bluuebunny/crossref_metadata_2025 huggingface dataset:
Induction of Angiogenesis by Genetically Modified Human Umbilical Cord Blood Mononuclear Cells
Authors: Gatina Dilara Z. , Gazizov Ilnaz M. , Zhuravleva Margarita N. , Arkhipova Svetlana S. , Golubenko Maria A. , Gomzikova Marina O. , Garanina Ekaterina E. , Islamov Rustem R. , Rizvanov Albert A. , Salafutdinov Ilnur I.
Published: February 2023

Stimulating the process of angiogenesis in treating ischemia-related diseases is an urgent task for modern medicine, which can be achieved through the use of different cell types. Umbilical cord blood (UCB) continues to be one of the attractive cell sources for transplantation. The goal of this study was to investigate the role and therapeutic potential of gene-engineered umbilical cord blood mononuclear cells (UCB-MC) as a forward-looking strategy for the activation of angiogenesis. Adenovirus constructs Ad-VEGF, Ad-FGF2, Ad-SDF1α, and Ad-EGFP were synthesized and used for cell modification. UCB-MCs were isolated from UCB and transduced with adenoviral vectors. As part of our in vitro experiments, we evaluated the efficiency of transfection, the expression of recombinant genes, and the secretome profile. Later, we applied an in vivo Matrigel plug assay to assess engineered UCB-MC’s angiogenic potential. We conclude that hUCB-MCs can be efficiently modified simultaneously with several adenoviral vectors. Modified UCB-MCs overexpress recombinant genes and proteins. Genetic modification of cells with recombinant adenoviruses does not affect the profile of secreted pro- and anti-inflammatory cytokines, chemokines, and growth factors, except for an increase in the synthesis of recombinant proteins. hUCB-MCs genetically modified with therapeutic genes induced the formation of new vessels. An increase in the expression of endothelial cells marker (CD31) was revealed, which correlated with the data of visual examination and histological analysis. The present study demonstrates that gene-engineered UCB-MC can be used to stimulate angiogenesis and possibly treat cardiovascular disease and diabetic cardiomyopathy.
Lipids at the Nexus between Cerebrovascular Disease and Vascular Dementia: The Impact of HDL-Cholesterol and Ceramides
Authors: Sergi Domenico , Zauli Enrico , Tisato Veronica , Secchiero Paola , Zauli Giorgio , Cervellati Carlo
Published: February 2023

Cerebrovascular diseases and the subsequent brain hypoperfusion are at the basis of vascular dementia. Dyslipidemia, marked by an increase in circulating levels of triglycerides and LDL-cholesterol and a parallel decrease in HDL-cholesterol, in turn, is pivotal in promoting atherosclerosis which represents a common feature of cardiovascular and cerebrovascular diseases. In this regard, HDL-cholesterol has traditionally been considered as being protective from a cardiovascular and a cerebrovascular prospective. However, emerging evidence suggests that their quality and functionality play a more prominent role than their circulating levels in shaping cardiovascular health and possibly cognitive function. Furthermore, the quality of lipids embedded in circulating lipoproteins represents another key discriminant in modulating cardiovascular disease, with ceramides being proposed as a novel risk factor for atherosclerosis. This review highlights the role of HDL lipoprotein and ceramides in cerebrovascular diseases and the repercussion on vascular dementia. Additionally, the manuscript provides an up-to-date picture of the impact of saturated and omega-3 fatty acids on HDL circulating levels, functionality and ceramide metabolism.
Expression and Impact of Adenosine A3 Receptors on Calcium Homeostasis in Human Right Atrium
Authors: Tarifa Carmen , Jiménez-Sábado Verónica , Franco Rafael , Montiel José , Guerra José , Ciruela Francisco , Hove-Madsen Leif
Published: February 2023

Increased adenosine A2A receptor (A2AR) expression and activation underlies a higher incidence of spontaneous calcium release in atrial fibrillation (AF). Adenosine A3 receptors (A3R) could counteract excessive A2AR activation, but their functional role in the atrium remains elusive, and we therefore aimed to address the impact of A3Rs on intracellular calcium homeostasis. For this purpose, we analyzed right atrial samples or myocytes from 53 patients without AF, using quantitative PCR, patch-clamp technique, immunofluorescent labeling or confocal calcium imaging. A3R mRNA accounted for 9% and A2AR mRNA for 32%. At baseline, A3R inhibition increased the transient inward current (ITI) frequency from 0.28 to 0.81 events/min (p < 0.05). Simultaneous stimulation of A2ARs and A3Rs increased the calcium spark frequency seven-fold (p < 0.001) and the ITI frequency from 0.14 to 0.64 events/min (p < 0.05). Subsequent A3R inhibition caused a strong additional increase in the ITI frequency (to 2.04 events/min; p < 0.01) and increased phosphorylation at s2808 1.7-fold (p < 0.001). These pharmacological treatments had no significant effects on L-type calcium current density or sarcoplasmic reticulum calcium load. In conclusion, A3Rs are expressed and blunt spontaneous calcium release at baseline and upon A2AR-stimulation in human atrial myocytes, pointing to A3R activation as a means to attenuate physiological and pathological elevations of spontaneous calcium release events.
Effects of Florfenicol on Intestinal Histology, Apoptosis and Gut Microbiota of Chinese Mitten Crab (Eriocheir sinensis)
Authors: Guo Xinping , Qian Ziang , Pan Qiqi , Hu Yuqing , Mei Wangxin , Xing Xiumei , Yin Shaowu , Ji Jie , Zhang Kai
Published: February 2023

Excessive use of antibiotics in aquaculture causes residues in aquatic animal products and harms human health. However, knowledge of florfenicol (FF) toxicology on gut health and microbiota and their resulting relationships in economic freshwater crustaceans is scarce. Here, we first investigated the influence of FF on the intestinal health of Chinese mitten crabs, and then explored the role of bacterial community in FF-induced intestinal antioxidation system and intestinal homeostasis dysbiosis. A total of 120 male crabs (48.5 ± 4.5 g) were experimentally treated in four different concentrations of FF (0, 0.5, 5 and 50 μg/L) for 14 days. Responses of antioxidant defenses and changes of gut microbiota were assessed in the intestine. Results revealed that FF exposure induced significant histological morphology variation. FF exposure also enhanced immune and apoptosis characteristics in the intestine after 7 days. Moreover, antioxidant enzyme catalase activities showed a similar pattern. The intestinal microbiota community was analyzed based on full-length 16S rRNA sequencing. Only the high concentration group showed a marked decrease in microbial diversity and change in its composition after 14 days of exposure. Relative abundance of beneficial genera increased on day 14. These findings illustrate that exposure to FF could cause intestinal dysfunction and gut microbiota dysbiosis in Chinese mitten crabs, which provides new insights into the relationship between gut health and gut microbiota in invertebrates following exposure to persistent antibiotics pollutants.
In Vitro and In Silico Study on the Molecular Encapsulation of α-Tocopherol in a Large-Ring Cyclodextrin
Authors: Sangkhawasi Mattanun , Kerdpol Khanittha , Ismail Abbas , Nutho Bodee , Hanpiboon Chonnikan , Wolschann Peter , Krusong Kuakarun , Rungrotmongkol Thanyada , Hannongbua Supot
Published: February 2023

α-tocopherol is the physiologically most active form of vitamin E, with numerous biological activities, such as significant antioxidant activity, anticancer capabilities, and anti-aging properties. However, its low water solubility has limited its potential use in the food, cosmetic, and pharmaceutical industries. One possible strategy for addressing this issue is the use of a supramolecular complex with large-ring cyclodextrins (LR-CDs). In this study, the phase solubility of the CD26/α-tocopherol complex was investigated to assess the possible ratios between host and guest in the solution phase. Next, the host–guest association of the CD26/α-tocopherol complex at different ratios of 1:2, 1:4, 1:6, 2:1, 4:1, and 6:1 was studied by all-atom molecular dynamics (MD) simulations. At 1:2 ratio, two α-tocopherol units interact spontaneously with CD26, forming an inclusion complex, as supported by the experimental data. In the 2:1 ratio, a single α-tocopherol unit was encapsulated by two CD26 molecules. In comparison, increasing the number of α-tocopherol or CD26 molecules above two led to self-aggregation and consequently limited the solubility of α-tocopherol. The computational and experimental results indicate that a 1:2 ratio could be the most suitable stoichiometry to use in the CD26/α-tocopherol complex to improve α-tocopherol solubility and stability in inclusion complex formation.
New Echocardiographic Parameters Predicting Successful Trans-Ventricular Beating-Heart Mitral Valve Repair with Neochordae at 3 Years: Monocentric Retrospective Study
Authors: Vairo Alessandro , Gaiero Lorenzo , Marro Matteo , Russo Caterina , Bolognesi Marco , Soro Paolo , Gallone Guglielmo , Fioravanti Francesco , Desalvo Paolo , D’Ascenzo Fabrizio , Alunni Gianluca , Sebastiano Viviana , Barbero Cristina , Pocar Marco , De Ferrari Gaetano Maria , Rinaldi Mauro , Salizzoni Stefano
Published: February 2023

The NeoChord procedure is an echo-guided trans-ventricular beating-heart mitral valve repair technique to treat degenerative mitral regurgitation (MR) due to prolapse and/or flail. The aim of this study is to analyze echocardiographic images to find pre-operative parameters to predict procedural success (≤moderate MR) at 3-year follow-up. Seventy-two consecutive patients with severe MR underwent the NeoChord procedure between 2015 and 2021. MV pre-operative morphological parameters were assessed using 3D transesophageal echocardiography with dedicated software (QLAB, Philips). Three patients died during their hospitalization. The remaining 69 patients were retrospectively analyzed. At follow-up, MR > moderate was found in 17 patients (24.6%). In the univariate analysis, end-systolic annulus area (12.5 ± 2.5 vs. 14.1 ± 2.6 cm2; p = 0.038), end-systolic annulus circumference (13.2 ± 1.2 vs. 14 ± 1.3 cm; p = 0.042), indexed left atrial volume (59 ± 17 vs. 76 ± 7 mL/m2; p = 0.041), and AF (25% vs. 53%; p = 0.042) were lower in the 52 patients with ≤ MR compared to those with > moderate MR. Annular dysfunction parameters were the best predictors of procedural success: 3D early-systolic annulus area (AUC 0.74; p = 0.004), 3D early-systolic annulus circumference (AUC 0.75; p = 0.003), and 3D annulus area fractional change (AUC 0.73; p = 0.035). Patient selection relying on 3D dynamic and static MA dimensions may improve the maintenance of procedural success at follow-up.
The Evolving Role of Immune-Checkpoint Inhibitors in Malignant Pleural Mesothelioma
Authors: Borgeaud Maxime , Kim Floryane , Friedlaender Alex , Lococo Filippo , Addeo Alfredo , Minervini Fabrizio
Published: February 2023

Malignant pleural mesothelioma (MPM) is a rare cancer usually caused by asbestos exposure and associated with a very poor prognosis. After more than a decade without new therapeutic options, immune checkpoint inhibitors (ICIs) demonstrated superiority over standard chemotherapy, with improved overall survival in the first and later-line settings. However, a significant proportion of patients still do not derive benefit from ICIs, highlighting the need for new treatment strategies and predictive biomarkers of response. Combinations with chemo-immunotherapy or ICIs and anti-VEGF are currently being evaluated in clinical trials and might change the standard of care in the near future. Alternatively, some non-ICI immunotherapeutic approaches, such as mesothelin targeted CAR-T cells or denditric-cells vaccines, have shown promising results in early phases of trials and are still in development. Finally, immunotherapy with ICIs is also being evaluated in the peri-operative setting, in the minority of patients presenting with resectable disease. The goal of this review is to discuss the current role of immunotherapy in the management of malignant pleural mesothelioma, as well as promising future therapeutic directions.
The Protective Role of Cognitive Reserve in Mild Cognitive Impairment: A Systematic Review
Authors: Corbo Ilaria , Marselli Giulia , Di Ciero Valerio , Casagrande Maria
Published: February 2023

Cognitive reserve (CR) represents the ability to optimize performance and functioning to cope with brain damage or disease. CR reflects the capability to adaptively and flexibly use cognitive processes and brain networks to compensate for the deterioration typical of aging. Several studies have investigated the potential role of CR in aging, especially from the perspective of preventing and protecting against dementia and Mild Cognitive Impairment (MCI). This systematic literature review aimed to investigate the role of CR as a protective factor against MCI and associated cognitive decline. The review process was conducted according to the PRISMA statement. For this purpose, ten studies were analyzed. The results of this review show that high CR is significantly associated with a reduced risk of MCI. In addition, a significant positive relationship between CR and cognitive functioning is observed when comparing subjects with MCI and healthy subjects and within people with MCI. Thus, the results confirm the positive role of cognitive reserve in mitigating cognitive impairment. The evidence from this systematic review is consistent with the theoretical models of CR. Indeed, previous research hypothesized that specific individual experiences (such as leisure activities) allow a person to acquire successful neural resources over the years to cope with cognitive decline.
Association between Otosclerosis and Rubella in Taiwan: A Nationwide Case-Control Study
Authors: Hwang Juen-Haur , Yu Ben-Hui , Chen Yi-Chun
Published: February 2023

Otosclerosis is an early adult-onset disease that is associated with 5–9% and 18–22% of all cases of hearing and conductive hearing loss, respectively, and it is suspected to have a viral etiology. However, the role of viral infection in otosclerosis is still inconclusive. This study aimed to investigate whether rubella infection was associated with otosclerosis risk. We conducted a nationwide case-control study in Taiwan. Data were retrospectively analyzed from the Taiwan National health Insurance Research Database. Cases consisted of all patients who were aged ≥6 years and had a first-time diagnosis of otosclerosis for the period between 2001 and 2012. The controls were exact matched to cases in a 4:1 ratio by birth year, sex, and must survive in the index year of their matched cases. Adjusted odds ratio (OR) and 95% confidence interval (CI) were estimated by using conditional logistic regression. We examined 647 otosclerosis cases and 2588 controls without otosclerosis. Among the 647 patients with otosclerosis, 241 (37.2%) were male and 406 (62.8%) were female, with most aged between 40 and 59 years, with a mean age of 44.9 years. After adjusting for age and sex, conditional logistic regression revealed that exposure to rubella was not associated with a significant increase in otosclerosis risk (adjusted OR, 2.0; 95% CI, 0.18–22.06, p = 0.57). In conclusion, this study did not show that rubella infection was associated with the risk of otosclerosis in Taiwan.
The Influence of Adherence to Orthosis and Physiotherapy Protocol on Functional Outcome after Proximal Humeral Fracture in the Elderly
Authors: Fleischhacker Evi , Gleich Johannes , Smolka Vera , Neuerburg Carl , Böcker Wolfgang , Helfen Tobias
Published: February 2023

In the treatment of proximal humeral fractures (PHF), patients are often recommended to wear a sling or orthosis and to perform physiotherapy. However, some patients, especially elderly ones, struggle to comply with these rehabilitation regimens. Therefore, the aim of the study was to evaluate whether these incompliant patients have a worse functional outcome than those who adhere to the rehabilitation protocol. After receiving a diagnosis of a PHF, patients were divided into four groups according to fracture morphology: conservative with sling, operative with sling, conservative with abduction orthosis, and operative with abduction orthosis. At the 6-week follow-up, compliance regarding brace use and physiotherapy performance were assessed, as well as the constant score (CS) and complications or revision surgeries. The CS as well as the complications and revision surgeries were also surveyed after one year. In 149 participants, with a mean age of 73.9 ± 7.2 years, only 37% terminated orthosis and only 49% underwent physiotherapy as recommended. The statistical analysis showed no significant difference in the CS, complications, and revision surgeries between the groups.
An Adequate Infusion Rate of Remimazolam for Induction of General Anesthesia in Adult Patients: A Prospective Up-and-Down Dose-Finding Study
Authors: Jeong Heejoon , Kim Hara , Ahn Hyun Joo
Published: February 2023

Remimazolam is a recently developed anesthetic agent for general anesthesia and sedation. Currently, the optimal infusion rate for the induction of general anesthesia within two minutes remains unclear. We estimated the 50% and 90% effective doses (ED50 and ED90) of remimazolam required for loss of responsiveness within two minutes in adult patients using the up-and-down method. The starting infusion rate of remimazolam was 0.1 mg/kg/min and was increased or decreased by 0.02 mg/kg/min intervals in the following patient according to the success or failure of the previous patient. Success was defined as a loss of responsiveness within two minutes. Patient enrollment continued until six crossover pairs were observed. The ED50 and ED90 were estimated by centered isotonic regression and the pooled adjacent violators algorithm with bootstrapping, respectively. Twenty patients were included in the analysis. The ED50 and ED90 of remimazolam for loss of responsiveness within two minutes were 0.07 mg/kg/min (90% CI: 0.05, 0.09 mg/kg/min) and 0.10 mg/kg/min (90% CI: 0.10, 0.15 mg/kg/min), respectively. Vital signs were stable with an infusion rate of 0.10 mg/kg/min, and no patients required inotrope/vasopressor. Intravenous infusion of remimazolam at a rate of 0.10 mg/kg/min can be an effective approach to inducing general anesthesia in adult patients.
Simulators and Simulations for Extracorporeal Membrane Oxygenation: An ECMO Scoping Review
Authors: Duinmeijer Wytze C. , Fresiello Libera , Swol Justyna , Torrella Pau , Riera Jordi , Obreja Valentina , Puślecki Mateusz , Dąbrowski Marek , Arens Jutta , Halfwerk Frank R.
Published: February 2023

High-volume extracorporeal membrane oxygenation (ECMO) centers generally have better outcomes than (new) low-volume ECMO centers, most likely achieved by a suitable exposure to ECMO cases. To achieve a higher level of training, simulation-based training (SBT) offers an additional option for education and extended clinical skills. SBT could also help to improve the interdisciplinary team interactions. However, the level of ECMO simulators and/or simulations (ECMO sims) techniques may vary in purpose. We present a structured and objective classification of ECMO sims based on the broad experience of users and the developer for the available ECMO sims as low-, mid-, or high-fidelity. This classification is based on overall ECMO sim fidelity, established by taking the median of the definition-based fidelity, component fidelity, and customization fidelity as determined by expert opinion. According to this new classification, only low- and mid-fidelity ECMO sims are currently available. This comparison method may be used in the future for the description of new developments in ECMO sims, making it possible for ECMO sim designers, users, and researchers to compare accordingly, and ultimately improve ECMO patient outcomes.
Gut Microbiota Dysbiosis Ameliorates in LNK-Deficient Mouse Models with Obesity-Induced Insulin Resistance Improvement
Authors: Chen Jingbo , Xu Jiawen , Sun Yan , Xue Yuhuan , Zhao Yang , Yang Dongzi , Li Shuijie , Zhao Xiaomiao
Published: February 2023

Purpose: To investigate the potential role of gut microbiota in obesity-induced insulin resistance (IR). Methods: Four-week-old male C57BL/6 wild-type mice (n = 6) and whole-body SH2 domain-containing adaptor protein (LNK)-deficient in C57BL/6 genetic backgrounds mice (n = 7) were fed with a high-fat diet (HFD, 60% calories from fat) for 16 weeks. The gut microbiota of 13 mice feces samples was analyzed by using a 16 s rRNA sequencing analysis. Results: The structure and composition of the gut microbiota community of WT mice were significantly different from those in the LNK-/- group. The abundance of the lipopolysaccharide (LPS)-producing genus Proteobacteria was increased in WT mice, while some short-chain fatty acid (SCFA)-producing genera in WT groups were significantly lower than in LNK-/- groups (p < 0.05). Conclusions: The structure and composition of the intestinal microbiota community of obese WT mice were significantly different from those in the LNK-/- group. The abnormality of the gut microbial structure and composition might interfere with glucolipid metabolism and exacerbate obesity-induced IR by increasing LPS-producing genera while reducing SCFA-producing probiotics.
Cerclage Wiring Improves Biomechanical Stability in Distal Tibia Spiral Fractures Treated by Intramedullary Nailing
Authors: Förch Stefan , Sandriesser Sabrina , von Rüden Christian , Mayr Edgar , Augat Peter
Published: February 2023

Background: Partial weight-bearing after operatively treated fractures has been the standard of care over the past decades. Recent studies report on better rehabilitation and faster return to daily life in case of immediate weight-bearing as tolerated. To allow early weight-bearing, osteosynthesis needs to provide sufficient mechanical stability. The purpose of this study was to investigate the stabilizing benefits of additive cerclage wiring in combination with intramedullary nailing of distal tibia fractures. Methods: In 14 synthetic tibiae, a reproducible distal spiral fracture was treated by intramedullary nailing. In half of the samples, the fracture was further stabilized by additional cerclage wiring. Under clinically relevant partial and full weight-bearing loads the samples were biomechanically tested and axial construct stiffness as well as interfragmentary movements were assessed. Subsequently, a 5 mm fracture gap was created to simulate insufficient reduction, and tests were repeated. Results: Intramedullary nails offer already high axial stability. Thus, axial construct stiffness cannot be significantly enhanced by an additive cerclage (2858 ± 958 N/mm NailOnly vs. 3727 ± 793 N/mm Nail + Cable; p = 0.089). Under full weight-bearing loads, additive cerclage wiring in well-reduced fractures significantly reduced shear (p = 0.002) and torsional movements (p = 0.013) and showed similar low movements as under partial weight-bearing (shear 0.3 mm, p = 0.073; torsion 1.1°, p = 0.085). In contrast, additional cerclage had no stabilizing effect in large fracture gaps. Conclusions: In well-reduced spiral fractures of the distal tibia, the construct stability of intramedullary nailing can be further increased by additional cerclage wiring. From a biomechanical point of view, augmentation of the primary implant reduced shear movement sufficiently to allow immediate weight-bearing as tolerated. Especially, elderly patients would benefit from early post-operative mobilization, which allows for accelerated rehabilitation and a faster return to daily activities.
Sticking to the Rules: Outcome and Success Rate of Guideline-Based Diarrhea Management in Metastatic Breast Cancer Patients Treated with Abemaciclib
Authors: Jacobs Flavia , Agostinetto Elisa , Solferino Alessandra , Torrisi Rosalba , Masci Giovanna , Santoro Armando , De Sanctis Rita
Published: February 2023

In clinical trials testing abemaciclib in patients with hormone-receptor-positive (HR+), HER2-negative (HER2-) advanced breast cancer, diarrhea is a very common adverse event (occurring in approximately 85% of patients, any grade). Nonetheless, this toxicity leads to abemaciclib discontinuation in a small proportion of patients (approximately 2%) thanks to the use of effective loperamide-based supportive therapy. We aimed to determine whether the incidence of abemaciclib-induced diarrhea in real-world trials was higher than the one reported in clinical trials, where patients are highly selected, and to evaluate the success rate of standard supportive care in this setting. We conducted a retrospective, observational, monocentric study including 39 consecutive patients with HR+/HER2- advanced breast cancer treated with abemaciclib and endocrine therapy at our institution from July 2019 to May 2021. Overall, diarrhea of any grade occurred in 36 patients (92%), of whom 6 (17%) had diarrhea of grade ≥3. In 30 patients (77%), diarrhea was associated with other adverse events, including fatigue (33%), neutropenia (33%), emesis (28%), abdominal pain (20%), and hepatotoxicity (13%). Loperamide-based supportive therapy was administered to 26 patients (72%). Abemaciclib dose was reduced in 12 patients (31%) due to diarrhea, and treatment was permanently discontinued in 4 patients (10%). In 58% of patients (15/26), diarrhea was effectively managed with supportive care and did not require abemaciclib dose reduction and/or discontinuation. In our real-world analysis, we observed a higher incidence of diarrhea related to abemaciclib compared to data from clinical trials, and a higher rate of permanent treatment discontinuation due to gastrointestinal toxicity. Better implementation of guideline-based supportive care could help to manage this toxicity.
Alterations in Cervical Nerve Root Function during Different Sitting Positions in Adults with and without Forward Head Posture: A Cross-Sectional Study
Authors: Kamel Maryam , Moustafa Ibrahim M. , Kim Meeyoung , Oakley Paul A. , Harrison Deed E.
Published: February 2023

The current study aimed to determine whether participants with and without forward head posture (FHP) would respond differently in cervical nerve root function to various sitting positions. We measured peak-to-peak dermatomal somatosensory-evoked potentials (DSSEPs) in 30 participants with FHP and in 30 participants matched for age, sex, and body mass index (BMI) with normal head posture (NHP), defined as having a craniovertebral angle (CVA) >55°. Additional inclusion criteria for recruitment were individuals between the ages of 18 and 28 who were in good health and had no musculoskeletal pain. All 60 participants underwent C6, C7, and C8 DSSEPs evaluation. The measurements were taken in three positions: erect sitting, slouched sitting, and supine. We identified statistically significant differences in the cervical nerve root function in all postures between the NHP and FHP groups (p < 0.001), indicating that the FHP and NHP reacted differently in different positions. No significant differences between groups for the DSSEPs were identified for the supine position (p > 0.05), in contrast to the erect and slouched sitting positions, which showed a significant difference in nerve root function between the NHP and FHP (p < 0.001). The NHP group results were consistent with the prior literature and had the greatest DSSEP peaks when in the upright position. However, the participants in the FHP group demonstrated the largest peak-to-peak amplitude of DSSEPs while in the slouched position as opposed to an erect position. The optimal sitting posture for cervical nerve root function may be dependent upon the underlying CVA of a person, however, further research is needed to corroborate these findings.
Deep Brain Stimulation Electrode Reconstruction: Comparison between Lead-DBS and Surgical Planning System
Authors: Xu Yichen , Qin Guofan , Tan Bojing , Fan Shiying , An Qi , Gao Yuan , Fan Houyou , Xie Hutao , Wu Delong , Liu Huanguang , Yang Guang , Fang Huaying , Xiao Zunyu , Zhang Jianguo , Zhang Hua , Shi Lin , Yang Anchao
Published: February 2023

Background: Electrode reconstruction for postoperative deep brain simulation (DBS) can be achieved manually using a surgical planning system such as Surgiplan, or in a semi-automated manner using software such as the Lead-DBS toolbox. However, the accuracy of Lead-DBS has not been thoroughly addressed. Methods: In our study, we compared the DBS reconstruction results of Lead-DBS and Surgiplan. We included 26 patients (21 with Parkinson’s disease and 5 with dystonia) who underwent subthalamic nucleus (STN)-DBS, and reconstructed the DBS electrodes using the Lead-DBS toolbox and Surgiplan. The electrode contact coordinates were compared between Lead-DBS and Surgiplan with postoperative CT and MRI. The relative positions of the electrode and STN were also compared between the methods. Finally, the optimal contact during follow-up was mapped onto the Lead-DBS reconstruction results to check for overlap between the contacts and the STN. Results: We found significant differences in all axes between Lead-DBS and Surgiplan with postoperative CT, with the mean variance for the X, Y, and Z coordinates being −0.13, −1.16, and 0.59 mm, respectively. Y and Z coordinates showed significant differences between Lead-DBS and Surgiplan with either postoperative CT or MRI. However, no significant difference in the relative distance of the electrode and the STN was found between the methods. All optimal contacts were located in the STN, with 70% of them located within the dorsolateral region of the STN in the Lead-DBS results. Conclusions: Although significant differences in electrode coordinates existed between Lead-DBS and Surgiplan, our results suggest that the coordinate difference was around 1 mm, and Lead-DBS can capture the relative distance between the electrode and the DBS target, suggesting it is reasonably accurate for postoperative DBS reconstruction.
Deprescribing Strategies for Opioids and Benzodiazepines with Emphasis on Concurrent Use: A Scoping Review
Authors: Wang Yanning , Wilson Debbie L. , Fernandes Deanna , Adkins Lauren E. , Bantad Ashley , Copacia Clint , Dharma Nilay , Huang Pei-Lin , Joseph Amanda , Park Tae Woo , Budd Jeffrey , Meenrajan Senthil , Orlando Frank A. , Pennington John , Schmidt Siegfried , Shorr Ronald , Uphold Constance R. , Lo-Ciganic Wei-Hsuan
Published: February 2023

While the Food and Drug Administration’s black-box warnings caution against concurrent opioid and benzodiazepine (OPI–BZD) use, there is little guidance on how to deprescribe these medications. This scoping review analyzes the available opioid and/or benzodiazepine deprescribing strategies from the PubMed, EMBASE, Web of Science, Scopus, and Cochrane Library databases (01/1995–08/2020) and the gray literature. We identified 39 original research studies (opioids: n = 5, benzodiazepines: n = 31, concurrent use: n = 3) and 26 guidelines (opioids: n = 16, benzodiazepines: n = 11, concurrent use: n = 0). Among the three studies deprescribing concurrent use (success rates of 21–100%), two evaluated a 3-week rehabilitation program, and one assessed a 24-week primary care intervention for veterans. Initial opioid dose deprescribing rates ranged from (1) 10–20%/weekday followed by 2.5–10%/weekday over three weeks to (2) 10–25%/1–4 weeks. Initial benzodiazepine dose deprescribing rates ranged from (1) patient-specific reductions over three weeks to (2) 50% dose reduction for 2–4 weeks, followed by 2–8 weeks of dose maintenance and then a 25% reduction biweekly. Among the 26 guidelines identified, 22 highlighted the risks of co-prescribing OPI–BZD, and 4 provided conflicting recommendations on the OPI–BZD deprescribing sequence. Thirty-five states’ websites provided resources for opioid deprescription and three states’ websites had benzodiazepine deprescribing recommendations. Further studies are needed to better guide OPI–BZD deprescription.
Caregiving in Older Adults; Experiences and Attitudes toward Smart Technologies
Authors: Piau Antoine , Steinmeyer Zara , Mattek Nora , Lindauer Allison , Sharma Nicole , Bouranis Nicole , Wild Katherine , Kaye Jeffrey
Published: February 2023

(1) Background: The development of assistive technologies has become a key solution to reduce caregiver burden. The objective of this study was to survey caregivers on perceptions and beliefs about the future of modern technology in caregiving. (2) Methods: Demographics and clinical caregiver characteristics were collected via an online survey along with the perceptions and willingness to adopt technologies to support caregiving. Comparisons were made between those who considered themselves caregivers and those who never did. (3) Results: 398 responses (mean age 65) were analyzed. Health and caregiving status of the respondents (e.g., schedule of care) and of the care recipient were described. The perceptions and willingness to use technologies were generally positive without significant differences between those who ever considered themselves as caregivers and those who never did. The most valued features were the monitoring of falls (81%), medication use (78%), and changes in physical functioning (73%). For caregiving support, the greatest endorsements were reported for one-on-one options with similar scores for both online and in-person alternatives. Important concerns were expressed about privacy, obtrusiveness, and technological maturity. (4) Conclusions: Online surveys as a source of health information on caregiving may be an effective guide in developing care-assisting technologies receiving end users’ feedback. Caregiver experience, whether positive or negative, was correlated to health habits such as alcohol use or sleep. This study provides insight on caregivers’ needs and perceptions regarding caregiving according to their socio-demographic and health status.
Aspartate Reduces Liver Inflammation and Fibrosis by Suppressing the NLRP3 Inflammasome Pathway via Upregulating NS3TP1 Expression
Authors: Zhou Li , Zhao Jing , Han Ming , Ma Anlin , Yang Song , Zeng Yilan , Cheng Jun
Published: February 2023

Aspartate (Asp) can act on liver Kupffer cells, inhibit NOD-like receptor-P 3 (NLRP3) inflammatory bodies, and improve liver inflammation in acute hepatitis. However, the effect of Asp on the role of hepatic stellate cells (HSCs) in the pathogenesis of liver fibrosis in chronic liver injury remains unexplored. This study aimed to investigate the effects of Asp on CCl4-induced liver fibrosis in mice and HSCs via the NF-κB/NLRP3 signaling pathway. Liver fibrosis was induced in C57BL/6J mice by intraperitoneally (IP) injecting 0.5 mL/kg 2% CCl4 three times weekly for 8 weeks. Asp was administered to mice by gavage once every morning for 4 weeks. Masson’s trichrome staining, Sirius red staining and hematoxylin and eosin staining were used to detect and analyze the pathological changes in liver tissues. Western blot analysis and immunohistochemistry were applied to determine the protein expression levels of α-smooth muscle actin (α-SMA), collagen Ⅲ (COL III), NLRP3, and IL-1β. In addition, reverse transcription-quantitative PCR was performed to detect the mRNA expression levels. In the liver fibrosis model, the pathological changes in liver tissues improved following treatment with Asp. A marked decrease was observed in protein and mRNA expression levels of α-SMA, COL III, NLRP3, and IL-1β. In addition, HSCs were treated with Asp. The expression levels of α-SMA, COL III, NLRP3, and IL-1β reduced in dose- and time-dependent manners. Furthermore, Asp upregulated the expression of NS3TP1 in vivo and in vitro, and NS3TP1 had a significant inhibitory effect on liver fibrosis. Asp attenuated liver fibrosis and reduced collagen production by suppressing the NF-κB/NLRP3 signaling pathway via upregulating the expression of NS3TP1.
Automated Lung Cancer Segmentation in Tissue Micro Array Analysis Histopathological Images Using a Prototype of Computer-Assisted Diagnosis
Authors: Althubaity DaifAllah D. , Alotaibi Faisal Fahad , Osman Abdalla Mohamed Ahmed , Al-khadher Mugahed Ali , Abdalla Yahya Hussein Ahmed , Alwesabi Sadeq Abdo , Abdulrahman Elsadig Eltaher Hamed , Alhemairy Maram Abdulkhalek
Published: February 2023

Background: Lung cancer is a fatal disease that kills approximately 85% of those diagnosed with it. In recent years, advances in medical imaging have greatly improved the acquisition, storage, and visualization of various pathologies, making it a necessary component in medicine today. Objective: Develop a computer-aided diagnostic system to detect lung cancer early by segmenting tumor and non-tumor tissue on Tissue Micro Array Analysis (TMA) histopathological images. Method: The prototype computer-aided diagnostic system was developed to segment tumor areas, non-tumor areas, and fundus on TMA histopathological images. Results: The system achieved an average accuracy of 83.4% and an F-measurement of 84.4% in segmenting tumor and non-tumor tissue. Conclusion: The computer-aided diagnostic system provides a second diagnostic opinion to specialists, allowing for more precise diagnoses and more appropriate treatments for lung cancer.
Glaciers Landscapes during the Pleistocene in Trevinca Massif (Northwest Iberian Peninsula)
Authors: Pérez-Alberti Augusto , Gómez-Pazo Alejandro
Published: February 2023

The Trevinca Massif is in the northwestern Iberian Peninsula, on the border between Galicia and Castilla-León. Its highest elevation is 2124 m at the Trevinca peak. During the Pleistocene, an extensive icefield developed in this area, occupying the flattened surfaces in the high massif zones, and generating several glacier valleys. In the occidental sector, the identified paleoglaciers reached 187 km2, and glacier tongues up to 30 km in the Bibei valley, where the ice thickness came to 527 m. The glacial forms and deposits were mapped and analyzed in the entire Trevinca massif, whereas the paleoglacial reconstruction was carried out in the occidental sector (previous works analyzed the oriental sector). The reconstruction was performed by using high-resolution orthophotography, digital elevation models with a spatial resolution of 2 m, and fieldwork surveys to identify the primary forms and estimate the ice cover in the past through the GlaRe methodology. Moreover, the paleo-ELA was estimated for this sector, and the values of the ice thickness, the ELA position, and the moraines were related to other nearest sectors to analyze their similarities and differences. Three main paleoglaciers were identified in the occidental Trevinca massif (Xares, Canda, and Bibei-Barxacova). Bibei showed the highest ice thickness and ice extension, occupying more than 140 km2 and with a thickness above 500 m some areas. Concerning the ELA, the values varied between the minimum at Xares with 1427 m and the maximum at Bibei-Barxacova with 1839 m. Four groups were identifying based on moraine ridges and were related to the different climatic phases in that sector.
Understanding Land-Use Trade-off Decision Making Using the Analytical Hierarchy Process: Insights from Agricultural Land Managers in Zambia
Authors: Kwenye Jane Musole , Jones Xiaoting Hou , Renwick Alan
Published: February 2023

Understanding factors that influence trade-offs between agricultural expansion and forest conservation is important in managing competing land-use objectives. This paper applies elements of the Analytical Hierarchy Process (AHP) to distinct farming business ownership models in Zambia to gain insights into factors that agricultural land managers take into account when considering land-use trade-off decisions which involve agricultural expansion into natural habitats. Results showed that the market domain was weighted above other domains, followed by the financial domain. When environmental considerations were pitted against other factors such as markets and finance, agricultural land managers were likely to trade off environmental concerns. Furthermore, availability of input subsidies via the agricultural Food Input Support Programme (FISP) influenced the decision to expand, particularly for the small-scale ownership model. This suggests that agricultural policies and strategies aimed at promoting agricultural productivity may require accompanying measures to safeguard forest ecosystems from agricultural expansion. Key differences in the factors influencing expansion decisions were evident among ownership models suggesting that ownership types do have an impact on factors considered. This highlights the need to advance tailored strategies that address differences in priorities and decision making emanating from variations in farming business ownership models.
Assessment of Water Yield and Water Purification Services in the Arid Zone of Northwest China: The Case of the Ebinur Lake Basin
Authors: Duolaiti Xilinayi , Kasimu Alimujiang , Reheman Rukeya , Aizizi Yimuranzi , Wei Bohao
Published: February 2023

Assessing how land-use changes will affect water-producing ecosystem services is particularly important for water resource management and ecosystem conservation. In this study, the InVEST model and geographical detector were used to assess the water ecosystem service functions of the Ebinur Lake Basin and analyze their relationship with land-use changes. The results show that in the past 25 years, the water yield of the study area showed a trend of a strong yield at first and then a weaker one; there was a relatively large water yield in the west and southeast regions of the basin. The order of water yield for different land-use types is as follows: forest land > grassland > water area > unused land > crop land > construction land. After 2010, the output load of nitrogen and phosphorus increased; thus, the water purification ability weakened. The main land-use types in areas that demonstrate a large change rate in water purification capacity in the basin are cultivated land and construction land. Changes in the two water ecosystem services were associated with land-use changes. Geodetector analysis results further validated this conclusion. This study proposes a viable, replicable framework for land-use decisions in ecologically fragile watersheds. This study not only helps to gain insight into urban growth patterns in the study area but also helps to inform different land-use stakeholders.
Future Scenarios for Aridity under Conditions of Global Climate Change in Extremadura, Southwestern Spain
Authors: Moral Francisco J. , Aguirado Cristina , Alberdi Virginia , Paniagua Luis L. , García-Martín Abelardo , Rebollo Francisco J.
Published: February 2023

Aridity conditions in semi-arid lands with warm climates are key variables that must be assessed to properly manage water and plan to minimise the threat of desertification. This study analyses the spatial distribution of aridity in Extremadura, southwestern Spain, using the De Martonne aridity index (IDM), considering a historical reference period (1971–2005) and three-time intervals: 2006–2035 (near future), 2036–2065 (mid-century) and 2066–2095 (end of the century). Projections were computed using a set of ten global climate model (GCM) and regional climate model (RCM) combinations under two representative concentration pathways (RCPs), RCP4.5, an intermediate anthropogenic radiative forcing scenario, and RCP8.5, a fossil-intensive emission scenario. Progressive strengthening of aridity conditions over Extremadura was evident until the end of the century, mainly under the RCP8.5 scenario. From the predominance of the Mediterranean aridity class in the south of the region during the reference period, semi-arid conditions will soon spread across this zone, occupying most of it during mid-century and later. In the north of Extremadura, less arid conditions will be reduced to the highest elevations, increasing the Mediterranean and semi-arid categories, particularly under the RCP8.5 scenario. Consequently, the projected increase in aridity conditions in Extremadura will make this region more vulnerable to climate change. Policies devoted to adapting to the expected conditions and controlling aridity in vulnerable areas will be necessary to mitigate the negative impacts, with significant environmental and socio-economic implications in the region.
Criminal Compliance Program as a Tool for Criminal Liability Exculpation of Legal Persons in the Czech Republic
Authors: Kotlán Pavel , Ondrúš Miroslav , Kozlová Alena , Kotlán Igor , Petr Pavel , Kalabis Radim
Published: February 2023

Criminal liability of legal entities has gained an inalienable place in the system of legal liability in most European jurisdictions, including the Czech Republic. Departing from the premise that it is a suitable supplement to the liability of a legal entity in the event of serious unlawful acts of natural persons from which the legal entity benefits, this article aims to characterize the position and role of this form of liability in the Czech legal system. Essentially, however, it seeks to determine under which circumstances it is possible for legal entities to be relieved of liability using an exculpatory clause. Based on a case study of the Czech Republic, it illustrates the added value of criminal compliance programs, which, if properly set up and implemented in practice and complemented by prevention, detection and response measures, play a decisive role in establishing such criminal exculpation. The article further finds that rules pertaining to ethical codes of conduct are in fact ‘elevated’ to the level of legal rules through compliance programs. Compliance, one of the components of Corporate Social Responsibility, thus becomes an expression of a legal obligation, i.e., the obligation to properly manage and control the corporation, which has important legal implications.
‘We Got Lucky with the Judge’: Access to Justice for Disabled Women in Iceland
Authors: Gjecaj Eliona , Lawson Anna , Traustadóttir Rannveig , Rice James Gordon
Published: February 2023

In this paper we aim to make a valuable contribution to the surprisingly limited body of research on access to justice for disabled women who have been subjected to violence. Using an interdisciplinary sociolegal approach, this paper carries out an empirical qualitative study of one Icelandic court case and draws on this to provide a critical analysis of access to justice issues for disabled women who have been subjected to gender-based violence. Much about this case suggests that it is a positive example of justice being accessed, and we identify a number of features of the case as particularly significant in this regard. We reflect on how these positive aspects of the case can inform initiatives to enhance access to justice for disabled women and highlight ways in which Icelandic justice processes could more firmly embed the international human rights standards set out in the UN Convention on the Rights of Persons with Disabilities.