bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effects of Anti-Sclerostin Antibody Release from Porous Microparticles on
Bone Resorption Inhibition of Osteoblasts
Authors: Watanabe Hajime , Nakagawa Yasuhiro , Ikoma Toshiyuki , Hattori Shinya , Minowa Takashi , Hanagata Nobutaka 
Published: March 2023

Background:
Anti-sclerostin antibodies are among the most efficient drugs for the treatment of osteoporosis, and have been also expected for the treatment of local bone disorders. We have previously developed porous microparticles of hydroxyapatite and chondroitin sulfate loading anti-sclerostin antibodies formulated with zinc cations. However, the biological behavior and con-centration dependence of anti-sclerostin antibodies in vitro released from the microparticles remain unclear.

Objective:
Bolus administration and the subsequent release of anti-sclerostin antibodies from the microparticles formulated with or without zinc cations were investigated; bone-resorptive inhibitory effects on mouse MC3T3-E1 osteoblast function were revealed by cell culture using a cell culture insert plate.

Methods:
Differentiation induction culture of osteoblasts was performed after maintaining the concentrations of anti-sclerostin antibodies and sclerostin at previously reported concentrations of 5.0 and 1.0 µg/mL for the first 3 days. Subsequently, the medium was replaced with fresh medium that did not contain anti-sclerostin antibodies but microparticles loading anti-sclerostin antibodies (20 or 80 µg/mg) with or without zinc cations in the cell culture insert. After 11 days of incubation, the bioactivity of the osteoblasts was evaluated using the polymerase chain reaction method.

Results:
The formulation using zinc cations showed an increase of anti-sclerostin antibodies re-leased from the microparticles, which increased the expression of receptor activator of the nuclear factor kappa-B ligand in the osteoblasts on day 14. This result indicates the inhibition of sclerostin-mediated bone resorption. However, the increase of loading amounts of anti-sclerostin antibodies extremely enhanced the subsequent release of anti-sclerostin antibodies, which decreased the inhibition of bone resorption contrary to expectations.

Conclusion:
The moderately sustained release of anti-sclerostin antibodies from the microparticles can promote the inhibition of bone resorption in osteoblasts, supporting the potential of this formulation for the treatment of localized bone disorders.
Application of Face Centered Central Composite Design in Evolution of
Optimized Drug Delivery System of Golden Nutraceutical with Frame
Independent Variables
Authors: Sharma Vijay , Singh Pawan , Singh Lalit , Verma Navneet 
Published: March 2023

Background:
Poor solubility of curcumin results in poor rate of absorption, rapid biotransformation
as well as rapid rate of elimination. Due to this curcumin does not show better therapeutic effect
through oral administration, to avoid poor rate of absorption, rapid biotransformation and topical drug delivery
system plays a vital role.

Objective:
The objective of the present work was the successful implementation of face-centered central
composite design (FCCCD) to study various independent variables to develop an optimized formulation.

Methods:
Carbopol 934 P and menthol were considered as independent variables and their impact was determined
on dependent responses like drug content, viscosity, and percent drug release by developing topical
gels using 32 central composite design. Thirteen curcumin loaded topical gels were prepared employing 32
CCD. Characterization of these formulations was done by drug content, viscosity, and percent drug release.

Results:
The effect of independent variable, i.e., the concentration of Carbopol 934P and menthol was determined
over the dependent variables by developing a response surface methodology. Optimized batch was
investigated employing design expert software by overlay plot developed by statistical software with drug
content, viscosity, and percent drug release 99.34%, 82.10 cps, and 65.576% respectively. Optimized data
was evaluated by formulating four validation check batches. Promising results were observed by comparing
the predicted values with experimental values, which proves the validity of the optimized data.

Conclusion:
Therefore, it can be concluded that the application of face-centered central composite design is
a useful statistical tool to get the optimized formulation with the least manpower, material, and money.
Essential Oils as Alternative Antimicrobials: Current Status
Authors: Sahu Ashish , Parai Debaprasad , Choudhary Hari Ram , Singh Desh Deepak 
Published: March 2023

Abstract:It is becoming increasingly difficult to treat bacterial infections with conventional antibiotics as resistance increases with time. Common antibiotics have been irrationally used in the general community, which has resulted in the selection of antibiotic-resistant genes. Despite various modifications that have been done to restore the antimicrobial activities of conventional antibiotics against an array of multi-drug resistant (MDR) strains, it has been unattainable to overcome this hurdle for a long time. Parallelly, the search for a new and alternative drug has become a high priority in every part of the world.:In the last two decades, immense interest has grown in natural products as alternative therapeutics due to their lower toxicity, chemical group diversity and biochemical specificity, which are the upper hand compared to antibiotics. Essential oils are naturally found phytochemicals obtained from approximately 60 families of plants. These are composed of 20 to 60 different bioactive components at different concentrations and have already been reported for their antibacterial, antifungal, antiviral, anti-parasitic, insecticidal activities, antioxidant and antiseptic properties. This review focuses on antimicrobial activities, detailed mode of action and the latest progress in the research on the essential oil.
Transcriptomic Profiling Reveals Chemokine CXCL1 as a Mediator for Neutrophil Recruitment Associated With Blood-Retinal Barrier Alteration in Diabetic Retinopathy
Authors: Monickaraj Finny , Acosta Gabriella , Cabrera Andrea P. , Das Arup 
Published: March 2023

Inflammation plays an important role in the pathogenesis of diabetic retinopathy (DR). To precisely define the inflammatory mediators, we examined the transcriptomic profile of human retinal endothelial cells exposed to advanced glycation end products, which revealed the neutrophil chemoattractant chemokine CXCL1 as one of the top genes upregulated. The effect of neutrophils in the alteration of the blood-retinal barrier (BRB) was further assessed in wild-type C57BL/6J mice intravitreally injected with recombinant CXCL1 as well as in streptozotocin-induced diabetic mice. Both intravitreally CXCL1-injected and diabetic animals showed significantly increased retinal vascular permeability, with significant increase in infiltration of neutrophils and monocytes in retinas and increased expression of chemokines and their receptors, proteases, and adhesion molecules. Treatment with Ly6G antibody for neutrophil depletion in both diabetic mice as well as CXCL1-injected animals showed significantly decreased retinal vascular permeability accompanied by decreased infiltration of neutrophils and monocytes and decreased expression of cytokines and proteases. CXCL1 level was significantly increased in the serum samples of patients with DR compared with samples of those without diabetes. These data reveal a novel mechanism by which the chemokine CXCL1, through neutrophil recruitment, alters the BRB in DR and, thus, serves as a potential novel therapeutic target.

Article Highlights
Intravitreal CXCL1 injection and diabetes result in increased retinal vascular permeability with neutrophil and monocyte recruitment. Ly6G antibody treatment for neutrophil depletion in both animal models showed decreased retinal permeability and decreased cytokine expression. CXCL1 is produced by retinal endothelial cells, pericytes, and astrocytes. CXCL1 level is significantly increased in serum samples of patients with diabetic retinopathy. CXCL1, through neutrophil recruitment, alters the blood-retinal barrier in diabetic retinopathy and, thus, may be used as a therapeutic target.
Combined PTEN Knockdown and Local Insulin in Chronic Experimental Diabetic Neuropathy
Authors: Pham Vuong M. , Komirishetty Prashanth , Areti Aparna , Poitras Trevor , Thakor Nitish , Zochodne Douglas W. 
Published: March 2023

Diabetic polyneuropathy (DPN) renders progressive sensory neurodegeneration linked to hyperglycemia and its associated metabolopathy. We hypothesized that there may be additive impacts of direct insulin signaling, independent of glycemia and phosphatase and tensin homolog deleted on chromosome 10 (PTEN) knockdown on neuropathy. Our targets for combined interventions were neurons and Schwann cells (SCs) in vitro and chronic type 1 DPN in mice. Insulin receptor expression was not altered by high-glucose conditions in neurons or SCs, and insulin promoted survival of neurons and proliferation of SCs in vitro. There were additive impacts between insulin signaling and PTEN knockdown in sensory neuron outgrowth and in axon myelination by SCs. In a chronic mouse model of experimental DPN, unilateral intra–hind paw injections of a PTEN siRNA and local insulin had additive impacts on correcting key features of chronic experimental DPN independent of glycemia, including motor axon conduction and thermal and mechanical sensory loss. Moreover, combined interventions improved sural and tibial nerve myelin thickness, hind paw epidermal innervation, and pAkt expression in dorsal root ganglion sensory neurons. We conclude that local PTEN inhibition or knockdown and insulin provide additive trophic support for sensory neurons and SCs while reversing key abnormalities of experimental DPN but without requiring metabolic correction.

Article Highlights
Impaired growth and plasticity of neurons may contribute to chronic diabetic polyneuropathy. Both direct insulin signaling of neurons and neuron knockdown of the protein phosphatase and tensin homolog deleted on chromosome 10 (PTEN), a roadblock to neuronal regenerative growth, offer direct support of neurons. Direct insulin and PTEN knockdown using siRNA had additive impacts on neuron survival, Schwann cell proliferation, neuron outgrowth, and myelination in vitro. Combined local insulin and PTEN siRNA hind paw injections improved abnormalities in chronic experimental diabetic polyneuropathy, including sensory axon loss, independently of glycemia.
Development and Validation of a Diabetic Retinopathy Risk Stratification Algorithm
Authors: Tarasewicz Dariusz , Karter Andrew J. , Pimentel Noel , Moffet Howard H. , Thai Khanh K. , Schlessinger David , Sofrygin Oleg , Melles Ronald B. 
Published: March 2023

OBJECTIVEAlthough diabetic retinopathy is a leading cause of blindness worldwide, diabetes-related blindness can be prevented through effective screening, detection, and treatment of disease. The study goal was to develop risk stratification algorithms for the onset of retinal complications of diabetes, including proliferative diabetic retinopathy, referable retinopathy, and macular edema.RESEARCH DESIGN AND METHODSRetrospective cohort analysis of patients from the Kaiser Permanente Northern California Diabetes Registry who had no evidence of diabetic retinopathy at a baseline diabetic retinopathy screening during 2008–2020 was performed. Machine learning and logistic regression prediction models for onset of proliferative diabetic retinopathy, diabetic macular edema, and referable retinopathy detected through routine screening were trained and internally validated. Model performance was assessed using area under the curve (AUC) metrics.RESULTSThe study cohort (N = 276,794) was 51.9% male and 42.1% White. Mean (±SD) age at baseline was 60.0 (±13.1) years. A machine learning XGBoost algorithm was effective in identifying patients who developed proliferative diabetic retinopathy (AUC 0.86; 95% CI, 0.86–0.87), diabetic macular edema (AUC 0.76; 95% CI, 0.75–0.77), and referable retinopathy (AUC 0.78; 95% CI, 0.78–0.79). Similar results were found using a simpler nine-covariate logistic regression model: proliferative diabetic retinopathy (AUC 0.82; 95% CI, 0.80–0.83), diabetic macular edema (AUC 0.73; 95% CI, 0.72–0.74), and referable retinopathy (AUC 0.75; 95% CI, 0.75–0.76).CONCLUSIONSRelatively simple logistic regression models using nine readily available clinical variables can be used to rank order patients for onset of diabetic eye disease and thereby more efficiently prioritize and target screening for at risk patients.
Abatacept for Delay of Type 1 Diabetes Progression in Stage 1 Relatives at Risk: A Randomized, Double-Masked, Controlled Trial
Authors: E. Russell William , Bundy Brian N. , S. Anderson Mark , Cooney Laura A. , Gitelman Stephen E. , Goland Robin S. , Gottlieb Peter A. , J. Greenbaum Carla , Haller Michael J. , Krischer Jeffrey P , Libman Ingrid M. , Linsley Peter S. , Alice Long S. , Lord Sandra M. , J. Moore Daniel , Moore Wayne V , Moran Antoinette M. , Muir Andrew B. , Raskin Phillip , Skyler Jay S. , Wentworth John M , Wherrett Diane K. , Wilson Darrell M. , Ziegler Anette-Gabriele , C. Herold Kevan 
Published: March 2023

<p> </p>
<p><strong>Objective</strong></p>
<p>Previous studies showed that inhibiting lymphocyte costimulation reduces declining beta cell function in individuals newly-diagnosed with type 1 diabetes. We tested whether abatacept would delay or prevent progression of type 1 diabetes from normal (NGT) to abnormal (AGT) glucose tolerance or to diabetes and the effects of treatment on immune and metabolic responses. </p>
<p><strong>Research Design and Methods</strong></p>
<p>We conducted a phase-2, randomized, placebo-controlled, double-masked trial of abatacept</p>
<p>in antibody-positive participants with NGT who received monthly abatacept/placebo infusions for 12 months. The endpoint was AGT or diabetes, assessed by oral glucose-tolerance tests. </p>
<p><strong>Results</strong></p>
<p>101 participants received abatacept and 111 placebo. Eighty-one (35 abatacept/46 placebo) met the endpoint of AGT or type 1 diabetes diagnosis (HR=0.702 (0.452, 1.09)(p=0.11) The C-peptide responses to OGTTs were higher in the abatacept arm (p<.03) . Abatacept reduced the frequency of ICOS+PD1+ T-follicular helper (Tfh) cells during treatment (p<0.0001), increased naïve CD4+ T cells, and also reduced the frequency of CD4+ Tregs from the baseline (p=0.0067). Twelve months after treatment, the frequency of ICOS+ Tfh, naïve CD4+ T, and Treg cells returned to baseline. </p>
<p><strong>Conclusions</strong></p>
<p>Although abatacept treatment for one year did not significantly delay progression to glucose intolerance in at-risk individuals, it impacted immune cell subsets and preserved insulin secretion suggesting that costimulation blockade may modify progression of type 1 diabetes.</p>
Pet Families. Modos de leer nuevas formas de vivir juntos
Authors: Linne Joaquín , Angilletta Florencia 
Published: March 2023

Este artículo explora modos de vivir característicos en sectores medios juveniles urbanos. Tras una encuesta, 27 entrevistas en profundidad y revisión de 4 000 perfiles en redes sociales y apps de citas, nuestra hipótesis es que la pet family es un dispositivo de subjetivación que enlaza prácticas afectivas, económicas, medioambientales y arquitectónicas que involucran la priorización de la amistad, alternancia de parejas, ambivalencia frente a la maternidad/paternidad y habitar departamentos pequeños. Además, implica una recolocación ontológica de la mascota: de asistente/guardián a familiar/roommate/amistad íntima. También proponemos la noción eco-familiy como dispositivo de subjetivación que incorpora hábitos ecológicos a las formas de vida. Estos modos de vivir juntos desbordan el concepto de familia y actualizan la pregunta sobre qué es lo común.
Performing an ovariohysterectomy at the time of c-section does not pose an increase in risk of mortality, intra- or postoperative complications, or decreased mothering ability of the bitch
Authors: Guest Kelsea E. , Ellerbrock Robyn E. , Adams Daniel J. , Reed Rachel A. , Grimes Janet A. 
Published: March 2023

Abstract

OBJECTIVE
Ovariohysterectomy (OVH) is frequently recommended at the time of c-section in canines, yet prior literature suggests poor mothering ability and increased morbidity to the bitch with c-section with concurrent OVH (CSOVH). The study objective was to compare maternal survival, complications, and mothering ability between bitches that underwent c-section alone (CS) or CSOVH.

ANIMALS
125 bitches.

PROCEDURES
Medical records from 2014 through 2021 were retrospectively reviewed; owners were surveyed for information up to weaning.

RESULTS
80 bitches undergoing CS and 45 bitches undergoing CSOVH were identified. There was no difference in anesthesia duration, intraoperative complications, postoperative complications, mothering ability, puppy survival to weaning, or other variables compared between groups. CSOVH bitches had longer surgery times (P = .045; 54.4 ± 20.7 min vs 46.9 ± 16.6 min) and longer time from delivery to nursing (P = .028; 75.4 ± 22.3 min vs 65.2 ± 19.5 min). Ninety (72%) owners responded to the survey. All 90 bitches survived until puppy weaning. CSOVH bitches were more frequently perceived as painful postoperatively (P = .015).

CLINICAL RELEVANCE
Performing an OVH at the time of c-section does not pose a significant increase in risk of mortality, intraoperative complications, postoperative complications, or decreased mothering ability of the bitch. The increased duration of surgery and increased time from delivery to nursing in the CSOVH group were clinically insignificant. Appropriate postoperative pain management should be emphasized post-CSOVH. Based on these results, OVH should be performed concurrently with c-section if indicated.
Modal Instabilities over Blunted Cones at Angle of Attack in Hypersonic Flow
Authors: Paredes Pedro , Scholten Anton , Choudhari Meelan M. , Li Fei 
Published: March 2023

The effects of nose radius and angle of attack on the linear modal amplification over blunt circular cones at hypersonic speeds are computationally investigated. The three-dimensional laminar flow solutions over a 1.5-m-long, 7°-half-angle cone with 5.080, 9.525, and 25.40 mm nosetip radii are computed for selected angle-of-attack values and freestream conditions that match the Mach 10 experiments at a freestream unit Reynolds number of 17.1 million per meter conducted within the Hypervelocity Wind Tunnel 9 at the Air Force Arnold Engineering Development Complex (AEDC). Results indicate that the linear amplification of stationary and traveling crossflow waves along inflection lines increases with the angle of attack and decreases with the nosetip radius. The trend in transition front with respect to increasing angle of attack and bluntness is found to be consistent with the predicted increase in the amplification factors for Mack’s second mode (MM) disturbances along the streamline trajectories for the small and medium bluntness cases. The increase in the MM amplification along the windward ray for higher angles of attack is shown to be the result of a progressively earlier entropy-layer swallowing. Computations also indicate that the transition amplification factor along the windward ray increases with the angle of attack and decreases with the nosetip radius. Furthermore, the transition [Formula: see text]-factors along the leeward ray are below 2 and, therefore, rather small to lead to transition.
Facility Effects on the Ion Characteristics of a 12.5-Kilowatt Hall Thruster
Authors: Huang Wensheng , Kamhawi Hani 
Published: March 2023

During a laser-induced fluorescence test of a 12.5 kW magnetically shielded Hall thruster, ion characteristics in the discharge channel and near the poles were measured as the background pressure and electrical configuration were varied. The acceleration zone of the thruster moved upstream by 2 and 10% of the channel length when the background pressure was raised to 1.8 times and seven times the lowest achievable pressure, respectively. Examination of the characteristics of the ions near the pole covers suggested that as the background pressure decreased, the pole covers might be experiencing more erosion. When operating at a discharge voltage of 300 V, the acceleration zone was observed to be at the same location for all electrical configurations. When operating at a discharge voltage of 600 V, the acceleration zone was observed to move 3% of the channel length upstream when the thruster body was floated instead of tied to the cathode or grounded to the facility. Characteristics of the ions bombarding the pole covers did not vary across the tested electrical configurations. This observation combined with thruster body voltage measurements suggested that varying the electrical configuration only affected the thruster body sheath voltage and did not affect the plasma potential beyond the sheath.
Женщины в публичном дискурсе в период Тувинской Народной Республики (историко-социологический анализ по материалам периодической печати)
Authors: Натсак Органа Доржуевна 
Published: March 2023

В статье на основе материалов тувинских журналов и газет Тувинской Народной Республики (ТНР) проведён историко-социологический анализ формирования современной тувинской женщины. Через анализ публичного дискурса определено содержание политики в отношении женщин, описаны идеологически маркированные образы женщин, которые соотнесены с социокультурным и политическим контекстом рассматриваемого периода. В статье показаны методы и особенности правовой социализации женщин.
Автором описаны практики репрезентации женщин в тувинских журналах и газетах, а также через газетные нарративы раскрыто содержание социального проектирования «новой тувинской женщины». Представлены результаты интерпретативного анализа лозунгов для женщин, раскрывающих проблемы и задачи, которые решались на уровне государства, и целевая модель, к которой стремились. Раскрыты принципы работы араткоров (народных корреспондентов) и последствия их писем в газеты для женских карьер в условиях формировавшейся тогда новой политической культуры, которая характеризуется признаками, схожими с чертами современной «культуры отмены», распространением борьбы с «врагами народа» и проникновением языка насилия в политическую коммуникацию.
Сделан вывод о том, что тувинские журналы и газеты периода ТНР способствовали ролевой революции женщин.