bluuebunny/crossref_metadata_2025_split huggingface dataset:
Non‐ObeseMKRMouse Model of Type 2 Diabetes Reveals Skeletal Alterations in Mineralization and Material Properties
Authors: Tice Matthew J.L. , Bailey Stacyann , Sroga Grażyna E. , Gallagher Emily J. , Vashishth Deepak 
Published: November 2021

ABSTRACTObesity is a common comorbidity of type 2 diabetes (T2D). Therefore, increased risk of fragility fractures in T2D is often confounded by the effects of obesity. This study was conducted to elucidate the mechanistic basis by which T2D alone leads to skeletal fragility. We hypothesized that obesity independent T2D would deteriorate bone's material quality by accumulating defects in the mineral matrix and undesired modifications in its organic matrix associated with increased oxidative stress and hyperglycemia. To test this hypothesis, we used 15‐week‐old male non‐obese mice with engineered muscle creatine kinase promoter/human dominant negative insulin growth factor 1 (IGF‐I) receptor (MKR) and FVB/N wild‐type (WT) controls (n = 12/group). MKR mice exhibit reduced insulin production and loss of glycemic control leading to diabetic hyperglycemia, verified by fasting blood glucose measurements (>250 mg/dL), without an increase in body weight. MKR mice showed a significant decrease in femoral radial geometry (cortical area, moment of inertia, cortical thickness, endosteal diameter, and periosteal diameter). Bone mineral density (BMD), as assessed by micro–computed tomography (μCT), remained unchanged; however, the quality of bone mineral was altered. In contrast to controls, MKR mice had significantly increased hydroxyapatite crystal thickness, measured by small‐angle X‐ray scattering, and elongatedc‐axis length of the crystals evaluated by confocal Raman spectroscopy. There was an increase in changes in the organic matrix of MKR mice, associated with enhanced glycoxidation (carboxymethyl‐lysine [CML] and pentosidine) and overall glycation (fluorescent advanced glycation end products), both of which were associated with various measures of bone fragility. Moreover, increased CML formation positively correlated with elongated mineral crystal length, supporting the role of this negatively charged side chain to attract calcium ions, promote growth of hydroxyapatite, and build a physical link between mineral and collagen. Collectively, our results show, for the first time, changes in bone matrix in a non‐obese T2D model in which skeletal fragility is attributable to alterations in the mineral quality and undesired organic matrix modifications. © 2021 The Authors.JBMR Pluspublished by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.
Myeloid-Specific PTP1B Deficiency Attenuates Inflammation-Induced and Ovariectomy-Induced Bone Loss in Mice by Inhibiting Osteoclastogenesis
Authors: Kim Hyo Jeong , Ryu Ka-Young , Kim Yong-Gun , Kim Myoung Ok , Lee Ji Hye , Song Min-Kyoung , Youn Young-Jin , Pokhrel Nitin Kumar , Kim Sung-Hyun , Kim Jae-Young , Jung Hye-Jin , Kim Woo-Shin , Hong Chang-Won , Kim Hong-Hee , Lee Youngkyun 
Published: November 2021

ABSTRACT
The differentiation and activity of bone-resorbing osteoclasts are tightly regulated to maintain the homeostasis of healthy bones. In this study, the role of protein tyrosine phosphatase 1B (PTP1B) during osteoclastogenesis was studied in myeloid-specific Ptpn1-deficient (conditional knockout [cKO]) mice. The mRNA and protein expression of PTP1B increased during the formation of mature osteoclasts from mouse bone macrophages on stimulation with macrophage-colony stimulating factor (M-CSF) and receptor activator of nuclear factor κB ligand (RANKL). The Ptpn1 cKO mice exhibited increased femoral trabecular bone volume with a decreased number and activity of osteoclasts compared with control mice. The in vitro culture of osteoclast precursors corroborated the inhibition of osteoclastogenesis in cKO cells compared with control, with concomitantly decreased RANKL-dependent proliferation, lower osteoclast marker gene expression, reduced nuclear expression of nuclear factor of activated T cells cytoplasmic 1 (NFATc1), diminished intracellular Ca2+ oscillations, and increased phosphorylation of proto-oncogene tyrosine-protein kinase Src on inhibitory tyrosine residue. In a ligature-induced periodontitis model, Ptpn1 cKO mice exhibited attenuated osteoclastogenesis and alveolar bone loss following the induction of inflammation. The Ptpn1-deficient mice were similarly protected from ovariectomy-induced bone loss compared with control mice. These results provide a novel regulatory role of PTP1B in osteoclastogenesis and suggest a potential as a therapeutic target for bone-lytic diseases. © 2021 American Society for Bone and Mineral Research (ASBMR).
Measurement of synovium and serum dual specificity phosphatase 22 level: Their inter‐correlation and potency as biomarkers in rheumatoid arthritis
Authors: Qian Chen , Chen Jie , Xu Xiaopeng , Liu Qingyang , Gu Minhong , Lu Sheng , Bai Hongxia , Wang Qiubo , Xue Mingyu 
Published: November 2021

AbstractBackgroundDual specificity phosphatase 22 (DUSP22), also named as Jun N‐terminal kinase pathway associated phosphatase recently, is reported to be closely engaged in immune and inflammation regulation. This study aimed to investigate the interaction between synovium DUSP22 and serum DUSP22 levels and to explore their correlation with rheumatoid arthritis (RA) risk, inflammation, and disease activity.MethodsSynovium and serum samples from 42 RA patients with knee involvement underwent arthroscopy, and 20 knee trauma patients were collected. Besides, serum samples from 40 healthy controls were also obtained. Synovium DUSP22 expression was detected by reverse transcription quantitative polymerase chain reaction, while serum DUSP22 level was detected by enzyme‐linked immunosorbent assay.ResultsSynovium DUSP22 level was greatly decreased in RA patients compared to trauma controls (p < 0.001), and it was negatively correlated with tender joint count (TJC) (r = −0.318, p = 0.040), C‐reactive protein (CRP) (r = −0.330, p = 0.033), and Lysholm score (r = −0.423, p = 0.005) in RA patients. Serum DUSP22 level was lowest in RA patients, followed by trauma controls, then highest in healthy controls (p < 0.001). Serum DUSP22 level was negatively associated with TJC (r = −0.438, p = 0.004), swollen joint count (SJC) (r = −0.372, p = 0.015), CRP (r = −0.391, p = 0.011), and disease activity score in 28 joints (DAS28ESR) score (r = −0.406, p = 0.008), and it increased after treatment (p = 0.001) in RA patients. In addition, serum DUSP22 level positively related to synovium DUSP22 level in RA patients (r = 0.394, p = 0.010).ConclusionSynovium and serum DUSP22 are intercorrelated and insufficiently expressed in RA patients; meanwhile, their deficiency correlates with increased systemic inflammation, disease activity, and joint dysfunction.
Combination of artificial intelligence‐based endoscopy and miR148a methylation for gastric indefinite dysplasia diagnosis
Authors: Watanabe Yoshiyuki , Oikawa Ritsuko , Agawa Shuhei , Matsuo Yasumasa , Oda Ichiro , Futagami Seiji , Yamamoto Hiroyuki , Tada Tomohiro , Itoh Fumio 
Published: November 2021

AbstractBackground and AimGastrointestinal endoscopy and biopsy‐based pathological findings are needed to diagnose early gastric cancer. However, the information of biopsy specimen is limited because of the topical procedure; therefore, pathology doctors sometimes diagnose as gastric indefinite for dysplasia (GIN).MethodsWe compared the accuracy of physician‐performed endoscopy (trainee, n = 3; specialists, n = 3), artificial intelligence (AI)‐based endoscopy, and/or molecular markers (DNA methylation: BARHL2, MINT31, TET1, miR‐148a, miR‐124a‐3, NKX6‐1; mutations: TP53; and microsatellite instability) in diagnosing GIN lesions. We enrolled 24,388 patients who underwent endoscopy, and 71 patients were diagnosed with GIN lesions. Thirty‐two cases of endoscopic submucosal dissection (ESD) in 71 GIN lesions and 32 endoscopically resected tissues were assessed by endoscopists, AI, and molecular markers to identify benign or malignant lesions.ResultsThe board‐certified endoscopic physicians group showed the highest accuracy in the receiver operative characteristic curve (area under the curve [AUC]: 0.931), followed by a combination of AI and miR148a DNA methylation (AUC: 0.825), and finally trainee endoscopists (AUC: 0.588).ConclusionAI with miR148s DNA methylation‐based diagnosis is a potential modality for diagnosing GIN.
iTRAQ‐based proteomic analysis of differentially expressed proteins in sera of seronegative and seropositive rheumatoid arthritis patients
Authors: He Yujue , Lin Junyu , Tang Jifeng , Yu Ziqing , Ou Qishui , Lin Jinpiao 
Published: November 2021

AbstractObjectiveThe diagnosis of seronegative rheumatoid arthritis (SNRA) is often difficult due to the unavailability of reliable laboratory markers. The aim of this study was to identify differentially expressed proteins in sera of SNRA, seropositive RA (SPRA), and healthy donors (HD).MethodsA total of 32 seropositive RA patients, 32 SNRA patients, and 35 HD were enrolled in our study. Differentially expressed proteins between 3 groups were identified via isobaric tags for relative and absolute quantitation (iTRAQ)‐based proteomic analysis, and an ELISA test was used for the validation test. Correlation analysis was conducted by GraphPad Prism.ResultsUsing iTRAQ quantitative proteomics, we identified 14 proteins were significantly different between SPRA and SNRA, including 4 upregulated proteins and 10 downregulated proteins. Four differentially expressed proteins were validated by ELISA test, and the results showed that SAA1 protein was significantly higher in SPRA and SNRA patients compared with HD, and PSME1 was elevated in SPRA patients. What's more, SAA1 was increased in the anti‐CCP or RF high‐level group in RA patients, and PSME1 was increased in the RF high‐level group. Alternatively, SAA1 was positively correlated with inflammation indicators in RA patients, while PSME1 showed no correlation with inflammation indicators.ConclusionsiTRAQ proteomic approaches revealed variations in serum protein composition among SPRA patients, SNRA patients, and HD and provided new idea for advanced diagnostic methods and precision treatment of RA.
The best mirror of the students' longitudinal performance: Portfolio or structured oral exam assessment at clerkship?
Authors: Isbej Lorena , Cantarutti Cynthia , Fuentes‐Cimma Javiera , Fuentes‐López Eduardo , Montenegro Uriel , Ortuño Duniel , Oyarzo Natacha , Véliz Claudia , Riquelme Arnoldo 
Published: November 2021

AbstractObjectiveThis study aimed to compare the strength of association (i.e., explained variability) of the cumulative grade point average (GPA) with the grades obtained in the clerkship portfolio and the final structured oral exam by dental students.MethodsA prospective longitudinal study was designed to analyze quantitative data from three cohorts of dental school students. Univariate and multivariate linear regression models were built to evaluate the association between the students' cumulative GPA with the grades obtained in their clerkship portfolio and the final structured oral exam.ResultsIn total, 171 students in the last year of the undergraduate program were considered (76% women, age average 24.8 ± 1.6 years). The dental students' grades of both portfolio and structured oral exam were significantly associated with the GPA score but with different strengths of association. The clerkship portfolio was more strongly associated with cumulative GPA than the structured oral exam (R2 = 19.6% versus R2 = 7.6%). On the opposite, the association between the structured oral exam and GPA can be interpreted as a lower precision in its practical significance and thus reflecting different concurrent validity.ConclusionsConsidering the results of this study, it could probably incline the balance toward the portfolio because it may be closer to a programmatic assessment model, with timely feedback, development of metacognition, and the achievement of formative process measurement rather than evidence of a single instance of examination.
New indications and platforms for CAR‐T therapy in lymphomas beyond DLBCL
Authors: Iqbal Madiha , Savani Bipin N , Hamadani Mehdi 
Published: November 2021

AbstractCD19‐directed chimeric antigen receptor T‐cell therapy (CAR‐T) represents a significant advancement for patients with relapsed/refractory large B‐cell lymphoma (LBCL). Long‐term follow‐up confirms durable remissions in nearly half of the patients, a population that was previously estimated to have a median survival of around 6 months with standard salvage therapy. This initial success of CAR‐T has led to significant expansion across other lymphoma histologies resulting in the recent regulatory approval of CAR‐T in mantle cell lymphoma and follicular lymphoma. Additionally, multiple novel platforms of CAR‐T therapy are under development to improve efficacy and limit toxicity such dual antigen targeting, allogeneic and natural killer CARs. In this review, we focus on the new indications of CAR‐T in lymphomas beyond LBCL as well as emerging platforms of CAR‐T therapy.
A study of the evolution of the third COVID‐19 pandemic wave in the Athens metropolitan area, Greece, through two cross‐sectional seroepidemiological surveys: March, June 2021
Authors: Maltezou Helena C. , Krumbholz Bettina , Mavrouli Maria , Tseroni Maria , Gamaletsou Maria N. , Botsa Evanthia , Anastassopoulou Cleo , Gikas Aristofanis , Fournarakou Evanthia , Kavieri Maria , Koureli Aikaterini , Mandilara Dionysia , Marinopoulou Aikaterini , Theodorikakou Argyro , Tsiahris Panagiotis , Zarzali Anastasia , Pournaras Spyridon , Lourida Athanasia , Elefsiniotis Ioannis , Vrioni Georgia , Sipsas Nikolaos V. , Tsakris Athanasios 
Published: November 2021

AbstractWe studied the third coronavirus disease 2019 (COVID‐19) pandemic wave in Athens metropolitan area (3 738 901 inhabitants) through two seroepidemiological surveys. Persons presenting in 12 healthcare facilities across Athens in March and June 2021 were studied (764 and 901, respectively). Immunoglobulin G antibodies against severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) spike protein were measured by a chemiluminescent microparticle immunoassay. In March the seroprevalence rate was 11.6%, meaning that 435 208 residents of Athens had evidence of immunity. The respective values in June were 55.7% and 2 082 568 residents. The highest seroprevalence rates attributed to SARS‐CoV‐2 infection were recorded in persons <18 years (16.3% in March and 31.6% in June), while immunity was mainly vaccine‐induced in persons 18–64 years and >65 years. Infection‐attributed immunity also increased in older‐age groups. Wide ranges in seroprevalence rates were noted across areas in March and June. The highest seroprevalence rates were recorded in Piraeus (47.2%) and West Attica (37.5%). However, the highest increase (>5 times) occurred in Piraeus and the South Section of Athens, which are among the most densely populated areas in Athens. In both study periods, history of COVID‐19 or febrile episode, and having a cohabitant with COVID‐19 were associated with increased risk for seropositivity among unvaccinated persons (p values <0.001 for all). Residing in Piraeus, the South Section or West Attica was associated with increased risk for seropositivity in June (p values <0.001). Wide heterogeneity in seroprevalence rates was found across areas in Athens, which is mainly attributed to population density. The impact of population mobility and socioeconomic status should be explored.
Activation of canonical Wnt signaling accelerates intramembranous bone regeneration in male mice
Authors: Ko Frank C. , Moran Meghan M. , Ross Ryan D. , Sumner D. Rick 
Published: November 2021

AbstractCanonical Wnt signaling plays an important role in skeletal development, homeostasis, and both endochondral and intramembranous repair. While studies have demonstrated that the inhibition of Wnt signaling impairs intramembranous bone regeneration, how its activation affects intramembranous bone regeneration has been underexplored. Therefore, we sought to determine the effects of activation of canonical Wnt signaling on intramembranous bone regeneration by using the well‐established marrow ablation model. We hypothesized that mice with a mutation in the Wnt ligand coreceptor gene Lrp5 would have accelerated intramembranous bone regeneration. Male and female wild‐type and Lrp5‐mutant mice underwent unilateral femoral bone marrow ablation surgery in the right femur at 4 weeks of age. Both the left intact and right operated femurs were assessed at Days 3, 5, 7, 10, and 14. The intact femur of Lrp5 mutant mice of both sexes had higher bone mass than wild‐type littermates, although to a greater degree in males than females. Overall, the regenerated bone volume in Lrp5 mutant male mice was 1.8‐fold higher than that of littermate controls, whereas no changes were observed between female Lrp5 mutant and littermate control mice. In addition, the rate of intramembranous bone regeneration (from Day 3 to Day 7) was higher in Lrp5 mutant male mice compared to their same‐sex littermate controls with no difference in the females. Thus, activation of canonical Wnt signaling increases bone mass in intact bones of both sexes, but accelerates intramembranous bone regeneration following an injury challenge only in male mice.
Functional tissue engineering of articular cartilage for biological joint resurfacing—The 2021 Elizabeth Winston Lanier Kappa Delta Award
Authors: Guilak Farshid , Estes Bradley T. , Moutos Franklin T. 
Published: November 2021

AbstractBiological resurfacing of entire articular surfaces represents a challenging strategy for the treatment of cartilage degeneration that occurs in osteoarthritis. Not only does this approach require anatomically sized and functional engineered cartilage, but the inflammatory environment within an arthritic joint may also inhibit chondrogenesis and induce degradation of native and engineered cartilage. Here, we present the culmination of multiple avenues of interdisciplinary research leading to the development and testing of bioartificial cartilage for tissue‐engineered resurfacing of the hip joint. The work is based on a novel three‐dimensional weaving technology that is infiltrated with specific bioinductive materials and/or genetically‐engineered stem cells. A variety of design approaches have been tested in vitro, showing biomimetic cartilage‐like properties as well as the capability for long‐term tunable and inducible drug delivery. Importantly, these cartilage constructs have the potential to provide mechanical functionality immediately upon implantation, as they will need to replace a majority, if not the entire joint surface to restore function. To date, these approaches have shown excellent preclinical success in a variety of animal studies, including the resurfacing of a large osteochondral defect in the canine hip, and are now well‐poised for clinical translation.
Patient‐specific apparent diffusion maps used to model nutrient availability in degenerated intervertebral discs
Authors: Shalash Ward , Ahrens Sonia R. , Bardonova Liudmila A. , Byvaltsev Vadim A. , Giers Morgan B. 
Published: November 2021

AbstractIntroductionIn this study, magnetic resonance imaging data was used to (1) model IVD‐specific gradients of glucose, oxygen, lactate, and pH; and (2) investigate possible effects of covariate factors (i.e., disc geometry, and mean apparent diffusion coefficient values) on the IVD’s microenvironment. Mathematical modeling of the patient’s specific IVD microenvironment could be important when selecting patients for stem cell therapy due to the increased nutrient demand created by that treatment.Materials and MethodsDisc geometry and water diffusion coefficients were extracted from MRIs of 37 patients using sagittal T1‐weighted images, T2‐weighted images, and ADC Maps. A 2‐D steady state finite element mathematical model was developed in COMSOL Multiphysics® 5.4 to compute concentration maps of glucose, oxygen, lactate and pH.ResultsConcentration of nutrients (i.e., glucose, and oxygen) dropped with increasing distance from the cartilaginous endplates (CEP), whereas acidity levels increased. Most discs experienced poor nutrient levels along with high acidity values in the inner annulus fibrosus (AF). The disc’s physiological microenvironment became more deficient as degeneration progressed. For example, minimum glucose concentration in grade 4 dropped by 31.1% compared to grade 3 (p < 0.0001). The model further suggested a strong effect of the following parameters: disc size, AF and CEP diffusivities, metabolic reactions, and cell density on solute concentrations in the disc (p < 0.05).ConclusionThe significance of this work implies that the individual morphology and physiological conditions of each disc, even among discs of the same Pfirrmann grade, should be evaluated when modeling IVD solute concentrations.
A method to choose water depths for zooplankton samples in lakes
Authors: Rippey Brian , Macintosh Katrina A. , McElarney Yvonne , Douglas Richard 
Published: November 2021

AbstractAs methods in the literature to sample zooplankton in lakes mostly offered general guidance on the sample depths, a new one was developed. Using the principle of volume‐weighted sampling of the lake volume and an empirical function for the hypsometric curve, formulae for the volumes and areas of five equal sections of the lake were derived, which were then used to calculate section mean depths. Vertical net hauls taken at the mean depths are combined using a relation between their mean depths to produce one unbiased composite sample of the zooplankton. While generic formulae were derived, starting values for the depths that divide the lake volume into five equal sections are needed in order to apply the method, which then optimizes the depths; the method is implemented in a spreadsheet. The method was applied to four hypothetical lakes of maximum depth 12 m that cover a wide variation of lake form and how the sample depths vary with form was described; as lake form becomes more convex, the sample depths decrease, reflecting that more of the lake volume is at shallower depth. The method was used to estimate the whole‐lake abundance of zooplankton in 51 lakes and no practical difficulties were encountered. It can be used in lakes up to a few tens of km2 in area.
Fluorine and Siloxane Free Waterborne Near Superhydrophobic Organic Coating Based on Styrene Acrylic Polymer Emulsion through Surface Engineering
Authors: Mirchandani Girish , Basutkar Sachin , Raghavendra Venugopal B. , Samanta Sarthik , Bhavsar Ritesh , Shyamroy Subarna , Singha Nikhil K. 
Published: November 2021

AbstractA superhydrophobic coating, free of fluorinated and siloxane materials, has been prepared via reactive compatibilization of all organic blends of hydrophilic and hydrophobic materials. In this case, styrene acrylic emulsion and a combination of hydrophobic waxes (functional rice bran wax and functional polypropylene wax) are blended together in the presence of polycarbodiimide as the reactive compatibilizer. The effect of blending and crosslinking on surface morphology is studied by Fourier transform infrared spectroscopy analysis, microscopy analyses (SEM and AFM), contact angle, and surface energy measurements. After heat treatment and crosslinking, synergistic improvements of surface properties with a gradual trend toward superhydrophobicity are observed (water contact angle ≈144° and roll‐off angle of <10°). The system is free of nanoparticles, and the desired surface morphology and microstructure is formed from the mixture of renewable (rice bran) wax and petrochemical (polypropylene) wax. These coatings are shown to have easy‐cleaning as well as self‐cleaning characteristics. Further, the coatings can withstand exposure to solvents as well as mechanical abrasion.