Machine learning models for predicting unscheduled return visits of patients with abdominal pain at emergency department and validation during COVID-19 pandemic: A retrospective cohort study.

Machine learning (ML) models for predicting 72-hour unscheduled return visits (URVs) for patients with abdominal pain in the emergency department (ED) were developed in a previous study. This study refined the data to adjust previous prediction models and evaluated the model performance in future data validation during the COVID-19 era. We aimed to evaluate the practicality of the ML models and compare the URVs before and during the COVID-19 pandemic. We used electronic health records from Chang Gung Memorial Hospital from 2018 to 2019 as a training dataset, and various machine learning models, including logistic regression (LR), random forest (RF), extreme gradient boosting (XGB), and voting classifier (VC) were developed and subsequently used to validate against the 2020 to 2021 data. The models highlighted several determinants for 72-hour URVs, including patient age, prior ER visits, specific vital signs, and medical interventions. The LR, XGB, and VC models exhibited the same AUC of 0.71 in the testing set, whereas the VC model displayed a higher F1 score (0.21). The XGB model demonstrated the highest specificity (0.99) and precision (0.64) but the lowest sensitivity (0.01). Among these models, the VC model showed the most favorable, balanced, and comprehensive performance. Despite the promising results, the study illuminated challenges in predictive modeling, such as the unforeseen influences of global events, such as the COVID-19 pandemic. These findings not only highlight the significant potential of machine learning in augmenting emergency care but also underline the importance of iterative refinement in response to changing real-world conditions.

A Machine Learning Model for Predicting Unscheduled 72 h Return Visits to the Emergency Department by Patients with Abdominal Pain.

Seventy-two-hour unscheduled return visits (URVs) by emergency department patients are a key clinical index for evaluating the quality of care in emergency departments (EDs). This study aimed to develop a machine learning model to predict 72 h URVs for ED patients with abdominal pain. Electronic health records data were collected from the Chang Gung Research Database (CGRD) for 25,151 ED visits by patients with abdominal pain and a total of 617 features were used for analysis. We used supervised machine learning models, namely logistic regression (LR), support vector machine (SVM), random forest (RF), extreme gradient boosting (XGB), and voting classifier (VC), to predict URVs. The VC model achieved more favorable overall performance than other models (AUROC: 0.74; 95% confidence interval (CI), 0.69-0.76; sensitivity, 0.39; specificity, 0.89; F1 score, 0.25). The reduced VC model achieved comparable performance (AUROC: 0.72; 95% CI, 0.69-0.74) to the full models using all clinical features. The VC model exhibited the most favorable performance in predicting 72 h URVs for patients with abdominal pain, both for all-features and reduced-features models. Application of the VC model in the clinical setting after validation may help physicians to make accurate decisions and decrease URVs.

Specialized medial prefrontal-amygdala coordination in other-regarding decision preference.

Social behaviors recruit multiple cognitive operations that require interactions between cortical and subcortical brain regions. Interareal synchrony may facilitate such interactions between cortical and subcortical neural populations. However, it remains unknown how neurons from different nodes in the social brain network interact during social decision-making. Here we investigated oscillatory neuronal interactions between the basolateral amygdala and the rostral anterior cingulate gyrus of the medial prefrontal cortex while monkeys expressed context-dependent positive or negative other-regarding preference (ORP), whereby decisions affected the reward received by another monkey. Synchronization between the two nodes was enhanced for a positive ORP but suppressed for a negative ORP. These interactions occurred in beta and gamma frequency bands depending on the area contributing the spikes, exhibited a specific directionality of information flow associated with a positive ORP and could be used to decode social decisions. These findings suggest that specialized coordination in the medial prefrontal-amygdala network underlies social-decision preferences.

Time-resolved inline digital holography for the study of noncollinear degenerate phase modulation.

Recent works demonstrated that digital time-resolved holography is the prospective approach to study nonlinear light-matter interaction processes. In this Letter, we present a straightforward inline holographic approach for studying degenerate phase modulation induced by an inclined collimated pump beam in the isotropic sample. The method is based on a minimization of the difference between experimentally acquired data and simulated inline holograms obtained from a numerical model of pump-probe interaction in optical nonlinear media. A sophisticated experimental data processing algorithm is implemented to provide high sensitivity and a signal-to-noise ratio eligible for soft interaction with a collimated pump beam. The integral phase shift determined by our method can be used to estimate the nonlinear refractive index and the relaxation time for material with a low damage threshold. We validated our approach for the case of soda-lime and BK7 glasses.

Expression of miR-146a-5p in patients with intracranial aneurysms and its association with prognosis.

OBJECTIVE: The study aims to detect the association of miR-146a-5p with intracranial aneurysms (IAs). PATIENTS AND METHODS: The expression of miR-146a-5p was compared from plasma samples between 72 patients with intracranial aneurysms (IAs) and 40 healthy volunteers by quantitative Real-time polymerase chain reaction (qRT-PCR). Statistical analysis was performed to analyze the relationship between miR-146a-5p expression and clinical data and overall survival (OS) time of IAs patients. Univariate and multivariate Cox proportional hazards have also been performed. RESULTS: Notably, higher miR-146a-5p expression was found in plasma samples from 72 patients with intracranial aneurysms (IAs) compared with 40 healthy controls. Higher miR-146a-5p expression was significantly associated with rupture and Hunt-Hess level in IAs patients. Kaplan-Meier survival analysis verified that higher miR-146a-5p expression predicted a shorter overall survival (OS) compared with lower miR-146a-5p expression in IAs patients. Univariate and multivariate Cox proportional hazards demonstrated that higher miR-146a-5p expression, rupture, and Hunt-Hess were independent risk factors of OS in patients with intracranial aneurysms (IAs). CONCLUSIONS: MiR-146a-5p expression may serve as a biomarker for predicting prognosis in patients with IAs.

Emerging Targets of Diuretic Therapy.

Diuretics are commonly prescribed for treatment in patients with hypertension, edema, or heart failure. Studies on hypertensive and salt-losing disorders and on urea transporters have contributed to better understanding of mechanisms of renal salt and water reabsorption and their regulation. Proteins involved in the regulatory pathways are emerging targets for diuretic and aquaretic therapy. Integrative high-throughput screening, protein structure analysis, and chemical modification have identified promising agents for preclinical testing in animals. These include WNK-SPAK inhibitors, ClC-K channel antagonists, ROMK channel antagonists, and pendrin and urea transporter inhibitors. We discuss the potential advantages and side effects of these potential diuretics.

Therapeutic effect of prenatal alkalization and PTC124 in Na(+)/HCO3(-) cotransporter 1 p.W516* knock-in mice.

We created Na(+)/HCO3(-) cotransporter 1 (NBCe1) p.W516* knock-in mice as a model of isolated proximal renal tubular acidosis showing early lethality associated with severe metabolic acidosis to investigate the therapeutic effects of prenatal alkalization or posttranscriptional control 124 (PTC124). NBCe1(W516*/W516*) mice were treated with non-alkalization (control, n=12), prenatal alkalization postcoitus (prenatal group, n=7) and postnatal alkalization from postnatal day 6 (postnatal group, n=12). Mutation-specific therapy, PTC124 (60 mg kg(-1)) or gentamicin (30 mg kg(-1)), was administered intraperitoneally from postnatal day 6. Blood and urine biochemistry, acid-base analysis, survival rate and renal histology were examined. NBCe1 protein, mRNA abundance and activity ex vivo were assessed after PTC124 and gentamicin treatment. Prenatal group mice had similar initial body weight to wild-type mice and achieved significant weight gain thereafter compared with controls. They had higher serum bicarbonate level (15.5 ± 1.4 vs 5.5 ± 0.1 mmol l(-1), P<0.05) on postnatal day 14 and better renal function, histology and survival rates (60.8 ± 23.5 vs 41.1 ± 15.8 days, P<0.05) than the postnatal group. Compared with the control and gentamicin therapies, PTC124 therapy significantly increased NBCe1 protein abundance despite unchanged mRNA transcription. Only PTC124 therapy significantly increased survival rate and partially rescued NBCe1 activity ex vivo. In NBCe1(W516*/W516*) mice, prenatal alkali therapy achieved higher survival rates and ameliorated organ dysfunction. PTC124 therapy for this nonsense mutation was partially effective in increasing NBCe1 expression and activity.

Talin1 phosphorylation activates ß1 integrins: a novel mechanism to promote prostate cancer bone metastasis.

Talins are adaptor proteins that regulate focal adhesion signaling by conjugating integrins to the cytoskeleton. Talins directly bind integrins and are essential for integrin activation. We previously showed that ß1 integrins are activated in metastatic prostate cancer (PCa) cells, increasing PCa metastasis to lymph nodes and bone. However, how ß1 integrins are activated in PCa cells is unknown. In this study, we identified a novel mechanism of ß1 integrin activation. Using knockdown experiments, we first demonstrated that talin1, but not talin2, is important in ß1 integrin activation. We next showed that talin1 S425 phosphorylation, but not total talin1 expression, correlates with metastatic potential of PCa cells. Expressing a non-phosphorylatable mutant, talin1(S425A), in talin1-silenced PC3-MM2 and C4-2B4 PCa cells, decreased activation of ß1 integrins, integrin-mediated adhesion, motility and increased the sensitivity of the cells to anoikis. In contrast, reexpression of the phosphorylation-mimicking mutant talin1(S425D) led to increased ß1 integrin activation and generated biologic effects opposite to talin1(S425A) expression. In the highly metastatic PC3-MM2 cells, expression of a non-phosphorylatable mutant, talin1(S425A), in talin1-silenced PC3-MM2 cells, abolished their ability to colonize in the bone following intracardiac injection, while reexpression of phosphorylation-mimicking mutant talin1(S425D) restored their ability to metastasize to bone. Immunohistochemical staining demonstrated that talin S425 phosphorylation is significantly increased in human bone metastases when compared with normal tissues, primary tumors or lymph node metastases. We further showed that p35 expression, an activator of Cdk5, and Cdk5 activity were increased in metastatic tumor cells, and that Cdk5 kinase activity is responsible for talin1 phosphorylation and subsequent ß1 integrin activation. Together, our study reveals Cdk5-mediated phosphorylation of talin1 leading to ß1 integrin activation is a novel mechanism that increases metastatic potential of PCa cells.

Tuning dissimilarity explains short distance decline of spontaneous spike correlation in macaque V1.

Fast spike correlation is a signature of neural ensemble activity thought to underlie perception, cognition, and action. To relate spike correlation to tuning and other factors, we focused on spontaneous activity because it is the common 'baseline' across studies that test different stimuli, and because variations in correlation strength are much larger across cell pairs than across stimuli. Is the probability of spike correlation between two neurons a graded function of lateral cortical separation, independent of functional tuning (e.g. orientation preferences)? Although previous studies found a steep decline in fast spike correlation with horizontal cortical distance, we hypothesized that, at short distances, this decline is better explained by a decline in receptive field tuning similarity. Here we measured macaque V1 tuning via parametric stimuli and spike-triggered analysis, and we developed a generalized linear model (GLM) to examine how different combinations of factors predict spontaneous spike correlation. Spike correlation was predicted by multiple factors including color, spatiotemporal receptive field, spatial frequency, phase and orientation but not ocular dominance beyond layer 4. Including these factors in the model mostly eliminated the contribution of cortical distance to fast spike correlation (up to our recording limit of 1.4mm), in terms of both 'correlation probability' (the incidence of pairs that have significant fast spike correlation) and 'correlation strength' (each pair's likelihood of fast spike correlation). We suggest that, at short distances and non-input layers, V1 fast spike correlation is determined more by tuning similarity than by cortical distance or ocular dominance.

Rhabdomyolysis induced by excessive coffee drinking.

Excessive ingestion of caffeine-containing beverages is a rare cause of rhabdomyolysis. Here, we describe the case of a 44-year-old woman presented with nausea, vomiting, palpitations, and tea-colored urine 6 h after drinking a liter of black coffee containing approximately 565 mg of caffeine for mental alertness. Laboratory studies were notable for myoglobinuria and markedly elevated plasma creatine kinase (CK) level of 7315 U/L. With volume expansion and alkalization, her plasma CK level returned to normal within 5 days. Rhabdomyolysis should be considered a potential health hazard from excessive consumption of caffeine-containing products.

Atomic-scale evolution of modulated phases at the ferroelectric-antiferroelectric morphotropic phase boundary controlled by flexoelectric interaction.

Physical and structural origins of morphotropic phase boundaries (MPBs) in ferroics remain elusive despite decades of study. The leading competing theories employ either low-symmetry bridging phases or adaptive phases with nanoscale textures to describe different subsets of the macroscopic data, while the decisive atomic-scale information has so far been missing. Here we report direct atomically resolved mapping of polarization and structure order parameter fields in a Sm-doped BiFeO(3) system and their evolution as the system approaches a MPB. We further show that both the experimental phase diagram and the observed phase evolution can be explained by taking into account the flexoelectric interaction, which renders the effective domain wall energy negative, thus stabilizing modulated phases in the vicinity of the MPB. Our study highlights the importance of local order-parameter mapping at the atomic scale and establishes a hitherto unobserved physical origin of spatially modulated phases existing in the vicinity of the MPB.

Epithelioid leiomyosarcoma of the uterus: computed tomography findings.

Uterine epithelioid leiomyosarcoma is a rare neoplasm. There have been no previous reports describing computed tomography (CT) findings for this tumor. A 31-year-old woman presented with a heterogeneous enhancing mass, with internal septa, in the uterus, which was shown on CT images. Histological diagnosis was compatible with epithelioid leiomyosarcoma.

Plasma-cell cheilitis: successful treatment with intralesional injections of corticosteroids.

Plasma-cell cheilitis is a rare inflammatory disorder of the lip characterized histologically by a band-like infiltrate of plasma cells in the upper dermis. It is considered an oral counterpart of plasma-cell balanitis. Clinically, it presents as a circumscribed, flat to slightly raised, eroded area of the lip. The cause of plasma-cell cheilitis is unknown, and the treatment is often disappointing. We describe a 55-year-old woman who had a long-lasting painful, swollen, and eroded area on her lips, which responded poorly to various topical treatments. Biopsy showed a band-like infiltrate composed mainly of mature plasma cells in the dermis. A diagnosis of plasma-cell cheilitis was made after excluding contact dermatitis, lichen planus, bacterial, fungal and spirochaete infections, and an extramedullary plasmacytoma. Dramatic improvements were observed after intralesional injections of corticosteroids. The lesion cleared up after two treatments, and there has been no recurrence in 1 year of follow-up.

A 45-kDa ErbB3 secreted by prostate cancer cells promotes bone formation.

ErbB3 is a transmembrane growth factor receptor that has been implicated in the pathogenesis of human cancer. After finding that a truncated form of ErbB3 was present and upregulated in metastatic prostate cancer cells in lymph nodes and bone, we explored the pathophysiological functions of this unusual form of ErbB3 in the context of mouse calvaria as well as osteoblasts in vitro and the femur microenvironment in vivo. Here we demonstrate that prostate cancer cells expressed an alternatively spliced transcript that encodes a 45-kDa glycosylated protein (p45-sErbB3). The recombinant p45-sErbB3 purified from conditioned medium stimulated calvarial bone formation and induced osteoblast differentiation. Overexpression of p45-sErbB3 in the osteolytic prostate cancer cell line PC-3 converted its phenotype from bone lysing to bone forming upon injection into the femurs of immunodeficient mice. Further, we detected sErbB3 in plasma samples from patients with castration-resistant prostate cancer with bone metastasis. These observations establish that p45-sErbB3 is a structurally and functionally unique gene product of ErbB3 and suggest that p45-sErbB3 is likely one of the factors involved in the osteoblastic bone metastases of prostate cancer.

Unusual causes of hypokalaemia and paralysis.

We demonstrate how the application of physiological principles may help to identify unusual causes of a very low plasma potassium (K+) concentration (P(K)) and paralysis. In the two patients described, the short time course of the illness suggested that there was an acute shift of K+ into cells. The combination of a low rate of excretion of K+, the absence of a metabolic acid-base disorder, and the fact that the clinical findings occurred very soon after a large intake of carbohydrate supported this impression. Surprisingly, the P(K) remained low for many hours after these stimuli to shift K+ into cells had abated. The missing link in this story was eventually provided by the attending medical team with the help of their mentor, Professor McCance.

Endometrial stromal sarcoma mimicking submucosal myoma protruding to the vagina: MRI findings.

A 46-year-old woman complained of persistent abnormal vaginal bleeding over ten days. Her intrauterine device had been removed two years before. Soon after, she suffered from menorrhagia and metrorrhagia. An incidental finding of severe anemia was also noted. In this admission, our initial T2-weighted magnetic resonance imaging (MRI) revealed a well-demarcated mass predominantly in the uterine cavity. The mass was depicted by an isointense signal relative to the myometrium on T1-weighted images, high signal intensity on T2-weighted images, and slightly heterogeneous enhancement on post-contrast images. The patient refused surgery. After two years, follow-up MRI showed a pedunculated mass protruding into the upper third of the vagina with a stalk connecting to the posterior wall of the uterine cavity, simulating submucosal myoma. Histological diagnosis was compatible with low-grade endometrial stromal sarcoma.