Miracle-dz/UniFAR-FTUs huggingface dataset:
Utilization and Outcomes of Local Anesthesia and Peripheral Nerve Block for Hybrid Lower Extremity Revascularization

Purpose: To investigate the utilization of local anesthesia or peripheral nerve block with monitored anesthesia care (LPMAC) and its impact on the perioperative outcomes of hybrid lower extremity revascularization (LER) compared with general anesthesia (GA). Materials and Methods: A search of the ACS-NSQIP database between 2005 and 2017 identified 9430 patients who underwent hybrid LER for peripheral artery disease. Excluding 449 ineligible cases left 8981 hybrid LER patients for analysis. The patients were dichotomized based on the anesthetic technique: 8631 (96.1%) GA and 350 (3.9%) LPMAC. The GA patients were matched 3:1 based on propensity scores to patients in the LPMAC group based on gender, age, race, functional status, transfer status, chronic obstructive pulmonary disease (COPD), dialysis status, American Society of Anesthesiologists (ASA) class, emergent surgery, preoperative sepsis, indication, and type of open and endovascular procedure. Outcomes including complications, mortality, procedure time, and hospital length of stay were compared between the matched groups (801 GA vs 267 LPMAC). Results: Comparing the unmatched groups, those treated under LPMAC were older (72.7±9 vs 68±8.4 years, p<0.001) and had higher rates of COPD (24.3% vs 17%, p=0.001), dialysis dependence (8.1% vs 4.2%, p=0.002), preoperative sepsis (6.6% vs 4.2%, p=0.029), and ASA class ≥IV (29.1% vs 24.1%, p=0.036) than in the unmatched GA cohort. In the matched comparison, LPMAC was associated with lower overall morbidity (25.5% vs 32.3%, p=0.042) and shorter operating time (202.7±98 vs 217.7±102 minutes, p=0.034) compared with GA. The rate of myocardial infarction was lower (1.1% vs 2.4%) and ventilator use for >48 hours was less frequent (0.4% vs 2.6%) for LPMAC patients, though statistical significance was not reached. There was no difference in mortality or hospital length of stay. Conclusion: LPMAC is an infrequent anesthetic technique for hybrid LER and is primarily used for patients with a high burden of comorbidities. LPMAC is associated with reduced overall morbidity and operating time. Further studies are needed to identify which patients undergoing hybrid LER benefit most from LPMAC.
Maxillary sinus floor elevation using hydroxyapatite nano particles vs tenting technique with simultaneous implant placement: A randomized clinical trial.

PURPOSE The present study was conducted to evaluate the amount of bone height gain, density values, and implant stability after maxillary sinus floor elevation using graftless tenting technique or the use of Hydroxyapatite Nanoparticles bone substitute for augmentation with simultaneous implant placement. MATERIALS AND METHODS A total of 20 sinuses with a residual alveolar bone height ranging from 4-6 mm were divided into two groups and underwent sinus augmentation using nano hydroxyapatite bone substitute material and the graftless tenting technique with simultaneous implant placement. Computed tomography CT scans and ISQ measurements were conducted to evaluate bone quality, quantity, and implant stability. RESULTS Radiographic analysis revealed that the mean bone height gain of the nano group was (7.0 ± 0.8 mm) compared to (5.0 ± 1.5 mm) in the tent group, which was statistically significant (P = .002) being higher in the nano group. The mean bone density value of the nano group was (548 ± 25 HU) compared to (420 ± 23 HU) in the tent group, which was statistically significant (P < .001) being higher in the nano group. The mean ISQ value after 6 months in the nano group was (78 ± 5) compared to (77 ± 5) in the tent group, which was statistically nonsignificant (P = .901). CONCLUSION Nano hydroxyapatite bone graft offered superior results in terms of the bone height gain and the relative bone density as compared to graftless tenting technique. However, both techniques showed accepted results regarding implant stability.
Human Leukocyte Antigen (HLA) Subtype-Dependent Development of Myasthenia Gravis, Type-1 Diabetes Mellitus, and Hashimoto Disease: A Case Report of Autoimmune Polyendocrine Syndrome Type 3

Patient: Female, 40 Final Diagnosis: Autoimmune polyendocrine syndrome type 3 Symptoms: Thirst • polyuria • weight-loss Medication: — Clinical Procedure: — Specialty: Endocrinology and Metabolic Objective: Rare co-existance of disease or pathology Background: Patients with type 1 diabetes mellitus, myasthenia gravis (MG), and Hashimoto disease are diagnosed as having autoimmune polyendocrine syndrome type 3 (APS3). APS3 is rare, and its pathogenesis is unclear. We describe a female patient with APS3 whose human leukocyte antigen (HLA) type could provide a clue to the pathogenesis of APS3. Case Report: A 40-year-old Japanese female patient who had been diagnosed with MG at 5 years of age, and which had been treated with cholinesterase inhibitors, was referred to our hospital with thirst, polydipsia, polyuria, weight loss, and hyperglycemia. She was found to have type 1 diabetes mellitus based on laboratory tests. She was also positive for anti-thyroid peroxidase antibody and was thus diagnosed with Hashimoto disease. This combination of type 1 diabetes mellitus, myasthenia gravis, and Hashimoto disease led to a diagnosis of APS3. Her HLA serotype was A24; B46/54; DR4/9; DQ8/9, and genotype was A*24: 02; B*46: 01: 01/54: 01: 01; C*01: 02; DRB1*04: 06/09: 01: 02; DQB1*03: 02: 01/03: 03: 02; and DQA1*03: 01/03: 02: 01. We subsequently reviewed 10 cases of APS3 combined with MG, including the present case and cases reported in Japanese. This review revealed that HLA-DR9/DQ9 might be a specific HLA subtype associated with APS3 with MG. Four of the 10 cases had MG diagnosed before diabetes mellitus and autoimmune thyroid disease. Conclusions: The present case showed that, in people with HLA-B46 and -DR9, antibody-negative MG can precede the development of APS3 by many years. Physicians should consider the possibility of APS3 when evaluating patients with ocular-type myasthenia gravis, and screen them for type 1 diabetes.
A Role for Both V1a and V2 Receptors in Renal Heat Stress Injury Amplified by Rehydration with Fructose

Chronic vasopressin secretion induced by recurrent mild heat stress exposure is significantly enhanced by limited rehydration with a fructose-containing beverage both in rodents and in humans. Moreover, this effect has been associated with upregulation of the polyol–fructokinase pathway and increased renal oxidative stress. Previously, we have shown that pharmacological inhibition of both V1a and V2 vasopressin receptors with conivaptan improved such renal alterations. The aim of this study was to evaluate the independent contributions of V1a and V2 receptors to the renal damage caused by mild heat stress and limited rehydration with a fructose-containing beverage. Osmotic minipumps were used to deliver either relcovaptan (0.64 mg/day) or tolvaptan (0.25 mg/day) in male Wistar rats for two weeks. Corresponding dilution vehicles were used as controls. To induce dehydration, rats were exposed to mild heat stress (37 °C for 1 h, Monday to Friday). All groups received a 10% fructose solution as a rehydration fluid for 2 h after mild heat stress. For the remainder of the day and on weekends, rats received tap water. The independent blockade of either the V1a or the V2 receptor prevented renal damage, reduced oxidative stress, and decreased plasma cortisol and systemic inflammation. However, the beneficial effects were regulated by different mechanisms. Tolvaptan inhibited polyol–fructokinase pathway overactivation, while relcovaptan prevented upregulation of the renin–angiotensin system and SGK1 expression. These data suggest that both V1a and V2 receptors participate in renal damage caused by heat stress-induced dehydration when fructose-containing beverages are used as rehydration fluids.
Mitochondrion as a Selective Target for the Treatment of Atherosclerosis: Role of Mitochondrial DNA Mutations and Defective Mitophagy in the Pathogenesis of Atherosclerosis and Chronic Inflammation

Background Atherosclerosis is a chronic inflammatory condition that affects different arteries in the human body and often leads to severe neurological complications, such as stroke and its sequelae. Affected blood vessels develop atherosclerotic lesions in the form of focal thickening of the intimal layer, so called atherosclerotic plaques. Objectives Despite the high priority of atherosclerosis research for global health and the numerous preclinical and clinical studies conducted, currently, there is no effective pharmacological treatment that directly impacts atherosclerotic plaques. Many knowledge gaps exist in our understanding of the mechanisms of plaque formation. In this review, we discuss the role of mitochondria in different cell types involved in atherogenesis and provide information about mtDNA mutations associated with the disease. Results Mitochondria of blood and arterial wall cells appear to be one of the important factors in disease initiation and development. Significant experimental evidence connects oxidative stress associated with mitochondrial dysfunction and vascular disease. Moreover, mitochondrial DNA (mtDNA) deletions and mutations are being considered as potential disease markers. Further study of mtDNA damage and associated dysfunction may open new perspectives for atherosclerosis treatment. Conclusion Mitochondria can be considered as important disease-modifying factors in several chronic pathologies. Deletions and mutations of mtDNA may be used as potential disease markers. Mitochondria-targeting antioxidant therapies appear to be promising for the development of treatment of atherosclerosis and other diseases associated with oxidative stress and chronic inflammation.
Evaluation of automatic milking system variables in dairy cows with different levels of lactation stage and reproduction status

Abstract In this study, we hypothesized that differences of automatic milking systems (AMS) variables in dairy cows during estrus and through diverse stages of lactation can be suggested as alternative indicators to support the pregnancy in dairy farms using automatic milking systems. The key objectives were: (1) to determine the variation of automatic milking system indicators during lactation and to estimate the relationship with reproduction status in dairy cows; (2) to test the hypothesis that milking traits of cows can be influenced by estrus and conceiving, and can be used as a predictor of the likelihood of reproductive success in dairy herds. Estrus synchronization was performed in 368 healthy Lithuanian Black and White cows. All cows (n = 368) were synchronized and inseminated for the first time on the 91st day in milk (DIM). Cows not pregnant (17.39%) were synchronized and inseminated again at 132 DIM. After the first insemination pregnant (n = 304) cows were identified as group 1, after the second insemination pregnant (n = 58) cows – as group 2. Overall, 12 01 713 records of udder quarters in cows from 5 to 305 DIM were evaluated. The results revealed the reduction in milk yield during estrus 11.05% on 91 DIM and 13.89% on 132 DIM (P < 0.001) and an increment in milk flow traits in cows after 91 DIM (P < 0.05), also a slight decline in milk flow traits on 132 DIM. Furthermore, milking frequency (MF) of cows decreased significantly (P < 0.001) after conceiving. The interval between milkings (MI) increased (40.30%) during estrus of cows in group 1 (P < 0.001), and thereafter gradually increased, however in group 2 there was a temporary increment (6.06%) on the 91 DIM and steady rise (42.13%) on 132 DIM was noticed. The results highlight that changes in AMS indicators of cows may be considered as an additional tool for improvement of reproductive management in dairy herds, but further research-based studies are necessary before practical application.
Preparation of Lipid Nanodiscs with Lipid Mixtures

Lipid nanodiscs provide a native‐like lipid environment for membrane proteins, and they have become a valuable platform for the study of membrane biophysics. A range of biophysical and biochemical analyses are enabled when membrane proteins are captured in lipid nanodiscs. Two parameters that can be controlled when capturing membrane proteins in lipid nanodiscs are the radius, and hence the surface area of the lipid surface, and the composition of the lipid bilayer. Despite their emergence as a versatile tool, most studies with lipid nanodiscs in the literature have focused on nanodiscs of a single radius with a single lipid. In light of the complexity of biological membranes, it is likely that nanodiscs with multiple membrane components would be more sophisticated models for membrane research. It is possible to prepare nanodiscs with more complex lipid mixtures to probe the effects of lipid composition on several aspects of membrane biochemistry. Detailed protocols are described here for the preparation of nanodiscs with mixtures of phospholipids, incorporation of cholesterol, and incorporation of a spectroscopic lipid probe. These protocols provide starting points for the construction of nanodiscs with more physiological membrane compositions or with useful biophysical probes. © 2019 by John Wiley & Sons, Inc.
Charge Scaling Manifesto: A Way of Reconciling the Inherently Macroscopic and Microscopic Natures of Molecular Simulations.

Electronic polarization effects play an important role in the interactions of charged species in biologically relevant aqueous solutions, such as those involving salt ions, proteins, nucleic acids, or phospholipid membranes. Explicit inclusion of electronic polarization in molecular modeling is tedious both from the point of view of force field parameterization and actual performance of the simulations. Therefore, the vast majority of biomolecular simulations is performed using non-polarizable force fields, which can lead to artifacts such as dramatically overestimated ion pairing, particularly when polyvalent ions are involved. Here, we show that many of these issues can be remedied without extra computational costs by including electronic polarization in a mean field way via charge rescaling. We also lay the solid physical foundations of this approach and reconcile from this perspective the microscopic vs. macroscopic natures of non-polarizable force fields.
In utero Exposure to Genotoxicants Leading to Genetic Mosaicism: An Overlooked Window of Susceptibility in Genetic Toxicology Testing?

In utero development represents a sensitive window for the induction of mutations. These mutations may subsequently expand clonally to populate entire organs or anatomical structures. Although not all adverse mutations will affect tissue structure or function, there is growing evidence that clonally expanded genetic mosaics contribute to various monogenic and complex diseases, including cancer. We posit that genetic mosaicism is an underestimated potential health problem that is not fully addressed in the current regulatory genotoxicity testing paradigm. Genotoxicity testing focuses exclusively on adult exposures and thus may not capture the complexity of genetic mosaicisms that contribute to human disease. Numerous studies have shown that conversion of genetic damage into mutations during early developmental exposures can result in much higher mutation burdens than equivalent exposures in adults in certain tissues. Therefore, we assert that analysis of genetic effects caused by in utero exposures should be considered in the current regulatory testing paradigm, which is possible by harmonization with current reproductive/developmental toxicology testing strategies. This is particularly important given the recent proposed paradigm change from simple hazard identification to quantitative mutagenicity assessment. Recent developments in sequencing technologies offer practical tools to detect mutations in any tissue or species. In addition to mutation frequency and spectrum, these technologies offer the opportunity to characterize the extent of genetic mosaicism following exposure to mutagens. Such integration of new methods with existing toxicology guideline studies offers the genetic toxicology community a way to modernize their testing paradigm and to improve risk assessment for vulnerable populations. Environ. Mol. Mutagen. 61:55–65, 2020. © 2019 The Authors. Environmental and Molecular Mutagenesis published by Wiley Periodicals, Inc. on behalf of Environmental Mutagen Society.
Feasibility of contrast-enhanced MRI derived textural features to predict overall survival in locally advanced breast cancer

Background The prognosis for women with locally advanced breast cancer (LABC) is poor and there is a need for better treatment stratification. Gray-level co-occurrence matrix (GLCM) texture analysis of magnetic resonance (MR) images has been shown to predict pathological response and could become useful in stratifying patients to more targeted treatments. Purpose To evaluate the ability of GLCM textural features obtained before neoadjuvant chemotherapy to predict overall survival (OS) seven years after diagnosis of patients with LABC. Material and Methods This retrospective study includes data from 55 patients with LABC. GLCM textural features were extracted from segmented tumors in pre-treatment dynamic contrast-enhanced 3-T MR images. Prediction of OS by GLCM textural features was assessed and compared to predictions using traditional clinical variables. Results Linear mixed-effect models showed significant differences in five GLCM features (f1, f2, f5, f10, f11) between survivors and non-survivors. Using discriminant analysis for prediction of survival, GLCM features from 2 min post-contrast images achieved a classification accuracy of 73% (P < 0.001), whereas traditional prognostic factors resulted in a classification accuracy of 67% (P = 0.005). Using a combination of both yielded the highest classification accuracy (78%, P < 0.001). Median values for features f1, f2, f10, and f11 provided significantly different survival curves in Kaplan–Meier analysis. Conclusion This study shows a clear association between textural features from post-contrast images obtained before neoadjuvant chemotherapy and OS seven years after diagnosis. Further studies in larger cohorts should be undertaken to investigate how this prognostic information can be used to benefit treatment stratification.
Abnormal Photic Entrainment to Phase-Delaying Stimuli in the R6/2 Mouse Model of Huntington's Disease, despite Retinal Responsiveness to Light

The circadian clock located in the suprachiasmatic nucleus (SCN) in mammals entrains to ambient light via the retinal photoreceptors. This allows behavioral rhythms to change in synchrony with seasonal and daily changes in light period. Circadian rhythmicity is progressively disrupted in Huntington’s disease (HD) and in HD mouse models such as the transgenic R6/2 line. Abstract The circadian clock located in the suprachiasmatic nucleus (SCN) in mammals entrains to ambient light via the retinal photoreceptors. This allows behavioral rhythms to change in synchrony with seasonal and daily changes in light period. Circadian rhythmicity is progressively disrupted in Huntington’s disease (HD) and in HD mouse models such as the transgenic R6/2 line. Although retinal afferent inputs to the SCN are disrupted in R6/2 mice at late stages, they can respond to changes in light/dark cycles, as seen in jet lag and 23 h/d paradigms. To investigate photic entrainment and SCN function in R6/2 mice at different stages of disease, we first assessed the effect on locomotor activity of exposure to a 15 min light pulse given at different times of the day. We then placed the mice under five non-standard light conditions. These were light cycle regimes (T-cycles) of T21 (10.5 h light/dark), T22 (11 h light/dark), T26 (13 h light/dark), constant light, or constant dark. We found a progressive impairment in photic synchronization in R6/2 mice when the stimuli required the SCN to lengthen rhythms (phase-delaying light pulse, T26, or constant light), but normal synchronization to stimuli that required the SCN to shorten rhythms (phase-advancing light pulse and T22). Despite the behavioral abnormalities, we found that Per1 and c-fos gene expression remained photo-inducible in SCN of R6/2 mice. Both the endogenous drift of the R6/2 mouse SCN to shorter periods and its inability to adapt to phase-delaying changes will contribute to the HD circadian dysfunction.
Biomarkers of fitness and welfare in dairy animals: healthy living

Abstract Increased animal productivity has reduced animal fitness, resulting in increased susceptibility to infectious and metabolic diseases, locomotion problems and subfertility. Future animal breeding strategies should focus on balancing high production levels with health status monitoring and improved welfare. Additionally, understanding how animals interact with their internal and external environment is essential for improving health, fitness, and welfare. In this context, the continuous validation of existing biomarkers and the discovery and field implementation of new biomarkers will enable us to understand the specific physiological process and regulatory mechanisms used by the organism to adapt to different environmental conditions. Thus, biomarkers may be used to monitor welfare and improve management and breeding strategies. In this article, we describe major achievements in the establishment of biomarkers in dairy cows and small ruminants. This review mainly focuses on the physiological biomarkers used to monitor animal responses to, and recovery from, environmental perturbations. We highlight future avenues for research in this field and present a timely positioning document to the scientific community.