bluuebunny/crossref_metadata_2025_split huggingface dataset:
Light‐exercise‐induced dopaminergic and noradrenergic stimulation in the dorsal hippocampus: Using a rat physiological exercise model
Authors: Hiraga Taichi , Hata Toshiaki , Soya Shingo , Shimoda Ryo , Takahashi Kanako , Soya Mariko , Inoue Koshiro , Johansen Joshua P. , Okamoto Masahiro , Soya Hideaki 
Published: December 2024

AbstractExercise activates the dorsal hippocampus that triggers synaptic and cellar plasticity and ultimately promotes memory formation. For decades, these benefits have been explored using demanding and stress‐response‐inducing exercise at moderate‐to‐vigorous intensities. In contrast, our translational research with animals and humans has focused on light‐intensity exercise (light exercise) below the lactate threshold (LT), which almost anyone can safely perform with minimal stress. We found that even light exercise can stimulate hippocampal activity and enhance memory performance. Although the circuit mechanism of this boost remains unclear, arousal promotion even with light exercise implies the involvement of the ascending monoaminergic system that is essential to modulate hippocampal activity and impact memory. To test this hypothesis, we employed our physiological exercise model based on the LT of rats and immunohistochemically assessed the neuronal activation of the dorsal hippocampal sub‐regions and brainstem monoaminergic neurons. Also, we monitored the extracellular concentration of monoamines in the dorsal hippocampus using in vivo microdialysis. We found that even light exercise increased neuronal activity in the dorsal hippocampal sub‐regions and elevated the extracellular concentrations of noradrenaline and dopamine. Furthermore, we found that tyrosine hydroxylase‐positive neurons in the locus coeruleus (LC) and the ventral tegmental area (VTA) were activated even by light exercise and were both positively correlated with the dorsal hippocampal activation. In conclusion, our findings demonstrate that light exercise stimulates dorsal hippocampal neurons, which are associated with LC‐noradrenergic and VTA‐dopaminergic activation. This shed light on the circuit mechanisms responsible for hippocampal neural activation during exercise, consequently enhancing memory function.
Original Research: Is Your Outpatient Office Prepared to Manage an Opioid Overdose?
Authors: Goldstein Nancy S. , Grubb Claire 
Published: December 2024

ABSTRACT

Background:
Outpatient facilities, such as family and adult practice offices, psychiatric offices, and substance use treatment centers, should be equipped to manage medical emergencies and facilitate hospital transfers. Clinics that treat patients with opioid use disorder must be especially prepared to address respiratory arrest due to opioid overdose.

Purpose:
The objective of this integrative review was to identify emergency response initiatives already investigated or developed that could be adapted to address opioid-related medical emergencies in the outpatient adult treatment setting.

Methods:
Initial and updated literature searches were conducted using MEDLINE and PubMed. These searches yielded 207 and 60 articles of interest, respectively, and a total of 6 and 18 were selected for retrieval. Of these, 5 and 8, for a total of 13, met the inclusion criteria.

Results:
We found few publications in the mental health literature to inform or guide outpatient practitioners in preparing their offices for emergencies. This integrative review draws from all areas of the medical literature to identify emergency response strategies that have been developed for outpatient settings. We identified 4 major themes in office emergency preparedness: simulation training, response team organization, equipment readiness, and emergency action protocols.

Conclusion:
These 4 themes can provide guidance for improving readiness in medical offices, and in ambulatory mental health and substance use clinics. Researchers will need to develop emergency response algorithms that address these themes and assess patient outcomes.
Deep learning segmentation architectures for automatic detection of pancreatic ductal adenocarcinoma in EUS-guided fine-needle biopsy samples based on whole-slide imaging
Authors: Udriștoiu Anca Loredana , Podină Nicoleta , Ungureanu Bogdan Silviu , Constantin Alina , Georgescu Claudia Valentina , Bejinariu Nona , Pirici Daniel , Burtea Daniela Elena , Gruionu Lucian , Udriștoiu Stefan , Săftoiu Adrian 
Published: December 2024

ABSTRACT

Background
EUS-guided fine-needle biopsy is the procedure of choice for the diagnosis of pancreatic ductal adenocarcinoma (PDAC). Nevertheless, the samples obtained are small and require expertise in pathology, whereas the diagnosis is difficult in view of the scarcity of malignant cells and the important desmoplastic reaction of these tumors. With the help of artificial intelligence, the deep learning architectures produce a fast, accurate, and automated approach for PDAC image segmentation based on whole-slide imaging. Given the effectiveness of U-Net in semantic segmentation, numerous variants and improvements have emerged, specifically for whole-slide imaging segmentation.

Methods
In this study, a comparison of 7 U-Net architecture variants was performed on 2 different datasets of EUS-guided fine-needle biopsy samples from 2 medical centers (31 and 33 whole-slide images, respectively) with different parameters and acquisition tools. The U-Net architecture variants evaluated included some that had not been previously explored for PDAC whole-slide image segmentation. The evaluation of their performance involved calculating accuracy through the mean Dice coefficient and mean intersection over union (IoU).

Results
The highest segmentation accuracies were obtained using Inception U-Net architecture for both datasets. PDAC tissue was segmented with the overall average Dice coefficient of 97.82% and IoU of 0.87 for Dataset 1, respectively, overall average Dice coefficient of 95.70%, and IoU of 0.79 for Dataset 2. Also, we considered the external testing of the trained segmentation models by performing the cross evaluations between the 2 datasets. The Inception U-Net model trained on Train Dataset 1 performed with the overall average Dice coefficient of 93.12% and IoU of 0.74 on Test Dataset 2. The Inception U-Net model trained on Train Dataset 2 performed with the overall average Dice coefficient of 92.09% and IoU of 0.81 on Test Dataset 1.

Conclusions
The findings of this study demonstrated the feasibility of utilizing artificial intelligence for assessing PDAC segmentation in whole-slide imaging, supported by promising scores.
An Approach for Improving the Detection and Quantitation of Buprenorphine and Its Metabolites in Maternal and Neonatal Hair
Authors: Alshogran Osama Y. , Zhao Wenchen , Krans Elizabeth E. , Caritis Steve , Shaik Imam H. , Venkataramanan Raman 
Published: December 2024

Background:
Buprenorphine (BUP) use is prevalent in pregnant women with opioid use disorder (OUD). Drug monitoring during pregnancy is critical for optimizing dosing regimen and achieving the desired clinical outcomes. Hair can be used as a critical biological matrix for monitoring long-term exposure to drugs. The aim of this study was to optimize the methodology used to quantify BUP and its metabolites in hair samples.

Methods:
Conditions for hair sample processing (ie, hair washing, incubation temperature, and extraction time) were optimized to maximize extraction recovery. The LC-MS/MS strategy employed here used 4 deuterated internal standards for quantifying BUP and its major metabolites [norbuprenorphine (NBUP), buprenorphine glucuronide (BUP-G), and norbuprenorphine-glucuronide (NBUP-G)] in human hair samples. The optimized conditions were used to measure BUP and its metabolites in hair samples of 5 women undergoing OUD treatment and their neonates.

Results:
Unwashed hair samples processed by shaking with acetonitrile for 24 hours at 37 °C showed higher BUP (36%) and NBUP (67%) recovery, compared with those processed by incubation at room temperature. The standard curves showed excellent linearity over 0.05–100 ng/mL for BUP and NBUP and 0.1–200 ng/mL for BUP-G and NBUP-G. The assay was partially validated for reproducibility and accuracy and was successfully used for measuring BUP and metabolites in aforementioned hair samples. BUP was identified in all hair samples, while BUP-G was not. BUP was the primary analyte in maternal hair (median: 38.3 pg/mg; 25–75 percentile: 17–152.4 pg/mg), while NBUP-G was predominant in neonatal hair (median: 28.6 pg/mg; 25%–75% percentile: 1.9–112.8 pg/mg).

Conclusions:
The methodology used for quantifying BUP and its metabolites in hair samples of maternal female patients and their neonates is simple, accurate, and reproducible. The developed method may be useful for measuring fetal exposure to BUP during gestation.
Simultaneous Combination Therapy of Free Anterolateral Thigh Flap and Negative-pressure Wound Therapy With Penrose Drains for Thoracic Dead Space
Authors: Taga Marie , Umezawa Hiroki , Hokazono Yu , Kondo Akatsuki , Aoki Hironobu , Ogawa Rei 
Published: December 2024

Summary:
Open-window thoracostomy is an effective treatment for refractory postpneumonectomy empyema. However, it can leave large thoracic dead space, and bronchopleural fistulas (BPF) are a common major complication. These problems can be treated with myocutaneous flap transfer or negative-pressure wound therapy (NPWT). However, treatment is often difficult and prolonged. Here, we report 2 cases of free anterolateral thigh flap transfer followed immediately by NPWT combined with Penrose drains. Both patients, including 1 with BPF, had favorable postoperative courses and were discharged 28 and 14 days after reconstruction. Dead space infection and BPF recurrence were not observed after discharge. Following free flap transfer with NPWT combined with Penrose drains may efficiently eliminate dead space and accelerate wound healing in a large three-dimensional space.
Vessels encapsulating tumor clusters contribute to the intratumor heterogeneity of HCC on Gd-EOB-DTPA–enhanced MRI
Authors: Matsuda Kosuke , Ueno Akihisa , Tsuzaki Junya , Kurebayashi Yutaka , Masugi Yohei , Yamazaki Ken , Tamura Masashi , Abe Yuta , Hasegawa Yasushi , Kitago Minoru , Jinzaki Masahiro , Sakamoto Michiie 
Published: December 2024

Background:
Vessels encapsulating tumor clusters (VETC) pattern is tumor vasculature of HCC and is a predictor of prognosis and therapeutic efficacy. Recent radiological studies have demonstrated the predictability of VETC from preoperative images, but the mechanisms of image formation are not elucidated. This study aims to determine the relationship between VETC and intratumor heterogeneity in Gd-EOB-DTPA–enhanced magnetic resonance imaging (EOB-MRI) and to provide its pathological evidence.

Methods:
Radiologists visually classified preoperative arterial- and hepatobiliary-phase EOB-MRI images of 204 surgically resected HCCs into patterns based on heterogeneity and signal intensity; these classifications were validated using texture analysis. Single and multiplex immunohistochemistry for CD34, h-caldesmon, and OATP1B3 were performed to evaluate VETC, arterial vessel density (AVD), and OATP1B3 expression. Recurrence-free survival was assessed using the generalized Wilcoxon test. The contribution of clinicoradiological factors to the prediction of VETC was evaluated by random forest and least absolute shrinkage and selection operator regression.

Results:
VETC was frequently found in tumors with arterial-phase heterogeneous hyper-enhancement patterns and in tumors with hepatobiliary-phase heterogeneous hyperintense/isointense patterns (HBP-Hetero). AVD and OATP1B3 expression positively correlated with signal intensity in the arterial and hepatobiliary phases, respectively. Intratumor spatial analysis revealed that AVD and OATP1B3 expression were lower in VETC regions than in tumor regions without VETC. Patients with HBP-Hetero tumors had shorter recurrence-free survival. Machine learning models highlighted the importance of serum PIVKA-II, tumor size, and enhancement pattern of arterial and hepatobiliary phase for VETC prediction.

Conclusions:
VETC is associated with local reductions of both AVD and OATP1B3 expression, likely contributing to heterogeneous enhancement patterns in EOB-MRI. Evaluation of the arterial and hepatobiliary phases of EOB-MRI would enhance the predictability of VETC.
Quantitative fibrosis identifies biliary tract involvement and is associated with outcomes in pediatric autoimmune liver disease
Authors: Khendek Leticia , Castro-Rojas Cyd , Nelson Constance , Alquraish Mosab , Karns Rebekah , Kasten Jennifer , Teng Xiao , Miethke Alexander G. , Taylor Amy E. 
Published: December 2024

Background:
Children with autoimmune liver disease (AILD) may develop fibrosis-related complications necessitating a liver transplant. We hypothesize that tissue-based analysis of liver fibrosis by second harmonic generation (SHG) microscopy with artificial intelligence analysis can yield prognostic biomarkers in AILD.

Methods:
Patients from single-center studies with unstained slides from clinically obtained liver biopsies at AILD diagnosis were identified. Baseline demographics and liver biochemistries at diagnosis and 1 year were collected. Clinical endpoints studied included the presence of varices, variceal bleeding, ascites, HE, and liver transplant. In collaboration with HistoIndex, unstained slides underwent SHG/artificial intelligence analysis to map fibrosis according to 10 quantitative fibrosis parameters based on tissue location, including total, periportal, perisinusoidal, and pericentral area and length of strings.

Results:
Sixty-three patients with AIH (51%), primary sclerosing cholangitis (30%), or autoimmune sclerosing cholangitis (19%) at a median of 14 years old (range: 3–24) were included. An unsupervised analysis of quantitative fibrosis parameters representing total and portal fibrosis identified a patient cluster with more primary sclerosing cholangitis/autoimmune sclerosing cholangitis. This group had more fibrosis at diagnosis by METAVIR classification of histopathological review of biopsies (2.5 vs. 2; p = 0.006). This quantitative fibrosis pattern also predicted abnormal 12-month ALT with an OR of 3.6 (1.3–10, p = 0.014), liver complications with an HR of 3.2 (1.3–7.9, p = 0.01), and liver transplantation with an HR of 20.1 (3–135.7, p = 0.002).

Conclusions:
The application of SHG/artificial intelligence algorithms in pediatric-onset AILD provides improved insight into liver histopathology through fibrosis mapping. SHG allows objective identification of patients with biliary tract involvement, which may be associated with a higher risk for refractory disease.
Pain in chronic liver disease compared to other chronic conditions: Results from a contemporary nationally representative cohort study
Authors: Zhang Grace Y. , Cortella Aly , Lai Jennifer C. , Rubin Jessica B. 
Published: December 2024

Background:
Pain is common in patients with chronic liver disease. Our limited understanding of patterns and severity of pain in this population hinders the development of effective cirrhosis-specific pain management strategies.

Methods:
Using cross-sectional data from the 2016–2021 National Health Interview Survey, we examined rates, severity, and functional limitations due to pain in respondents with liver disease (viral hepatitis, cirrhosis, and liver cancer), compared to the general population and those with other chronic conditions associated with pain (ie, arthritis, diabetes, and chronic kidney disease). Categorical and continuous variables were compared using χ2 and t test. Multivariable logistic regression was used to determine the predictors associated with pain and opioid use.

Results:
Our liver disease cohort comprised 5267 participants (63% viral hepatitis, 49% cirrhosis, and 2% liver cancer). Participants with liver disease were more likely to report pain than those without liver disease (42% vs. 22%); they were also more likely to report severe pain (42% vs. 30%) and functional limitations by pain (28% vs. 13%) (p < 0.001 for all). On multivariable logistic regression, liver disease is an independent predictor of pain (OR: 2.31, 95% CI: 2.05–2.59, p < 0.001), even after adjustment for demographic factors. Liver disease respondents had similar rates of pain as those with diabetes (p = 0.8) and were more functionally limited by pain than those with arthritis (p < 0.001). Adjusted for demographic and pain-related factors, liver disease was also an independent predictor of chronic opioid use (OR: 1.47, 95% CI: 1.12–1.92, p = 0.0054).

Conclusions:
Liver disease independently increases the likelihood of experiencing widespread and debilitating pain. Clinicians should consider liver disease a painful condition, ensuring that they are frequently assessing and appropriately treating pain in all liver disease patients.
Systemic immune-inflammation index and long-term mortality in patients with hypertension: a cohort study
Authors: Zheng Yaling , Zhong Dongling , Li Juan , Zhang Yue , Li Huijing , Liu Luoji , Ren Chi , Zhong Shan , Liu Xicen , He Xia , Jin Shiqi , Luo Lun 
Published: December 2024

Objective:
The objective of this study was to examine the relationship between systemic inflammation and long-term mortality in patients with hypertension.

Methods:
The study employed a retrospective cohort design. The study population was derived from the National Health and Nutrition Examination Survey (NHANES), and the mortality data for this population was acquired from the National Death Index (NDI) database. Systemic inflammation was quantified by the Systemic Immune Inflammation Index (SII) and the Systemic Inflammatory Response Index (SIRI), which were then categorized into four groups (Q1–Q4, with Q4 representing the highest level of SII or SIRI). Weighted Cox regression models were constructed to investigate the association between mortality and SII and SIRI, with hazard ratios (HRs) subsequently calculated.

Results:
A total of 7431 participants were included in the analysis. The highest quantile (Q4) of SII was associated with a higher risk of all-cause mortality (hazard ratio 1.36, 95% CI 1.1–1.69, P < 0.001). After adjustment for important covariates, the association remained significant (hazard ratio 1.70, 95% CI 1.27–2.30, P < 0.001). The highest quantile (Q4) of SIRI was also associated with the highest risk of mortality (hazard ratio 2.11, 95% CI 1.64–2.70, P < 0.001), and this association remained significant after adjustment for important covariates (hazard ratio 1.64, 95% CI 0.61–1.22, P = 0.001).

Conclusion:
Both SII and SIRI scores were found to be associated with mortality rates in patients with hypertension. The findings suggest that these scores may serve as complementary biomarkers to the neutrophil-to-lymphocyte ratio (NLR) for assessing mortality risk in patients with hypertension. Further investigation is warranted to elucidate the underlying mechanisms that underpin this association.
Three Developments Related to ANSI/HPS Standard N13.56
Authors: Evans William 
Published: December 2024

Abstract
Three topics related to ANSI/HPS Standard N13.56, Sampling and Monitoring Releases of Airborne Radioactivity in the Workplace, are discussed. First, due to the omission of consideration of the activity’s half-life in the standard's continuous particulate air monitor (CPAM) quantitative method, it is possible for concentration estimates produced by that calculation to be underestimated. Second, the concentration estimate found in air grab sampling, as discussed in the standard, is not, as claimed, an average unless the activity is “long-lived” (negligible decay during sampling). It is nonetheless possible for this calculation to produce a concentration estimate that is not significantly different from the average, depending on both the half-life of the activity and the sampling time. Third, the issue of when to change the filter for the CPAM method is addressed.
A patient with long-term diabetes dies following infection with Francisella novicida in Guangdong province, China: a case report
Authors: Fan Linjin , Guan Jialong , Feng Lizhi , Wang Yulong , Zeng Huimin , Zhu Ying , Li Hao , Chen Qiang , Li Linghua , Qian Jun , Liu Linna , Li Yueping 
Published: December 2024

Abstract
The rarity of Francisella novicida infection in humans is well-known, and the F. novicida cases occur in immunocompromised patients or those with underlying health problems. Herein, we report the case of a patient with long-term diabetes who died following F. novicida infection that caused multiple organ failure, although F. novicida was effectively eliminated using antimicrobial therapy. Microbiological confirmation of F. novicida infection relies on metagenomic next-generation sequencing (mNGS) and pdpD-2 gene-specific identification. This study highlights the importance of early pathogen diagnosis in severely infected patients, particularly in cases of F. novicida, and indicates that mNGS is a useful tool for early diagnosis.
Association Between Alcohol Use and Primary Open Angle Glaucoma
Authors: Meller Leo L.T. , Saseendrakumar Bharanidharan Radha , Mahmoudinezhad Golnoush , Tavakoli Kiana , Wu Jo-Hsuan , Parikh Aman , Bhanvadia Sonali , Moghimi Sasan , Zangwill Linda , Weinreb Robert N. , Baxter Sally L. 
Published: December 2024

Précis:
In a diverse database (All of Us), we report significant dose-response associations between alcohol use frequency and glaucoma, with alcohol use of 4 or more drinks per week associated with significantly increased odds of glaucoma.

Purpose:
Current evidence on the association between alcohol use and primary open angle glaucoma (POAG) is mixed. We utilize the diverse All of Us Research Program to further examine this relationship.

Methods:
This is a retrospective cohort study using the diverse All of Us Research Program, a nationwide effort by the United States National Institutes of Health to recruit those historically under-represented in biomedical research. Electronic health records and survey data from the All of Us program were analyzed. A randomized 1:4 case/control ratio was utilized for POAG patients and randomly selected control patients. χ2, bivariable, and multivariable regression were utilized to examine the associations between alcohol use and POAG.

Results:
Of the 3876 POAG patients, 2015 (52%) were female, 1943 (50%) were White, 1152 (30%) were Black, 117 (3%) were Asian, and 584 (15%) were Hispanic. Alcohol use of 4 or more drinks per week was significantly higher in the glaucoma cohort relative to controls (15% vs. 12%, P<0.001). On bivariate analysis, diagnosed alcohol misuse was associated with higher odds of POAG [odds ratio (OR): 1.20, 95% CI: 1.17–1.23, P<0.001]. In multivariable regression, more frequent alcohol use was associated with higher odds of glaucoma; alcohol use with a frequency of 4 or more drinks per week was significantly associated with increased odds of glaucoma (OR: 1.22, 95% CI: 1.03–1.44, P=0.023). This dose-response relationship was also observed and more pronounced for female participants, where alcohol use frequency of monthly or less was already associated with increased odds of glaucoma (OR: 1.21, 95% CI: 1.002–1.46, P=0.048).

Conclusion:
In the diverse All of Us database, there was a dose-response relationship between alcohol consumption and POAG risk, which was more pronounced in female participants. Overall, a higher frequency of alcohol consumption was associated with an increased risk of POAG; 4 or more drinks per week significantly was associated with higher glaucoma risk.