bluuebunny/crossref_metadata_2025_split huggingface dataset:
HYPOGLYCEMIC EFFECT OF SITAGLIPTIN AND AMINOGUANIDINE COMBINATION IN EXPERIMENTAL DIABETES MELLITUS
Authors: Kurkin D. V. , Bakulin D. A. , Morkovin E. I. , Gorbunova Yu. V. , Strygin A. V. , Andriashvili T. M. , Sokolova A. A. , Bolokhov N. S. , Pustynnikov V. E. , Fomichev E. A. 
Published: February 2023

The aim of the work was to determine the antidiabetic effect of a sitagliptin and aminoguanidine combination in rats with experimental diabetes mellitus.Materials and methods. The study was carried out on male Wistar rats and C57BL/KsJ-db/db mice. According to the models used, it was divided into 4 series, in which alloxan, steroid-induced (dexamethasone) and streptozotocin-nicotinamide-induced diabetes mellitus (DM) were formed, respectively, in rats, and in the 4 series, obese C57BL/KsJ-db/db mice were used. In the 1 and 2 series, the treatment was started prophylactically – 3 h after the alloxan administration and simultaneously with the dexamethasone administration, in the 3rd and 4th series, the treatment was carried out after the pathology had developed – 7 days after the streptozotocin with nicotinamide administration, and in the obese mice – immediately after their distribution according to the groups. The treatment was carried out with sitagliptin (10 mg/kg), aminoguanidine (25 mg/kg), or a combination thereof. The treatment was continued till the end of the experiment, which was completed with an oral glucose tolerance test (OGTT) after 4 h of fasting. The obtained data were subjected to statistical processing.Results. In the course of the experiments, it was found out that the prophylactic administration of a sitagliptin and aminoguanidine combination, unlike each of the components, prevented the development of alloxan DM. More effectively than the administration of sitagliptin alone, it reduced the severity of steroid-induced DM, which was expressed in a significantly lower level of fasting glycemia (after 4 h of fasting) and postprandial glycemia (during OGTT). Under the conditions of streptozotocin-nicotinamide-induced DM, the studied combination slowed down the progression of the pathology, and in the obese mice, the course therapeutic administration of sitagliptin and its combination reduced the severity of carbohydrate metabolism disorders (fasting glycemia) and increased the rate of glucose utilization.Conclusion. As an iNOS blocker, aminoguanidine enhances the antidiabetic effect of sitagliptin, preventing the development of alloxan diabetes and reducing the severity of steroid-induced DM when administered prophylactically. When administered therapeutically, it reduces the severity of streptozotocin-nicotinamide-induced DM in rats and type 2 DM in mice with a predisposition to obesity.
DF-5 COMPOUND DELAYS DEVELOPMENT OF DIABETIC NEPHROPATHY IN RATS
Authors: Spasov A. A. , Zhukovskaya O. N. , Rashchenko A. I. , Brigadirova A. A. , Litvinov R. A. , Gurova N. A. , Smirnov A. V. , Pan’shin N. G. , Abbas H. S.A. , Morkovnik A. S. 
Published: February 2023

Advanced glycation end-products play an important role in the development of diabetic complications, so slowing down of glycated proteins’ cross-links formation have been suggested as a potential therapeutic option for the treatment of vascular diabetic complications and preventing their progression.The aim of the work was to assess the influence of novel anticrosslinking agent DF-5 on the renal advanced glycation end-products and collagen contents, body weight, blood glucose and glycated hemoglobin levels and the development of early renal disease in streptozotocin-induced diabetic rats.Materials and methods. 40 male Sprague-Dawley rats were used in the study. Two months after inducing diabetes, the study substance was administered intragastrically once a day for 28 days (12.5 mg/kg). Measurements included the assessment of blood glucose and HbA1c levels, the evaluation of the renal function, and the results of histology and immunohistochemical staining of kidneys.Results. A repeated intragastric administration of DF-5 for 30 days significantly reduced the level of HbA1c in the blood, but did not affect the level of fasting blood glucose. DF-5 compound significantly reduced proteinuria and prevented kidney damage in experimental animals by limiting damage of the glomeruli and tubules. It was found that DF-5 inhibits the progression of an early renal dysfunction in rats with streptozotocin-induced diabetic nephropathy. This was associated with a decreased accumulation of advanced glycation end-products in the kidney, accompanied by the improvement of both renal morphology and function.Conclusion. The results obtained provide investigators with additional therapeutic options for the treatment of diabetic nephropathy and possibly other complications of diabetes.
BIOEQUIVALENCE STUDY OF GENERIC MOLNUPIRAVIR IN HEALTHY VOLUNTEERS
Authors: Vasilyuk V. B. , Boroduleva A. Yu. , Sobolev P. D. , Nikiforova A. G. , Mozgovaya V. G. , Filon O. V. , Zinkovskaya A. V. , Ignatiev V. G. , Samsonov M. Yu. , Kozlova I. S. , Khanonina E. K. 
Published: February 2023

Molnupiravir is one of the drugs for the etiotropic therapy of a new coronavirus infection COVID-19. It has confirmed its clinical efficacy in the treatment of patients with mild and moderate COVID-19, including those who are at high risk of progressing to severe disease.The aim of the study was to evaluate bioequivalence of the generic drug molnupiravir ALARIO-TL and the original drug Lagevrio with a single oral administration in healthy volunteers.Materials and methods. This bioequivalence study was an open, randomized, two-period crossover study. In each of the two periods, volunteers received a single dose of the test drug, or reference drug molnupiravir, in the form of capsules at the dose of 200 mg. The washout period between the doses was 3 days. To determine pharmacokinetic (PK) parameters and bioequivalence, the concentration the concentration of N-hydrozycytidine (NHC), the main molnupiravir metabolit in the blood plasma of volunteers was evaluated. The blood plasma sampling was carried out in the range from 0 to 16 hours in each of the study periods. Bioequivalence was assessed by comparing 90% confidence intervals (CIs) for the ratio of geometric means of AUC(0–16) and Cmax of the test drug and reference drugs with the established equivalence limits of 80.00 – 125.00%.Results. A total of 28 healthy male volunteers were included in the study. According to the results of the statistical analysis, after the administration of the test and reference drugs, the 90% CIs for the ratio of the geometric means of AUC (0–16) and Cmax were 96.31% – 113.64% and 91.37% – 114.8%, respectively. These intervals fit within the established limits of 80.00–125.00%, which confirms the bioequivalence of the drugs. When comparing the frequency of the individual adverse events registration, no significant differences were found out after the administration of the test and reference drugs.Conclusion. Based on the results of this study, it can be concluded that the test and reference drugs of molnupiravir are bioequivalent. In addition, the data obtained indicate that the drugs have similar safety profiles.
Guiding Epilepsy Surgery by Intraoperatively Visualizing Proinflammatory Microglia via a Ratiometric Surface-Enhanced Raman Scattering Nanosensor
Authors: Wang Cong , Li Zhi , Zhu Xiao , Ding Yue , Duan Wenjia , Sun Wanbing , Jiang Yiqing , Chen Ming , Hu Jiayi , Cai Zheping , Zhao Jing , Fan Zhen , Zheng Faming , Zhou Xingyu , Xie Fang , Zhang Jianping , Guan Yihui , Xiao Xiao , Chen Liang , Li Cong , Mao Ying 
Published: February 2023

Abstract
Resective surgery is used for long-term seizure control in drug-resistant focal epilepsy when the epileptic focus (EF) can be accurately delineated and removed. However, as the “gold standard” technique for mapping EF intraoperatively, electroencephalography is laborious, time-consuming and highly vulnerable to anaesthesia. Here, we demonstrated hypochlorous acid (HOCl), a bioproduct of activated proinflammatory microglia, can be reliable biomarkers for EF localization. With a newly developed HOCI ratiometric Raman nanosensor, ultraHOCls, we can accurately locate EF in live kainic-acid-induced mice by visualizing proinflammatory microglia ignoring the interference of anaesthesia. Moreover, ultraHOCls provided a 1-hour stable imaging time-window for locating EF, which is more than 100 times longer than single neuroelectric activity recorded by electroencephalography. UltraHOCls-guided surgery showed a 72% reduction in total seizure time in mice in comparison to electroencephalography-guided surgery. This work provides an alternative strategy for locating EF intraoperatively and holds promise in improving surgical outcomes in epilepsy patients.
Application of Machine Learning in Predicting Frailty Syndrome in Patients with Heart Failure
Authors: Szczepanowski Remigiusz , Pasieczna Aleksandra H. , Sobecki Janusz , Katarzyniak Radoslaw , Kołaczek Grzegorz , Lorkiewicz Wojciech , Kędras Maja , Uchmanowicz Izabella , Biegus Jan , Wleklik Marta , Gobbens Robbert J.J. , Hill Loreena , Jaarsma Tiny , Hussain Amir , Barbagallo Mario , Veronese Nicola , Morabito Francesco C. , Dixit Anant , Kahsin Aleksander 
Published: February 2023

Abstract
Background
Prevention and diagnosis of frailty syndrome (FS) in patients with heart failure (HF) requires innovative systems supporting medical personnel to tailor and optimize their treatment and care. Classical methods of diagnosing the FS in patients are not entirely satisfactory. Healthcare personnel in clinical setting use a combination of test and self-reports to diagnose patients and those at risk of frailty, which is time-consuming and costly. Modern medicine uses artificial intelligence (AI) to study the physical and psychosocial domains of frailty in cardiac patients with HF.
Methods
This paper aimed to present the potential of using the AI approach, emphasizing machine learning in predicting frailty in patients with HF. Our team critically scrutinized the literature on machine learning applications for FS syndrome, as well as reviewed frailty measurements applied to modern clinical practice.
Results
Our approach analysis resulted in recommendations of machine learning algorithms for predicting frailty in patients. We also presented the exemplary application of machine learning for frailty syndrome in HF patients based on TFI questionnaire measurements, taking into account psychosocial variables
Conclusions
We recommend AI and machine learning for the holistic and personalized care of patients at risk of the consequences of FS, improve diagnostic tools examining this syndrome, and effective collaboration between psychologists and health care professionals.
Rapid Implementation of Veterans Health Administration Telehealth Creative Arts Therapies: Survey Evaluation of Adoption and Adaptation
Authors: Story Kristin M , Flanagan Mindy , Robb Sheri L. , Bravata Dawn M. , Bair Matthew J. , Otto David , Damush Teresa M. 
Published: February 2023

Abstract
Background: Creative Arts Therapies (CAT) are employed throughout the Veterans Health Administration (VHA) and are predominantly delivered in-person. Due to guidance from the Center for Disease Control and VHA that temporarily suspended or reduced in-person services, CAT therapists adopted telehealth delivery. The aims of this study were to evaluate adoption and adaptation of CAT telehealth delivery and identify related barriers and facilitators.
Methods: We deployed a survey guided by the Consolidated Framework for Implementation Research and administered it via email to all VHA CAT therapists (N=120). Descriptive statistics were used to summarize data and responses were compared based on therapists’ age, years of experience and CAT discipline. Open survey field responses were summarized, qualitatively coded, and analyzed thematically.
Results: Most therapists (76%) reported adopting telehealth with 74% each delivering >50 CAT sessions in the prior year. Therapists adapted interventions or created new ones to be delivered through telehealth. Barriers included: technical challenges, control of the virtual space, and building rapport. Facilitators included added equipment, software, and infrastructure. CAT therapists adapted their session preparation, session content, outcome expectations, and equipment. CAT therapists reported being able to reach more patients and improved access to care with telehealth compared to in person visits. Additional benefits were patient therapeutic effects from attending sessions from home, therapist convenience, and clinician growth.
Conclusions: VHA CAT therapists used their inherent creativity to problem solve difficulties and make adaptations for CAT telehealth adoption. Future studies may explore CAT telehealth sustainment and its effectiveness on clinical processes and outcomes.
Application of the Composite Quality Score (CQS-2B) in systematic reviews of prospective, controlled, clinical therapy trials – a pilot study (Protocol v.2.0)
Authors: Mickenautsch Steffen , Rupf Stefan , Yengopal Veerasamy 
Published: February 2023

Abstract
Objectives: To establish, whether clinical conclusions from systematic reviews that applied the second version of Cochrane’s Risk of Bias tool (RoB 2) remain the same when the Composite Quality Score (CQS-2B) is used, instead.
Methods: PubMed will be searched for one systematic review that complies with the following criteria: At least 20 prospective, clinical, controlled therapy trials included into meta-analyses; computable data for test- and control group reported; trial appraisal using the RoB 2 tool; inclusion of at least 5 trials in at least one single comparison per measured outcome; published in English. All trial reports included in the systematic review will be traced in full copy and the following data extracted per trial: Full reference details; overall RoB 2 appraisal decision; computable datasets. All trial reports will be re-appraised using the CQS-2B. All datasets will be stratified by overall bias risk (RoB 2 tool) and per corroboration (C-) level (CQS-2B). Trial data for each bias risk and C-level will be statistically pooled using Mantel-Haenszel statistics with random-effects model. All pooled ‘low bias risk’ effect estimates (RoB 2) and all pooled effect estimates of the highest C-level with data (CQS-2B) will in turn each be pooled by use of a random effects meta-analysis. DerSimonian and Laird’s method of moments estimator will be used to estimate the between-study variance. Statistical inconsistency will be quantified using the I2 statistic. The pooled effect estimates of both appraisal tools will be statistically compared using the Wald-test and the null-hypothesis tested that both are not significantly different. Clinical conclusions based on the pooled ‘low bias risk’ estimates (RoB 2) and the C4-level (CQS-2B) will be qualitatively compared.
Reporting: The final report will be made available online as preprint in one of the major preprint repositories and submitted to a peer-reviewed journal.
The Dynamic Effects on Bone Mass of Chemotherapy and Surgery in Lung Cancer Patients
Authors: Wang Guoqing , Li Tianyu , Zhang Le , Li Changcheng , LI Jinglei , Cong Jicong , Qin Jian , Li Changqin , Zhu Jianzhong , Li Shen-jiang 
Published: February 2023

Abstract
Background The aim of this study was to evaluate the dynamic effects on bone mass of chemotherapy and surgery in lung cancer patients by computed tomography (CT).
Methods This was a retrospective study, 147 patients with lung cancer from June to December 2021 in our hospital were finally selected. Data consisted of cycle of chemotherapy and surgery. CT scans before chemotherapy and cycle 1-6 after chemotherapy were performed.The CT values of the T11-L1 vertebral body were recorded and compared.
Results The mean CT values of T11-L1 vertebral body in cycle 1, 5and 6 were lower than that in pre-chemotherapy (P=0.007＜0.05，P=0.038＜0.05，P=0.048＜0.05). There was no significant difference among the rest groups (all P＞0.05）. The CT value of T11 was higher than those of L1 in pre-chemotherapy and cycle 1, 2 after chemotherapy (P＜0.001，P=0.042< 0.05，P=0.015< 0.05). There was no statistically significant difference in CT values among the T11,T12 and L1 in cycle 3, 4, 5 and 6 (all P＞0.05). There was no statistical significant difference in the mean CT values of the T11-L1 vertebral body between operation group and non-operation group in pre-chemotherapy and same cycle after chemotherapy (all P＞0.05).
Conclusions Osteodeficiency exacerbated by ongoing chemotherapy and unaffected by operation in lung cancer patients indicates the need for the development of antiosteoporosis treatment and osteoporosis prophylaxis for lung cancer patients.
Outcome and Decision-making Process in Penile Curvature Surgery: a Single-centre Preliminar Experience
Authors: Loria Giada , Stranieri Giuseppe , Talarico Valentina , Fava Antonietta , Raiola Giuseppe , Galati Maria Concetta , Salerno Domenico 
Published: February 2023

Abstract
Penile curvature could represent a great challenge to the paediatric urologist. Surgeons have to choose among several surgical techniques. Degloving and chordee section techniques are able to correct the majority of congenital bent penis. More invasive surgeries should be considered for residual curvature or severe cases. We report 35 cases of paediatric patients suffering from anomalies of penile curvature treated with different surgical approaches. No major complications are disclosed. In the majority of patients, degloving and chordee section resulted to be sufficient to correct the curvature. Further studies on a bigger patients’ population are required to assess the most correct approach to each degree of curvature and associated anomalies. Besides every peculiar anatomic condition, to deal with difficult situation where the line of must-treat is not so marked, in our opinion it is crucial to be able to count on multi-disciplinary teamwork which can accomplish a 360-degrees evaluation of the patients’ health and mental status.
The DUBA-SLC7A11-c-Myc axis is critical for stemness and ferroptosis
Authors: Tao Yongguang , Wang Zuli , Ouyang Lianlian , Liu Na , Li Tiansheng , Yan Bokang , Mao Chao , Xiao Desheng , Gan Boyi , Liu Shuang 
Published: February 2023

Abstract
Ferroptosis is characterized by the accumulation of lipid peroxidation as a unique iron-dependent cell death. However, the interplay between stemness and ferroptosis remains unknown. Here, we demonstrate that undifferentiated cells are more sensitive to ferroptosis than differentiated cells, and cystine transporter SLC7A11 protein is highly up-regulated by deubiquitinase DUBA in differentiated cells. Additionally, DUBA promotes stemness by deubiquitinating SLC7A11. Moreover, SLC7A11 drastically increases the expression of c-Myc through cysteine, the combination of sorafenib and c-Myc inhibitor EN4 has a synergetic effect on cancer therapy. Together, our results reveal that enhanced stemness increases the susceptibility to ferroptosis, and the DUBA-SLC7A11-c-Myc axis is pivotal for differentiated cancer stem cells (CSCs) resistant to ferroptosis, providing a promised targets to eradicate CSCs through ferroptosis.
Development and implementation of site-specific Hepatitis C Virus treatment workflows for treating vulnerable, high-risk populations: protocol of the Erase Hep C study, a prospective single-arm intervention trial
Authors: Desai Anmol , O’Neal Lauren , Reinis Kia , Chang Patrick , Brown Cristal , Stefanowicz Michael , Kuang Audrey , Agrawal Deepak , Bhavnani Darlene , Mercer Tim 
Published: February 2023

Abstract
Background: Hepatitis C virus (HCV) is the leading indication for liver transplantation and liver-related mortality. The development of direct acting antivirals (DAA) and a simplified treatment algorithm with a >97% cure rate should make global elimination of HCV an achievable goal. Yet, vulnerable populations with high rates of HCV still have limited access to treatment. By designing locally contextualized site-specific HCV treatment workflows, we aim to cure HCV in vulnerable, high-risk populations, including people experiencing homelessness (PEH) and people who inject drugs (PWID), in Austin, Texas.
Methods: Our implementation science study will utilize a mixed methods approach to characterize patient and systemic barriers and facilitators to HCV treatment in vulnerable, high-risk populations seeking care across seven diverse primary care clinics serving PEHs and PWIDs. Qualitative interviews guided by the Practical, Robust Implementation and Suitability Model (1)framework will identify barriers and facilitators by leveraging knowledge and experience from both clinic staff and patients. Data synthesized using thematic analysis and design thinking will feed into workshops with clinic stakeholders for idea generation to design site-specific HCV treatment workflows. Providers will be trained on the use of a simplified HCV treatment algorithm with DAAs, and clinic staff on the new site-specific HCV treatment workflows. These workflows will be implemented by the seven diverse primary care clinics serving vulnerable, high-risk populations. Implementation and clinical outcomes will be measured using data collected through interviews with staff as well as through medical chart review.
Discussion: Our study provides a model of how to contextualize and implement site-specific HCV treatment workflows targeting vulnerable, high-risk populations in other geographic locations. This model can be adopted for future implementation research programs aiming to develop and implement site-specific treatment workflows for vulnerable, high-risk populations and in primary care clinical settings for other disease states beyond just HCV.
Trial Registration: Registered on ClinicalTrials.govon July, 14, 2022. Identifier: NCT05460130. https://clinicaltrials.gov/ct2/show/NCT05460130
Quantitation of Dynamic Total-Body PET Imaging: Recent Developments and Future Perspectives
Authors: Gu Fengyun , Wu Qi 
Published: February 2023

Abstract
Positron emission tomography (PET) scanning is an important diagnostic imaging technique used in disease diagnosis, therapy planning, treatment monitoring and medical research. The standardized uptake value (SUV) obtained at a single time frame has been widely employed in clinical practice. Well beyond this simple static measure, more detailed metabolic information can be recovered from dynamic PET scans, followed by the recovery of arterial input function and application of appropriate tracer kinetic models. Many efforts have been devoted to the development of quantitative techniques over the last couple of decades.
The advent of new-generation total-body PET scanners characterized by ultra-high sensitivity and long axial field of view, i.e., uEXPLORER (United Imaging Healthcare), PennPET Explorer (University of Pennsylvania) and Biograph Vision Quadra (Siemens Healthineers), further stimulate valuable inspiration to map kinetics for multiple organs simultaneously. But some emerging issues also need to be addressed, e.g., the large-scale data size and organ-specific physiology. The direct implementation of classical methods for total-body PET imaging without proper validation may lead to less accurate results.
In this contribution, the published dynamic total-body PET datasets are outlined and several challenges/opportunities for quantitation of such types of studies are presented. An overview of the basic equation, calculation of input function (based on blood sampling, image, population or mathematical model) and kinetic analysis encompassing parametric (compartmental model, graphical plot and spectral analysis) and non-parametric (B-spline and piece-wise basis elements) approaches is provided. The discussion mainly focuses on the feasibilities, recent developments and future perspectives of these methodologies for a diverse-tissue environment.