 Elite Syringe pump (Holliston, MA, USA) at 2 mg/kg. Animals were randomized to receive chlorpyrifos versus the vehicle (10% DMSO) for 60 min which would realistically present an acute exposure with continued absorption. At the end of the exposure (60 min), isolated mitochondria were measured for mitochondrial respiration along with measures of acetylcholinesterase activity, cfDNA, cytokines and western blot. Results: The Chlorpyrifos group showed a significant decrease in heart rate but no change in the blood pressure. There was a significant increase in bulk cfDNA concentrations and overall decrease in mitochondrial respiration from brain tissue obtained from animals in the Chlorpyrifos group when compared to the Control group with no difference in acetylcholinesterase activity. In addition, there was a significant increase in both IL-2 and IL-12 in the Chlorpyrifos group. Conclusions: In our study, we found that the total cfDNA concentration may serve as a more accurate biomarker of OP exposure compared to acetylcholinesterase activity. In addition, there was an overall decrease in cerebral mitochondrial function in the Chlorpyrifos group when compared to the Control group. [ABSTRACT FROM AUTHOR]

Children's psychological well-being is critical for students' school performance and mental health. This study developed the Chinese Children's Subjective Well-being Scale and explored an appropriate strategy to improve children's subjective well-being from the collaboration between school and home perspective. Based on a literature review, focus group interviews, expert validity, factor structure and confirmatory factor analysis, this study developed the Chinese Children's Subjective Well-being Scale. We then enrolled 289 grade 3–6 students from a public primary school in southeastern China to conduct multiple linear regression analysis. The Chinese Children's Subjective Well-being Scale had good reliability and validity. Homework anxiety was negatively associated with subjective well-being (β = -0.21. p = 0.011). Family interaction and support improved subjective well-being. Less parental supervision and family conflict could buffer the negative effect of homework anxiety on subjective well-being. The Chinese Children's Subjective Well-being Scale can be used with primary school students in China. This study also recommended that governments and education practitioners focus on optimizing collaboration between school and home to improve children's subjective well-being by reducing their homework anxiety and increasing the harmonious family atmosphere (more family interaction and support and less parental supervision and family conflict). [ABSTRACT FROM AUTHOR]

The current study investigated the differences between environmental volunteering program and natural experience program in natural benefits, place attachment and pro-environmental behaviours. Fifty-eight college students were recruited to participate in these two programs which were conducted in a highland farm. Comparing to those in natural experience program, the results indicated that participants in the environmental volunteering program perceived greater natural benefits, expressed a stronger place attachment to activity site, as well as reported a better human-nature relationship and improved pro-environmental behaviours. The findings of this study also presented how these measurements predict volunteers' natural benefits and pro-environmental behaviours. Environmental volunteering is an environmental health strategy that could be incorporated into individuals' health promotion. Suggestions for promoting environmental volunteering, and their implementations are proposed. [ABSTRACT FROM AUTHOR]

Accessible urban greenery allows short breaks and leisure activities while experiencing nature. Studies have shown that contact with nature elicits psychological and physical health benefits. However, the immediate impact and influence of exposure to artificial versus rural ecological nature have yet to be examined. This study investigates their psychophysiological restorative effects onsite, specifically when individuals view a ubiquitous urban public greenery space or a more indigenous ecological forest-like nature area, to compare levels of restorativeness and relaxation. Participants were asked to sit and view a scene onsite for 6 min while their facial muscle tension was recorded. The data were used to evaluate the degree of facial relaxation for both scenes. In addition, participant self-reports measured perceived restorativeness after the 6-min period. The self-reported data showed that the ecological farm scene was rated significantly higher for perceived restorativeness (t [49.136] = 9.094, p <.001) after 6 min of viewing. The muscle tension analysis showed that facial tension significantly declined when participants viewed the farm scene compared to the urban greenery space. These results, especially those on the farm, show that nature with more forest-like and rural elements elicited more powerful restorative effects and significantly lowered facial muscle tension (t [65] = − 2.785, p <.05), thus verifying that a more ecological nature landscape provides immediate, significant health benefits through attention recovery and reduced facial muscle stress. [ABSTRACT FROM AUTHOR]

ZnO/carbon-black heterostructures were synthesized using a sol–gel method and crystallized by annealing at 500 °C under 2 × 10−2 Torr for 10 min. The crystal structures and binding vibration modes were determined by XRD, HRTEM, and Raman spectrometry. Their surface morphologies were observed by FESEM. The Moiré pattern that is observed in the HRTEM images confirms that the carbon-black nanoparticles were covered by the ZnO crystals. Measurements of optical absorptance revealed that the optical band gap of the ZnO/carbon-black heterostructures increased from 2.33 to 2.98 eV as the carbon-black nanoparticle content increases from 0 to 8.33 × 10−3 mol owing to the Burstein–Moss effect. The photoluminescence intensities at the near-band edge and of the violet, and blue light were increased by factors about 68.3, 62.8, and 56.8, respectively, when the carbon-black contents is of the 2.03 × 10−3 mol. This work reveals that the proper carbon-black nanoparticle content involved increases the PL intensities of the ZnO crystals in the short wavelength regime, supporting their potential application in the light-emitting devices. [ABSTRACT FROM AUTHOR]

The sterilisation of surgical instruments is a major factor in infection control in the operating room (OR). All items used in the OR must be sterile for patient safety. Therefore, the present study evaluated the effect of far-infrared radiation (FIR) on the inhibition of colonies on packaging surface during the long-term storage of sterilised surgical instruments. From September 2021 to July 2022, 68.2% of 85 packages without FIR treatment showed microbial growth after incubation at 35 °C for 30 days and at room temperature for 5 days. A total of 34 bacterial species were identified, with the number of colonies increasing over time. In total, 130 colony-forming units were observed. The main microorganisms detected were Staphylococcus spp. (35%) and Bacillus spp. (21%) , Kocuria marina and Lactobacillus spp. (14%), and mould (5%). No colonies were found in 72 packages treated with FIR in the OR. Even after sterilisation, microbial growth can occur due to movement of the packages by staff, sweeping of floors, lack of high-efficiency particulate air filtration, high humidity, and inadequate hand hygiene. Thus, safe and simple far-infrared devices that allow continuous disinfection for storage spaces, as well as temperature and humidity control, help to reduce microorganisms in the OR. [ABSTRACT FROM AUTHOR]

Introduction: Cyanide exposure can occur in various settings such as industry and metallurgy. The primary mechanism of injury is cellular hypoxia from Complex IV (CIV) inhibition. This leads to decreased ATP production and increased reactive oxygen species production. The brain and the heart are the organs most affected due to their high metabolic demand. While the cardiac effects of cyanide are well known, the cerebral effects on cellular function are less well described. We investigated cerebral metabolism with a combination of brain respirometry, microdialysis, and western blotting using a rodent model of sub-lethal cyanide poisoning. Methods: Twenty rodents were divided into two groups: control (n = 10) and sub-lethal cyanide (n = 10). Cerebral microdialysis was performed during a 2 mg/kg/h cyanide exposure to obtain real-time measurements of cerebral metabolic status. At the end of the exposure (90 min), brain-isolated mitochondria were measured for mitochondrial respiration. Brain tissue ATP concentrations, acyl-Coenzyme A thioesters, and mitochondrial content were also measured. Results: The cyanide group showed significantly increased lactate and decreased hypotension with decreased cerebral CIV-linked mitochondrial respiration. There was also a significant decrease in cerebral ATP concentration in the cyanide group and a significantly higher cerebral lactate-to-pyruvate ratio (LPR). In addition, we also found decreased expression of Complex III and IV protein expression in brain tissue from the cyanide group. Finally, there was no change in acyl-coenzyme A thioesters between the two groups. Conclusions: The key finding demonstrates mitochondrial dysfunction in brain tissue that corresponds with a decrease in mitochondrial function, ATP concentrations, and an elevated LPR indicating brain dysfunction at a sub-lethal dose of cyanide. [ABSTRACT FROM AUTHOR]

Although machine learning (ML) has shown promise across disciplines, out-of-sample generalizability is concerning. This is currently addressed by sharing multi-site data, but such centralization is challenging/infeasible to scale due to various limitations. Federated ML (FL) provides an alternative paradigm for accurate and generalizable ML, by only sharing numerical model updates. Here we present the largest FL study to-date, involving data from 71 sites across 6 continents, to generate an automatic tumor boundary detector for the rare disease of glioblastoma, reporting the largest such dataset in the literature (n = 6, 314). We demonstrate a 33% delineation improvement for the surgically targetable tumor, and 23% for the complete tumor extent, over a publicly trained model. We anticipate our study to: 1) enable more healthcare studies informed by large diverse data, ensuring meaningful results for rare diseases and underrepresented populations, 2) facilitate further analyses for glioblastoma by releasing our consensus model, and 3) demonstrate the FL effectiveness at such scale and task-complexity as a paradigm shift for multi-site collaborations, alleviating the need for data-sharing. Federated ML (FL) provides an alternative to train accurate and generalizable ML models, by only sharing numerical model updates. Here, the authors present the largest FL study to-date to generate an automatic tumor boundary detector for glioblastoma. [ABSTRACT FROM AUTHOR]

Purpose: Anti-granulocyte–macrophage colony-stimulating factor autoantibodies (anti-GM-CSF Abs) are a predisposing factor for pulmonary alveolar proteinosis (PAP) and Cryptococcus gattii cryptococcosis. This study aimed to investigate clinical manifestations in anti-GM-CSF Ab-positive patients with C. gattii cryptococcosis and analyze the properties of anti-GM-CSF Abs derived from these patients and patients with PAP. Methods: Thirty-nine patients diagnosed with cryptococcosis (caused by C. neoformans or C. gattii) and 6 with PAP were enrolled in the present study. Clinical information was obtained from medical records. Blood samples were collected for analysis of autoantibody properties. We also explored the National Health Insurance Research Database (NHIRD) of Taiwan to investigate the epidemiology of cryptococcosis and PAP. Results: High titers of neutralizing anti-GM-CSF Abs were identified in 15 patients with cryptococcosis (15/39, 38.5%). Most anti-GM-CSF Ab-positive cryptococcosis cases had central nervous system (CNS) involvement (14/15, 93.3%). Eleven out of 14 (78.6%) anti-GM-CSF Ab-positive CNS cryptococcosis patients were confirmed to be infected with C. gattii, and PAP did not occur synchronously or metachronously in a single patient from our cohort. Exploration of an association between HLA and anti-GM-CSF Ab positivity or differential properties of autoantibodies from cryptococcosis patients and PAP yielded no significant results. Conclusion: Anti-GM-CSF Abs can cause two diseases, C. gattii cryptococcosis and PAP, which seldom occur in the same subject. Current biological evidence regarding the properties of anti-GM-CSF Abs cannot provide clues regarding decisive mechanisms. Further analysis, including more extensive cohort studies and investigations into detailed properties, is mandatory to better understand the pathogenesis of anti-GM-CSF Abs. [ABSTRACT FROM AUTHOR]

Au-decorated Bi2Se3 nanoplatelet heterostructures are fabricated by a two-step process of thermal CVD at 600 °C and magnetron sputtering at room-temperature. The crystal structures and binding energies of rhombohedral Bi2Se3 and FCC Au are determined by XRD, HRTEM, XPS, and Raman spectroscopy. XPS and Raman spectroscopy reveal the interaction between Au and Bi2Se3 by shifting in the binding energies of Au–Au, Au–Se and Bi–Se bonds and the wavenumber of A1g2 and Eg2 modes. Au-decorated Bi2Se3 nanoplatelet heterostructures are observed using FESEM, and confirmed by XPS, Raman spectroscopy, and HRTEM imaging. Their optical band gap of the Au-decorated Bi2Se3 nanoplatelet heterostructures increases with Au thickness about 1.92-fold as much as that of pristine Bi2Se3 (0.39 eV), owing to the Burstein-Moss effect. The optical absorptance of the Au-decorated Bi2Se3 nanoplatelet heterostructures revealed increment with wavelength from 200 to 500 nm and decrement with increasing wavelength from 500 to 800 nm. [ABSTRACT FROM AUTHOR]

Introduction: Carbon monoxide (CO) is a colorless and odorless gas that is a leading cause of environmental poisoning in the USA with substantial mortality and morbidity. The mechanism of CO poisoning is complex and includes hypoxia, inflammation, and leukocyte sequestration in brain microvessel segments leading to increased reactive oxygen species. Another important pathway is the effects of CO on the mitochondria, specifically at cytochrome c oxidase, also known as Complex IV (CIV). The purpose of this ongoing study is the preliminary development of a porcine model of CO poisoning for investigation of alterations in brain mitochondrial physiology. Methods: Four pigs (10 kg) were divided into two groups: Sham (n = 2) and CO (n = 2). Administration of a dose of CO at 2000 ppm to the CO group over 120 minutes followed by 30 minutes of re-oxygenation at room air. The control group received room air for 150 minutes. Non-invasive optical monitoring was used to measure CIV redox states. Cerebral microdialysis was performed to obtain semi real-time measurements of cerebral metabolic status. At the end of the exposure, fresh brain tissue (cortical and hippocampal) was immediately harvested to measure mitochondrial respiration. Snap frozen cortical tissue was also used for ATP concentrations and western blotting. Results: While a preliminary ongoing study, animals in the CO group showed possible early decreases in brain mitochondrial respiration, citrate synthase density, CIV redox changes measured with optics, and an increase in the lactate-to-pyruvate ratio. Conclusions: There is a possible observable phenotype highlighting the important role of mitochondrial function in the injury of CO poisoning. [ABSTRACT FROM AUTHOR]

Texture modification of foods by using thickening agents is a routine practice for assessing and treating dysphagic patients. However, a powder-thickened fluid's viscosity might change over time, and little has been proposed to overcome this inconsistency. This study aimed to evaluate variations in the thickness of a fluid thickened with a common xanthan gum–based powder and to explore the feasibility of a simple advanced preparation method for thickened liquids to improve thickness stability. Thickened fluids with concentrations of 1.0 g/100 mL, 0.7 g/100 mL, and 0.5 g/100 mL were prepared from both freshly opened and previously opened thickening powders. Fluid thickness was measured every 10 min in a series of International Dysphagia Diet Standardization Initiative flow tests. A significant time-dependent decline in thickness was observed for all three concentrations in both groups, namely those prepared with freshly opened and previously opened thickening powders, and the shortest periods to achieve a stable viscosity after liquid preparation for the two groups were 80 and 70 min, respectively. On diluting the thickened liquids from the base liquid, which was prepared at a concentration of 1.0 g/100 mL and stored at room temperature for 90 min, no significant time-dependent thickness changes were observed over the following 60 min. The simple protocol of preparing the thickest "base" liquid in advance and then diluting it to the desired thickness resulted in a consistent liquid thickness, with the prepared liquids ready to be clinically applied and consumed, with high stability within 60 min. [ABSTRACT FROM AUTHOR]

Purpose: The link between human papillomavirus (HPV) infections and salivary gland cancer is still a subject of ongoing debate. This study aimed to explore the association between HPV infections and salivary gland cancer in a Taiwanese cohort. We hypothesize that HPV infection is associated with an increased risk of developing salivary gland cancer.This case-control study included 416 individuals aged ≥ 20 years who had received their first diagnosis of salivary gland cancer as cases, and 2080 propensity-score-matched controls. We performed multivariate logistic regressions to evaluate the association of salivary gland cancer with HPV infections while considering sociodemographic characteristics and medical comorbidities.Statistical analysis showed a significant difference in the prevalence of HPV infections between patients diagnosed with salivary gland cancer and the controls, with rates of 10.8% and 6.2%, respectively (p < 0.001). The odds ratio for having prior HPV infections among patients with salivary gland cancer compared to controls was 1.885, with a 95% confidence interval of 1.315 to 2.701 after adjusting for variables such as age, sex, monthly income, geographic location, urbanization level, diabetes, hypertension, hyperlipidemia, tobacco use, and alcohol abuse/alcohol dependence syndrome.Our study adds to the evidence suggesting an association between HPV infections and salivary gland cancer. Individuals with a history of HPV infection have an approximately 88% higher likelihood of developing salivary gland cancer.Methods: The link between human papillomavirus (HPV) infections and salivary gland cancer is still a subject of ongoing debate. This study aimed to explore the association between HPV infections and salivary gland cancer in a Taiwanese cohort. We hypothesize that HPV infection is associated with an increased risk of developing salivary gland cancer.This case-control study included 416 individuals aged ≥ 20 years who had received their first diagnosis of salivary gland cancer as cases, and 2080 propensity-score-matched controls. We performed multivariate logistic regressions to evaluate the association of salivary gland cancer with HPV infections while considering sociodemographic characteristics and medical comorbidities.Statistical analysis showed a significant difference in the prevalence of HPV infections between patients diagnosed with salivary gland cancer and the controls, with rates of 10.8% and 6.2%, respectively (p < 0.001). The odds ratio for having prior HPV infections among patients with salivary gland cancer compared to controls was 1.885, with a 95% confidence interval of 1.315 to 2.701 after adjusting for variables such as age, sex, monthly income, geographic location, urbanization level, diabetes, hypertension, hyperlipidemia, tobacco use, and alcohol abuse/alcohol dependence syndrome.Our study adds to the evidence suggesting an association between HPV infections and salivary gland cancer. Individuals with a history of HPV infection have an approximately 88% higher likelihood of developing salivary gland cancer.Results: The link between human papillomavirus (HPV) infections and salivary gland cancer is still a subject of ongoing debate. This study aimed to explore the association between HPV infections and salivary gland cancer in a Taiwanese cohort. We hypothesize that HPV infection is associated with an increased risk of developing salivary gland cancer.This case-control study included 416 individuals aged ≥ 20 years who had received their first diagnosis of salivary gland cancer as cases, and 2080 propensity-score-matched controls. We performed multivariate logistic regressions to evaluate the association of salivary gland cancer with HPV infections while considering sociodemographic characteristics and medical comorbidities.Statistical analysis showed a significant difference in the prevalence of HPV infections between patients diagnosed with salivary gland cancer and the controls, with rates of 10.8% and 6.2%, respectively (p < 0.001). The odds ratio for having prior HPV infections among patients with salivary gland cancer compared to controls was 1.885, with a 95% confidence interval of 1.315 to 2.701 after adjusting for variables such as age, sex, monthly income, geographic location, urbanization level, diabetes, hypertension, hyperlipidemia, tobacco use, and alcohol abuse/alcohol dependence syndrome.Our study adds to the evidence suggesting an association between HPV infections and salivary gland cancer. Individuals with a history of HPV infection have an approximately 88% higher likelihood of developing salivary gland cancer.Conclusions: The link between human papillomavirus (HPV) infections and salivary gland cancer is still a subject of ongoing debate. This study aimed to explore the association between HPV infections and salivary gland cancer in a Taiwanese cohort. We hypothesize that HPV infection is associated with an increased risk of developing salivary gland cancer.This case-control study included 416 individuals aged ≥ 20 years who had received their first diagnosis of salivary gland cancer as cases, and 2080 propensity-score-matched controls. We performed multivariate logistic regressions to evaluate the association of salivary gland cancer with HPV infections while considering sociodemographic characteristics and medical comorbidities.Statistical analysis showed a significant difference in the prevalence of HPV infections between patients diagnosed with salivary gland cancer and the controls, with rates of 10.8% and 6.2%, respectively (p < 0.001). The odds ratio for having prior HPV infections among patients with salivary gland cancer compared to controls was 1.885, with a 95% confidence interval of 1.315 to 2.701 after adjusting for variables such as age, sex, monthly income, geographic location, urbanization level, diabetes, hypertension, hyperlipidemia, tobacco use, and alcohol abuse/alcohol dependence syndrome.Our study adds to the evidence suggesting an association between HPV infections and salivary gland cancer. Individuals with a history of HPV infection have an approximately 88% higher likelihood of developing salivary gland cancer. [ABSTRACT FROM AUTHOR]

Despite recent advances of data acquisition and algorithms development, machine learning (ML) faces tremendous challenges to being adopted in practical catalyst design, largely due to its limited generalizability and poor explainability. Herein, we develop a theory-infused neural network (TinNet) approach that integrates deep learning algorithms with the well-established d-band theory of chemisorption for reactivity prediction of transition-metal surfaces. With simple adsorbates (e.g., *OH, *O, and *N) at active site ensembles as representative descriptor species, we demonstrate that the TinNet is on par with purely data-driven ML methods in prediction performance while being inherently interpretable. Incorporation of scientific knowledge of physical interactions into learning from data sheds further light on the nature of chemical bonding and opens up new avenues for ML discovery of novel motifs with desired catalytic properties. Machine learning faces challenges in catalyst design due to its black-box nature. Here, the authors develop a theory-infused neural network approach that integrates deep learning algorithms with the well-established d-band theory of chemisorption for reactivity prediction of transition-metal surfaces. [ABSTRACT FROM AUTHOR]

This study investigated the association between visual impairment and cognitive decline among the elderly in Taiwan. The data were obtained from a government-sponsored, annual physical examination program for elderly citizens ≥ 65 years in Taipei City during 2005–2012. Distance presenting visual acuity was measured using the Snellen chart. Visual impairment was classified into low vision and blindness. The Short Portable Mental Status Questionnaire (SPMSQ) was selected to measure cognitive decline. The confounding factors including age, sex, sociodemographic factors: living status, marital status, education level, health behaviors: smoking, alcohol consumption, betel nut chewing, and physical comorbidities: BMI, hypertension, diabetes, cholesterol and triglyceride were collected for analysis. We recruited 105,208 participants and 4542 (4.3%) have abnormal SPMSQ. The abnormal SPMSQ had significantly higher prevalence of low vision (44.52% vs 18.79%) and blindness (8.89% vs 0.93%) compared with normal SPMSQ. The hazard ratios of abnormal SPMSQ in low vision and blindness were 2.34 (95% CI 2.17–2.52), and 5.13 (95% CI 4.50–5.85), after adjustment for confounders. In conclusion, visual impairment was independently and significantly associated with greater incident cognitive decline among elderly Asian people. Prevention of visual impairment may help to reduce the incidence of cognitive decline in the aged Asian population. [ABSTRACT FROM AUTHOR]

The association among sugar sweetened beverages (SSB) consumption, addiction and depression in adults, children and adolescents is widely reported. Dieting patterns during pregnancy is complicated by maternal fetal concerns. Specifically, restrained use of SSB might be potentially a source of perinatal distress. The current study modified diagnostic criteria for Substance Use Disorder (SUD) in Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5), into SSB-specific questions to assess SSB use tendency. Edinburgh Postpartum Depression Scores (EPDS) is used to assess maternal distress during pregnancy. One hundred and ninety-six consecutive pregnant women receiving antenatal care at Kaohsiung Medical University Hospital were invited to participate in this study. In the first trimester, 46.6% of women had none or 1 DSM-5 symptom, 27.0% had 2–3 symptoms, while 26.4% had ≥ 4 symptoms. The mean numbers of DSM-5 symptoms in each trimester were found to be 2.5 ± 2.25, 2.6 ± 2.45, 2.4 ± 2.43 for the first, second and third trimester, respectively, p = 0.750. While EPDS score showed no difference among DSM-5 symptoms 0–1, 2–3 and ≥ 4 groups in the first trimester (8.1 ± 4.59, 8.4 ± 5.00, 8.8 ± 4.82, p = 0.343), women with ≥ 4 DSM-symptoms was found significantly higher EPDS scores than those with < 4 DSM-symptoms in the second (7.2 ± 4.81, 7.7 ± 4.98, 8.8 ± 4.33, p = 0.030) and third trimester (6.8 ± 5.00, 7.2 ± 4.63, 8.7 ± 5.24, p = 0.019). The relationship remained significant after adjusting for covariates including actual SSB amount consumed (adjusted β = 0.25 with 95% confident interval (CI) 0.04–0.45 and 0.21 with 95% CI 0.04–0.38 for the second and third trimesters, respectively). Overall, the study is the first to characterize the positive relationship between SSB use tendency and antenatal distress in pregnancy, independent of actual SSB amount consumed. The observational nature of the study design precludes inferences of its underlying socio-psychomotor mechanisms, although restrained SSB use in pregnancy is suspected to contribute. The novel employment of modified SSB-specific DSM-5 scores and EPDS in this setting is feasible and further validation is promising. With better understanding and awareness, pregnant women with increased SSB use tendency should be properly counseled with special attention to their mental state. [ABSTRACT FROM AUTHOR]

Due to the continuous evolving of mobile communication technologies, deploying small cells (SCs), also known as SC base stations (SBSs), is regarded as one of the feasible alternatives to provide better indoor signal quality to meet the ever-increasing demand for mobile broadband data in indoor environments. However, the co-tier uplink interference, i.e., interference between SBSs, increases when SBSs are densely deployed. Consequently, the sum-capacity of the small cell network (SCN) is deteriorated. To manage such interference, a co-tier uplink power control scheme which combines the Stackelberg game with two-way pricing mechanism is proposed. In this scheme, among the SBSs, one is selected as the leader and the rest are the followers. Under the premise of not violating the maximum tolerable uplink co-tier interference constraint, leader UE and follower UEs achieve the compromised uplink transmit power based on the proposed two-way bargaining procedure. The average sum-capacity of the SCN and the average uplink transmit power of leader UE and follower UEs are used as the major metrics to evaluate the performance of the proposed scheme. Compared with the simulation results obtained by only controlling the transmit power of follower UEs, i.e., Stackelberg game with one-way pricing, the proposed co-tier uplink power control scheme, i.e., Stackelberg game with two-way pricing, attains higher sum-capacity with smaller transmit power. [ABSTRACT FROM AUTHOR]

Defects in DNA repair frequently lead to neurodevelopmental and neurodegenerative diseases, underscoring the particular importance of DNA repair in long-lived post-mitotic neurons1,2. The cellular genome is subjected to a constant barrage of endogenous DNA damage, but surprisingly little is known about the identity of the lesion(s) that accumulate in neurons and whether they accrue throughout the genome or at specific loci. Here we show that post-mitotic neurons accumulate unexpectedly high levels of DNA single-strand breaks (SSBs) at specific sites within the genome. Genome-wide mapping reveals that SSBs are located within enhancers at or near CpG dinucleotides and sites of DNA demethylation. These SSBs are repaired by PARP1 and XRCC1-dependent mechanisms. Notably, deficiencies in XRCC1-dependent short-patch repair increase DNA repair synthesis at neuronal enhancers, whereas defects in long-patch repair reduce synthesis. The high levels of SSB repair in neuronal enhancers are therefore likely to be sustained by both short-patch and long-patch processes. These data provide the first evidence of site- and cell-type-specific SSB repair, revealing unexpected levels of localized and continuous DNA breakage in neurons. In addition, they suggest an explanation for the neurodegenerative phenotypes that occur in patients with defective SSB repair.DNA single-strand breaks in neurons accumulate at high levelsin functional enhancers. [ABSTRACT FROM AUTHOR]

Construction of a coseismic displacement grid model (hereafter referred to as the grid model) is a critical strategy for maintaining the precision of the semi-kinematic reference frame. However, no unequivocal criteria have yet been suggested for the timing of grid model construction. To clarify this timing, the observations of continuous global navigation satellite system in Taiwan were evaluated using coordinate time series analysis from 2003 to 2018 and a horizontal precision of approximately 14 mm was proposed as the threshold to construct a grid model. Next, two strategies were proposed to evaluate the timing on the basis of earthquake information. For Strategy I, the possible maximum surface displacement was derived using the forward dislocation model based on the hypocenter, moment magnitude and focal mechanism solution provided by the Real-Time Moment Tensor Monitoring System. For Strategy II, a required minimum magnitude (RMM) checking grid was constructed using the hypocenter and local magnitude data from the Central Weather Bureau, Taiwan. If the forwarded maximum surface displacement from Strategy I is larger than the threshold of 14 mm or the local magnitude of an earthquake is larger than the RMM from Strategy II, it represents the timing for the grid model construction. On the basis of the validation results for 20 selected earthquakes, both two strategies were proposed to be implemented simultaneously for timing evaluation to avoid overlooking detectable events. [ABSTRACT FROM AUTHOR]

Patients with ovarian cancer exhibit no clear symptoms. Ovarian cancer can be detected early only through internal diagnosis, ultrasound, and a carcinoma antigen 125 (CA125) tumor index test. More than 60% of patients have advanced ovarian cancer at diagnosis. The traditional chemical fluorescence immunoassay is used to measure CA125 levels; its lowest detection limit is only 35 U mL−1, but it does not adequately demonstrate early symptoms. Moreover, endometriosis, pelvic cavity inflammation, and other gynecological diseases may increase CA125 levels. Therefore, a method for extracting CA125 information is urgently required for ovarian cancer diagnosis. This information can include the glycosylated state of CA125. In this study, a new ultrasensitive electrochemical immunosensor composed of reduced graphene oxide (rGO), gold nanoparticles, thionine chloride, bovine serum albumin, and two antibodies was developed. Through hydrogen peroxide reduction, the sensor can detect glycosylated CA125 from ovarian cancer cells and human blood serum by using differential pulse voltammetry. O2 reacts with H+ that the H+ is formed from altered glycan core structures, producing a strong signal for malignancy detection. With the lowest detection limit of 4.10 pg mL−1 (127 nU mL−1), the sensor can be used for early ovary cancer detection. Furthermore, the results of a clinical test in healthy individuals and patients demonstrated the high selectivity of the immunosensor, and the high-regression-curve rate obtained from human blood serum analysis could be used to distinguish ovarian cancer from other gynecological diseases. This is the first study employing an electrochemical immunosensor to define and identify ovarian cancer to achieve highly specific and accurate detection. [ABSTRACT FROM AUTHOR]

In this paper, we propose a novel laser direct micron-scale texturing technology. We utilized arranged liquid droplets as lenses to generate micron-scale patterns on a silicon surface. The breath figure method was employed to generate the arranged liquid droplets by self-assembly. The humidity source was a mix of glycerin and water at a volume ratio of 1:1. The solvent and polymer used were toluene and poly(methyl methacrylate (PMMA), respectively. The arranged liquid droplets were formed by the breath figure method and were followed by laser texturing on the Si substrate. Each laser pulse produced an area with a diameter of around 10 μm depending on the defocusing distance. Inside each laser pulse, the diameters of patterned holes were between 1.5 and 2 μm while the depths were between 17 and 22 nm. In conclusions, we demonstrated the liquid lenses arranged by the breath figure method could be utilized to generate micron-scale patterns. Meanwhile, the formed patterns showned that the liquid lenses outside the pattern area were not affected by neighboring pulses. [ABSTRACT FROM AUTHOR]

High quality factor (High-Q) and transmission optical devices are required for various applications in the fields of physics and engineering. Critical for these applications is the realization of a structure with high-Q, complete transmission and small volume. A robust high-Q filter with complete transmission by conjugated topological photonic crystals (CTPC) is presented. The study shows that an ultra-high-Q of more than 108 with complete transmission is obtained by the CTPC with 2 μm long due to the excitation of conjugated topological edge-states (CTES). It is also found that even though the quality factor of resonances increases as the periodic number of multilayers increases, these resonances are still complete transmission. A novel concept of CTES is first proposed in this study and investigated the effect of its topological phenomenon on high quality factor via CTPC. We theoretically realize the robust high-Q and complete transmission in the CTPC, which is different from those in periodic, quasi-periodic, Fabry-Perot photonic crystals and traditional topological photonic crystals (TPC). [ABSTRACT FROM AUTHOR]

Background: Dysregulation of pericellular proteolysis usually accounts for cancer cell invasion and metastasis. Isolation of a cell-surface protease system for lung cancer metastasis is an important issue for mechanistic studies and therapeutic target identification.Methods: Immunohistochemistry of a tissue array (n = 64) and TCGA database (n = 255) were employed to assess the correlation between serine protease inhibitors (SPIs) and lung adenocarcinoma progression. The role of SPI in cell motility was examined using transwell assays. Pulldown and LC/MS/MS were performed to identify the SPI-modulated novel protease(s). A xenografted mouse model was harnessed to demonstrate the role of the SPI in lung cancer metastasis.Results: Hepatocyte growth factor activator inhibitor-2 (HAI-2) was identified to be downregulated following lung cancer progression, which was related to poor survival and tumour invasion. We further isolated a serum-derived serine protease, plasmin, to be a novel target of HAI-2. Downregulation of HAI-2 promotes cell surface plasmin activity, EMT, and cell motility. HAI-2 can suppress plasmin-mediated activations of HGF and TGF-β1, EMT and cell invasion. In addition, downregulated HAI-2 increased metastasis of lung adenocarcinoma via upregulating plasmin activity.Conclusion: HAI-2 functions as a novel inhibitor of plasmin to suppress lung cancer cell motility, EMT and metastasis. [ABSTRACT FROM AUTHOR]

These authors contributed equally: Sarthak Pati, Ujjwal Baid, Brandon Edwards. Correction to: I Nature Communications i https://doi.org/10.1038/s41467-022-33407-5, published online 05 December 2022 In this article the author name Carmen Balaña was incorrectly written as Carmen Balaña Quintero. [Extracted from the article]

DNA mutations are known cancer drivers. Here we investigated whether mRNA events that are upregulated in cancer can functionally mimic the outcome of genetic alterations. RNA sequencing or 3′-end sequencing techniques were applied to normal and malignant B cells from 59 patients with chronic lymphocytic leukaemia (CLL)1-3. We discovered widespread upregulation of truncated mRNAs and proteins in primary CLL cells that were not generated by genetic alterations but instead occurred by intronic polyadenylation. Truncated mRNAs caused by intronic polyadenylation were recurrent (n = 330) and predominantly affected genes with tumour-suppressive functions. The truncated proteins generated by intronic polyadenylation often lack the tumour-suppressive functions of the corresponding full-length proteins (such as DICER and FOXN3), and several even acted in an oncogenic manner (such as CARD11, MGA and CHST11). In CLL, the inactivation of tumour-suppressor genes by aberrant mRNA processing is substantially more prevalent than the functional loss of such genes through genetic events. We further identified new candidate tumour-suppressor genes that are inactivated by intronic polyadenylation in leukaemia and by truncating DNA mutations in solid tumours4,5. These genes are understudied in cancer, as their overall mutation rates are lower than those of well-known tumour-suppressor genes. Our findings show the need to go beyond genomic analyses in cancer diagnostics, as mRNA events that are silent at the DNA level are widespread contributors to cancer pathogenesis through the inactivation of tumour-suppressor genes. The inactivation of tumour suppressor genes at the level of mRNA occurs by the generation of truncated proteins in leukaemia. [ABSTRACT FROM AUTHOR]

Anaplasma phagocytophilum is transmitted mainly by hard ticks and can cause potentially fatal granulocytic anaplasmosis in humans, but its occurrence in ticks in Taiwan has never been investigated although this pathogen has been detected in Taiwanese rodents before. Ticks collected from small mammals in Hualien, eastern Taiwan, were assayed for Anaplasma infections; infections of Rickettsia and Apicomplexa protozoans were also studied. Of the 270 individually assayed Rhipicephalus haemaphysaloides ticks, A. phagocytophilum was identified in a nymphal tick. Parasites most similar to Anaplasma bovis, Rickettsia rickettsii, Rickettsia sp. TwKM01, and at least seven apicomplexan species (including genera Cryptosporidium, Hepatozoon, and Theileria) were also identified. This study shows that A. phagocytophilum does occur in the hard tick in Taiwan, although whether R. haemaphysaloides can vector this pathogen remains to be determined. This work also reveals a high diversity of tick-borne bacteria and protozoans circulating in a small region and calls for further research on their potential risks for human health. [ABSTRACT FROM AUTHOR]

Drosophila olfactory local interneurons (LNs) in the antennal lobe are highly diverse and variable. How and when distinct types of LNs emerge, differentiate, and integrate into the olfactory circuit is unknown. Through systematic developmental analyses, we found that LNs are recruited to the adult olfactory circuit in three groups. Group 1 LNs are residual larval LNs. Group 2 are adult-specific LNs that emerge before cognate sensory and projection neurons establish synaptic specificity, and Group 3 LNs emerge after synaptic specificity is established. Group 1 larval LNs are selectively reintegrated into the adult circuit through pruning and re-extension of processes to distinct regions of the antennal lobe, while others die during metamorphosis. Precise temporal control of this pruning and cell death shapes the global organization of the adult antennal lobe. Our findings provide a road map to understand how LNs develop and contribute to constructing the olfactory circuit. [ABSTRACT FROM AUTHOR]

Alternative cleavage and polyadenylation (ApA) is known to alter untranslated region (3ʹUTR) length but can also recognize intronic polyadenylation (IpA) signals to generate transcripts that lose part or all of the coding region. We analyzed 46 3ʹ-seq and RNA-seq profiles from normal human tissues, primary immune cells, and multiple myeloma (MM) samples and created an atlas of 4927 high-confidence IpA events represented in these cell types. IpA isoforms are widely expressed in immune cells, differentially used during B-cell development or in different cellular environments, and can generate truncated proteins lacking C-terminal functional domains. This can mimic ectodomain shedding through loss of transmembrane domains or alter the binding specificity of proteins with DNA-binding or protein–protein interaction domains. MM cells display a striking loss of IpA isoforms expressed in plasma cells, associated with shorter progression-free survival and impacting key genes in MM biology and response to lenalidomide. [ABSTRACT FROM AUTHOR]

Introduction: Autoantibodies to granulocyte-macrophage colony-stimulating factor (GM-CSF) can cause acquired pulmonary alveolar proteinosis (PAP). Cases of acquired PAP susceptible to typical respiratory pathogens and opportunistic infections have been reported. Anti-GM-CSF autoantibodies have been reported in a few patients with cryptococcal meningitis. This study evaluated the presence of neutralizing anti-GM-CSF autoantibodies in patients without known congenital or acquired immunodeficiency with severe pulmonary or extrapulmonary cryptococcal infection but without PAP. Methods: We took a clinical history and performed an immunologic evaluation and screening of anti-cytokine autoantibodies in patients with cryptococcal meningitis. The impact of autoantibodies to GM-CSF on immune function was assessed by intracellular staining of GM-CSF-induced STAT5 phosphorylation and MIP-1α production in normal peripheral blood mononuclear cells incubated with plasma from patients or normal control subjects. Results: Neutralizing anti-GM-CSF autoantibodies were identified in four patients with disseminated cryptococcosis, none of whom exhibited PAP. Plasma from patients blocked GM-CSF signaling and inhibited STAT5 phosphorylation and production of MIP-1α. One patient died of disseminated cryptococcosis involving the central nervous system, which was associated with defective GM-CSF activity. Conclusions: Anti-GM-CSF autoantibodies increase susceptibility to cryptococcal infection in adults without PAP. Cryptococcal central nervous system infection associated with anti-GM-CSF autoantibodies could result in neurological sequelae or be life-threatening. Therefore, timely detection of neutralizing anti-GM-CSF autoantibodies and development of an effective therapy are necessary to prevent deterioration of cryptococcal infection in these patients. [ABSTRACT FROM AUTHOR]

While conservative approaches for chronic sialoadenitis are in current use, the utility of intraductal injection therapy remains unclear. The purpose of this study is to provide evidence that substances delivered through intraductal injection of the salivary gland are able to be effectively distributed throughout the gland. Methylene blue dye (0.1 %) was injected intraductally into a porcine parotid gland (5 ml) of one group and the porcine submandibular gland (1 or 2 ml, n = 6 for each preparation) of another group. After the injection, the ductal systems were evaluated, sectioned, and observed microscopically. Color area analysis was performed on submandibular gland sections, and the infiltration ratio of the dye was calculated. The papillae of both Stensen's and Wharton's duct openings were easily identified with intraductally delivered methylene blue dye. The dye infiltration began from the central ductal region of the gland and could be easily observed to gradually disperse to the peripheral regions in each acinar. There were no statistically significant differences in infiltration ratios between anterior, midline, and posterior section of the submandibular gland. Also, there were no statistically significant differences in the ratios between 1 and 2 ml injections at all the three section positions. This study demonstrated that desired substances can be evenly delivered throughout the salivary gland through intraductal injections. The use of intraductal injections might serve as a potential therapeutic procedure in the management of salivary gland diseases. [ABSTRACT FROM AUTHOR]

Purpose: This study aimed to investigate associations between obstructive sleep apnea (OSA) and urological comorbidities using a large population-based dataset. Methods: This cross-sectional study used the Taiwan Longitudinal Health Insurance Database 2005. We included 1236 males with OSA in the study group and 4944 males without OSA in the comparison group. Conditional logistic regressions were performed to examine relationships between OSA and urological comorbidities. Results: We found that patients with OSA had significantly greater prevalences of hypertrophy of the prostate (15.13 vs. 7.28 %), chronic prostatitis (4.37 vs. 2.16 %,), urinary incontinence (3.32 vs. 0.87 %), nocturia (2.02 vs. 0.61 %), erectile dysfunction (2.91 vs. 0.97 %), urinary calculi (12.06 vs. 6.80 %), and prostate cancer (0.97 vs. 0.40 %) than the comparison group. Additionally, the adjusted odds ratios in males with OSA for hypertrophy of prostate, chronic prostatitis, urinary incontinence, nocturia, erectile dysfunction, urinary calculi, and prostate cancer were 2.54 (95 % confidence interval (CI) 2.05~3.15), 1.95 (95 % CI 1.38~2.74), 4.13 (95 % CI 2.63~6.50), 3.54 (95 % CI 2.03~6.18), 2.95 (95 % CI 1.89~4.61), 1.89 (95 % CI 1.53~2.33), and 2.14 (95 % CI 1.03~4.43) than those without OSA, respectively. Conclusions: This study concluded that males with OSA had higher odds ratios of hypertrophy of the prostate, chronic prostatitis, urinary incontinence, nocturia, erectile dysfunction, urinary calculi, and prostate cancer than comparison group. [ABSTRACT FROM AUTHOR]

Correction to: I Nature Communications i https://doi.org/10.1038/s41467-023-36322-5, published online 11 February 2023 The original version of the published article omitted acknowledgement to the U.S. DOE. The original article can be found online at https://doi.org/10.1038/s41467-023-36322-5. The following statement is now added in the Acknowledgement section in both HTML and the PDF versions of the article: "F.A-P. would like to acknowledge support from the U.S. DOE, Office of Science, Office of Basic Energy Sciences, Chemical Sciences, Geosciences, and Biosciences Division, Catalysis Science Program to the SUNCAT Center for Interface Science and Catalysis". [Extracted from the article]

It is important to have a standardized tympanic membrane (TM) perforation platform to evaluate the various myringoplasty materials that have been studied and developed extensively during recent years. However, currently there are no cellular models specifically designed for this purpose, and animal models remain unsatisfactory. The purpose of this study is to propose an inexpensive, readily available, well-controlled, and easy-to-create cellular model as a substitute for use in the evaluation of TM repairing materials. A trans-well model was created using a cell culture insert with a round hole created at the center of the polycarbonate membrane. HaCaT cells were cultured on the fenestrated culture insert, and the desired myringoplasty graft was placed at the center of the window for one week and observed by fluorescent microscopy under vital staining. Under this cellular model, there was notable migration of HaCaT cells onto the positive control graft (rabbit fascia), while only a few cell clusters were observed on the negative control graft (paper). Model validation showed that the cell migration ratio for the PLLA + 1% hyaluronic acid (HA) graft is significantly higher than using myringoplasty paper, poly l-lactide (PLLA), or PLLA + 0.5% HA ( p < 0.05). This trans-well-based cellular model might be a useful pre-evaluation platform for the evaluation of TM repairing materials. The model is inexpensive, readily available, easy to create, and standardized for use. [ABSTRACT FROM AUTHOR]