Miracle-dz/UniFAR-FTUs huggingface dataset:
Treatment with Anlotinib After Chemotherapy and EGFR-TKI Resistance in Lung Adenosquamous Carcinoma with Concurrent EGFR and PIK3CA Mutations: A Case Report and Literature Review

Abstract Concurrent mutations of epidermal growth factor receptor (EGFR) and phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA) in non-small cell lung cancer (NSCLC) are rare, and the presence of concurrent mutations may complicate treatment. Herein, we report a case of primary lung adenosquamous carcinoma with concurrent EGFR 21 (L858R) and PIK3CA (H1047R/E545K) mutations, and the results of a literature review to help management and treatment. A 49-year-old female was admitted our department for coughing and excessive sputum production for more than 1 month. Computed tomography (CT) of the chest identified a lesion, and a CT-guided needle biopsy was performed. Pathological examination and immunohistochemistry (IHC) staining confirmed a diagnosis of primary lung adenosquamous carcinoma. Amplification refractory mutation system-polymerase chain reaction (ARMS-PCR) gene sequencing demonstrated mutations in both EGFR 21 (L858R) and PIK3CA (H1047R/E545K) mutations in adenocarcinoma (AC) component. She was treated with pemetrexed plus platinum-based chemotherapy and an EGFR-tyrosine kinase inhibitor (TKI). Disease progression occurred with gefitinib or osimertinib as maintenance therapy. A repeat CT-guided needle biopsy was performed, and generation sequencing (NGS) revealed EGFR 21 (L858R) and PIK3CA (H1047R/E545K) mutations. Anlotinib monotherapy was then administered as the third-line treatment, and there was a PR. The patient is currently still receiving treatment and follow-up. To our knowledge, there is little evidence that anlotinib is beneficial when there are concurrent EGFR and PIK3CA mutations. PIK3CA mutations are associated with poor therapeutic effects and short survival time. Concurrent EGFR and PIK3CA mutations do not respond to EGFR-TKI treatment. Chemotherapy should be given in combination with a TKI and can prolong the progression-free survival (PFS) and overall survival (OS) of patients with lung cancer.
Correlation of Transferrin Saturation and Serum Ferritin with Bone Mass Density in Adult Transfusion Dependent Beta-Thalassemia Patients

Background The use of regular blood transfusions and iron chelation therapy to treat thalassemia has improved survival and increased the incidence of osteoporosis. Moreover, iron toxicity is one of the contributing factors that reduce bone mass density in adult transfusion-dependent beta-thalassemia patients. Therefore, this study aims to determine the proportion of low bone mass density in adult thalassemia patients and transferrin saturation, as well as serum ferritin, which correlates to the skeletal condition. Methods This is a cross-sectional study conducted in Thalassemia and Hematology Medical Oncology Clinics of Cipto Mangunkusumo Hospital in March 2016. The anthropometric data and hemoglobin levels were obtained before transfusion. Subsequently, the average ferritin levels, bone mineral density, and radiographic results were obtained. Results The percentage of adult thalassemia major and intermedia patients with low bone mass density was 68%. Also, there was a weak inverse correlation between bone mass density and transferrin saturation (r = −0.329, p = 0.01), while no correlation was shown between bone mass density and ferritin (r = −0.088, p = 0.504). The transferrin saturation cutoff point value used to distinguish the incidence of low and normal bone density in patients with transfusion-dependent beta-thalassemia was 89.5%. In addition, there was weak correlation between Singh index and bone mass density (r = 0.273, p = 0.038). Conclusion Among the transfusion-dependent beta-thalassemia patients, 68% had low bone mass density, which inversely correlated to transferrin saturation. Furthermore, the cutoff value of transferrin saturation to differentiate the incidence of low and normal bone density in thalassemia major compared to thalassemia intermedia was 89.5%. Singh Index correlates weakly with bone mass density and might be used to detect low bone mass density in remote healthcare facilities.
Platelet Aggregation Assays Do Not Reliably Diagnose Platelet Delta Granule Storage Pool Deficiency

Background Patients with platelet dysfunction disorders present with a variety of mucocutaneous bleeding symptoms including easy bruising, frequent epistaxis, bleeding gums upon tooth brushing and for women, heavy menstrual bleeding. Available laboratory assays to evaluate platelet function include the platelet function analyzer (PFA) and in larger centers with coagulation laboratories, light transmission platelet aggregometry (LTA) analyses. Both assays are known to have a number of limitations, especially in the diagnosis of platelet delta granule storage pool deficiency (δ-SPD). δ-SPD is an underdiagnosed condition caused by decreased numbers of platelet dense granules (DGs) and is best diagnosed by electron microscopy (EM). Patients with platelet δ-SPD have a decreased response to low levels of the agonist adenosine diphosphate (ADP) in the second wave of light transmittance with LTA or decreased ADP secretion by fluorescence lumiaggregometry. There are few reports that have evaluated patients with δ-SPD and their respective LTA results. One report published in 1987 described normal LTA assays in 23% of patients with δ-SPD; a more recent report described LTA as having the sensitivity to detect only about 52% of patients with δ-SPD. The purpose of our study was intended to review the LTA and EM results of patients suspected of having a platelet function disorder at our institution for comparison with previously published studies. Methods Our study included 344 patients who had been evaluated by both LTA and whole mount EM. Aggregometry utilized five agonists: ADP, epinephrine, collagen, arachidonic acid, and ristocetin. DGs were enumerated in 100 whole-mounted platelets to determine a mean number of dense granules per platelet (DGs/PL). Results Seventy-seven percent of our patients were found to have δ-SPD (264/344); 68% (179/264) of these subjects had an abnormal platelet LTA. Thirty-two percent (85/264) of our patients had normal LTA results but were found to have δ-SPD with a mean of 2.54 ± 0.15 DG/PL (normal = 4 - 6 DG/PL). Conclusion These data confirm previous reports suggesting the utilization of LTA alone in patients with histories of unexplained bleeding may miss the diagnosis of platelet δ-SPD. It is, therefore, prudent to assess platelet DG number by EM, especially if platelet LTA assessment is normal.
Association between non-culprit healed plaque and plaque progression in acute coronary syndrome patients: an optical coherence tomography study

BACKGROUND Healed plaques are frequently found in patients with acute coronary syndrome, but the prognostic value is debatable. This study investigated the clinical features of non-culprit healed plaques detected by optical coherence tomography (OCT) with the aim of predicting plaque progression of healed plaques. METHODS This study retrospectively analyzed 113 non-culprit lesions from 85 patients who underwent baseline OCT imaging and follow-up angiography from January 2015 to December 2019. Plaque progression predictors were assessed by multivariate analysis. RESULTS Among 113 non-culprit lesions, 27 healed plaques (23.9%) were identified. Patients with non-culprit healed plaques had prior antiplatelet therapy (65.0% vs. 33.8%, P = 0.019), hypertension (85.0% vs. 50.7%, P = 0.009), and dyslipidemia (70.0% vs. 41.5%, P = 0.04) which were more frequently than those without healed plaques. The thickness (r = 0.674, P < 0.001), arc ( r = 0.736, P < 0.001), and volume ( r = 0.541, P = 0.004) of healed plaque were correlated with minimum lumen diameter changes. At a mean follow-up of 11.5 months, the non-culprit healed plaques had a lower minimum lumen diameter (1.61 ± 0.46 mm vs. 1.91 ± 0.73 mm, P = 0.016), lower average lumen diameter (1.86 mm vs. 2.10 mm, P = 0.033), and a higher degree of diameter stenosis (41.4% ± 11.9% vs. 35.5% ± 13.1%, P = 0.031) when compared to baseline measurements. The plaque progression rate was higher in the healed plaque group (33.3% vs. 8.1%, P = 0.002), and multivariate analysis identified healed plaques [odds ratio (OR) = 8.49, 95% CI: 1.71−42.13] and lumen thrombus (OR = 10.69, 95% CI: 2.21−51.71) as predictors of subsequent lesion progression. CONCLUSIONS Healed plaques were a predictor for rapid plaque progression. The quantitative parameters of healed plaque showed a good agreement with plaque progression. Patients with healed plaque were associated with prior antiplatelet therapy and high level of low-density lipoprotein cholesterol. Bifurcation lesions might be the predilection sites of healed plaques.
The Influence of Gamification and Information Technology Identity on Postadoption Behaviors of Health and Fitness App Users: Empirical Study in the United States

Background The use of health and fitness apps has been on the rise to monitor personal fitness and health parameters. However, recent research discovered that many users discontinue using these apps after only a few months. Gamification has been suggested as a technique to increase users’ interactions with apps. Nevertheless, it is still not clear how gamification mechanisms encourage continued use and inspire user self-management. Objective The main objective of this study was to articulate how gamification mechanisms in studies of designing and using health and fitness apps can contribute to the realization of information technology (IT) identity and positive behavioral outcomes. The broader goal was to shed light on how gamification mechanisms will translate into positive use behaviors in the context of mobile health apps. Methods Data were collected from 364 users of health and fitness apps through an online survey to empirically examine the proposed model. Results Based on identity theories, this study suggests the fully mediating role of IT identity to describe how gamification elements can lead to continued intention to use health and fitness apps, and increase users’ tendency for information sharing through the apps. The findings indicate that perceived gamification can increase users’ IT identity. In turn, a higher IT identity would encourage users to continue using the apps and share more personal health information with others through the apps. Conclusions The results of this study can have practical implications for app designers to use gamification elements to increase users’ dependency, relatedness, and emotional energy associated with health apps. Moreover, the findings can have theoretical contributions for researchers to help better articulate the process in which gamification can be translated into positive use behaviors.
The Role of Clinical Characteristics in Stratifying Sedation Risk: A Cohort Study

Background Determination of sedation type during gastrointestinal procedures is generally based on risk assessment via the American Society of Anesthesiologists (ASA) classification system, but the reliance of anesthesia risk on clinical factors remains largely uninvestigated. We aim to determine the association between various clinical factors and choice of sedation type during gastrointestinal procedures. Methods This single-center, retrospective cohort study used electronic medical records to identify patients receiving colonoscopy or endoscopy at Rhode Island Hospital. The electronic medical record was queried for history of alcohol abuse, opioid abuse, polysubstance abuse, prescriptions for psychotropic or opioid medications and ASA classification. Logistic regression was used to measure how patient characteristics correlated with sedation type. Results Totally, 2,033 patients were included in the study; 1,080 patients received moderate sedation and 853 received monitored anesthesia care (MAC). Three hundred fifty-four (60.2%) MAC patients had a history of alcohol abuse compared to 234 (39.8%) moderate sedation patients (P < 0.2334); 178 (62.9%) MAC and 105 (37.1%) moderate sedation patients had a history of opioid abuse (P < 0.001); 203 (73.6%) MAC and 73 (26.4%) moderate sedation patients had a history of polysubstance abuse (P < 0.001); and 815 (75.1%) MAC patients had psychiatric comorbidities versus 270 (24.9%) in the moderate sedation group (P < 0.001). In the MAC cohort, alcohol, opioid, polysubstance abuse and psychiatric history were associated with previous failure of moderate sedation (P < 0.0001). Conclusions For a subset of patients, clinical factors including alcohol, opioid, polysubstance abuse and psychiatric history, in addition to ASA classification, play an important role in sedation management.
Individual corporate reputation and perception of collective corporate reputation regarding stock market investments

There are two different concepts of corporate reputation grounded in individual and collective perceptions, respectively. The aim of this study was to identify how these two ways of conceiving of corporate reputation affect investors’ decisions about whether or not to buy stock in a given company. As this problem tackles individual decision-making processes, we designed and applied an incentivised economic experiment based on vignette studies and focused on individual decisions of single investors. Subjects took part in an online game that imitates stock exchange conditions and that concerns corporate reputation and investing. We found that the individual propensity to invest is not directly based on an investor’s perception (rooted in historical share price and other objective metrics) of a firm’s reputation but rather on an investor’s subjective recognition of collective corporate reputation in the market. This suggests a need to rethink the popular measures of corporate reputation in the context of studies of stock market investor decisions.
Fecal Microbiota Transplantation in Patients With Recurrent Clostridium difficile Infection: A Four-Year Single-Center Retrospective Review

Background Clostridium difficile infection (CDI) is a common cause of hospital and community-acquired diarrhea with an annual incidence of 453,000 cases in the USA. The white race, female gender, and age over 65 years are known risk factors. Recurrence of CDI is a major problem in patients taking antibiotics for prolonged periods. These patients are observed to have reduced diversity of the intestinal microbiome. Fecal microbiota transplantation (FMT) can restore the healthy flora in the gut, thus breaking the cycle of recurrent infection. Our study aimed to analyze the efficacy of FMT and the recurrence of CDI after FMT. We also aimed to investigate the effects of comorbidities on the outcome of FMT. Methods After obtaining approval from the institutional review board, we included 64 patients who had received FMT at our institution from October 2015 to November 2019. All the patients over 16 years of age in both inpatient and outpatient settings were included. Patients under 16 years of age and patients treated without FMT were excluded. Frozen stool from a standardized stool bank (OpenBiome) was used. The thawed specimen was instilled into the terminal ileum or the cecum. Patients were followed up for the next 1 year for analysis of improvement in symptoms, recurrence, and repeat FMT. Results On the 2-months follow-up, 75% of patients reported symptomatic improvement, 15.6% reported no improvement while 9.4% did not follow up. Twenty-six (40.6%) patients had CDI recurrence in the following year; and 69.2% of patients with recurrence underwent a repeat FMT. There was no statistically significant correlation between CDI recurrence and the age (P value = 0.68), gender (P value = 0.61), previous use of proton pump inhibitors (PPIs, P value = 0.11) or antibiotics (P value = 0.45). There was a statistically significant correlation noted with the use of immunosuppressants and recurrence (P value = 0.04). Conclusions FMT is a successful treatment modality for refractory and recurrent CDI. Repeat treatments can be beneficial if there is a lack of initial response. Being immunosuppressed with medications is associated with the risk of recurrence.
Clinical characteristics and outcomes for pregnant women diagnosed with COVID-19 disease at the University of Benin Teaching Hospital, Benin City, Nigeria

Introduction the novel coronavirus disease (COVID-19) pandemic has challenged health systems around the world. This study was designed to describe the socio-demographic characteristics of pregnant women with COVID-19 infection, the common clinical features at presentation and the pregnancy outcome at the University of Benin Teaching Hospital, Edo State, Nigeria. Methods a cross-sectional analytical study of all confirmed cases of COVID-19 infection from April to September 2020. Results out of 69 suspected cases that were tested, 19 (28.4%) were confirmed with COVID-19 infection. The common presenting complaints were fever (68.4 %), cough (57.9 %), sore throat (31.6%), malaise (42.1%), loss of taste (26.3%), anosmia (21.1%), and difficulty with breathing (10.6%). In terms of treatment outcome, 57.9% delivered while 36.8% recovered with pregnancy on-going, and 1 (5.3%) maternal death. Of the 11 women who delivered, 45.4% had vaginal deliveries and 54.6 % had Caesarean section. The mean birth weight was 3.1kg and most of the neonates (81.8%) had normal Apgar scores at birth. There was 1 perinatal death from prematurity, birth asphyxia, and intrauterine growth restriction. The commonest diagnosed co-morbidity of pregnancy was preeclampsia and it was significantly associated with severe COVID-19 disease requiring oxygen supplementation (P = 0.028). Conclusion the clinical symptoms of COVID-19 in pregnancy are similar to those described in the non-pregnant population. It did not seem to worsen the maternal or foetal pregnancy outcome. The occurrence of preeclampsia is significantly associated with severe COVID-19 infection requiring respiratory support.
Targeting Notch4 in Cancer: Molecular Mechanisms and Therapeutic Perspectives

Abstract The dysregulation of Notch signaling is found in many cancers and is closely related to cancer progression. As an important Notch receptor, abnormal Notch4 expression affects several tumor-cell behaviors, including stemness, the epithelial–mesenchymal transition, radio/chemoresistance and angiogenesis. In order to inhibit the oncogenic effects of Notch4 activation, several methods for targeting Notch4 signaling have been proposed. In this review, we summarize the known molecular mechanisms through which Notch4 affects cancer progression. Finally, we discuss potential Notch4-targeting therapeutic strategies as a reference for future research.
Combinatorial liposomal peptide vaccine induces IgA and confers protection against influenza virus and bacterial super‐infection

The upper respiratory tract is the major entry site for Streptococcus pyogenes and influenza virus. Vaccine strategies that activate mucosal immunity could significantly reduce morbidity and mortality because of these pathogens. The severity of influenza is significantly greater if a streptococcal infection occurs during the viraemic period and generally viral infections complicated by a subsequent bacterial infection are known as super‐infections. We describe an innovative vaccine strategy against influenza virus:S. pyogenes super‐infection. Moreover, we provide the first description of a liposomal multi‐pathogen‐based platform that enables the incorporation of both viral and bacterial antigens into a vaccine and constitutes a transformative development.
An exploration of the nomological network of trypophobia

Background Trypophobia is characterised by an aversion to or even revulsion for patterns of holes or visual stimuli featuring such patterns. Past research has shown that trypophobic stimuli trigger emotional and physiological reactions, but relatively little is known about the antecedents, prodromes, or simply covariates of trypophobia. Aim The goals of this study were (a) to draw the contours of the nomological network of trypophobia by assessing the associations of symptoms of trypophobia with several constructs that were deemed relevant from past research on anxiety disorders and specific phobias, (b) to compare such associations with those found for symptoms of spider phobia and blood and injection phobia (alternative dependent variables), and (c) to investigate the main effect of gender on symptoms of trypophobia and replicate the association of gender with symptoms of spider phobia and blood and injection phobia (higher scores for women). Methods Participants (N = 1,134, 53% men) in this cross-sectional study completed an online questionnaire assessing the constructs of interest. Results Most assessed constructs typically associated with anxiety disorders (neuroticism, conscientiousness, anxiety sensitivity, trait anxiety, disgust sensitivity, and disgust propensity) were also associated with trypophobia in the predicted direction. All of these constructs were also associated with spider phobia and blood and injection phobia. Behavioral inhibition was negatively associated with trypophobia and spider phobia—contrary to what was expected, but positively with blood and injection phobia. We found no gender difference in trypophobia, whereas women scored higher on spider phobia and blood and injection phobia. Discussion Although some differences were observed, the nomological network of trypophobia was largely similar to that of spider phobia and blood and injection phobia. Further studies are needed to clarify similarities and dissimilarities between trypophobia and specific phobia.
A Fatal Case of Concurrent Disseminated Tuberculosis, Pneumocystis Pneumonia, and Bacterial Septic Shock in a Patient with Rheumatoid Arthritis Receiving Methotrexate, Glucocorticoid, and Tocilizumab: An Autopsy Report

Recently, treatment for rheumatoid arthritis has dramatically improved but increases the risk of bacterial and opportunistic infections. Herein, we report a fatal case of concurrent disseminated tuberculosis, pneumocystis pneumonia, and septic shock due to pyelonephritis caused by extended-spectrum β-lactamase-producing Escherichia coli in a patient with rheumatoid arthritis who received methotrexate, glucocorticoid, and tocilizumab. Despite undergoing intensive treatment, the patient developed respiratory failure and died after 7 days of admission. An autopsy indicated that pulmonary tuberculosis were the ultimate causes of death, while pyelonephritis was controlled.
Identification of Novel Choroidal Neovascularization-Related Genes Using Laplacian Heat Diffusion Algorithm

Choroidal neovascularization (CNV) is a type of eye disease that can cause vision loss. In recent years, many studies have attempted to investigate the major pathological processes and molecular pathogenic mechanisms of CNV. Because many diseases are related to genes, the genes associated with CNV need to be identified. In this study, we proposed a network-based approach for identifying novel CNV-associated genes. To execute such method, we first employed a protein-protein interaction network reported in STRING. Then, we applied a network diffusion algorithm, Laplacian heat diffusion, on this network by selecting validated CNV-related genes as the seed nodes. As a result, some novel genes that had unknown but strong relationships with validated genes were identified. Furthermore, we used a screening procedure to extract the most essential genes. Eleven latent CNV-related genes were finally obtained. Extensive analyses were performed to confirm that these genes are novel CNV-related genes.