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The Indian Borage plant (Plectranthus amboinicus) is a traditional medicinal ingredient in Indonesia, containing flavonoids, alkaloids, polyphenols, saponins, and essential oils. Therefore, this study aimed to determine the antibacterial activity of P. amboinicus leaves ethyl acetate fraction using the disc diffusion method and identify the composition with LC-MS. The antibacterial activity test was conducted with concentration variations of 15%, 20%, and 25% with Chloramphenicol 500 mg and 5% DMSO as a positive and negative control, respectively. The results showed that the ethyl acetate fraction at a concentration of 20% had the largest inhibition zone diameter, with an average of 30 mm. The LC-MS results identified 115 compounds, and the highest concentration values were found in kaempferol 3-(6”-caffeoylglucoside) and kaempferol 3-glucosyl-(1→2) galactosyl-(1→2)-glucoside, with a composition of 3.26109% and 3.26141%, respectively.

An increasing number of guests in hotels evaluate the quality by reading online reviews. A deeper analysis of the attitude and behavior of the visitors is conducted to understand the experiences of guests, considering the diverse backgrounds and needs. This study aims to analyze the selection process of family-friendly hotels by guests, using available TripAdvisor online reviews, as well as for hotel management to better understand the comments left by guests and create more organized plans and policies. A model is devised that integrates clustering and Multi-Criteria Decision-Making-VIKOR (MCDM-VIKOR) method to prioritize the attributes of hotels based on the significance within each cluster of guests. Data is collected from online reviews of guests in family-friendly hotels in Indonesia. The features used for ranking preferences are the numerical ratings assigned to four attributes on the platform. These four features included “location”, “cleanliness”, “service”, and “value”. The results showed that “cleanliness” evolved as the most critical factor in the majority of segments for selecting family-friendly hotels. To further comprehend the behavioral trends of guests and assist in decision-making, this study proposed a model capable of analyzing online reviews and ratings provided by customers.

Abstract Lyme disease is a tick-borne disease caused by bacteria of the genus Borrelia. The host factors that modulate susceptibility for Lyme disease have remained mostly unknown. Using epidemiological and genetic data from FinnGen and Estonian Biobank, we identify two previously known variants and an unknown common missense variant at the gene encoding for Secretoglobin family 1D member 2 (SCGB1D2) protein that increases the susceptibility for Lyme disease. Using live Borrelia burgdorferi (Bb) we find that recombinant reference SCGB1D2 protein inhibits the growth of Bb in vitro more efficiently than the recombinant protein with SCGB1D2 P53L deleterious missense variant. Finally, using an in vivo murine infection model we show that recombinant SCGB1D2 prevents infection by Borrelia in vivo. Together, these data suggest that SCGB1D2 is a host defense factor present in the skin, sweat, and other secretions which protects against Bb infection and opens an exciting therapeutic avenue for Lyme disease.

Abstract Nightmares are vivid, extended, and emotionally negative or negative dreams that awaken the dreamer. While sporadic nightmares and bad dreams are common and generally harmless, frequent nightmares often reflect underlying pathologies of emotional regulation. Indeed, insomnia, depression, anxiety, or alcohol use have been associated with nightmares in epidemiological and clinical studies. However, the connection between nightmares and their comorbidities are poorly understood. Our goal was to examine the genetic risk factors for nightmares and estimate correlation or causality between nightmares and comorbidities. We performed a genome-wide association study (GWAS) in 45,255 individuals using a questionnaire-based assessment on the frequency of nightmares during the past month and genome-wide genotyping data. While the GWAS did not reveal individual risk variants, heritability was estimated at 5%. In addition, the genetic correlation analysis showed a robust correlation (rg > 0.4) of nightmares with anxiety (rg = 0.671, p = 7.507e−06), depressive (rg = 0.562, p = 1.282e−07) and posttraumatic stress disorders (rg = 0.4083, p = 0.0152), and personality trait neuroticism (rg = 0.667, p = 4.516e−07). Furthermore, Mendelian randomization suggested causality from insomnia to nightmares (beta = 0.027, p = 0.0002). Our findings suggest that nightmares share genetic background with psychiatric traits and that insomnia may increase an individual’s liability to experience frequent nightmares. Given the significant correlations with psychiatric and psychological traits, it is essential to grow awareness of how nightmares affect health and disease and systematically collect information about nightmares, especially from clinical samples and larger cohorts.

Generative artificial intelligence (AI) can exhibit biases, compromise data privacy, misinterpret prompts that are adversarial attacks, and produce hallucinations. Despite the potential of generative AI for many applications in digital health, practitioners must understand these tools and their limitations. This scoping review pays particular attention to the challenges with generative AI technologies in medical settings and surveys potential solutions. Using PubMed, we identified a total of 120 articles published by March 2024, which reference and evaluate generative AI in medicine, from which we synthesized themes and suggestions for future work. After first discussing general background on generative AI, we focus on collecting and presenting 6 challenges key for digital health practitioners and specific measures that can be taken to mitigate these challenges. Overall, bias, privacy, hallucination, and regulatory compliance were frequently considered, while other concerns around generative AI, such as overreliance on text models, adversarial misprompting, and jailbreaking, are not commonly evaluated in the current literature.

China has a 9000-year-long history of cereal-based alcohol production, with the use of molds (filamentous fungi) likely being one of the earliest fermentation techniques. This method later developed into the uniquely East Asian qu (koji) starter compound, containing grains, molds, yeasts, and bacteria. Recent studies have revealed that this method was already widely applied during the Neolithic period. However, much less is known about its development during the early dynastic times, and our knowledge of this innovation has mainly relied on textual materials. Here, we present direct evidence, based on microbotanical, microbial, and chemical analyses, for the fermentation method of a 2300-year-old liquid preserved in a sealed bronze bottle unearthed in a Qin tomb at Yancun, Shaanxi. The results of this research suggest that this liquid is likely a fermented beverage made from wheat/barley, rice, Job’s tears, broomcorn millet, and pulses. The fermentation starter may have been a cereal-based qu, consisting of a wide range of microorganisms, including molds (Aspergillus and Monascus), yeasts, and bacteria. Our findings suggest that the tradition of selecting suitable grains and microbial communities for brewing alcohol, possibly with a maiqu starter (primarily wheat/barley-based qu), may have been well established more than two thousand years ago.

Quabodepistat [(5-{[(3R,4R)-1-(4-chloro-2,6-difluorophenyl)-3,4-dihydroxypiperidin-4-yl]methoxy}-8-fluoro-3,4-dihydroquinolin-2(1H)-one); C21H20ClF3N2O4] and 2,5-dihydroxybenzoic acid (2,5DHBA; C7H6O4) were successfully co-crystallized. Given the small size of the crystals (1 × 0.2 × 0.2 µm) the structure was solved via microcrystal electron diffraction (MicroED). The C—O and C=O bond-length ratio of the carboxylic group in 2,5DHBA is 1.08 (1.34 Å/1.24 Å), suggesting that 2,5DHBA remains protonated. Therefore, the material is a co-crystal rather than a salt. The amide group of quabodepistat participates in a cyclic hydrogen bond with the carboxylic group of the 2,5DHBA. Additional hydrogen bonds involving the quabodepistat amide and hydroxyl groups result in a three-dimensional network.

Autosomal recessive limb-girdle muscular dystrophy 21 (LGMDR21) is caused by pathogenic variants in protein O-glucosyltransferase 1 (POGLUT1), which is responsible for O-glucosylation of specific epidermal growth factor (EGF) repeats found in ∼50 mammalian proteins, including Notch receptors. Previous data from patient biopsies indicated that impaired Notch signaling, reduction of muscle stem cells, and accelerated differentiation are probably involved in disease etiopathology. Using patient induced pluripotent stem cells (iPSCs), their corrected isotypes, and control iPSCs, gene expression profiling indicated dysregulation of POGLUT1, NOTCH, muscle development, extracellular matrix (ECM), cell adhesion, and migration as involved pathways. They also exhibited reduced in vitro POGLUT1 enzymatic activity and NOTCH signaling as well as defective myogenesis, proliferation, migration and differentiation. Furthermore, in vivo studies demonstrated significant reductions in engraftment, muscle stem cell formation, PAX7 expression, and maintenance, along with an increased percentage of mislocalized PAX7+ cells in the interstitial space. Gene correction in patient iPSCs using CRISPR-Cas9 nickase led to the rescue of the main in vitro and in vivo phenotypes. These results demonstrate the efficacy of iPSCs and gene correction in disease modeling and rescue of the phenotypes and provide evidence of the involvement of muscle stem cell niche localization, PAX7 expression, and cell migration as possible mechanisms in LGMDR21.

Abstract Narcolepsy type 1 (NT1) is caused by a loss of hypocretin/orexin transmission. Risk factors include pandemic 2009 H1N1 influenza A infection and immunization with Pandemrix®. Here, we dissect disease mechanisms and interactions with environmental triggers in a multi-ethnic sample of 6,073 cases and 84,856 controls. We fine-mapped GWAS signals within HLA (DQ0602, DQB1*03:01 and DPB1*04:02) and discovered seven novel associations (CD207, NAB1, IKZF4-ERBB3, CTSC, DENND1B, SIRPG, PRF1). Significant signals at TRA and DQB1*06:02 loci were found in 245 vaccination-related cases, who also shared polygenic risk. T cell receptor associations in NT1 modulated TRAJ*24, TRAJ*28 and TRBV*4-2 chain-usage. Partitioned heritability and immune cell enrichment analyses found genetic signals to be driven by dendritic and helper T cells. Lastly comorbidity analysis using data from FinnGen, suggests shared effects between NT1 and other autoimmune diseases. NT1 genetic variants shape autoimmunity and response to environmental triggers, including influenza A infection and immunization with Pandemrix®.

Polygenic risk scores (PRSs) estimate genetic liability for diseases and traits. However, the portability of PRSs in sleep traits has remained elusive. We generated PRSs for self-reported insomnia, chronotype and sleep duration using summary data from genome-wide association studies (GWASs) performed in 350,000 to 697,000 European-ancestry individuals. We then projected the scores in two independent Finnish population cohorts (N = 33,493) and tested whether the PRSs were associated with their respective sleep traits. We observed that all the generated PRSs were associated with their corresponding traits (p < 0.05 in all cases). Furthermore, we found that there was a 22.2 min difference in reported sleep between the 5% tails of the PRS for sleep duration (p < 0.001). Our findings indicate that sleep-related PRSs show portability across cohorts. The findings also demonstrate that sleep measures using PRSs for sleep behaviors may provide useful instruments for testing disease and trait associations in cohorts where direct sleep parameters have not yet been measured.

Hotel management uses customers' online reviews to uncover the most essential criteria for hotel selection to support sustainable tourism development and strengthen their marketing strategy as well as decision-making. This study implemented the Multi-Criteria Decision-Making (MCDM) to identify customers’ satisfaction and preferences. Data were collected from online reviews on eight hotels in Ubud, Bali Islands, submitted on TripAdvisor. The findings demonstrate that customers have varying levels of satisfaction when it comes to dissimilar preferences. Five major criteria influence their choices, namely price, cleanliness, location, facility, and food. The result of this study will help hotel management to set priority instructions for improving the corresponding hotel features.

Notch signaling is known to control neuroendocrine fate in the lungs. Shue and colleagues further identify the REST and YAP transcriptional regulators as key components of the Notch signaling pathway in the control of the neuroendocrine cell fate in lung development, lung injury response, and small-cell lung cancer.

Abstract In computer science, clustering is a technique for grouping data. Ising machines can solve distance-based clustering problems described by quadratic unconstrained binary optimization (QUBO) formulations. A typical simple method using an Ising machine makes each cluster size equal and is not suitable for clustering unevenly distributed data. We propose a new clustering method that provides better performance than the simple method, especially for unevenly distributed data. The proposed method is a hybrid algorithm including an iterative process that comprises solving a discrete optimization problem with an Ising machine and calculating parameters with a general-purpose computer. To minimize the communication overhead between the Ising machine and the general-purpose computer, we employed a low-latency Ising machine implementing the simulated bifurcation algorithm with a field-programmable gate array attached to a local server. The proposed method results in clustering 200 unevenly distributed data points with a clustering score 18% higher than that of the simple method. The discrete optimization with 2000 variables is performed 100 times per iteration, and the overhead time is reduced to approximately 20% of the total execution time. These results suggest that hybrid algorithms using Ising machines can efficiently solve practical optimization problems.

Pleiotropy and genetic correlation are widespread features in genome-wide association studies (GWAS), but they are often difficult to interpret at the molecular level. Here, we perform GWAS of 16 metabolites clustered at the intersection of amino acid catabolism, glycolysis, and ketone body metabolism in a subset of UK Biobank. We utilize the well-documented biochemistry jointly impacting these metabolites to analyze pleiotropic effects in the context of their pathways. Among the 213 lead GWAS hits, we find a strong enrichment for genes encoding pathway-relevant enzymes and transporters. We demonstrate that the effect directions of variants acting on biology between metabolite pairs often contrast with those of upstream or downstream variants as well as the polygenic background. Thus, we find that these outlier variants often reflect biology local to the traits. Finally, we explore the implications for interpreting disease GWAS, underscoring the potential of unifying biochemistry with dense metabolomics data to understand the molecular basis of pleiotropy in complex traits and diseases.

Pooled nucleic acid amplification tests for severe acute respiratory syndrome coronavirus 2 could increase availability of testing at decreased cost. However, the effect of dilution on analytical sensitivity through sample pooling has not been well characterized. We tested 1,648 prospectively pooled specimens by using 3 nucleic acid amplification tests for severe acute respiratory syndrome coronavirus 2: a laboratory-developed real-time reverse transcription PCR targeting the envelope gene, and 2 commercially available Panther System assays targeting open reading frame 1ab. Positive percent agreement (PPA) of pooled versus individual testing ranged from 71.7% to 82.6% for pools of 8 and from 82.9% to 100.0% for pools of 4. We developed and validated an independent stochastic simulation model to estimate effects of dilution on PPA and efficiency of a 2-stage pooled real-time reverse transcription PCR testing algorithm. PPA was dependent on the proportion of tests with positive results, cycle threshold distribution, and assay limit of detection.

Mendelian randomization is a popular method to detect causal relationships between traits, but can be confounded by instances of horizontal pleiotropy. Here, the authors present a Mendelian randomization workflow which includes causal discovery analysis and filtering of genetic instruments based on their conditional independencies.

Abstract Background Factors affecting the safety of bronchoscopy in patients with malignant hematologic disorders have not been well described. We evaluated the safety of bronchoscopy and describe factors affecting its complication rate in such patients. Methods Between January 2009 and December 2018, 316 bronchoscopies in 282 patients with malignant hematologic disorders and pulmonary infiltrates were performed at our institution. The bronchoscopic procedure used and its complications were evaluated. Results The most common underlying disease was acute myeloid leukemia (134/282 patients, 47.5%). Platelet transfusion was performed the day before or the day of bronchoscopy in 42.4%, supplemental oxygen was administered before the procedure in 23.1%, and midazolam was used in 74.4%. Thirty-five bronchoscopies (11.1%) were complicated by hemoptysis and 7 patients developed pneumothorax, 4 of whom required thoracic drainage. Two patients (0.6%) were intubated within 48 h of the procedure and prolonged oxygen desaturation (> 48 h) occurred in 3.8%. Multivariate analysis showed that only use of midazolam significantly reduced the risk of prolonged oxygen desaturation (hazard ratio 0.28, 95% confidence interval 0.09–0.85, p = 0.03). Transbronchial lung biopsy significantly increased the risk of hemoptysis (hazard ratio 10.40, 95% confidence interval 4.18–25.90, p = 0.00), while use of midazolam significantly reduced the risk (hazard ratio 0.31, 95% confidence interval 0.14–0.73, p = 0.01). Conclusions Bronchoscopy is relatively safe in patients with malignant hematologic disorders. Caution and judicious use of sedatives may improve the patient’s procedural tolerance and lower complications.

The epigenetic landscape of esophageal squamous cell carcinoma (ESCC) at genome-wide high resolution is incompletely studied. Here, the authors performed an integrated multi-omics analysis of ESCC and non-tumor tissues to define the genome-wide methylome landscape and epigenetic alterations to uncover oncogenic drivers of ESCC.

Pola jejaring industri lurik tradisional merupakan suatu pola yang terbentuk berdasarkan aktivitas industri lurik tradisional yang dihubungkan dengan sistem transportasi, yang meliputi aktivitas pengadaan bahan baku, proses produksi hingga pemasaran. Aktivitas industri lurik tradisional berpengaruh terhadap keberlanjutan proses produksi tenun lurik tradisional di Desa Tlingsing. Desa Tlingsing pada tahun 2011 telah ditetapkan sebagai Desa Wisata tenun Tradisional sehingga pola jejaring yang terbentuk berdasarkan aktivitas industri juga akan berdampak dengan pengembangan Desa Wisata Tlingsing. Jumlah pengrajin lurik dan pengunjung desa wisata Tlingsing dari tahun 2011-2017 mengalami peningkatan. Penelitian ini bertujuan untuk mengetahui pengaruh pola jejaring industri lurik tradisional terhadap pengembangan desa wisata Tlingsing. Metode penelitian yang digunakan adalah analisis skoring dan analisis regresi linier berganda untuk mengetahui pengaruh pola jejaring industri lurik tradisional terhadap pengembangan desa wisata Tlingsing. Berdasarkan analisis regresi linier berganda didapatkan hasil tingkat pengaruh pola jejaring industri lurik tradisional terhadap pengembangan desa wisata Tlingsing dari pengaruh lemah – kuat yaitu (1) rumah makan, (2) dekat dengan jalan raya dan fasilitas transportasi, (3) toko cinderamata, (4) pusat informasi, (5) atraksi yang unik, (6) moda transportasi, (7) rambu jalan, (8) akomodasi, (9) ATM, dan (10) adanya masyarakat atau organisasi pengelola desa wisata.

Background: Employees of technology companies evaluate their experience through online reviews. Online reviews of companies from employees or former employees help job seeker to find out the weaknesses and strengths of the companies. The reviews can be used as an evaluation tool for each technology company to understand their employee’s perceptions. However, most information on online reviews is not well responded since some of the detailed information of the company is missing. Objective: This study aims to generate an Aspect-based Sentiment Analysis using user review data. The review data were then extracted and classified into five aspects: work balance, culture value, career opportunities, company benefit, and management. The output of this study is the aspect score from each company. Methods: This study suggests a method to analyze online reviews from employees in detail, so it can prevent the missing of specific information. The analysis was sequentially carried out in five stages. First, user review data were crawled from Glassdoor and stored in a database. Second, the raw data were processed in the data pre-processing stage to delete the incomplete data. Third, the words other than noun keyword were eliminated using Standford POS Tagger. Fourth, the noun keywords were then classified into each aspect. Finally, the aspect score was calculated based on the aspect-based sentiment analysis. Results: Result showed that the proposed method managed to turn raw review data into five aspects based on user perception. Conclusion: The study provides information for two parties, job seeker and the company. The analysis of the review could help the job seeker to decide which company that suits his need and ability. For the companies, it can be a great assistance because they will be more aware of their strengths and weaknesses. This study could possibly also provide ratings to the companies based on the aspects that have been determined.

ABSTRACT: This paper discusses the effectiveness of visual learning environment which is used to help students in university to study programming course. The visual learning environment which is used in this study is Greenfoot and Alice. The main goal of this article is to obtain the correlation between students‘ satisfaction level and their grades in studying programming course using visual learning environment tools. The participants were conducted on 110 students who took programming course during their first year. A survey was sent to students about their satisfaction level in learning programming course. Two-variable correlation analysis, significance test and descriptive analysis were conducted to find out the relationship between students' learning satisfaction level and their grades in programming course. This study discusses the student perspectives that are summarized in ten questions. There is a significant correlation between independent and dependent variables. The ? value is 2.09 which proves that the independent variable in the form of student's learning satisfaction level is useful to obtain better assessment of their grades. Based on their perspectives, it is found that visual learning environment tools have more significant influence in improving the students‘ grade than traditional learning method. Further research is needed to find out other impact factors. ABSTRAK: Makalah ini membincangkan keberkesanan persekitaran pembelajaran visual yang digunakan untuk membantu pelajar di universiti untuk mempelajari kursus pengaturcaraan. Persekitaran pembelajaran visual yang digunakan dalam kajian ini ialah Greenfoot dan Alice. Matlamat utama artikel ini adalah untuk mendapatkan korelasi antara tahap kepuasan pelajar dan gred mereka dalam mengkaji kursus pengaturcaraan menggunakan alat-alat persekitaran pembelajaran visual. Para peserta telah diadakan pada 110 orang pelajar yang mengambil kursus pengaturcaraan pada tahun pertama mereka. Satu tinjauan telah dihantar kepada pelajar tentang tahap kepuasan mereka dalam pembelajaran kursus pengaturcaraan. Analisis korelasi dua-pembolehubah, ujian penting dan analisis deskriptif telah dijalankan untuk mengetahui hubungan antara tahap kepuasan belajar pelajar dan gred mereka dalam kursus pengaturcaraan. Kajian ini membincangkan perspektif pelajar yang diringkaskan dalam sepuluh soalan. Terdapat korelasi yang signifikan antara pembolehubah bebas dan bergantung. Nilai ? ialah 2.09 yang membuktikan bahawa pemboleh ubah bebas dalam bentuk tahap kepuasan pembelajaran pelajar adalah berguna untuk mendapatkan penilaian yang lebih baik dari gred mereka. Berdasarkan perspektif mereka, didapati alat persekitaran pembelajaran visual mempunyai pengaruh yang lebih besar dalam meningkatkan gred pelajar daripada kaedah pembelajaran tradisional. Kajian lanjut diperlukan untuk mengetahui faktor-faktor kesan yang lain.

Abstract Background Pneumatosis intestinalis is a rare adverse event that occurs in patients with lung cancer, especially those undergoing treatment with epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKI). Osimertinib is the most recently approved EGFR-TKI, and its usage is increasing in clinical practice for lung cancer patients who have mutations in the EGFR gene. Case presentation A 74-year-old woman with clinical stage IV (T2aN2M1b) lung adenocarcinoma was determined to have EGFR gene mutations, namely a deletion in exon 19 and a point mutation (T790 M) in exon 20. Osimertinib was started as seventh-line therapy. Follow-up computed tomography on the 97th day after osimertinib administration incidentally demonstrated intra-mural air in the transverse colon, as well as intrahepatic portal vein gas. Pneumatosis intestinalis and portal vein gas improved by fasting and temporary interruption of osimertinib. Osimertinib was then restarted and continued without recurrence of pneumatosis intestinalis. Overall, following progression-free survival of 12.2 months, with an overall duration of administration of 19.4 months (581 days), osimertinib was continued during beyond-progressive disease status, until a few days before the patient died of lung cancer. Conclusions Pneumatosis intestinalis should be noted as an important adverse event that can occur with administration of osimertinib; thus far, such an event has never been reported. This was a valuable case in which osimertinib was successfully restarted after complete recovery from pneumatosis intestinalis, such that further extended administration of osimertinib was achieved.

Millions of enhancers are predicted, but their validation remains challenging. Here, the authors report genome-wide enhancer function quantification and high-resolution dissection for millions of accessible DNA fragments, revealing driver nucleotides and helping interpret non-coding disease variants.

Genome-wide association studies (GWAS) have been used to study the genetic basis of a wide variety of complex diseases and other traits. We describe UK Biobank GWAS results for three molecular traits—urate, IGF-1, and testosterone—with better-understood biology than most other complex traits. We find that many of the most significant hits are readily interpretable. We observe huge enrichment of associations near genes involved in the relevant biosynthesis, transport, or signaling pathways. We show how GWAS data illuminate the biology of each trait, including differences in testosterone regulation between females and males. At the same time, even these molecular traits are highly polygenic, with many thousands of variants spread across the genome contributing to trait variance. In summary, for these three molecular traits we identify strong enrichment of signal in putative core gene sets, even while most of the SNP-based heritability is driven by a massively polygenic background.

We present the case of an 80-year-old woman with Mendelson's syndrome complicated by bacterial aspiration pneumonia caused by consciousness loss followed by vomiting resulting from putamen bleeding. Her condition worsened rapidly to develop respiratory failure, within a few hours; thereafter, she was intubated. Streptococcus agalactiae and Klebsiella oxytoca were detected from the aspirated sputum sample culture. She was diagnosed with acute respiratory distress syndrome with Mendelson's syndrome complicated by bacterial aspiration pneumonia. Corticosteroid and antibiotic administration improved her condition and led to successful extubation; therefore, these treatment modalities were invaluable. We suggest the clinical considerations for the corticosteroid and antibiotic use in such cases.

Cancer and osteoporosis have high incidence rates in older populations. However, the treatment of osteoporosis among cancer patients has not been adequately described. Our purpose was to clarify the current practice patterns of osteoporosis treatment among cancer patients in an academic cancer center, and to analyze the efficacy of treatment interventions. Patient records from April 2009 to March 2018 were retrospectively reviewed, and the study included a total of 316 cancer patients with osteoporosis. After patients' data extraction, the patients were divided into two groups, with (n = 144) or without treatment (n = 172), and compared the outcomes of these groups to evaluate the medication effect. The primary outcome was new radiographic fragility fractures during the study period. The related factors associated with fracture injuries and the rate of adverse events, such as osteonecrosis in the jaw and atypical femoral fractures, were analyzed. The rate of treatment intervention was 45.6% among the patient groups. Among patients in the study group, breast cancer patients (n = 107) were mostly treated (n = 79, 73.8%) with oral bisphosphonate. A significant difference in new fracture rate was observed between the two groups (treatment group, 30.6%; non-treatment group, 54.7%), and the risk of fracture was 42% lower in the treatment group (hazard ratio, 0.58; 95% confidence interval, 0.39-0.86; p

Abstract IgG4‐related disease is an evolving entity of immune‐mediated origin. We report a case of IgG4‐related disease mimicking lung cancer with pleural dissemination. A 76‐year‐old male non‐smoker was admitted to our hospital because of chest X‐ray abnormality. Chest computed tomography scan showed a lung nodule measuring 26 × 14 mm with tiny nodules on the adjacent pleural surface. Wedge resection by video‐assisted thoracoscopic surgery (VATS) was performed to aid diagnosis. Pathological findings of the nodule consisted of lymphoid follicular hyperplasia with lymphoplasmacytic infiltrate, fibrosis, and obstructive vasculitis. Focal and scattered thickening of the pleura with lymphoplasmacytic infiltrate was also observed. The IgG4/IgG ratio in the most prominent area exceeded 80%. Thus, we made a diagnosis of IgG4‐related lung and pleural disease. To our knowledge, there has been no report of IgG4‐related lung disease mimicking lung cancer with pleural dissemination.

This study analyzes and extracts the TripAdvisor customers’ experiences from the user-generated data as the topic of interest from online review customers in TripAdvisor application. The aims of this study were to illustrate on how customers’ reviews on social media are able to be used as an evaluation and visual modeling tool. The online review customers are processed using sentiment analysis and text mining. Findings show that customers often review their experience where they have stayed based on their last stay period. The Decision Tree Algorithm is better to classify the sentiment analysis result than the Naïve Bayes Algorithm in the field of accuracy. However, in the field of precision and recall, Naïve Bayes Algorithm is often better than the Decision Tree Algorithm. The text mining results reveal that TripAdvisor customers tend to use words such as “night”, “pool”, and “time” in negative sentiments expressed after or during a stay.

Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) constitutes a group of blood vessel inflammation diseases of autoimmune origin. Myeloperoxidase (MPO) ANCA is closely related to ANCA associated AAV. The MPO-ANCA positive AAV patients have lung involvement at high rates; however, there are only a few reported cases with organizing pneumonia (OP). A 78-year-old man was presented to our hospital due to a fever of 38 °C despite a whole month of antibiotics treatment. Chest computed tomography image revealed restricted consolidations visible in the middle lobe of the right lung and the upper lobe of the left lung, which suggested an OP pattern. MPO-ANCA and urine occult blood tests were positive. Histopathological examination of the transbronchial biopsy revealed OP and mucus plug. Histological findings on renal biopsy showed necrotizing glomerulonephritis related to AAV. The patient was diagnosed with MPO-ANCA positive AAV and was treated with systemic corticosteroid therapy, from which he recovered rapidly. Thus, when diagnosing OP, the possibility of AAV should be considered by ordering patients’ serum ANCA and occult hematuria tests.

BackgroundLifestyle interventions to reduce body mass index (BMI) are critical public health strategies for type 2 diabetes prevention. While weight loss interventions have shown demonstrable benefit for high-risk and prediabetic individuals, we aimed to determine whether the same benefits apply to those at lower risk.Methods and findingsWe performed a multi-stratum Mendelian randomization study of the effect size of BMI on diabetes odds in 287,394 unrelated individuals of self-reported white British ancestry in the UK Biobank, who were recruited from across the United Kingdom from 2006 to 2010 when they were between the ages of 40 and 69 years. Individuals were stratified on the following diabetes risk factors: BMI, diabetes family history, and genome-wide diabetes polygenic risk score. The main outcome measure was the odds ratio of diabetes per 1-kg/m2 BMI reduction, in the full cohort and in each stratum. Diabetes prevalence increased sharply with BMI, family history of diabetes, and genetic risk. Conversely, predicted risk reduction from weight loss was strikingly similar across BMI and genetic risk categories. Weight loss was predicted to substantially reduce diabetes odds even among lower-risk individuals: for instance, a 1-kg/m2 BMI reduction was associated with a 1.37-fold reduction (95% CI 1.12-1.68) in diabetes odds among non-overweight individuals (BMI < 25 kg/m2) without a family history of diabetes, similar to that in obese individuals (BMI ≥ 30 kg/m2) with a family history (1.21-fold reduction, 95% CI 1.13-1.29). A key limitation of this analysis is that the BMI-altering DNA sequence polymorphisms it studies represent cumulative predisposition over an individual's entire lifetime, and may consequently incorrectly estimate the risk modification potential of weight loss interventions later in life.ConclusionsIn a population-scale cohort, lower BMI was consistently associated with reduced diabetes risk across BMI, family history, and genetic risk categories, suggesting all individuals can substantially reduce their diabetes risk through weight loss. Our results support the broad deployment of weight loss interventions to individuals at all levels of diabetes risk.

Abstract Background Pneumatosis intestinalis (PI) is a rare complication of chemotherapy, characterized by multiple gas accumulations within the bowel wall. Case presentation A 71-year-old woman with epidermal growth factor receptor (EGFR) mutation-positive lung adenocarcinoma was admitted to our hospital because of reduced consciousness. She was diagnosed as having leptomeningeal carcinomatosis (LM) using lumbar puncture. Because she could not swallow a tablet, erlotinib was administered via a feeding tube. Her state of consciousness gradually improved, but she experienced diarrhea several times a day. After 3 weeks of erlotinib therapy, PI occurred. Erlotinib was discontinued and PI was resolved after treatment with conservative therapies. Erlotinib was re-administrated and PI occurred again. After improvement of erlotinib-induced PI, gefitinib was administered by a feeding tube and the patient did not experience PI or diarrhea. The patient survived 8 months from the diagnosis of LM. Conclusion PI is one of the side effects of erlotinib, and consecutive therapies are useful for the treatment of PI. In this patient, gefitinib was successfully administered after erlotinib-induced PI.

Advancements in reprogramming somatic cells into induced pluripotent stem cells (iPSCs) have provided a strong framework for in vitro disease modeling, gene correction and stem cell-based regenerative medicine. In cases of skeletal muscle disorders, iPSCs can be used for the generation of skeletal muscle progenitors to study disease mechanisms, or implementation for the treatment of muscle disorders. We have recently developed an improved directed differentiation method for the derivation of skeletal myogenic progenitors from hiPSCs. This method allows for a short-term (2 weeks) and efficient skeletal myogenic induction (45–65% of the cells) in human pluripotent stem cells (ESCs/iPSCs) using small molecules to induce mesoderm and subsequently myotomal progenitors, without the need for any gene integration or modification. After initial differentiation, skeletal myogenic progenitors can be purified from unwanted cells using surface markers (CD10+CD24−). These myogenic progenitors have been extensively characterized using in vitro gene expression/differentiation profiling as well as in vivo engraftment studies in dystrophic (mdx) and muscle injury (VML) rodent models and have been proven to be able to engraft and form mature myofibers as well as seeding muscle stem cells. The current protocol describes a detailed, step-by-step guide for this method and outlines important experimental details and troubleshooting points for its application in any human pluripotent stem cells.

Several recent papers have reported strong signals of selection on European polygenic height scores. These analyses used height effect estimates from the GIANT consortium and replication studies. Here, we describe a new analysis based on the the UK Biobank (UKB), a large, independent dataset. We find that the signals of selection using UKB effect estimates are strongly attenuated or absent. We also provide evidence that previous analyses were confounded by population stratification. Therefore, the conclusion of strong polygenic adaptation now lacks support. Moreover, these discrepancies highlight (1) that methods for correcting for population stratification in GWAS may not always be sufficient for polygenic trait analyses, and (2) that claims of differences in polygenic scores between populations should be treated with caution until these issues are better understood.Editorial note: This article has been through an editorial process in which the authors decide how to respond to the issues raised during peer review. The Reviewing Editor's assessment is that all the issues have been addressed (see decision letter).