Adverse Effect of the Duration of Antibiotic Use Prior to Immune Checkpoint Inhibitors on the Overall Survival of Patients with Recurrent Gynecologic Malignancies.

PURPOSE: Antibiotic use preceding immune checkpoint inhibitor (ICI) treatment has been associated with a decreased efficacy of ICI in solid tumors. In this study, we evaluated the effect of antibiotic use before ICI therapy on oncological outcomes. METHODS: We examined patients with recurrent gynecologic malignancies at two academic institutions. The clinical data, including antibiotic use within 60 days of ICI initiation, type of antibiotics, reasons for antibiotic use, body mass index, tumor site, chemotherapy-free interval, prior history of radiotherapy, disease control rate (DCR), and overall survival (OS), were assessed. RESULTS: Of 215 patients, 22.9% (n = 47) received antibiotics before ICI treatment. The most common cancer was ovarian (52.1%, n = 112), followed by cervical (24.7%, n = 53) and endometrial (16.7%, n = 36). When we divided the cohort based on antibiotic use before ICIs, there were no significant differences in the DCR and baseline characteristics between the two groups. On multivariate analyses, the variables associated with poor OS were previous use of antibiotics for a cumulative duration of >14 days (HR 2.286, 95% CI 1.210-4.318; p = 0.011); Eastern Cooperative Oncology Group 2 or 3 (HR 4.677, 95% CI 2.497-8.762; p < 0.001); and chemotherapy-free interval of <6 months (HR 2.007, 95% CI 1.055-3.819; p = 0.034). CONCLUSION: Prior use of antibiotics for a cumulative duration of >14 days was associated with reduced survival in recurrent gynecologic malignancies.

Unpacking the Drivers of Dissatisfaction and Satisfaction in a Fitness Mobile Application.

This research investigates the factors influencing user satisfaction and dissatisfaction in fitness mobile applications. It employs Herzberg's two-factor model through text mining to classify Fitbit mobile app attributes into satisfiers and dissatisfiers. The Fitbit app was chosen due to its prevalence in the United States. The study analyzes 100,000 English reviews from the Fitbit app on the Google Play Store, categorizing attributes. It identifies three dissatisfying categories (functional, compatibility, paid services) and three satisfying categories (gratification, self-monitoring, self-regulation), comprising 25 sub-attributes. This classification offers in-depth insights into what drives user contentment or discontent with fitness apps. The findings contribute to the fitness app domain by applying text-mining and Herzberg's model. Researchers can build upon this foundation, and practitioners can use it to enhance app experiences. However, this research relies on user reviews, often lacking comprehensive explanations. This limitation may hinder a profound understanding of the underlying psychological aspects in user sentiments. Nonetheless, this study takes strides toward optimizing fitness apps for users and developers.

Different effects of menopausal hormone therapy on non-alcoholic fatty liver disease based on the route of estrogen administration.

The effects of menopausal hormone therapy (MHT) on non-alcoholic fatty liver disease (NAFLD) were compared based on the route of estrogen administration. The study included 368 postmenopausal women who received MHT for 12 months. Patients were divided into transdermal (n = 75) and oral (n = 293) groups based on the estrogen route. Changes in the prevalence of NAFLD were compared between the two groups before and after 12 months of MHT. In addition, differences in the progression of NAFLD after MHT based on the dose of estrogen and type of progestogen were evaluated in the oral group. After MHT, the prevalence of NAFLD decreased from 24 to 17.3% in the transdermal group but increased from 25.3 to 29.4% in the oral group. Little or no change was found in clinical characteristics and laboratory tests in the transdermal group during MHT. However, serum levels of total cholesterol and low-density lipoprotein cholesterol decreased and triglycerides and high-density lipoprotein cholesterol increased significantly in the oral group. Furthermore, changes in the prevalence of NAFLD were not significantly different based on the dose of estrogen or type of progestogen. Our findings indicate that transdermal estrogen can be beneficial in terms of NAFLD progression.

How Can Restaurant Companies Effectively Deliver CSR Efforts to Consumers on Social Media?

This study emphasized the source credibility effect on consumers' responses to restaurant companies' CSR efforts on social media. Based on the source credibility brand development process (i.e., brand trust, brand affect, and brand engagement), this study employed an online survey-based experiment and revealed the meaningful associations among types of CSR posters (a restaurant brand vs. a nonprofit organization), brand trust, brand affect, and brand engagement. The empirical results indicated that the nonprofit organization has higher significant effects on brand trust and brand affect than those of the restaurant brand. Additionally, in the case of the nonprofit organization, the effects of brand trust and brand affect on brand engagement were significantly stronger than that of the restaurant brand. Based on the empirical findings, this study provided several theoretical and managerial implications for restaurant companies' CSR communication on social media.

First female Korean child with Coffin-Lowry syndrome: a novel variant in RPS6KA3 diagnosed by exome sequencing and a literature review.

Coffin-Lowry syndrome (CLS, OMIM # 303600) is a rare X-linked disorder caused by mutations in RPS6KA3. CLS is characterized by facial dysmorphism, digit abnormalities, developmental delays, growth retardation, and progressive skeletal changes in male patients. Females with CLS are variably affected, complicating diagnosis. Here, we describe the clinical and molecular findings in a female Korean child with CLS and review the associated literature. A 5-year-old girl presented with short stature and developmental delays. She had a coarse facial appearance characterized by a prominent forehead, hypertelorism, thick lips, and hypodontia. She also had puffy tapering fingers and pectus excavatum. We performed exome sequencing and identified a novel, likely pathogenic, heterozygous variant, c.326_338delinsCTCGAGAC (p.Val109Alafs*10), in RPS6KA3 (NM_004586.2). This is the first Korean female genetically diagnosed with CLS. In contrast to the delayed bone age reported in previous studies, our patient showed advanced bone age and central precocious puberty. CLS should be considered as a differential diagnosis of short stature, tapering fingers, and developmental delay. We suggest that molecular techniques can be a useful tool for diagnosis of rare disorders such as CLS because such conditions are not simple, and the associated spectrum of phenotypes can vary.

Health and weight attitudes of university recreation center leaders.

Objective: Emerging research suggests weight-neutral approaches to health promotion are effective in supporting overall health, but they have been minimally adopted within physical activity (PA) contexts. This is concerning as research shows PA-related professionals can perpetuate weight stigma, which can disrupt PA participation and enjoyment. Thus, the purpose of this study was to examine university recreation center (URC) leaders' attitudes toward health and weight. Participants and methods: One-hundred forty-one URC leaders completed the online Health and Weight Attitudes Scale. Results: Women and those who wanted to maintain weight had more positive attitudes toward not dieting than men (F (1,136)=5.090, p = 0.026, ηp2 = 0.036) and those who wanted to lose weight (p = 0.015). Participants' open-ended responses showed they held several misconceptions about the health and weight relationship and about weight-neutral eating and PA messaging. Conclusion: Educating PA professionals on weight-neutral approaches could benefit effective and inclusive PA and health promotion in URCs.

Does CEO tenure moderate the link between corporate social responsibility and business performance in small- and medium-sized enterprises?

This study investigates the effect of CSR activities on business performance of small- and medium-sized enterprises (SMEs) in South Korea setting. Based on upper echelons theory and stakeholder theory, the study further examines CEO tenure as a potential moderator between CSR activities and business performance. The study considers four dimensions of CSR (economic, legal, ethical, and philanthropic) and two types of business performance (financial and non-financial). To test the moderating effect of CEO tenure, we divided the sample into two groups: companies with short-term tenured CEOs and long-term tenured CEOs. The data were collected from 443 CEOs of SMEs in South Korea. We used a multi-group analysis with SmartPLS 4. The study finds that CEO tenure moderates the relationship between dimensions of CSR and business performance. More specifically, the study finds that CEOs in early-stage tenure focus on philanthropic activities to drive financial performance, while their counterparts focus on economic/legal dimension. CEOs, regardless of the length of tenure, consider the philanthropic dimension helpful for improving both financial and non-financial performance. This study expands prior research by examining the relationship between CSR and business performance in SMEs, considering the impact of the CEO tenure. The findings of this study make contributions to the literature by demonstrating that CEO tenure is an important factor in linking CSR to business performance. This research also adds evidence to the CSR literature that economic and legal dimensions are considered mandatory responsibilities, and CEOs of SMEs view them as interconnected. For practical implications, this study identifies different predictors of financial performance for companies with short-term vs. long-term CEO tenure. Short-term CEOs focus on philanthropy to improve financial performance, and both long- and short-term CEOs believe that philanthropy affects the company's financial and non-financial performance.

Development and performance evaluation of an artificial intelligence algorithm using cell-free DNA fragment distance for non-invasive prenatal testing (aiD-NIPT).

With advances in next-generation sequencing technology, non-invasive prenatal testing (NIPT) has been widely implemented to detect fetal aneuploidies, including trisomy 21, 18, and 13 (T21, T18, and T13). Most NIPT methods use cell-free DNA (cfDNA) fragment count (FC) in maternal blood. In this study, we developed a novel NIPT method using cfDNA fragment distance (FD) and convolutional neural network-based artificial intelligence algorithm (aiD-NIPT). Four types of aiD-NIPT algorithm (mean, median, interquartile range, and its ensemble) were developed using 2,215 samples. In an analysis of 17,678 clinical samples, all algorithms showed >99.40% accuracy for T21/T18/T13, and the ensemble algorithm showed the best performance (sensitivity: 99.07%, positive predictive value (PPV): 88.43%); the FC-based conventional Z-score and normalized chromosomal value showed 98.15% sensitivity, with 40.77% and 36.81% PPV, respectively. In conclusion, FD-based aiD-NIPT was successfully developed, and it showed better performance than FC-based NIPT methods.

Investigating the Effect of Compassion Fade in Volunteer Tourism.

This study investigated the relationship between the type of volunteer tourism (human vs. flora vs. fauna) and the type of message (individual with no statistic vs. individual with small statistic vs. individual with large statistic) and potential tourists' attitudes towards volunteer tourism and their intention to donate their time. To do so, this study conducted a between-subject 3 × 3 factorial design online experiment, where the influences of compassion fade on attitudes and behavioral intention to donate time for volunteer tourism, along with the impacts of positive affect, emotional involvement, and credibility, were examined. The results of the current study revealed that type of volunteer tourism and type of message do not affect attitude towards volunteer tourism and attitude towards the ad. Further analysis indicated that, among all three mediating variables, only positive affect mediated the relationship between type of volunteer tourism and attitude towards volunteer tourism, and all other hypotheses were not statistically significant. Moreover, the results indicated that there is a positive relationship between perceived ad credibility and attitude towards the ad, and also between perceived ad credibility and attitude towards volunteer tourism. The implications of these results are discussed based on the empirical findings.

Development and Evaluation of AccuPower COVID-19 Multiplex Real-Time RT-PCR Kit and AccuPower SARS-CoV-2 Multiplex Real-Time RT-PCR Kit for SARS-CoV-2 Detection in Sputum, NPS/OPS, Saliva and Pooled Samples.

Rapid and accurate detection of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is essential for the successful control of the current global COVID-19 pandemic. The real-time reverse transcription polymerase chain reaction (Real-time RT-PCR) is the most widely used detection technique. This research describes the development of two novel multiplex real-time RT-PCR kits, AccuPower® COVID-19 Multiplex Real-Time RT-PCR Kit (NCVM) specifically designed for use with the ExiStation™48 system (comprised of ExiPrep™48 Dx and Exicycler™96 by BIONEER, Korea) for sample RNA extraction and PCR detection, and AccuPower® SARS-CoV-2 Multiplex Real-Time RT-PCR Kit (SCVM) designed to be compatible with manufacturers' on-market PCR instruments. The limit of detection (LoD) of NCVM was 120 copies/mL and the LoD of the SCVM was 2 copies/µL for both the Pan-sarbecovirus gene and the SARS-CoV-2 gene. The AccuPower® kits demonstrated high precision with no cross reactivity to other respiratory-related microorganisms. The clinical performance of AccuPower® kits was evaluated using the following clinical samples: sputum and nasopharyngeal/oropharyngeal swab (NPS/OPS) samples. Overall agreement of the AccuPower® kits with a Food and Drug Administration (FDA) approved emergency use authorized commercial kit (STANDARD™ M nCoV Real-Time Detection kit, SD BIOSENSOR, Korea) was above 95% (Cohen's kappa coefficient ≥ 0.95), with a sensitivity of over 95%. The NPS/OPS specimen pooling experiment was conducted to verify the usability of AccuPower® kits on pooled samples and the results showed greater than 90% agreement with individual NPS/OPS samples. The clinical performance of AccuPower® kits with saliva samples was also compared with NPS/OPS samples and demonstrated over 95% agreement (Cohen's kappa coefficient > 0.95). This study shows the BIONEER NCVM and SCVM assays are comparable with the current standard confirmation assay and are suitable for effective clinical management and control of SARS-CoV-2.

Wilson disease diagnosed incidentally by targeted gene panel sequencing in a Korean boy with severe obesity.

Wilson disease (WD) is a relatively common genetic hepatic disease in children and is characterized by excessive copper accumulation, predominantly in the liver and brain. It is an autosomal recessive disease caused by an ATP7B mutation that causes brain degeneration and is potentially fatal if diagnosed late or untreated. In the early phase of WD, its initial presentation may include mild hepatic involvement. WD may be overlooked as a cause of liver disease due to severe obesity but should not be excluded from differential diagnosis. We report a case of WD with severe obesity and fatty liver diagnosed in the early phase by targeted gene panel sequencing and review the endocrine problems associated with WD. Early suspicion of WD is important for good prognosis.

Hypertriglyceridemia with acute pancreatitis in a 14-year-old girl with diabetic ketoacidosis.

Diabetic ketoacidosis (DKA) is a medically fatal condition in poorly controlled hyperglycemia or newly diagnosed diabetes mellitus. Severe hypertriglyceridemia (HTG) is an uncommon complication of DKA and can be associated with acute pancreatitis (AP). We present the clinical manifestations, laboratory findings, and management of AP associated with HTG in a 14-year-old girl with DKA. The patient, with a 7-year history of type 2 diabetes presented with epigastric pain, 1 month after stopping insulin injection. DKA, severe HTG, and AP were diagnosed based on the laboratory and imaging tests. She recovered from DKA after conventional treatment for DKA, and her triglyceride (TG) level was reduced from 10,867 mg/dL to the normal range after 7 days of admission without antilipid medication. Given that her C-peptide level was not too low and considering her negative diabetes-related antibodies and high TG level, targeted gene panel sequencing was performed on the genes associated with diabetes and HTG. We identified a heterozygous mutation, c.4607C>T (p. Ala1537Val), in ABCC8 related to maturityonset diabetes of the young (MODY) 12. To our knowledge, this is the first reported case of HTG-induced AP with DKA in a patient with MODY. In addition, we reviewed the literature for pediatric cases of HTG with DKA. In patients with DKA, timely awareness of severe HTG related to insulin deficiency is crucial for improving the consequences of AP. We recommend considering AP in all DKA patients presenting with severe HTG to ensure early and proper management.

A Case Report of Neglected Gossypiboma Causing Abdominal Pain for 20 Years Post-Cesarean Section.

Gossypiboma refers to a mass usually made of cotton (e.g., surgical gauze or sponge) that is accidentally left in a patient's body during surgery. We report the case of a 54-year-old multigravida menopausal woman who previously underwent cesarean section to deliver her second child. She was referred to our medical center after a 7 cm right ovarian mass with malignant potential was discovered. A diagnostic laparotomy was performed then confirmed the presence of a 10 cm gossypiboma attached to a metallic ring. This case is an alarming example highlighting the importance of adequate intraoperative counting of gauze and radiologic evaluation of chronic pelvic pain.

Genetic Analysis Using a Next Generation Sequencing-Based Gene Panel in Patients With Skeletal Dysplasia: A Single-Center Experience.

Skeletal dysplasia (SD), a heterogeneous disease group with rare incidence and various clinical manifestations, is associated with multiple causative genes. For clinicians, accurate diagnosis of SD is clinically and genetically difficult. The development of next-generation sequencing (NGS) has substantially aided in the genetic diagnosis of SD. In this study, we conducted a targeted NGS of 437 genes - included in the nosology of SD published in 2019 - in 31 patients with a suspected SD. The clinical and genetic diagnoses were confirmed in 16 out of the 31 patients, and the diagnostic yield was 51.9%. In these patients, 18 pathogenic variants were found in 13 genes (COL2A1, MYH3, COMP, MATN3, CTSK, EBP, CLCN7, COL1A2, EXT1, TGFBR1, SMAD3, FIG4, and ARID1B), of which, four were novel variants. The diagnosis rate was very high in patients with a suspected familial SD and with radiological evidence indicating clinical SD (11 out of 15, 73.3%). In patients with skeletal involvement and other clinical manifestations including dysmorphism or multiple congenital anomalies, and various degrees of developmental delay/intellectual disability, the diagnosis rate was low (5 out of 16, 31.2%) but rare syndromic SD could be diagnosed. In conclusion, NGS-based gene panel sequencing can be helpful in diagnosing SD which has clinical and genetic heterogeneity. To increase the diagnostic yield of suspected SD patients, it is important to categorize patients based on the clinical features, family history, and radiographic evidence.

Genetic Evaluation of Congenital Hypothyroidism with Gland in situ Using Targeted Exome Sequencing.

OBJECTIVE: To analyze the genetic causes of congenital hypothyroidism through the targeted exome sequencing of pediatric patients with congenital hypothyroidism with thyroid gland in situ. METHOD: The study population included 20 patients diagnosed with congenital hypothyroidism with thyroid gland in situ at the Pediatric Endocrinology Clinic of Pusan National University Hospital. Targeted exome sequencing was performed on eight causative genes, including thyroid stimulating hormone receptor (TSHR), mutation in which can cause hypothyroidism with a small or normal sized thyroid gland, and thyroglobulin (TG), thyroid peroxidase (TPO), dual oxidase 2 (DUOX2), dual oxidase maturation factor 2 (DUOXA2), iodotyrosine deiodinase (IYD), solute carrier family 26 member 4 (SLC26A4), and solute carrier family 5 member 5 (SLC5A5), mutations in which are known to cause thyroid dyshormonogenesis. RESULTS: Permanent, subclinical, and transient hypothyroidism were diagnosed in 15 (75%), three (15%), and two (10%) patients, respectively. Genetic mutations were identified in 16 patients (80% positivity rate). Targeted exome sequencing of eight genes identified 24 variants in these patients: 11 DUOX2 variants in eight patients; six TSHR variants in five patients; five TG variants in three patients; and two DUOXA2 variants in two patients. Of these 24 variants, 10 (41.6%) were novel. No variants were identified in TPO, IYD, SLC5A5, or SLC26A4. Two patients displayed triallelic (digenic) mutations (in TG and TSHR in one patient and DUOX2 and TSHR in the other). No variants were identified in three patients with permanent hypothyroidism and one patient with transient hypothyroidism. Genetic variations that could explain the congenital hypothyroidism phenotypes were identified in 12/15 cases (80%). CONCLUSIONS: Targeted exome sequencing identified the genetic causes of congenital hypothyroidism with thyroid gland in situ in 80% of the patients studied, with DUOX2 and TSHR mutations being the most common. As many of the identified variants were novel, additional studies on the genetic causes of congenital hypothyroidism are warranted.

A boy with Coffin-Siris syndrome with a novel frameshift mutation in ARID1B.

Coffin-Siris syndrome (OMIM #135900) is an autosomal dominant inherited disorder, characterized by dysmorphic features, congenital anomalies, and developmental delay. We report the clinical and molecular findings in a patient with Coffin-Siris syndrome. A 3-year-and-6-month-old boy presented with developmental delay, distinctive facial features, hypertrichosis, partial agenesis of the corpus callosum, fifth digit nail hypoplasia, congenital anomalies, and growth retardation. Targeted gene panel sequencing identified a novel heterozygous frameshift mutation c.2147_2148insAC in ARID1B which was predicted as a premature stop codon p. (Gln717Argfs*29). This is the second report of Coffin-Siris syndrome in Korea. Targeted gene panel sequencing can be used as an effective tool for the diagnosis of rare complex syndromes such as Coffin-Siris syndrome.

The First Korean Case of Baraitser-Winter Cerebro-Fronto-Facial Syndrome with a Novel Mutation in ACTB Diagnosed Via Targeted Gene Panel Sequencing and Literature Review.

Baraitser-Winter Cerebro-fronto-facial syndrome (BWCFF, OMIM #243310, #614583) is caused by a heterozygous gain-of-function mutation of ACTB and ACTG1 that encodes actin. The syndrome is characterized by striking facial features, structural brain abnormalities, ocular coloboma, hearing loss, cardiac defects, intellectual disabilities, short stature, and developmental delay. We report a two-year-old girl who had distinctive facial features, including hypertelorism, arched eyebrows, bilateral ptosis, short broad nose with a flat nasal tip, long philtrum, retrognathia, low-set ears, and a thin upper lip. In addition, she also exhibited short stature, pectus excavatum, developmental delay, brain malformation, and hearing loss. Targeted gene panel sequencing identified a de novo heterozygous missense variant c.826G>A (p.Glu276Lys) in ACTB This is the first Korean case of BWCFF with a novel mutation in ACTB.

Clinical characteristics and disease progression of retinitis pigmentosa associated with PDE6B mutations in Korean patients.

Due to the genotype-phenotype heterogeneity in retinitis pigmentosa (RP), molecular diagnoses and prediction of disease progression is difficult. This study aimed to report ocular and genetic data from Korean patients with PDE6B-associated RP (PDE6B-RP), and establish genotype-phenotype correlations to predict the clinical course. We retrospectively reviewed targeted next-generation sequencing or whole exome sequencing data for 305 patients with RP, and identified PDE6B-RP in 15 patients (median age, 40.0 years). Amongst these patients, ten previously reported PDE6B variants (c.1280G > A, c.1488del, c.1547T > C, c.1604T > A, c.1669C > T, c.1712C > T, c.2395C > T, c.2492C > T, c.592G > A, and c.815G > A) and one novel variant (c.712del) were identified. Thirteen patients (86.7%) experienced night blindness as the first symptom at a median age of 10.0 years. Median age at diagnosis was 21.0 years and median visual acuity (VA) was 0.20 LogMAR at the time of genetic analysis. Nonlinear mixed models were developed and analysis revealed that VA exponentially decreased over time, while optical coherence tomography parameters linearly decreased, and this was related with visual field constriction. A high proportion of patients with the c.1669C > T variant (7/9, 77.8%) had cystoid macular edema; despite this, patients with this variant did not show a higher rate of functional or structural progression. This study will help clinicians predict functional and structural progression in patients with PDE6B-RP.