bluuebunny/crossref_metadata_2025_split huggingface dataset:
Optimization of simvastatin transdermal patch for hyperlipidemia treatment in rat model
Authors: Neetu  , Anand Anubhav , Panjwani Dharamveer 
Published: February 2024

Abstract
Objective
Biopharmaceutics Classification System says that simvastatin (SMV) is a Class II drug with low bioavailability (5%). This is because it dissolves slowly and is broken down a lot in the first pass. Simvastatin transdermal patches were produced as part of this study's aim to treat hyperlipidemia. The Box–Behnken design (three-factor, three-level) was selected for optimization of patches.

Methodology
The optimization design involved 15 runs with independent factors hydroxypropyl methylcellulose K100, Eudragit L100, and polyethylene glycol 400 percentage, and dependent factors including folding endurance and in-vitro drug release.

Results
The results showed that the concentration of hydroxypropyl methylcellulose K-100 positively impacted the patch’s folding endurance. The fact that factor C was the only scenario where the p-value was less than 0.05 and the coefficient value was higher in the in vitro drug release model means that it has a greater influence on the release of medicines. The patches were also evaluated for drug content, swelling, moisture uptake, moisture content, etc. The optimized patch shows an in vitro drug release of 55.3% in up to 24 h. In vivo antihyperlipidemic activity was evaluated in albino Wistar rats. In the standard treatment (simvastatin oral) groups, there is a decrease in cholesterol (132.76 ± 0.35) and triglyceride level (139.80 ± 76) whereas in the test formulation group or test group, there is also a decrease in cholesterol (169.65 ± 0.21 mg/dL) and triglyceride level (151.20 ± 31 mg/dL) level.

Conclusion
Based on in-vitro and in-vivo results it can be concluded that simvastatin patches can be an alternative to traditional therapy.
Targeted irradiation in an autochthonous mouse model of pancreatic cancer
Authors: Tesson Mathias , Stevenson Katrina , Karim Saadia A. , Nixon Colin , Chalmers Anthony J. , Sansom Owen J. , O'Neill Eric , Jones Keaton , Morton Jennifer P. 
Published: February 2024

ABSTRACT
The value of radiotherapy in the treatment of pancreatic cancer has been the subject of much debate but limited preclinical research. We hypothesise that the poor translation of radiation research into clinical trials of radiotherapy in pancreatic cancer is due, in part, to inadequate preclinical study models. Here, we developed and refined methods for targeted irradiation in autochthonous mouse models of pancreatic cancer, using a small animal radiotherapy research platform. We tested and optimised strategies for administration of contrast agents, iohexol and the liver imaging agent Fenestra LC, to enable the use of computed tomography imaging in tumour localisation. We demonstrate accurate tumour targeting, negligible off-target effects and therapeutic efficacy, depending on dose, number of fractions and tumour size, and provide a proof of concept that precise radiation can be delivered effectively to mouse pancreatic tumours with a clinically relevant microenvironment. This advance will allow investigation of the radiation response in murine pancreatic cancer, discovery of mechanisms and biomarkers of radiosensitivity or resistance, and development of radiosensitising strategies to inform clinical trials for precision radiotherapy in this disease.
Crowdkeeping in Last-Mile Delivery
Authors: Wang Xin , Arslan Okan , Delage Erick 
Published: February 2024

In order to improve the efficiency of the last-mile delivery system when customers are possibly absent for deliveries, we propose the idea of employing the crowd to work as keepers and to provide storage services for their neighbors. Crowd keepers have extra flexibility, more availability, and lower costs than fixed storage options such as automated lockers, and this leads to a more efficient and a more profitable system for last-mile deliveries. We present a bilevel program that jointly determines the assignment, routing, and pricing decisions while considering customer preferences, keeper behaviors, and platform operations. We develop an equivalent single-level program, a mixed-integer linear program with subtour elimination constraints, that can be solved to optimality using a row generation algorithm. To improve the efficiency of the solution procedure, we further derive exact best response sets for both customers and keepers, and approximate optimal travel times using linear regression. We present a numerical study using a real-world data set from Amazon. The fixed-storage and no-storage systems are used as benchmarks to assess the performance of the crowdkeeping system. The results show that the crowdkeeping delivery system has the potential to generate higher profits because of its ability to consolidate deliveries and to eliminate failed deliveries. Funding: Funding provided by the Natural Sciences and Engineering Research Council of Canada [Grants 2022-04979 and 2022-05261], the Canada Research Chair program [Grant CRC-2018-00105], and the China Scholarship Council [Grant 202006190051] is gratefully acknowledged. Supplemental Material: The online appendix is available at https://doi.org/10.1287/trsc.2022.0323 .
On the Efficiency Impacts of Berthing Priority Provision
Authors: Lin Xi , Pu Xinyue , Bai Xiwen 
Published: February 2024

Facing intensified interport competition in the global container shipping market, an increasing number of ports choose to offer berthing priority for carriers to increase their attractiveness. This study is the first to theoretically analyze the efficiency impacts of such prioritization. Specifically, this study models the steady-state dynamics for each terminal in a biterminal port as a prioritized queuing system. We explore the equilibrated shipping flow distribution and resulting total system cost (i.e., bunker consumption cost and waiting time cost) with and without priority provision, along with their major analytical properties. Then, we examine the “second-order” effects of these priority schemes on just-in-time (JIT) arrivals, an increasingly popular green port management tool. Specifically, we investigate how the equilibrium state associated with JIT arrivals could change with priority berthing. These analyses generate some interesting results, including (1) the total system cost increases or remains unchanged when a priority scheme is implemented under a symmetric port with equal service capacities for both terminals; (2) under the asymmetric biterminal case, however, it is also possible that berth prioritization could reduce the total system cost, and such phenomenon occurs only if the terminal which offers prioritization owns larger service capacity; (3) the results indicate that the “price of prioritization” could reach [Formula: see text] in port operation when the berth loading is heavy, implying that priority provision may significantly harm the operational efficiency; and (4) lastly, priority provision has a negative second-order effect on JIT strategies in a symmetric port, and such negative effect may neutralize the positive ones. Those theoretical results are validated by numerical experiments, and some of them are also supported by empirical data. The results provide important practical implications for the decision making of the port (or terminal) agencies. Funding: This work was supported by the National Natural Science Foundation of China [Grants 72371143 and 72188101]. Supplemental Material: The online appendix is available at https://doi.org/10.1287/trsc.2022.0411 .
Sporadic gastrinoma with refractory benign esophageal stricture: A case report
Authors: Chen Qian-Nan , Bai Bing-Qing , Xu Yan , Mei Qiao , Liu Xiao-Chang 
Published: February 2024

BACKGROUND
Gastrinoma is characterized by an excessive release of gastrin, leading to hypersecretion of gastric acid, subsequently resulting in recurrent peptic ulcers, chronic diarrhea, and even esophageal strictures. This case report aims to improve awareness and facilitate early diagnosis and treatment of gastrinoma by presenting a rare case of gastrinoma with refractory benign esophageal stricture (RBES). Additionally, it highlights the persistent challenges that gastroenterologists encounter in managing RBES.
CASE SUMMARY
This case demonstrates a patient with gastrinoma who developed RBES and complete esophageal obstruction despite management with maximal acid suppressive therapy, multiple endoscopic bougie dilations and endoscopic incisional therapy (EIT).
CONCLUSION
It is essential to diagnose gastrinoma as early as possible, as inadequately controlled acid secretion over an extended period increases the risk of developing severe esophageal strictures. In patients with esophageal strictures causing complete luminal obstruction, blind reopening EIT presents challenges and carries a high risk of perforation.
Cardiac remodeling in patients with atrial fibrillation reversing bradycardia-induced cardiomyopathy: A case report
Authors: Gao De-Kui , Ye Xiang-Lin , Duan Zhen , Zhang Hong-Yang , Xiong Tao , Li Zheng-Hong , Pei Hai-Feng 
Published: February 2024

BACKGROUND
Bradycardia-induced cardiomyopathy (BIC), which is a disease resulting from bradycardia, is characterized by cardiac chamber enlargement and diminished cardiac function. The correction of bradycardia can allow for significant improvements in both cardiac function and structure; however, this disease has been infrequently documented. In this case, we conducted a longitudinal follow-up of a patient who had been enduring BIC for more than 40 years to heighten awareness and prompt timely diagnosis and rational intervention.
CASE SUMMARY
A woman who presented with postactivity fatigue and dyspnea was diagnosed with bradycardia at the age of 7. Since she had no obvious symptoms, she did not receive any treatment to improve her bradycardia during the 42-year follow-up, except for the implantation of a temporary pacemaker during labor induction surgery. As time progressed, the patient's heart gradually expanded due to her low ventricular rate, and she was diagnosed with BIC. In 2014, the patient developed atrial fibrillation, her ventricular rate gradually increased, and her heart shape gradually returned to normal. This report describes the cardiac morphological changes caused by the heart rate changes in BIC patients older than 40 years, introduces another possible outcome of BIC, and emphasizes the importance of early intervention in treating BIC.
CONCLUSION
BIC can induce atrial fibrillation, causing an increased ventricular rate and leading to positive cardiac remodeling.
Double plasma molecular adsorption system for Stevens–Johnson syndrome/toxic epidermal necrolysis: A case report
Authors: Tan You-Wen , Liu Li-Ping , Zhang Kai 
Published: February 2024

BACKGROUND
Stevens–Johnson syndrome and toxic epidermal necrolysis (SJS/TEN) are very serious skin allergies, with an etiology related to infections and medication. Since the coronavirus disease 2019 (COVID-19) pandemic, severe acute respiratory syndrome coronavirus-2 has also been considered to cause SJS/TEN.
CASE SUMMARY
We report the case of a woman in her thirties who took acetaminophen after contracting COVID-19. After 3 d of fever relief, she experienced high fever and presented with SJS/TEN symptoms, accompanied by intrahepatic cholestasis. Three days of corticosteroid treatment did not alleviate the skin damage; therefore, double plasma molecular adsorption system (DPMAS) therapy was initiated, with treatment intervals of 48 h. Her skin symptoms improved gradually and were resolved after seven DPMAS treatments.
CONCLUSION
DPMAS therapy is beneficial for abrogating SJS/TEN because plasma adsorption and perfusion techniques reduce the inflammatory mediators (e.g. , tumor necrosis factor-alpha and interleukin-10 and-12) speculated to be involved in the pathology of the skin conditions.
Changes in nonalcoholic fatty liver disease and M2BPGi due to lifestyle intervention in primary healthcare
Authors: Nah Eun-Hee , Choi Yong Jun , Cho Seon , Park Hyeran , Kim Suyoung , Kwon Eunjoo , Cho Han-Ik 
Published: February 2024

Background
A healthy lifestyle is the most important method for managing nonalcoholic fatty liver disease (NAFLD). Mac-2-binding protein glycosylated isomer (M2BPGi) has been suggested as a biomarker for NAFLD. This study aimed to determine the efficacy of personalized lifestyle interventions on NAFLD remission.

Methods
This single-arm intervention study recruited participants with NAFLD who underwent health checkups at seven health-promotion centers in five South Korean cities. Fatty liver diagnosis was based on ultrasonography (US). The 109 individuals were recruited for personalized lifestyle interventions of hypocaloric diets and exercise. The participants attended the lifestyle intervention programs once per month for the first 3 months, and once every 3 months for the subsequent 6 months. In addition to sessions through center visits, phone-based intervention and self-monitoring at 4-, 5-, 7-, and 8-month were provided during the 9-month intervention period. And phone-based self-monitoring were also provided monthly during the 3-month follow-up period. The primary outcome was NAFLD remission at month 12 as measured on US and magnetic resonance elastography. The secondary outcomes were the changes in metabolic factors and M2BPGi.

Results
The 108 individuals (62 males and 46 females; age 51.1±12.4 years, mean±standard deviation) were finally analyzed after the 12month intervention. Body mass index, waist circumference (WC), blood pressure, blood lipids (total cholesterol, triglycerides, and HDL-C), and fasting blood sugar levels were improved relative to baseline (all P<0.05). Fatty liver at or above the moderate grade according to US was decreased at month 12 relative to baseline (67.6% vs 50.9%) (P = 0.002). M2BPGi levels decreased during the 12-month study period (P<0.001). M2BPGi levels were moderately correlated with hepatic fat fraction by magnetic resonance imaging (r = 0.33, P = 0.05). WC (OR = 0.82, 95% CI = 0.67–1.00, P = 0.05) and HDL-C (OR = 1.17, 95% CI = 1.03–1.32, P = 0.014) were associated with remission of fatty liver in the multivariate analysis.

Conclusion
The personalized lifestyle intervention was effective in improving fatty liver and metabolic factors, but not hepatic stiffness, in NAFLD.

Trial registration
ICTRP, cris.nih.go.kr (KCT0006380).
Early full-day leg movement kinematics and swaddling patterns in infants in rural Guatemala: A pilot study
Authors: Oh Jinseok , Ordoñez Eva Leticia Tuiz , Velasquez Elisa , Mejía Marines , Grazioso Maria del Pilar , Rohloff Peter , Smith Beth A. 
Published: February 2024

Background
Tools to accurately assess infants’ neurodevelopmental status very early in their lives are limited. Wearable sensors may provide a novel approach for very early assessment of infant neurodevelopmental status. This may be especially relevant in rural and low-resource global settings.

Methods
We conducted a longitudinal observational study and used wearable sensors to repeatedly measure the kinematic leg movement characteristics of 41 infants in rural Guatemala three times across full days between birth and 6 months of age. In addition, we collected sociodemographic data, growth data, and caregiver estimates of swaddling behaviors. We used visual analysis and multivariable linear mixed models to evaluate the associations between two leg movement kinematic variables (awake movement rate, peak acceleration per movement) and infant age, swaddling behaviors, growth, and other covariates.

Results
Multivariable mixed models of sensor data showed age-dependent increases in leg movement rates (2.16 [95% CI 0.80,3.52] movements/awake hour/day of life) and movement acceleration (5.04e-3 m/s2 [95% CI 3.79e-3, 6.27e-3]/day of life). Swaddling time as well as growth status, poverty status and multiple other clinical and sociodemographic variables had no impact on either movement variable.

Conclusions
Collecting wearable sensor data on young infants in a rural low-resource setting is feasible and can be used to monitor age-dependent changes in movement kinematics. Future work will evaluate associations between these kinematic variables from sensors and formal developmental measures, such as the Bayley Scales of Infant and Toddler Development.
Machine learning approaches to enhance diagnosis and staging of patients with MASLD using routinely available clinical information
Authors: McTeer Matthew , Applegate Douglas , Mesenbrink Peter , Ratziu Vlad , Schattenberg Jörn M. , Bugianesi Elisabetta , Geier Andreas , Romero Gomez Manuel , Dufour Jean-Francois , Ekstedt Mattias , Francque Sven , Yki-Jarvinen Hannele , Allison Michael , Valenti Luca , Miele Luca , Pavlides Michael , Cobbold Jeremy , Papatheodoridis Georgios , Holleboom Adriaan G. , Tiniakos Dina , Brass Clifford , Anstee Quentin M. , Missier Paolo ,   on behalf of the LITMUS Consortium investigators
Published: February 2024

Aims
Metabolic dysfunction Associated Steatotic Liver Disease (MASLD) outcomes such as MASH (metabolic dysfunction associated steatohepatitis), fibrosis and cirrhosis are ordinarily determined by resource-intensive and invasive biopsies. We aim to show that routine clinical tests offer sufficient information to predict these endpoints.

Methods
Using the LITMUS Metacohort derived from the European NAFLD Registry, the largest MASLD dataset in Europe, we create three combinations of features which vary in degree of procurement including a 19-variable feature set that are attained through a routine clinical appointment or blood test. This data was used to train predictive models using supervised machine learning (ML) algorithm XGBoost, alongside missing imputation technique MICE and class balancing algorithm SMOTE. Shapley Additive exPlanations (SHAP) were added to determine relative importance for each clinical variable.

Results
Analysing nine biopsy-derived MASLD outcomes of cohort size ranging between 5385 and 6673 subjects, we were able to predict individuals at training set AUCs ranging from 0.719-0.994, including classifying individuals who are At-Risk MASH at an AUC = 0.899. Using two further feature combinations of 26-variables and 35-variables, which included composite scores known to be good indicators for MASLD endpoints and advanced specialist tests, we found predictive performance did not sufficiently improve. We are also able to present local and global explanations for each ML model, offering clinicians interpretability without the expense of worsening predictive performance.

Conclusions
This study developed a series of ML models of accuracy ranging from 71.9—99.4% using only easily extractable and readily available information in predicting MASLD outcomes which are usually determined through highly invasive means.
Longitudinal association between e-cigarette use and respiratory symptoms among US adults: Findings from the Population Assessment of Tobacco and Health Study Waves 4–5
Authors: Karey Emma , Xu Shu , He Pan , Niaura Raymond S. , Cleland Charles M. , Stevens Elizabeth R. , Sherman Scott E. , El-Shahawy Omar , Cantrell Jennifer , Jiang Nan 
Published: February 2024

Background
We assessed longitudinal effects of e-cigarette use on respiratory symptoms in a nationally representative sample of US adults by combustible tobacco smoking status.

Methods
We analyzed Waves 4–5 public-use data from the Population Assessment of Tobacco and Health Study. Study sample included adult respondents who reported no diagnosis of respiratory diseases at Wave 4, and completed Waves 4–5 surveys with no missing data on analytic variables (N = 15,291). Outcome was a validated index of functionally important respiratory symptoms based on 7 wheezing/cough questions (range 0–9). An index score of ≥2 was defined as having important respiratory symptoms. Weighted lagged logistic regression models were performed to examine the association between e-cigarette use status at Wave 4 (former/current vs. never use) and important respiratory symptoms at Wave 5 by combustible tobacco smoking status (i.e., never/former/current smokers), adjusting for Wave 4 respiratory symptom index, sociodemographic characteristics, secondhand smoke exposure, body mass index, and chronic disease.

Results
Among current combustible tobacco smokers, e-cigarette use was associated with increased odds of reporting important respiratory symptoms (former e-cigarette use: adjusted odds ratio [AOR] = 1.39, 95% confidence interval [CI]: 1.07–1.81; current e-cigarette use: AOR = 1.55, 95% CI: 1.17–2.06). Among former combustible tobacco smokers, former e-cigarette use (AOR = 1.51, 95% CI: 1.06–2.15)—but not current e-cigarette use (AOR = 1.59, 95% CI: 0.91–2.78)—was associated with increased odds of important respiratory symptoms. Among never combustible tobacco smokers, no significant association was detected between e-cigarette use and important respiratory symptoms (former e-cigarette use: AOR = 1.62, 95% CI: 0.76–3.46; current e-cigarette use: AOR = 0.82, 95% CI: 0.27–2.56).

Conclusions
The association between e-cigarette use and respiratory symptoms varied by combustible tobacco smoking status. Current combustible tobacco smokers who use e-cigarettes have an elevated risk of respiratory impairments.
Association between preoperative cholecalciferol therapy and hypocalcemia after parathyroidectomy in patients with primary hyperparathyroidism
Authors: Elfimova A. R. , Eremkina A. K. , Rebrova O. Yu. , Kovaleva E. V. , Mokrysheva N. G. 
Published: February 2024

BACKGROUND: Primary hyperparathyroidism (PHPT) is a endocrine disorder characterized by excessive secretion of parathyroid hormone (PTH) from parathyroid gland tumors. Parathyroidectomy (PTE) is the main treatment for PHPT, but it can lead to hypocalcemia in up to 46% of cases. Hypocalcemia is associated with seizures and life-threatening cardiac arrhythmias, and vitamin D deficiency can exacerbate PHPT severity and contribute to «hungry bones syndrome,» resulting in severe and persistent postoperative hypocalcemia.AIM: To evaluate the association and determine the strength of the relationship between preoperative cholecalciferol therapy and the occurrence of hypocalcemia within 1–3 days after PTE in patients with PHPT.MATERIALS AND METHODS: The study was conducted at the Endocrinology Research Centre, during the periods of 1993–2010 and 2017–2020. The inclusion criteria consisted of patients diagnosed with PHPT who required PTE, had a serum 25-hydroxyvitamin D (25(OH)D) level below 20 ng/mL, and a serum total calcium level below 3 mmol/L. The exclusion criterion was the use of medications that affect calcium-phosphorus metabolism, including cinacalcet, denosumab, or bisphosphonates, either as monotherapy or as part of combination therapy.RESULTS: There were 117 patients, including 110 (94%) females and 7 (6%) males. The median age and interquartile range were 58 [49; 65] years. Among the participants, 21 (18%) received cholecalciferol supplementation for a duration of 2 weeks to 2 months prior to PTE, aiming to address vitamin D deficiency. The remaining 96 (82%) participants did not receive ­cholecalciferol supplementation. Both groups, i.e., participants receiving cholecalciferol and those who did not, were similar in terms of anthropometric factors (sex and age at the time of surgery), preoperative clinical characteristics (BMD decrease), and laboratory parameters (PTH, total calcium, phosphorus, ALP, OC, CTX-1, and 25(OH)D levels). The occurrence of postoperative hypocalcemia was significantly lower in participants who received cholecalciferol supplementation (10% vs. 63%, p<0,001, FET2). Cholecalciferol intake showed a negative association with hypocalcemia development (RR=0,15, 95% CI (0,03; 0,51)).CONCLUSION: Preoperative cholecalciferol supplementation for 2 weeks to 2 months before PTE reduces the risk of postoperative hypocalcemia in patients with PHPT by 2–33 times.