bluuebunny/crossref_metadata_2025 huggingface dataset:
Ultrasound-guided Paravertebral Block Versus Intravenous Sedative Analgesic using Midazolam /Fentanyl in Patients Undergoing Extracorporeal Shock Wave Lithotripsy
Authors: Elaiashy Fatma M. , Elyazd Mohamed M. Abu , Eldaba Ahmed A. , Gameel Tarek A.
Published: March 2021

Background: Thoracic paravertebral block (TPVB) produces ipsilateral somatic and sympathetic nerve blockade in multiple contiguous dermatomes both above and below the site of injection.

 The Aim of This Study: was to compare the effectiveness of ultrasound-guided TPVB versus intravenous (IV) sedative analgesic using midazolam / fentanyl in patients undergoing extracorporeal shock wave lithotripsy (ESWL) procedure.

Patients and Methods: This prospective, randomized study was carried out on sixty patients aged 20-60 years, with radio-opaque renal stone not more than1.5cm. TPVB group (30 patients) received ipsilateral ultrasound-guided TPVB at the level T9-T10 using bupivacaine 0.25% (20 mL) about 30 minutes before the ESWL. Midazolam/fentanyl group (30 patients) received sedatives analgesic drugs using IV midazolam (0.05 mg / kg) and fentanyl (1 µg/kg) about 5 min before the ESWL. The VAS score during and 30 min post procedure, total dose of rescue analgesic consumption during ESWL procedure, the success rate of ESWL, the time needed to stone clearance, patient and operator satisfaction scores were recorded.

Result: During and after ESWL procedure, the VAS scores were significantly higher in midazolam/fentanyl group than TPVB group (P < 0.05). The number of patients required rescue analgesic during ESWL was significantly higher in midazolam/fentanyl group compared to TPVB group (P < 0.05).The success rate of ESWL was insignificantly different between both groups (P > 0.05). The time needed to stone clearance was significantly shorter in TPVB group compared to midazolam/fentanyl group (P < 0.05).

Conclusions: Ultrasound-guided TPVB provided more effective analgesia with reduced number of ESWL sessions and shorter time to renal stone clearance than IV midazolam/fentanyl.
Evaluation of Intralesional Injection of 5-fluorouracil in Treatment of Vitiligo
Authors: Anber D. M. Abo , Ali D. A. Mohammed , El-Tatawy R. A. , Elgarhy L. H.
Published: March 2021

Background: Vitiligo is a chronic cutaneous disease characterized by depigmented patches that leave psychological impact on the patients. New treatment modalities have been developed to improve the results vitiligo with less side effects.

Objective: To evaluate intralesional injection of 5-fluorouracil in treatment of vitiligo.

Patients and Methods: The study included 20 localized stable vitiligo patients. Each patient was treated with intralesional injection of 5-fluorouracil every 2 weeks for 3 sessions followed by narrow band sessions twice weekly for 3 months.

Results: There was statistically significant repigmentation after treatment with intralesional 5-FU (mean of 50.30 ± 34.60, P value =0.001 Wilcoxon signed ranks test between before and after). 55% of patients showed >50% repigmentation. after 3 months therapy. Side effects were minimal and transient.

Conclusion: Intralesional injection of 5-FU is safe and effective in the treatment of vitiligo.
Effect of the Brain Balance Program® on Cognitive Performance in Children and Adolescents with Developmental and Attentional Issues
Authors: Jackson Rebecca , Wild Conor J.
Published: March 2021

We reviewed the cognitive task performance of children and adolescents with developmental and attentional issues, before and after participation in the Brain Balance® (BB) program. The program consisted of three 1-hour sessions/week (sensorimotor stimulation and academic activities) with other multimodal activities, for 3 months. Participants were compared to a control group that had the same underlying demographic and phenotypical features but did not yet complete the program (participated on average for 27 days). For all ages (4-6 and 7+ years), we found a significant main effect of group, such that BB groups improved overall more than controls (CTRLs). More specifically, BB groups improved on all cognitive tests (three tests for ages 4-6 years; 12 tests for ages 7+ years), whereas CTRLs only improved on one test. These data support the potential of multimodal training programs toward the overarching goal of improving cognitive performance in children with developmental and attentional difficulties.
Effect of Intrathecal Dexmedetomidine in Preventing Intra-operative Shivering after Spinal Anesthesia
Authors: Ibrahim Hossam Ibrahim , Elashry Hesham Elsayed , Rahman Reda Sobhy Abdel , Shalaby Osama Mahmoud
Published: March 2021

Background: Dexmedetomidine (DEX) has sedative, analgesic, sympatholytic, anesthetic-sparing and hemodynamic-stabilizing properties. This study aims to evaluate the effects of intrathecal DEX as an adjuvant to hyperbaric bupivacaine in the prevention of shivering in patients who underwent surgeries under Intrathecal anesthesia.

Methods: A prospective double-blind, controlled, randomized study was conducted on 100 patients aged above 21 years old, ASA I & II undergoing lower limb orthopedic surgeries under intrathecal anesthesia. Patients were subdivided randomly into 2 equal group; Group Bupivacaine-Dexmedetomidine (BD): 5 µg dexmedetomidine diluted in 0.5 ml 0.9% normal saline was added to 12.5 mg heavy bupivacaine 0.5% and Group Bupivacaine (B): 0.5 ml 0.9% normal saline was added to 12.5mg heavy bupivacaine 0.5% (3ml volume).

Results: Shivering occurred in 9 patients (18%) in group BD and 23 patients (46%) in group B with a significant decrease in group BD compared to group B (P = 0.003). The relative risk of developing shivering was decreased 53% (95% Confidence Interval: 74 – 16%) with group BD compared to group B. Tsai and Chu score was significantly better in group BD (P = 0.013).

Conclusion: The use of intrathecal DEX (5μg) in conjugation with heavy bupivacaine help decrease the incidence and intensity of shivering when compared with heavy bupivacaine alone in surgeries under spinal anesthesia.
Antioxidant, Antibacterial, and Phytochemical Screening of Ethanolic Crude Extracts of Libyan Peganum harmala Seeds
Authors: Allaq Abdulmutalib Alabeed , Sidik Norrizah Jaafar , Abdul-Aziz Aziyah , Ahmed Idris Adewale
Published: March 2021

Peganum harmala is one of the most famous medicinal plants and natural products commonly used in traditional medicine and extensively spread in Middle and East Asia and North Africa. This study aimed to evaluate the radical scavenging activity of ethanolic crude extracts of P. harmala seeds from Libya using DPPH assay; to determine the minimum inhibitory concentration (MIC) and minimum bactericidal concentrations (MBC) of the P. harmala seeds crude extracts against Gram-negative Salmonella typhi ATCC14028 and Escherichia coli ATCC 25922 and also Gram-positive Bacillus subtilis ATCC 6633 and Staphylococcus aureus ATCC 33591; and to screen the phytochemicals in the ethanolic crude extracts of the Libyan P. harmala seeds using gas chromatography-mass spectrometry (GC-MS). The IC50 value of P. harmala seeds extract was 179.62±7.32 μg/mL. The MIC ranged from 1.95 to 31.25 mg/mL while the MBC ranged from 7.80 to 62.50 mg/mL. The eight compounds identified were harmine, harmaline, leptalorine, hexahydro fluorene, 3-methoxy-6-methyl, 1H-pyrido [3,4-b]indole,2,34,9- tetrahydro-6methoxy-1-methyl, 9,12-octadienoic acid ethyl ester, linoleic acid ethyl ester, 9,12-octadienoic acid (z,z). This study has, therefore, revealed the antixodant and antibacterial efficacy of P. harmala ethanolic extract. Thus, it could be further developed as a substitute for chemical antioxidants and as antibacterials agent.
Structural Optimization and the Study of the Electronic, Mechanical, Thermodynamic and Phonon Properties of Mg2sn from First Principle
Authors: Okunzuwa I. S. , Eddy E. Aigbekaen, , Chidubem T. Philips
Published: March 2021

First principles pseudopotential method based on density functional theory is used to investigate the Structural, Mechanical, Phonon, Thermodynamic and Electronic properties of Mg2Sn. The equilibrium properties including lattice constant, bulk modulus, pressure derivative cohesive energy, young modulus, shear modulus were determined. The results obtained were compared with available experimental and other available results. Mg2Sn was found to be brittle in nature with a non-metallic properties as shown by the value of the Cauchy pressure of -4.03. The Phonon dispersion curve of Mg2Sn was obtained utilizing the PBE-GGA exchange-correlation potential as employed in the Vienna Ab-Initio Simulation Package (VASP) computer code. The gap separating the acoustic and the optical branch of the curve was found to be about 50cm-1 at X-point. The thermodynamic properties of the material was investigated in the temperature of 0-800K. At room temperature, the calculated value of the specific heat capacity ( ) is 71.28J/mol which is in good agreement with experimental and other results. Mg2Sn was found to a narrow gap semiconductor with an indirect bandgap of magnitude of 0.175eV.
Missing piece of top predator‐based conservation: Demographic analysis of an owl population on a remote subtropical island
Authors: Sawada Akira , Iwasaki Tetsuya , Inoue Chitose , Nakaoka Kana , Nakanishi Takumi , Sawada Junpei , Aso Narumi , Nagai Syuya , Ono Haruka , Takagi Masaoki
Published: March 2021

Top predators are frequently the target of conservation programs. Owls are such predators. However, previous studies of owls are biased to species occurring in temperate regions, whereas most owl species occur in tropical or subtropical regions and are understudied. Furthermore, owls are often endemic to islands and of unknown conservation status. Demographic data for such species are especially scarce although they are essential for initiating and promoting their conservation. As a case study of demographic analysis of owls in a tropical or subtropical area and on islands, we applied an integrated population model to 7‐year monitoring data (2012–2018) of the Ryukyu Scops Owl population on Minami‐daito Island, Japan. We used survival history data from 903 individuals, reproduction and sex ratio data from 213 broods, and count data of 2,526 individuals in total. Long‐term averages of annual survival rates were 0.73 for adult females and 0.74 for adult males, although the sexual difference was not significant. Sex ratio estimates fluctuated annually and long‐term averages were slightly skewed to males: 0.51 among fledglings, 0.54 among yearlings, and 0.52 among adults. Long‐term averages of population size were estimated to be 273.4 females and 296.8 males. The long‐term average of population growth rate was 0.98, suggesting a slightly declining trend. It was fortunate to recognize the declining trend during the early phase. Considering the general lack of fundamental ecological data on owls of tropical or subtropical areas and on islands, it seems likely that many endangered owl populations await conservation efforts.
Machine Learning–Based Individualized Survival Prediction Model for Total Knee Replacement in Osteoarthritis: Data From the Osteoarthritis Initiative
Authors: Jamshidi Afshin , Pelletier Jean‐Pierre , Labbe Aurelie , Abram François , Martel‐Pelletier Johanne , Droit Arnaud
Published: March 2021

Objective

By using machine learning, our study aimed to build a model to predict risk and time to total knee replacement (TKR) of an osteoarthritic knee.

Methods

Features were from the Osteoarthritis Initiative (OAI) cohort at baseline. Using the lasso method for variable selection in the Cox regression model, we identified the 10 most important characteristics among 1,107 features. The prognostic power of the selected features was assessed by the Kaplan‐Meier method and applied to 7 machine learning methods: Cox, DeepSurv, random forests algorithm, linear/kernel support vector machine (SVM), and linear/neural multi‐task logistic regression models. As some of the 10 first‐found features included similar radiographic measurements, we further looked at using the least number of features without compromising the accuracy of the model. Prediction performance was assessed by the concordance index, Brier score, and time‐dependent area under the curve (AUC).

Results

Ten features were identified and included radiographs, bone marrow lesions of the medial condyle on magnetic resonance imaging, hyaluronic acid injection, performance measure, medical history, and knee‐related symptoms. The methodologies Cox, DeepSurv, and linear SVM demonstrated the highest accuracy (concordance index scores of 0.85, Brier score of 0.02, and an AUC of 0.87). DeepSurv was chosen to build the prediction model to estimate the time to TKR for a given knee. Moreover, we were able to decrease the features to only 3 and maintain the high accuracy (concordance index of 0.85, Brier score of 0.02, and AUC of 0.86), which included bone marrow lesions, Kellgren/Lawrence grade, and knee‐related symptoms, to predict risk and time of a TKR event.

Conclusion

For the first time, we developed a model using the OAI cohort to predict with high accuracy if a given osteoarthritic knee would require TKR, when a TKR would be required, and who would likely progress fast toward this event.
Atomic‐Layer‐Deposition‐Based 2D Transition Metal Chalcogenides: Synthesis, Modulation, and Applications
Authors: Kim Youngjun , Woo Whang Je , Kim Donghyun , Lee Sangyoon , Chung Seung‐min , Park Jusang , Kim Hyungjun
Published: March 2021

Transition metal chalcogenides (TMCs) are a large family of 2D materials with different properties, and are promising candidates for a wide range of applications such as nanoelectronics, sensors, energy conversion, and energy storage. In the research of new materials, the development and investigation of industry‐compatible synthesis techniques is of key importance. In this respect, it is important to study 2D TMC materials synthesized by the atomic layer deposition (ALD) technique, which is widely applied in industries. In addition to the synthesis of 2D TMCs, ALD is used to modulate the characteristic of 2D TMCs such as their carrier density and morphology. So far, the improvement of thin film uniformity without oxidation and the synthesis of low‐dimensional nanomaterials on 2D TMCs have been the research focus. Herein, the synthesis and modulation of 2D TMCs by ALD is described, and the characteristics of ALD‐based TMCs used in nanoelectronics, sensors, and energy applications are discussed.
A Tensile‐Strained Pt–Rh Single‐Atom Alloy Remarkably Boosts Ethanol Oxidation
Authors: Luo Shuiping , Zhang Long , Liao Yujia , Li Lanxi , Yang Qi , Wu Xiaotong , Wu Xiaoyu , He Dongsheng , He Chunyong , Chen Wen , Wu Qilong , Li Mingrui , Hensen Emiel J. M. , Quan Zewei
Published: March 2021

The rational design and control of electrocatalysts at single‐atomic sites could enable unprecedented atomic utilization and catalytic properties, yet it remains challenging in multimetallic alloys. Herein, the first example of isolated Rh atoms on ordered PtBi nanoplates (PtBi‐Rh1) by atomic galvanic replacement, and their subsequent transformation into a tensile‐strained Pt–Rh single‐atom alloy (PtBi@PtRh1) via electrochemical dealloying are presented. Benefiting from the Rh1‐tailored Pt (110) surface with tensile strain, the PtBi@PtRh1 nanoplates exhibit record‐high and all‐round superior electrocatalytic performance including activity, selectivity, stability, and anti‐poisoning ability toward ethanol oxidation in alkaline electrolytes. Density functional theory calculations reveal the synergism between effective Rh1 and tensile strain in boosting the adsorption of ethanol and key surface intermediates and the CC bond cleavage of the intermediates. The facile synthesis of the tensile‐strained single‐atom alloy provides a novel strategy to construct model nanostructures, accelerating the development of highly efficient electrocatalysts.
Insight into Nickel‐Cobalt Oxysulfide Nanowires as Advanced Anode for Sodium‐Ion Capacitors
Authors: Wang Shouzhi , Zhao Huaping , Lv Songyang , Jiang Hehe , Shao Yongliang , Wu Yongzhong , Hao Xiaopeng , Lei Yong
Published: March 2021

Transition metal oxides have a great potential in sodium‐ion capacitors (SICs) due to their pronouncedly higher capacity and low cost. However, their poor conductivity and fragile structure hinder their development. Herein, core‐shell‐like nickel‐cobalt oxysulfide (NCOS) nanowires are synthesized and demonstrated as an advanced SICs anode. The bimetallic oxysulfide with multiple cation valence can promote the sodium ion adsorption and redox reaction, massive defects enable accommodation of the volume change in the sodiation/desodiation process, meanwhile the core‐shell‐like structure provides abundant channels for fast transfer of sodium ions, thereby synergistically making the NCOS electrode exhibit a high reversible sodium ion storage capacity (1468.5 mAh g−1 at 0.1 A g−1) and an excellent cyclability (90.5% capacity retention after 1000 cycles). The in‐situ X‐ray diffraction analysis unravels the insertion and conversion mechanism for sodium storage in NCOS, and the enhanced capability of NCOS is further verified by the kinetic analysis and theoretical calculations. Finally, SICs consisting of the NCOS anode and a boron‐nitrogen co‐doped carbon nanotubes cathode deliver an energy density of 205.7 Wh kg−1, a power density of 22.5 kW kg−1, and an outstanding cycling lifespan. These results indicate an efficient strategy in designing a high‐performance anode for sodium storage based on bimetallic dianion compounds.
Assessment of skeletal age in youth female soccer players: Agreement between Greulich‐Pyle and Fels protocols
Authors: Martinho Diogo V. , Coelho‐e‐Silva Manuel J. , Valente‐dos‐Santos João , Minderico Cláudia , Oliveira Tomás G. , Rodrigues Inês , Conde Jorge , Sherar Lauren B. , Malina Robert M.
Published: March 2021

Objective

The purpose of the study was to evaluate the agreement between the Fels and Greulich‐Pyle methods for the assessment of skeletal age (SA) in female youth soccer players.

Methods

The sample included 441 Portuguese players 10.08–16.73 years of age who regularly participated in organized and competitive soccer. Standardized radiographs of the left hand‐wrist were obtained and analyzed by an experienced examiner. SA was estimated with the Fels and Greulich‐Pyle (GP) methods. Differences between SA and chronological age (CA) were used to define skeletal maturity groups: late, average and early maturing. In addition to descriptive statistics, Cohen's kappa and Lin concordance correlation coefficients were used to evaluate agreement between methods.

Results

Intraindividual differences in SA based on the two methods varied between 0.10 to 1.47 years among age groups with larger mean differences at older ages. Agreement of maturity classifications between methods was 74% at younger ages (under‐13: kappa = 0.48; under‐14: kappa = 0.39; Lin CCC = 0.68) and declined with increasing CA (under‐17: 19% agreement; kappa = 0.001; Lin CCC = 0.11). About 19% of the total sample was skeletally mature with the Fels method and an SA was not assigned; in contrast, no players were skeletally mature with the GP method.

Conclusions

GP SAs were systematically lower than Fels SAs among female soccer players. Intraindividual variability in SAs between methods was considerable. The findings highlight the impact of method on estimates of maturity status.
Patterns of congenital anomalies among individuals with trisomy 13 in Texas
Authors: Diaz Diego , Benjamin Renata H. , Navarro Sanchez Maria Luisa , Mitchell Laura E. , Langlois Peter H. , Canfield Mark A. , Chen Han , Scheuerle Angela E. , Schaaf Christian P. , Scott Daryl A. , Northrup Hope , Ray Joseph W. , McLean Scott D. , Swartz Michael D. , Ludorf Katherine L. , Lupo Philip J. , Agopian A. J.
Published: March 2021

Few population‐based studies have analyzed patterns of co‐occurring birth defects among those with trisomy 13. We evaluated the frequency of all possible combinations of any one, two, three, or four additional co‐occurring birth defects among 736 individuals with trisomy 13 using data from the Texas Birth Defects Registry for deliveries during 1999–2014. We calculated the observed‐to‐expected ratio for each combination, adjusting for the known tendency for birth defects to cluster non‐specifically. To address potential ascertainment differences among live births and non‐live births, we repeated analyses specifically among live births. The combination of defects with the largest observed‐to‐expected ratio was microcephalus, reduction deformities of brain (e.g., holoprosencephaly), anomalies of nose, and polydactyly. As expected, most of the highest 30 observed‐to‐expected ratios involved combinations with documented features of trisomy 13, including defects of the scalp (e.g., aplasia cutis) and heart. Results were similar among sensitivity analyses restricted to live births. Our findings may help further delineate the phenotypic spectrum for trisomy 13 and may inform future research related to improving screening and counseling for the condition.
Further expanding the mutational spectrum of brain abnormalities, neurodegeneration, and dysosteosclerosis: A rare disorder with neurologic regression and skeletal features
Authors: Kındış Erdem , Simsek‐Kiper Pelin Özlem , Koşukcu Can , Taşkıran Ekim Z. , Göçmen Rahşan , Utine Eda , Haliloğlu Göknur , Boduroğlu Koray , Alikaşifoğlu Mehmet
Published: March 2021

Colony stimulating factor 1 receptor (CSF1R, MIM# 164770) encodes a tyrosine‐kinase receptor playing an important role in development of osteoclasts and microglia. Heterozygous CSF1R variants have been known to cause hereditary diffuse leukoencephalopathy with spheroids (HDLS, MIM# 221820), an adult‐onset leukoencephalopathy characterized by loss of motor functions and cognitive decline. Recently, a new phenotype characterized by brain abnormalities, neurodegeneration, and dysosteosclerosis (BANDDOS) with biallelic CSF1R pathogenic variants in the etiology has been described. BANDDOS differs from HDLS by early‐onset neurodegenerative changes with additional structural brain abnormalities and skeletal findings resembling dysosteosclerosis (DOS). Described skeletal findings of the disease are highly variable ranging from absence of a skeletal phenotype and milder Pyle disease‐like to osteopetrosis and DOS. To date, only a few patients carrying biallelic CSF1R variants have been reported. In this clinical report, we describe three siblings with variable skeletal findings along with neurological symptoms ranging from mild to severe in whom exome sequencing revealed a novel homozygous splice site variant in canonical splice donor site of intron 21 adjacent to an exon, which encoding part of kinase domain of CSF1R along with a review of the literature.
The glass transition of amorphous polymers: About a continuous equation of state and its derivatives
Authors: Corbisieri Claudio , Jousset Pierre , Roos Markus
Published: March 2021

Describing the pressure‐volume‐temperature (PVT) behavior of polymers is often hindered due to limitations of models and theories. In this work, we propose the logistic function to derive a phenomenological equation of state (EOS) that overcomes these limitations. Without dividing the temperature domain into several intervals, this continuous EOS describes the PVT behavior of amorphous polymers in the equilibrium state, the vitreous state and at glass transition. Discontinuities at glass transition are inherently eliminated. The EOS is continuously differentiable with respect to temperature and pressure. The thermal expansion coefficient and compression modulus thus can be determined at any valid reference state. The EOS linearly depends on temperature both in the equilibrium state and vitreous state. Furthermore, a parameter of the EOS is interpreted as the pressure‐dependent glass transition temperature. Using PVT data of polyethersulfone (PES), measured in the temperature range of 20 − 360 °C and pressure range of 10 − 200 MPa in both the isobaric and standard isothermal mode, the validity of the EOS is discussed. Polymer processing simulation and solid mechanics benefit from the EOS and its derivatives, respectively. In addition, the EOS can be used to determine the glass transition temperature from PVT data.
Advances and challenges in marine conservation in Chile: A regional and global comparison
Authors: Fernández Miriam , Rodríguez‐Ruiz Montserrat , Gelcich Stefan , Hiriart‐Bertrand Luciano , Castilla Juan Carlos
Published: March 2021

Despite significant progress made in Chile, and globally, in establishing marine protected areas (MPAs), the actual contribution to marine biodiversity conservation needs to be revised, to focus on representativeness and the diversity of tools alongside effective implementation, management, and enforcement.

This study makes progress in this direction, describing the most recent advances in marine conservation in Chile and analysing the contribution of the different conservation instruments as well as the distribution of designated areas across ecoregions. Furthermore, it examines the potential contribution of alternative area‐based instruments to balance ocean protection. The advances observed in Chile were compared among four South American countries and five leading countries in ocean conservation, analysing protection levels in coastal areas, continental exclusive economic zones, and overseas territories.

Data on MPA boundaries and attributes were sourced from the World Database on Protected Areas and complemented the official information on MPAs and territorial user rights for fisheries and for indigenous people in South America.

The current level of protection in Chile is among the highest in the world in area coverage and in the proportion of the continental exclusive economic zone assigned to fully protected areas. However, it exhibits the strongest imbalances in the distribution of designated MPAs between coastal and oceanic waters, in comparison with the leading countries and also within South America (Perú, Chile, Argentina, and Uruguay), and among ecoregions.

The patterns observed suggest that Chile has advanced, but concentrated, conservation efforts in low‐threat, remote ecoregions. There is an urgent need to progress towards high‐threat ecoregions, which implies balancing the needs of nature and people. The distribution of ancillary conservation instruments can help double the level of protection in threatened coastal areas, filling gaps in marine conservation and creating an opportunity to progress and diversify conservation strategies.
Efficacy and Safety of Diclofenac–Hyaluronate Conjugate (Diclofenac Etalhyaluronate) for Knee Osteoarthritis: A Randomized Phase III Trial in Japan
Authors: Nishida Yoshihiro , Kano Kazuyuki , Nobuoka Yuji , Seo Takayuki
Published: March 2021

Objective

To confirm the efficacy and safety of intraarticular (IA) injection of diclofenac covalently linked to hyaluronic acid (diclofenac etalhyaluronate [DF‐HA]; ONO‐5704/SI‐613) in patients with knee osteoarthritis (OA).

Methods

In a phase III multicenter, randomized, double‐blind, placebo‐controlled trial, eligible subjects ages 40–75 years with symptomatic knee OA (Kellgren/Lawrence score of 2 or 3) were randomly assigned to receive IA injections of DF‐HA 30 mg or placebo (citric acid–sodium citrate buffered solution; 1:1) once every 4 weeks for 20 weeks (a total of 6 injections). Subjects were followed up for 24 weeks. The primary end point was the mean change from baseline to 12 weeks in Western Ontario and McMaster Universities Osteoarthritis Index version 3.1 (WOMAC) pain subscale scores, measured on a 100‐mm visual analog scale. Safety was evaluated by adverse event monitoring.

Results

All 440 subjects received investigational products (220 received placebo and 220 received DF‐HA). The full analysis set and safety population comprised 438 subjects (220 in the placebo group and 218 in the DF‐HA group) and 440 subjects, respectively. At 12 weeks, subjects receiving DF‐HA showed significant improvement from baseline in the WOMAC pain subscale score (–23.2 mm) compared to subjects receiving placebo ( −17.1 mm), with a difference of −6.1 mm (95% confidence interval −9.4, −2.8; P < 0.001). The difference between groups was significant as early as week 1, and a difference was maintained for 24 weeks, although the difference at week 24 was not significant. Anaphylactic reactions were observed in 2 subjects receiving DF‐HA.

Conclusion

Our findings indicate that treatment with DF‐HA results in significant improvement in the WOMAC pain subscale score compared to placebo over 12 weeks. Anaphylactic reactions were observed, and further safety evaluation is needed.
Risk Factors for Severe Outcomes in Patients With Systemic Vasculitis and COVID‐19: A Binational, Registry‐Based Cohort Study
Authors: Rutherford Matthew A. , Scott Jennifer , Karabayas Maira , Antonelou Marilina , Gopaluni Seerapani , Gray David , Barrett Joe , Brix Silke R. , Dhaun Neeraj , McAdoo Stephen P. , Smith Rona M. , Geddes Colin C. , Jayne David , Luqmani Raashid , Salama Alan D. , Little Mark A. , Basu Neil ,   the UK and Ireland Vasculitis Rare Disease Group (UKIVAS)
Published: March 2021

Objective

COVID‐19 is a novel infectious disease with a broad spectrum of clinical severity. Patients with systemic vasculitis have an increased risk of serious infections and may be at risk of severe outcomes following COVID‐19. We undertook this study to establish the risk factors for severe COVID‐19 outcomes in these patients, including the impact of immunosuppressive therapies.

Methods

A multicenter cohort was developed through the participation of centers affiliated with national UK and Ireland vasculitis registries. Clinical characteristics and outcomes are described. Logistic regression was used to evaluate associations between potential risk factors and a severe COVID‐19 outcome, defined as a requirement for advanced oxygen therapy, a requirement for invasive ventilation, or death.

Results

The cohort included 65 patients with systemic vasculitis who developed COVID‐19 (median age 70 years, 49% women), of whom 25 patients (38%) experienced a severe outcome. Most patients (55 of 65 [85%]) had antineutrophil cytoplasmic antibody–associated vasculitis (AAV). Almost all patients required hospitalization (59 of 65 [91%]), 7 patients (11%) were admitted to intensive care, and 18 patients (28%) died. Background glucocorticoid therapy was associated with severe outcomes (adjusted odds ratio [OR] 3.7 [95% confidence interval 1.1–14.9]; P = 0.047), as was comorbid respiratory disease (adjusted OR 7.5 [95% confidence interval 1.9–38.2]; P = 0.006). Vasculitis disease activity and nonglucocorticoid immunosuppressive therapy were not associated with severe outcomes.

Conclusion

In patients with systemic vasculitis, glucocorticoid use at presentation and comorbid respiratory disease were associated with severe outcomes in COVID‐19. These data can inform clinical decision‐making relating to the risk of severe COVID‐19 in this vulnerable patient group.
An Overview on Pt3X Electrocatalysts for Oxygen Reduction Reaction
Authors: Sarkar Shreya , Peter Sebastian C.
Published: March 2021

The activity of Pt towards oxygen reduction reaction (ORR) can be enhanced by alloying it with secondary metals. They can be grouped into three different classes: alloys, bimetallics and intermetallics. Although alloys and bimetallics exhibit enhanced performance, often they are limited by metal dissolution and resulted in poor durability. This invokes the need on the development of ordered intermetallics. In this minireview we comprehensively present the recent progress and developments of Pt3X alloys and intermetallics towards ORR. Additionally, major technical challenges and possible future research directions to overcome these challenges are discussed to facilitate further research in this area.
Single‐object localization using multiple ultrasonic sensors and constrained weighted least‐squares method
Authors: Juan Chung‐Wei , Hu Jwu‐Sheng
Published: March 2021

In this paper, an active single‐object localization system with U‐shaped ultrasonic module array is presented. The proposed algorithm in this system has two stages. The first stage is time‐of‐flight (TOF) estimation of reflected ultrasonic signals. We analyze several distortion cases of reflection signals and provide solutions to improve the performance of TOF estimation. The second stage is TOF‐based object localization. A good localization algorithm can suppress the problems caused by inaccurate TOF estimation and improve the accuracy of target positioning. We propose two object‐localization algorithms to estimate the object location. One is the unconstrained least‐squares method, and the other is the constrained weighted least‐squares method based on the eigenvalues‐analyzing technique. The simulation results suggest that the performance of the proposed constrained weighted method is better than that of the unconstrained method. In addition, the median smoother and the outlier exclusion scheme are implemented in the overall system to make the object location estimation more stable. The performance of the proposed system is confirmed by the experiment results, which show that the single‐object localization has a considerable degree of accuracy and stability.
Bioinformatics‐driven discovery of novel Clostridioides difficile lysins and experimental comparison with highly active benchmarks
Authors: Furlon Jacob M. , Mitchell Spencer J. , Bailey‐Kellogg Chris , Griswold Karl E.
Published: March 2021

Clostridioides difficile is the single most deadly bacterial pathogen in the United States, and its global prevalence and outsized health impacts underscore the need for more effective therapeutic options. Towards this goal, a novel group of modified peptidoglycan hydrolases with significant in vitro bactericidal activity have emerged as potential candidates for treating C. difficile infections (CDI). To date, discovery and development efforts directed at these CDI‐specific lysins have been limited, and in particular there has been no systematic comparison of known or newly discovered lysin candidates. Here, we detail bioinformatics‐driven discovery of six new anti‐C. difficile lysins belonging to the amidase‐3 family of enzymes, and we describe experimental comparison of their respective catalytic domains (CATs) with highly active CATs from the literature. Our quantitative analyses include metrics for expression level, inherent antibacterial activity, breadth of strain selectivity, killing of germinating spores, and structural and functional measures of thermal stability. Importantly, prior studies have not examined stability as a performance metric, and our results show that the panel of eight enzymes possess widely variable thermal denaturation temperatures and resistance to heat inactivation, including some enzymes that exhibit marginal stability at body temperature. Ultimately, no single enzyme dominated with respect to all performance measures, suggesting the need for a balanced assessment of lysin properties during efforts to find, engineer, and develop candidates with true clinical potential.
Development and optimization of a high‐throughput HPLC–MS/MS method for the simultaneous determination of naringenin and its valine carbamate prodrug in rat plasma
Authors: Xu Xiaolan , Shen Lulu , Xu Qiuchi , Bai Xiaochen , He Zhonggui , Zhang Tianhong , Jiang Qikun
Published: March 2021

A valine carbamate prodrug of naringenin (NAR) called 4'V was synthesized to enhance its oral bioavailability because of low water solubility and poor membrane permeability of NAR. This study developed and fully validated a sensitive, rapid, and robust HPLC–MS/MS method for the simultaneous determination of NAR and 4’V in plasma. The analytes were treated using liquid–liquid extraction, separated on a Phenomenex Kinetex XB‐C18 column, and detected using a triple‐quadrupole tandem mass spectrometer equipped with an electrospray ionization interface. The analytes were eluted within only 4 min by gradient procedure. The excellent linear correlations were validated over the range of 4–400 ng/mL (r = 0.9990) for NAR and 2–2000 ng/mL (r = 0.9951) for 4’V, with lower limits of quantification of 4 and 2 ng/mL, respectively. For all quality control samples, the intra‐day and inter‐day precision and accuracy were within ±15%. The validated method was economical, high throughput, and reliable and was first successfully applied to a pharmacokinetic study of NAR and 4’V after oral administration to Sprague–Dawley rats. The results of the pharmacokinetic study demonstrated that the idea of amino acid carbamate prodrug is a promising strategy to improve the bioavailability of NAR.
Interactions between methodological and interindividual variability: How Monetary Incentive Delay (MID) task contrast maps vary and impact associations with behavior
Authors: Demidenko Michael I. , Weigard Alexander S. , Ganesan Karthikeyan , Jang Hyesue , Jahn Andrew , Huntley Edward D. , Keating Daniel P.
Published: March 2021

Introduction

Phenomena related to reward responsiveness have been extensively studied in their associations with substance use and socioemotional functioning. One important task in this literature is the Monetary Incentive Delay (MID) task. By cueing and delivering performance‐contingent reward, the MID task has been demonstrated to elicit robust activation of neural circuits involved in different phases of reward responsiveness. However, systematic evaluations of common MID task contrasts have been limited to between‐study comparisons of group‐level activation maps, limiting their ability to directly evaluate how researchers’ choice of contrasts impacts conclusions about individual differences in reward responsiveness or brain‐behavior associations.

Methods

In a sample of 104 participants (Age Mean = 19.3, SD = 1.3), we evaluate similarities and differences between contrasts in: group‐ and individual‐level activation maps using Jaccard's similarity index, region of interest (ROI) mean signal intensities using Pearson's r, and associations between ROI mean signal intensity and psychological measures using Bayesian correlation.

Results

Our findings demonstrate more similarities than differences between win and loss cues during the anticipation contrast, dissimilarity between some win anticipation contrasts, an apparent deactivation effect in the outcome phase, likely stemming from the blood oxygen level‐dependent undershoot, and behavioral associations that are less robust than previously reported.

Conclusion

Consistent with recent empirical findings, this work has practical implications for helping researchers interpret prior MID studies and make more informed a priori decisions about how their contrast choices may modify results.
Enabling pathways to opportunity through a skills‐based architecture
Authors: DeMark Sarah , Kozyrev Joann
Published: March 2021

Individuals need the shortest path to opportunity and employers require the shortest path to a skilled diverse workforce. To solve for this, Western Governors University (WGU) has created a skills‐based architecture to map our competencies and credentials to high‐demand knowledge, and technical skills as well as powerful, enduring, employability skills like critical thinking, social‐emotional intelligence, creativity, and the ability to work with diverse collaborators. At WGU, these high‐demand industry‐relevant skills are mapped into educational experiences and credentials to better support the upskilling and reskilling needs required for our dramatically altered job market. WGU also intends to surface these skills and competency achievements to employers, thereby facilitating a more efficient and effective match of talent to opportunity. This skills‐based architecture enables WGU to create new in‐demand program offerings, better supporting underserved populations through new pathways and onramps to education while the alignment to skills ensures pathways to careers and a strong return on investment for students.
Theoretical Insights into the Formation Mechanism of Methane, Ethylene and Methanol in Fischer‐Tropsch Synthesis at Co2C Surfaces
Authors: Zaffran Jeremie , Yang Bo
Published: March 2021

Fischer‐Tropsch synthesis (FTS) is an attractive opportunity to prepare fuels and chemicals, avoiding fossil resources exploration. Co2C was recently demonstrated to exhibit outstanding properties in Fischer‐Tropsch to olefins (FTO) reaction, inhibiting methane formation. However, the exact mechanisms have not been entirely revealed yet. Here we are proposing a study combining DFT calculations and microkinetic modelling (MKM) in order to unveil the dominant reaction pathways of three products of interest in FTS, namely methane, ethylene, and methanol, over (020), (101) and (111) facets of Co2C. We found methane and ethylene share the same determining states, being responsible for the competition between the two species. Since our MKM gives results suggesting the surface is fully covered with CO at the steady‐state, we expect that including adsorbate‐adsorbate interactions both in DFT calculations and MKM simulations would be important in the future studies of FTS over Co2C surfaces.
Relationship Between Oral Semaglutide Tablet Erosion and Pharmacokinetics: A Pharmacoscintigraphic Study
Authors: Bækdal Tine A. , Donsmark Morten , Hartoft‐Nielsen Marie‐Louise , Søndergaard Flemming L. , Connor Alyson
Published: March 2021

Semaglutide, a glucagon‐like peptide‐1 (GLP‐1) analogue, has been coformulated in a tablet with the absorption enhancer, sodium N‐(8‐[2‐hydroxybenzoyl] amino) caprylate (SNAC). We investigated tablet erosion and the pharmacokinetics of oral semaglutide administered with 2 different water volumes and evaluated the relationships between these parameters. In a randomized, single‐center (Quotient Sciences, UK), open‐label, 2‐period crossover trial, 26 healthy men received single doses of 10 mg oral semaglutide with 50 or 240 mL water while fasting. Tablet erosion and gastrointestinal transit were assessed by gamma scintigraphy. Semaglutide and SNAC plasma concentrations were measured until 24 and 6 hours, respectively, after administration. Complete tablet erosion (CTE) occurred in the stomach irrespective of water volume administered with the tablet (primary end point). Mean time to CTE was 85 versus 57 minutes with 50 versus 240 mL water (ratio 50/240 mL, 1.51; 95% confidence interval, 0.96‐2.37; P = .072). Area under the semaglutide concentration‐time curve from 0 to 24 hours (AUC0‐24h,semaglutide) and maximum semaglutide concentration (Cmax,semaglutide) were ∼70% higher with 50 versus 240 mL water (P = .056 and P = .048, respectively). Median time to maximum semaglutide concentration (tmax,semaglutide) was 1.5 hours independent of water volume with dosing. Higher AUC0‐24h,semaglutide and Cmax,semaglutide and longer tmax,semaglutide were significantly correlated with longer time to CTE and later gastric emptying of tablet and water (all P < .05). The safety profile was as expected for the GLP‐1 receptor agonist drug class. In conclusion, the oral semaglutide tablet erodes in the stomach irrespective of water volume with dosing. Slower tablet erosion in the stomach results in higher semaglutide plasma exposure.
Effectiveness of self‐compassion‐related interventions for reducing self‐criticism: A systematic review and meta‐analysis
Authors: Wakelin Katherine E. , Perman Gemma , Simonds Laura M.
Published: March 2021

Self‐criticism is the process of negative self‐evaluation. High levels are associated with psychopathology and poorer therapeutic outcomes. Self‐compassion interventions were developed to explicitly target self‐criticism. The aim of this review was to estimate the overall effect of self‐compassion‐related interventions on self‐criticism outcomes and investigate potential moderating variables. A systematic search of the literature identified 20 randomized controlled trials (RCTs) that met the inclusion criteria. Nineteen papers, involving 1350 participants, had sufficient data to be included in the meta‐analysis. Pre‐ and post‐data points were extracted for the compassion and control groups. Study quality was assessed using an adapted version of the Cochrane Collaboration's risk of bias tool, which concluded that studies were of moderate quality. Meta‐analysis findings indicated that self‐compassion‐related interventions produce a significant, medium reduction in self‐criticism in comparison with control groups (Hedges' g = 0.51, 95% CI [0.33–0.69]). Moderator analysis found greater reductions in self‐criticism when self‐compassion‐related interventions were longer and compared with passive controls rather than active. The remaining moderators of forms of self‐criticism, sample type, intervention delivery, intervention setting and risk of bias ratings were insignificant. Overall, the review provides promising evidence of the effectiveness of self‐compassion‐related interventions for reducing self‐criticism. However, results are limited by moderate quality studies with high heterogeneity. Directions for future research indicate that more RCTs with active controls, follow‐ups, consistent use and reporting of measures and diverse samples are needed.
Facile Preparation of Peptides for Mass Spectrometry Analysis in Bottom‐Up Proteomics Workflows
Authors: Wojtkiewicz Melinda , Berg Luecke Linda , Kelly Maia I. , Gundry Rebekah L.
Published: March 2021

Mass spectrometry (MS) is routinely used to identify, characterize, and quantify biological molecules. For protein analysis, MS‐based workflows can be broadly categorized as top‐down or bottom‐up, depending on whether the proteins are analyzed as intact molecules or first digested into peptides. This article outlines steps for preparing peptide samples for MS as part of a bottom‐up proteomics workflow, providing versatile methods suitable for discovery and targeted analyses in qualitative and quantitative workflows. Resulting samples contain peptides of suitable size for analysis by MS instrumentation generally available to modern research laboratories, including MS coupled to either liquid chromatography (LC) or matrix‐assisted laser desorption/ionization (MALDI) interfaces. This article incorporates recent developments in methodologies and consumables to facilitate sample preparation. The protocols are well‐suited to users without prior experience in proteomics and include methods for universally applicable suspension trap processing and for alternate in‐solution processing to accommodate a range of sample types. Cleanup, quantification, and fractionation procedures are also described. © 2021 The Authors.

Basic Protocol: Preparation of high‐complexity peptide samples for mass spectrometry analysis using S‐Trap™ processing

Alternate Protocol 1: Preparation of low‐ to moderate‐complexity peptide samples for mass spectrometry analysis using in‐solution processing

Alternate Protocol 2: Detergent, polymer, and salt removal from peptide samples before mass spectrometry analysis using SP2 processing

Support Protocol 1: Protein quantification using Pierce 660 nm assay

Support Protocol 2: Peptide quantification using Pierce quantitative fluorometric peptide assay

Support Protocol 3: High‐pH fractionation of complex peptide samples