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Headache is a frequent complaint in coronavirus disease-19 (COVID-19) patients. Nevertheless, no detailed information on the pathophysiology of headache in COVID-19 infection is currently limited. We encountered a patient developing headache, diplopia, and intracranial hypertension after COVID-19 infection. The patient no more complained of headache and diplopia after the intracranial pressure was normalized. Our case suggests that intracranial hypertension is a mechanism of headache in COVID-19 infection. We report herein a case of transient intracranial hypertension after COCVID-19 infection.

Research exploring how to support decision-making has often used machine learning to automate or assist human decisions. We take an alternative approach for improving decision-making, using machine learning to help stakeholders surface ways to improve and make fairer decision-making processes. We created "Deliberating with AI", a web tool that enables people to create and evaluate ML models in order to examine strengths and shortcomings of past decision-making and deliberate on how to improve future decisions. We apply this tool to a context of people selection, having stakeholders -- decision makers (faculty) and decision subjects (students) -- use the tool to improve graduate school admission decisions. Through our case study, we demonstrate how the stakeholders used the web tool to create ML models that they used as boundary objects to deliberate over organization decision-making practices. We share insights from our study to inform future research on stakeholder-centered participatory AI design and technology for organizational decision-making., CSCW 2023

Background: Oral antifungal drugs are the primary treatment for onychomycosis. However, there are few studies on the effectiveness and safety of oral combination therapy after laser treatment. Objective: We sought to contrast the efficacy and safety of laser and oral combination therapy with that of oral monotherapy for non-responders to laser treatment. Methods: We retrospectively evaluated the medical charts and photographs of 20 patients who received four sessions of Nd:YAG laser. Among these patients, 11 were "laser non-responders" and 9 were "laser partial responders". Afterward, 10 patients received oral drugs in addition to laser treatment (combination therapy) and the other 10 were completely altered to oral drugs, with no laser treatment (oral monotherapy). Clinical evaluation was conducted at baseline and 3 months after treatment. Recurrence was evaluated 3 months after the final evaluation. Results: Clinical evaluation revealed that combining or switching to oral antifungal drugs was substantially effective in the laser non-responder group (Z = -2.481, p = 0.013). Combination therapy was more effective than oral monotherapy (Z = -1.324, p = 0.247). Furthermore, positive baseline mycological results demonstrated a higher possibility of laser monotherapy failure (χ2 = -5.089, p = 0.024). There were two cases of recurrence in the oral monotherapy group and no adverse effect was discovered in any patient. Conclusion: This study highlighted that the combination of oral drugs with laser therapy could be beneficial regarding efficacy, recurrence, and safety in the treatment of patients who are refractory to laser therapy.

Introduction: Patients with moyamoya disease (MMD) often have headaches after successful revascularization surgery. We aimed to characterize headache in surgically treated MMD patients and elucidate its clinical meaning and pathophysiology. Methods: Headache and related symptoms were surveyed using structured questionnaires in pediatric MMD patients with follow-up for 6 months or longer after indirect revascularization surgery. Clinical information including initial presentation, surgical method, and outcome was collected from medical records. Surgical outcomes were assessed clinically and by perfusion imaging. We defined “headache associated with MMD” as the headache accompanied by a transient ischemic attack or provoked by hyperventilation. Other headaches were further classified based on the diagnostic criteria of the International Headache Society-3. We analyzed the characteristics of “headache associated with MMD” and newly developed headache after surgery. Results: Among 90 participants, 65 (72.2%) had headaches within the last year before survey, including 28 (43.1%) with “headaches associated with MMD,” 10 (15.3%) with probable migraines, 2 (3.1%) with infrequent episodic tension-type headaches, and 4 (6.2%) with probable tension-type headaches. Headache quality was pulsatile in 27 (41.5%) patients and pressing or tightening in 27 (41.5%) patients. Nausea or vomiting was accompanied in 30 (46.2%) patients. Headache upon awakening was reported in 37 (57.8%) patients. Headache disturbed daily life in 12 (18.5%) patients. Among the 32 (35.6%) patients who suffered headache during both the pre- and postoperative period, the headache quality was similar in 27 (84.4%) patients, and its severity decreased in 24 (75.0%) and did not change in 8 (25.0%) patients. Twelve (13.3%) patients experienced newly developed headaches after surgery. Among them, six (50.0%) were classified as having “headaches associated with MMD.” They were predominantly electric shock-like or stabbing in 5 (45.6%) patients and nondisturbing in all patients. All 90 patients achieved improvement of ischemic symptoms after surgery. Conclusion: Headaches often persist or newly develop after revascularization surgery in MMD patients. Accompanying nausea or vomiting and occurrence upon awakening are characteristic features. Postoperative headache does not necessarily imply insufficient disease control.

Background/Aims: Daratumumab has shown an encouraging antitumor effect in patients with multiple myeloma (MM), and was known to alter the immune properties by off-targeting immunosuppressive cells. Here, we aimed to evaluate the change in absolute lymphocyte count (ALC) as a surrogate marker for predicting survival outcomes of patients treated with daratumumab.Methods: Between 2018 and 2021, the medical records of patients with relapsed/refractory MM (RRMM) treated with daratumumab monotherapy at 10 centers in South Korea were reviewed. We collected the ALC data at pre-infusion (D0), day 2 after the first infusion (D2), and prior to the third cycle of daratumumab therapy (D56).Results: Fifty patients who were administered at least two cycles of daratumumab were included. Overall response rate was 54.0% after two cycles of daratumumab treatment. On D2, almost all patients experienced a marked reduction in ALC. However, an increase in ALC on D56 (ALCD56) was observed in patients with non-progressive disease, whereas failure of ALC recovery was noted in those with progressive disease. Patients with ALCD56 > 700/μL (n = 39, 78.0%) had prolonged progression- free survival (PFS) and overall survival (OS) than those with ALCD56 ≤ 700/μL (median PFS: 5.8 months vs. 2.6 months, p = 0.025; median OS: 24.1 months vs. 6.1 months, p = 0.004). In addition, ALCD56 >700/μL was a significant favorable prognostic factor for PFS (hazard ratio [HR], 0.22; p = 0.003) and OS (HR, 0.23; p = 0.012).Conclusions: Increase in ALC during daratumumab treatment was significantly associated with prolonged survival outcomes in patients with RRMM. The ALC value can predict clinical outcomes in patients treated with daratumumab.

Escherichia coli single stranded (ss) DNA binding protein (SSB) plays essential roles in DNA maintenance. It binds ssDNA with high affinity through its N-terminal DNA binding core and recruits at least 17 different SSB interacting proteins (SIPs) that are involved in DNA replication, recombination, and repair via its nine amino acid acidic tip (SSB-Ct). E. coli RecO, a SIP, is an essential recombination mediator protein in the RecF pathway of DNA repair that binds ssDNA and forms a complex with E. coli RecR protein. Here, we report ssDNA binding studies of RecO and the effects of a 15 amino acid peptide containing the SSB-Ct monitored by light scattering, confocal microscope imaging, and analytical ultracentrifugation (AUC). We find that one RecO monomer can bind the oligodeoxythymidylate, (dT)15, while two RecO monomers can bind (dT)35 in the presence of the SSB-Ct peptide. When RecO is in molar excess over ssDNA, large RecO–ssDNA aggregates occur that form with higher propensity on ssDNA of increasing length. Binding of RecO to the SSB-Ct peptide inhibits RecO–ssDNA aggregation. RecOR complexes can bind ssDNA via RecO, but aggregation is suppressed even in the absence of the SSB-Ct peptide, demonstrating an allosteric effect of RecR on RecO binding to ssDNA. Under conditions where RecO binds ssDNA but does not form aggregates, SSB-Ct binding enhances the affinity of RecO for ssDNA. For RecOR complexes bound to ssDNA, we also observe a shift in RecOR complex equilibrium towards a RecR4O complex upon binding SSB-Ct. These results suggest a mechanism by which SSB recruits RecOR to facilitate loading of RecA onto ssDNA gaps.

COVID-19 vaccine hesitancy has emerged as a major public health challenge. Although medical and scientific misinformation has been known to fuel vaccine hesitancy in the past, misinformation surrounding COVID-19 seems to be rampant, and increasing evidence suggests that it is contributing to COVID-19 vaccine hesitancy today. The relationship between misinformation and COVID-19 vaccine hesitancy is complex, however, and it is relatively understudied.In this article, we report qualitative data from two related but distinct studies from a larger project. Study 1 included semi-structured, open-ended interviews conducted in October-November 2020 via phone with 30 participants to investigate the relationship between misinformation and COVID-19 vaccine hesitancy. Study 1's results then informed the design of open-ended questions for Study 2, an online survey conducted in May-June 2021 to consider the relationship between misinformation and vaccine hesitancy further. The data were examined with thematic analysis.Study 1 led to the identification of positive and negative themes related to attitudes toward COVID-19 vaccines. In Study 2, responses from vaccine-hesitant participants included six categories of misinformation: medical, scientific, political, media, religious, and technological. Across both Study 1 and Study 2, six vaccine hesitancy themes were identified from the data: concerns about the vaccines' future effects, doubts about the vaccines' effectiveness, commercial profiteering, preference for natural immunity, personal freedom, and COVID-19 denial.The relationship between misinformation and vaccine hesitancy is complicated. Various types of misinformation exist, with each related to a specific type of vaccine hesitancy-related attitude. Personal freedom and COVID-19 denial are vaccine attitudes of particular interest, representing important yet understudied phenomena. Medical and scientific approaches may not be sufficient to combat misinformation based in religion, media, or politics; and public health officials may benefit from partnering with experts from those fields to address harmful misinformation that is driving COVID-19 vaccine hesitancy.

The premature death and degeneration of striatal neurons are typical hallmarks of HtrA2-inactivated motor neuron degeneration 2 (mnd2) mice. Although HtrA2 has been extensively studied in relation to the regulation of apoptosis using mnd2 mice, little is known about the other physiological functions of HtrA2. In this study, we found that the skin color of wild-type (WT) and mnd2 mice was black and pink on postnatal day 32. Using histological and molecular assays (i.e., assessing the activation of MAPK and expression patterns of PCNA), we demonstrated that this differential skin color change is consistent with the delay in the telogen - to - anagen phase of the hair cycle in mnd2 mice. We also examined adipocytes in the subcutaneous skin layer, finding that HtrA2 inactivation leads to the growth retardation of adipocytes, thereby delaying the hair cycle of mnd2 mice. Collectively, these findings show for the first time that HtrA2 plays an essential role in regulating the adipogenesis-associated hair cycle.

Background/Aims: Women with rheumatoid arthritis (RA) are often diagnosed with the disease during their reproductive years; however, its incidence and prevalence among women of childbearing age have not been studied. The objective of this study was to estimate the incidence and prevalence of seropositive rheumatoid arthritis (SPRA) among Korean women of childbearing age.Methods: Women aged 20 to 44 years with SPRA were identified from National Health Insurance Service-National Health Information Database (2009 to 2016). SPRA was defined by International Classification of Diseases, 10th revision code, M05. Incidence and prevalence were calculated per 100,000 person-years and stratified by year and age.Results: The average incidence and prevalence of SPRA from 2011 to 2016 among women of childbearing age was 24.1/100,000 person-years (95% confidence interval [CI], 23.7 to 24.5) and 105.2/100,000 person-years (95% CI, 100.9 to 109.5), respectively. The incidence increased annually from 21.0/100,000 person-years (95% CI, 20.1 to 21.9) in 2009 to 28.4 person-years (95% CI, 27.3 to 29.5) in 2016. Similarly, the prevalence increased annually from 95.7/100,000 person-years (95% CI, 93.7 to 97.6) in 2009 to 111.0 person-years (95% CI, 108.9 to 113.2) in 2015, with a slight decrease in 2016 (110.4 person-years; 95% CI, 108.2 to 112.6). The incidence and prevalence of SPRA increased with advancing age. The peak age for both incidence and prevalence of SPRA among women of childbearing age was 40 to 44 years.Conclusions: The risk of SPRA is high in women during their childbearing years; this population bears a significant disease burden. This calls for special attention to this particular population group to reduce the risk and burden of this disease.

Although the proportion of patients with chronic respiratory failure requiring home mechanical ventilation (HMV) is increasing, hospital readmissions in these patients are also increasing.We investigated the factors for early readmission in patients receiving HMV.We retrospectively analyzed the data of adult patients readmitted to the hospital within a year who first received HMV and were discharged from the Asan Medical Center between March 2014 and February 2019. We compared the clinical characteristics at discharge before readmission between the early (readmission within 30 days) and late readmission groups (readmission between day 31 and 1 year) and investigated the clinical characteristics and outcomes at readmission.Of the 116 patients identified, 36.2% had been readmitted early. The patients who received invasive HMV had a higher rate of early readmission than those who received non-invasive HMV. Pneumonia was the most common reason of readmission in the two groups. The rate of aspiration was significantly higher in the early readmission group (28.6% vs. 8.1%; P = .003). In multivariate logistic regression analysis, nasogastric tube feeding, sequelae of pneumonia or acute respiratory distress syndrome, and central nervous system disorders as causes for HMV were significantly associated with early readmission.Feeding methods and causes for HMV were associated with early readmission. Educating caregivers on respiratory care (suction and feeding methods) is important for preventing early readmission.

Aggregation and misfolding of α-Synuclein (α-Syn), a causative agent for Parkinson's disease (PD), and oxidative stress are tightly implicated in the pathogenesis of PD. Although more than 20 genes including HtrA2 have been identified as causative genes for PD, the molecular mechanisms underlying the pathophysiological functions between HtrA2 and α-Syn in the pathogenesis of PD remain unclear. This study shows that HtrA2 serine protease selectively recognizes and interacts with the NAC region of α-Syn. Interestingly, we found that HtrA2 causes proteolysis of α-Syn to prevent mitochondrial accumulation of α-Syn, thereby inhibiting the production of reactive oxygen species (ROS) in the mitochondria. We have further demonstrated that HtrA2 knockdown promotes α-Syn-mediated mitochondrial ROS production, thereby activating microglial cells. This study is the first to demonstrate that the HtrA2/α-Syn cellular partner may play a crucial role in the pathogenesis of PD and provide new insights into the pathological processes and effective therapeutic strategies for PD.

This study aimed to evaluate the indoor air quality differences at 19 indoor play centers of cafés and play areas in Gyeonggi-do where were 430 m2 or larger. We examined concentrations of formaldehyde (HCHO), volatile organic compounds (VOC), particulate matter, and total airborne bacteria, and how their distributions varied with the number of visitors at the places. On weekdays, there were no statistically significant differences in mean indoor air pollutant concentrations between the cafés and play areas at 95% confidence intervals. However, significant differences were observed on weekends when the number of visitors increased. HCHO concentrations increased up to 159%, and VOC concentrations increased up to 210%. A higher increase rate of HCHO occurred at the cafés compared to the play areas since cooking operations were performed under natural ventilation. The PM10 concentration increased by approximately 33.2%, with an increase of 49.2% in the play areas and a 18.3% increase in the cafés on weekends. PM2.5 concentration particularly increased during weekends in the cafés and play areas by 113% and 63.6%, respectively. During cooking operations, the concentration of gaseous and particulate pollution increased more in the air pollutant concentration of cafés, and the overall bacterial concentration increased during weekends due to higher numbers of visitors. Therefore, indoor play centers with cooking operations require adequate air quality management to mitigate the indoor pollution.

Background/Aims: We aimed to estimate the prevalence of comorbidities and medication use in Korean women with rheumatic diseases (RDs) during their childbearing years.Methods: We included women aged 20 to 44 years with seropositive rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), and ankylosing spondylitis (AS) (n = 41,547) and age-matched women without seropositive RA, SLE, and AS (n = 208,941) from the National Health Insurance Service-National Health Information Database (2009 to 2016). The prevalence of hypertension (HTN), hyperlipidemia (HLD), diabetes mellitus (DM), and cancer and the use of nonsteroidal anti-inflammatory drugs (NSAIDs), corticosteroids (CSs), and disease-modifying anti-rheumatic drugs (DMARDs) were estimated.Results: Women of childbearing age with RDs were more likely to have at least one of the measured comorbidities than the controls (odds ratio [OR], 3.0; 95% confidence interval [CI], 2.9 to 3.1). The OR (95% CI) was 2.9 (2.8 to 3.0) for HTN, 2.8 (2.7 to 2.9) for HLD, 1.4 (1.4 to 1.5) for DM, and 1.3 (1.3 to 1.4) for cancer. The SLE group had the highest prevalence and odds of all four measured comorbidities. Almost all (97.9%) women of childbearing age with RDs were taking RD-related medications (NSAIDs, 81.6%; CSs, 77.8%; DMARDs, 87.3%). The RD group was 13.8 times more likely to take NSAIDs and 68.2 times more likely to take CSs than the controls. Use of NSAIDs was more prevalent in RA and AS than SLE, whereas use of CSs and DMARDs was more prevalent in RA and SLE than AS.Conclusions: Korean women with RDs have a greater burden of comorbidities and medication use during their childbearing years than women without RDs of the same age.

Multipass membrane proteins play numerous roles in biology and include receptors, transporters, ion channels, and enzymes(1,2). How multipass proteins are co-translationally inserted and folded at the endoplasmic reticulum (ER) is not well understood(2). The prevailing model posits that each transmembrane domain (TMD) of a multipass protein successively passes into the lipid bilayer through a front-side lateral gate of the Sec61 protein translocation channel(3–9). The PAT complex, an intramembrane chaperone comprising Asterix and CCDC47, engages early TMDs of multipass proteins to promote their biogenesis by an unknown mechanism(10). Here, biochemical and structural analysis of intermediates during multipass protein biogenesis revealed that the nascent chain is not engaged with Sec61, which is occluded and latched closed by CCDC47. Instead, Asterix binds to and redirects the substrate behind Sec61, where the PAT complex contributes to a multipass translocon surrounding a semi-enclosed lipid-filled cavity(11). Detection of multiple TMDs in this cavity after their emergence from the ribosome suggests that multipass proteins insert and fold behind Sec61. Accordingly, biogenesis of several multipass proteins was unimpeded by inhibitors of the Sec61 lateral gate. These findings elucidate the mechanism of an intramembrane chaperone and suggest a new framework for multipass membrane protein biogenesis at the ER.

Hypermobile Ehlers-Danlos Syndrome (hEDS) and Hypermobility Spectrum Disorders (HSD) are associated with hypermobility, musculoskeletal pain, a decreased bone mineral density (BMD) and gastrointestinal (GI) complications. The role of GI symptoms and diet in BMD has not been established in this population. The GI complications can lead to an energy deficit due to lack of essential macronutrients. The primary objective of this study was to determine the severity of GI symptoms compared to body composition and BMD in individuals with hEDS/HSD. The secondary objective is to examine GI symptoms on energy balance, body composition and strength.This study was IRB approved. Eighteen female participants (aged 28.2 ± 4.9; BMI 22.5 ± 4.9) with a diagnosis of hEDS or HSD and 18 female healthy control participants (aged 28.1 ± 3.8; BMI 22.8 ±3.9) signed consent to participate. Participants were matched by sex, age, and BMI. The Gastrointestinal Symptom Rating Scale (GSRS) was used to investigate severity of GI symptoms. Dual X-ray absorptiometry was used to determine body composition (body fat%, lean body mass (LBM). BMD was measured by Z- scores of both femurs and lumbar spine. Resting metabolic rate (RMR) was measured using indirect calorimetry and strength was determined using a hand grip dynamometer.All hEDS/HSD participants reported GI symptoms. There was no difference in body composition between hEDS/HSD and controls. Participants with hEDS/HSD had lower BMD both femoral z scores (p=0.02,0.004) and spine z scores (p= 0.04). There was no difference in caloric intake between groups; yet both groups demonstrated caloric deficits. Additionally, hEDS/HSD consumed less protein and more carbohydrates (p=0.03, p=0.03). There were no differences in grip strength.This study identified that pre-menopausal women with hEDS/HSD presented with significant GI complications and lower BMD than age matched controls. The GI complications and the reduced protein intake long-term may have a lasting impact on bone health. This study found that the GSRS identified and quantified GI symptoms in persons with hEDS/HSD. Future studies are needed for the longitudinal effects of a caloric/protein deficit in this population and to help guide future preventive and nutritional treatment approaches in individuals with hEDS/HSD.

The objectives of this study were to evaluate the reliability of a strip design as a monitoring flap in buried flap and to investigate whether strip design of radial forearm free flap (RFFF) could affect donor site morbidity in East Asian.Patients with externalized flap in buried RFFF were consecutively included in this study. For cases with mucosal defect repair, a skin strip with a 1.5 cm width was proximally positioned to the primary flap along with the pedicle. Compared to a mucosal defect, a skin strip was distally positioned overlying the pedicle (near the wrist) when the flap was used for reinforcing the facial contour, reconstructing sacrificed facial nerve, or reanimating facial expression. The externalized flap formation was performed after completion of anastomoses of vessels. Monitoring results of flap failure using an externalized monitoring flap and additional morbidity of donor site were evaluated.Nine patients were included in this study. Although there were two cases of pharyngeal fistula due to mucosal necrosis of resection margin, transferred RFFF was viable in all cases. The externalized flap provided reliable monitoring for the buried RFFF without a case of necrosis even in two cases with a partial detachment of septocutaneous branches between the radial artery and the designed skin strip. There was no false - positive case. Therefore, the sensitivity and positive predictive value of the externalized monitoring flap were 100%. All defects of radial forearm caused by skin strip harvest were also primarily closed without an additional skin graft.A strip design for externalized monitoring flap in RFFF can facilitate an easier creation of externalized monitoring flap in cases with buried RFFF without additional morbidity at the donor site compared to a conventional techniques.

Purpose: This study aims to obtain scientific data for establishing female images based on results from an evaluation of brainwaves and emotions, after applying five different forms of eyeliners on big and small eyes.Methods: We comparatively analyzed coefficients of variations for the brainwaves and average preference indexes (API) of 60 males and females (age 21–29), after applying five different kinds of eyeliners on big and small eyes.Results: The brainwave responses in males and females were examined by applying five kinds of eyeliners to their big and small eyes. This showed that the activity of the γ-wave was entirely higher in people when they were stimulated by pin-up eyeliner (PU) and the α-wave was less reduced than other frequency bands. The stimulation by the forms of eyeliners, rather than by those of the eyes of the people, could be a factor influencing the brainwave responses. The active sites of the brains of the males and females were examined. The results showed that each stimulus caused prominent activity in the brain, especially in the prefrontal lobe (Fp1, Fp2, Fpz). Differences were found only in the active sites and the degree of activity among their responses to each stimulus, but their response trends were similar. The API responses by various forms of eyeliners indicated negative emotional responses only when the eyes of the people were stimulated by PU, while the other API responses indicated positive emotional responses.Conclusion: The results of the comparative analysis on differences in brainwave and emotional responses, by applying different forms of eyeliners to people with big and small eyes, are thought to suggest a basic direction for expressing facial images. Therefore, it would be possible to collect huge scientific data for establishing female images, if the correlation among physiological and emotional responses can be drawn by applying eyeliners to people with big and small eyes.