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.

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.

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.

Machine Learning Models for Predicting Mortality in Patients with Cirrhosis and Acute Upper Gastrointestinal Bleeding at an Emergency Department: A Retrospective Cohort Study.

BACKGROUND: Cirrhosis is a major global cause of mortality, and upper gastrointestinal (GI) bleeding significantly increases the mortality risk in these patients. Although scoring systems such as the Child-Pugh score and the Model for End-stage Liver Disease evaluate the severity of cirrhosis, none of these systems specifically target the risk of mortality in patients with upper GI bleeding. In this study, we constructed machine learning (ML) models for predicting mortality in patients with cirrhosis and upper GI bleeding, particularly in emergency settings, to achieve early intervention and improve outcomes. METHODS: In this retrospective study, we analyzed the electronic health records of adult patients with cirrhosis who presented at an emergency department (ED) with GI bleeding between 2001 and 2019. Data were divided into training and testing sets at a ratio of 90:10. The ability of three ML models-a linear regression model, an XGBoost (XGB) model, and a three-layer neural network model-to predict mortality in the patients was evaluated. RESULTS: A total of 16,025 patients with cirrhosis and 32,826 ED visits for upper GI bleeding were included in the study. The in-hospital and ED mortality rates were 11.2% and 2.2%, respectively. The XGB model exhibited the highest performance in predicting both in-hospital and ED mortality (area under the receiver operating characteristic curve: 0.866 and 0.861, respectively). International normalized ratio, renal function, red blood cell distribution width, age, and white blood cell count were the strongest predictors in all the ML models. The median ED length of stay for the ED mortality group was 17.54 h (7.16-40.01 h). CONCLUSIONS: ML models can be used to predict mortality in patients with cirrhosis and upper GI bleeding. Of the three models, the XGB model exhibits the highest performance. Further research is required to determine the actual efficacy of our ML models in clinical settings.

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.

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.

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.

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.

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.

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.

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.

Potential value of urinary intercellular adhesion molecule-1 determination in patients with bladder cancer.

OBJECTIVE: Intercellular adhesion molecule-1 (ICAM-1) is known to play a role in immunity against bladder cancer and can be detected in the supernatants of cultured bladder cancer cells that constitutively express ICAM-1. This study was performed to examine the relevance of the ICAM-1 urine test in patients with bladder cancer. METHODS: A total of 53 patients with bladder carcinoma, 35 with history of bladder cancer, and 30 normal control subjects were included in this analysis. Urinary ICAM-1 (ulCAM-1) levels were measured by immunoassay and corrected for hydration status. RESULTS: Levels of ulCAM-1 were significantly elevated in patients with bladder cancer or those at tumor-free status compared with normal control subjects (P=0.001). However, there was no apparent difference between the two groups of urothelial disorders (P >0.1). ulCAM-1 did not correlate with clinicopathologic variables of bladder cancer or patient outcome (P >0.1). Six patients at tumor-free status had multiple ulCAM-1 determinations during the study period. Three of these 6 patients had elevated ulCAM-1 levels and proved to have recurrent tumors; 3 of the 6 had stable ulCAM-1 levels and were still free of disease. CONCLUSIONS: Our results suggest that urinary excretion of ICAM-1 is elevated in the early stage of bladder carcinogenesis, but is independent of biologic properties of bladder cancer. Serial monitoring of ulCAM-1 may be helpful in selecting patients who are at risk of tumor recurrence.

Expression of cyclooxygenase-2 in prostate adenocarcinoma and benign prostatic hyperplasia.

Elevated expression of cyclo-oxygenase (COX)-2 has been found in several human cancers, including prostate adenocarcinoma. To evaluate the potential prognostic role of COX-2 in prostate cancer, we assessed the expression of COX-2 in benign prostatic hyperplasia (BPH) and prostate cancer samples employing immunohistochemistry. COX-2 was over-expressed in 15 out of 18 (83%) prostate cancer samples whereas it was detected in only 22% (4 of 18) paired benign tissues. The intensity of immunostaining correlated with the tumor grading. In addition, COX-2 was expressed in 7 of the 22 (32%) BPH samples examined. The significance a COX-2 expression in the BPH samples is not known at present. This data suggest that COX-2 is over-expressed in prostate cancer and COX-2 inhibitors may be useful in combination chemotherapy or chemoprevention for prostate cancer.

Ocular penetration and pharmacokinetics of topical fluconazole.

The high bioavailability and low toxicity of fluconazole, a stable, water-soluble, low-molecular-weight bis-triazole antifungal, makes it a good candidate for consideration as a topical ocular agent. The penetration of fluconazole (0.2%) into the corneas and aqueous humors of New Zealand white rabbits was assayed by gas liquid chromatography (GLC). Peak corneal levels occurred essentially immediately at 5 min in the corneas [debrided, 8.2 +/- 1.2 micrograms/g; nondebrided, 1.6 +/- 0.6 microgram/g; (mean +/- SEM)] and at 15 min after application in the aqueous [debrided, 9.4 +/- 2.3 micrograms/ml; nondebrided, 1.6 +/- 0.6 microgram/ml; (mean +/- SEM)]. Estimating from semilogarithmic plots of the data, the halflife (t1/2) in the debrided eyes was 15 min; in the nondebrided eyes, t1/2 was 30 min. A loading dose of a 20-microliter drop per min for 5 min yielded levels of 59.9 +/- 11.3 micrograms/g (mean +/- SEM) in the debrided corneas and 32.4 +/- 1.9 micrograms/ ml (mean +/- SEM) in the corresponding aqueous humor. A regimen consisting of this loading dose followed by one 20 microliters drop/h for 6 h showed 45.9 +/- 3.5 micrograms/g (mean +/- SEM) in the debrided corneas and 8.8 +/- 1.7 micrograms/ml (mean +/- SEM) in the corresponding aqueous. The same regimen yielded values of 3.1 +/- 0.2 micrograms/g in the nondebrided corneas and 1.3 +/- 0.2 micrograms/ml (mean +/- SEM) in the aqueous. Minimal inhibitory concentrations (MIC) at 24 h for yeasts ranged from < 1.25 to 20 micrograms/ml, for hyaline molds from 2.5 to > 20 micrograms/ml, and dematiaceous molds from < 1.25 to > 20 micrograms/ml. Topical fluconazole exhibits pharmacokinetics and selective MICs that merit further evaluation for its ophthalmic use as a topical antifungal agent.

Doppler angle estimation using correlation.

Conventional Doppler techniques can only detect the axial component of blood flow. To obtain the transverse flow component, an approach based on the dependence of Doppler bandwidth on Doppler angle has been widely investigated. To compute the bandwidth, a full Doppler spectrum is often required. Therefore, this approach has not been applied to real-time, two-dimensional Doppler imaging because of the long data acquisition time. To overcome this problem, a correlation-based method is proposed. Specifically, variance of the Doppler spectrum is used to approximate the square of the Doppler bandwidth. Because variance is computed efficiently and routinely in correlation-based color Doppler imaging systems, implementation of this method is straightforward. In addition, the two-dimensional velocity vector can be calculated and mapped to different colors using the color mapping function of current systems. Simulations were performed, and experimental data were also collected using a string phantom with the Doppler angle varying from 23 degrees to 82 degrees . Results indicate that the correlation-based method may produce significant errors if only a limited number of flow samples are available. With averaging, however, the Doppler angles estimated by the correlation-based method can achieve good agreement with the true angles by using only four flow samples with proper variance averaging.

On velocity estimation using speckle decorrelation.

Quantitative estimation of blood velocity using Doppler techniques is fundamentally limited because only the axial component can be detected. Speckle decorrelation resulting from scatterer motion may be used to compute non-axial components and to obtain quantitative flow information. Based on both simulations and experimental results, it is shown that the decorrelation technique is feasible only for constant flows. If flow gradients are present, the correlation between two signals along the same line of observation may be significantly affected by the gradients. Therefore, the decorrelation method cannot be used for quantitative flow estimation if flow gradients are not accurately measured and effects on signal correlation are not fully compensated. Results in this paper show that accurate estimation of flow gradients is practically difficult. It is further shown that effects of signal-to-noise ratio (SNR) on the correlation must also be taken into account for quantitative flow analysis.

Immunohistochemical and ultrastructural study of malignant plasmacytoid myoepithelioma of the maxillary sinus.

Myoepithelioma is a rare salivary gland tumor which is composed exclusively of myoepithelial cells. Histologically, it can be divided into three cell types: spindle, plasmacytoid and mixed type. Malignant myoepithelioma is characterized by invasive growth. In March 1995, a 60-year-old man presented with a left cheek tumor which he had first noted 2 years previously. Computed tomography revealed a large expansile tumor in the maxillary sinus with invasion into the surrounding soft tissue. Partial resection of the tumor was performed because of extensive involvement of the surrounding tissue. The patient died due to spread to the brain 5 months after surgery. Histologically, the tumor was composed exclusively of plasmacytoid cells, with bone destruction. Immunohistochemically, these cells were negative for immunoglobulin light chains (kappa and lambda) and heavy chains (Ig G, A, M) but positive for S-100, cytokeratin, actin and vimentin.Ultrastructurally, the tumor cells contained numerous randomly oriented actin-like microfilaments in the cytoplasm, and had desmosomes on the cell membrane. Malignant plasmacytoid myoepithelioma of the maxillary sinus was diagnosed. In addition to our case, only five cases of pure plasmacytoid myoepithelioma have been reported. Plasmacytoid myoepithelioma tends to occur in the minor salivary glands and has more aggressive behavior than spindle cell myoepithelioma. Morphologically, it is very difficult to differentiate plasmacytoid myoepithelioma from plasmacytoma and immunohistochemical staining is necessary to make a correct diagnosis.

A new sperm collection method for treatment of retrograde ejaculation.

Retrograde ejaculation is an uncommon but treatable form of male infertility. Successful recovery of motile spermatozoa from a post-ejaculatory urine for artificial insemination is dependent on careful regulation of osmolarity and acidity of the bladder contents into which the ejaculate emanates, and the separation of the motile spermatozoa from the debris and cells which are found in these specimens. A pregnancy established by artificial insemination of spermatozoa recovered from bladder contents of a patient suffering from retrograde ejaculation is presented. The techniques for preparing the urinary bladder for spermatozoal survival and the removal of debris and cells by delicate centrifugation are discussed.