bluuebunny/crossref_metadata_2025 huggingface dataset:
Rapid recovery of male cats with postrenal acute kidney injury by treating with allogeneic adipose mesenchymal stem cell-derived extracellular vesicles
Authors: Li Weihui , Wang Wei , He Xin , Liao Zheng , Aierken Aili , Hua Jinlian , Wang Yan , Lu Dezhang , Zhang Shiqiang
Published: July 2022

Background

Acute kidney injury (AKI) is a complex disease and can be generally divided into prerenal, intrarenal, and postrenal AKI (PR-AKI). Previous studies have shown that mesenchymal stem cells (MSCs)-derived extracellular vesicles have protective function on prerenal and intrarenal AKI treatment, but whether they have therapeutic efficacy on PR-AKI remains unclear. In this study, we investigated the therapeutic efficacy of allogeneic adipose mesenchymal stem cell-derived extracellular vesicles (ADMSCEVs) on cat models of PR-AKI.

Methods

The cat models of PR-AKI were established by using artificial urinary occlusion and then treated with ADMSCEVs. Histopathological section analysis, blood routine analysis, plasma biochemical test, imaging analysis, and plasma ultra-high performance liquid chromatography-MS/MS (UHPLC-MS/MS) were performed to evaluate the therapeutic efficacy of ADMSCEVs.

Results

Physiological and biochemical test showed that the ADMSCEVs could recover creatinine, urea nitrogen and plasma phosphorus to homeostasis efficiently. Blood routine analysis showed that leukocytes in PR-AKI cats with ADMSCEVs treatment returned to normal physiological range more quickly than that of control. UHPLC-MS/MS analysis revealed that the plasma metabolome profile of PR-AKI cats treated with ADMSCEVs was highly similar to that of normal cats. Furthermore, UHPLC-MS/MS analysis also revealed six metabolites (carnitine, melibiose,d-Glucosamine, cytidine, dihydroorotic acid, stachyose) in plasma were highly correlated with the dynamic process of PR-AKI on cats.

Conclusions

We demonstrate the efficacy of ADMSCEVs in the treatment of PR-AKI on cats. Our study also suggests six metabolites to be novel PR-AKI markers and to be potential targets for ADMSCEVs therapy. Our findings will be useful to improve clinical treatment of both animal and human PR-AKI patients with ADMSCEVs in the future.
Human umbilical cord mesenchymal stem cell-derived exosomal miR-335-5p attenuates the inflammation and tubular epithelial–myofibroblast transdifferentiation of renal tubular epithelial cells by reducing ADAM19 protein levels
Authors: Qiu Zhenhua , Zhong Zhihui , Zhang Yuehan , Tan Haoling , Deng Bo , Meng Guohuang
Published: July 2022

Background

Renal tubular epithelial–myofibroblast transdifferentiation (EMT) plays a key role in the regulation of renal fibrosis. Exosomes derived from human umbilical cord mesenchymal stem cells (hucMSCs) play a crucial role in alleviating renal fibrosis and injury. Additionally, hucMSC-derived exosomes contain numerous microRNAs (miRNAs). However, it is unclear whether mesenchymal stem cells can regulate the transforming growth factor (TGF)-β1-induced EMT of human renal tubular epithelial cells (RTECs) through exosomal miRNAs.

Method

HK-2, a human RTEC line, was co-treated with TGF-β1 and hucMSC-derived exosomes. Additionally, TGF-β1-treated HK-2 cells were transfected with a miR-335-5p mimic and disintegrin and metalloproteinase domain-containing protein 19 (ADAM19)-overexpression plasmid. miR-335-5p expression and ADAM19 protein and inflammation levels were measured via quantitative reverse transcription polymerase chain reaction, western blotting, and enzyme-linked immunosorbent assays, respectively.

Results

TGF-β1 treatment changed the shape of HK-2 cells from a cobblestone morphology to a long spindle shape, accompanied by an increase in interleukin (IL)-6, tumor necrosis factor-α, IL-1β, collagen I, collagen III, α-smooth muscle actin, vimentin, and N-cadherin protein levels, whereas E-cadherin protein levels were reduced in these HK-2 cells, suggesting that TGF-β1 treatment induced the inflammation and EMT of HK-2 cells. HucMSC-exosomes improved the inflammation and EMT phenotype of TGF-β1-induced HK-2 cells by transferring miR-335-5p. miR-335-5p was found to bind theADAM193′-untranslated region to reduce ADAM19 protein levels. Additionally, miR-335-5p improved the inflammation and EMT phenotype of HK-2 cells by reducing ADAM19 protein levels with TGF-β1 induction.

Conclusions

HucMSC-derived exosomal miR-335-5p attenuates the inflammation and EMT of HK-2 cells by reducing ADAM19 protein levels upon TGF-β1 induction. This study provides a potential therapeutic strategy and identifies targets for clinically treating renal fibrosis.
RUNX1T1 function in cell fate
Authors: Hu Nan , Zou Linqing , Wang Cheng , Song Guoqi
Published: July 2022

RUNX1T1 (Runt-related transcription factor 1, translocated to 1), a myeloid translocation gene (MTG) family member, is usually investigated as part of the fusion protein RUNX1-RUNX1T1 for its role in acute myeloid leukemia. In the main, by recruiting histone deacetylases, RUNX1T1 negatively influences transcription, enabling it to regulate the proliferation and differentiation of hematopoietic progenitors. Moreover, the formation of blood vessels, neuronal differentiation, microglial activation following injury, and intestinal development all relate closely to the expression of RUNX1T1. Furthermore, through alternative splicing ofRUNX1T1, short and long isoforms have been noted to mediate adipogenesis by balancing the differentiation and proliferation of adipocytes. In addition, RUNX1T1 plays wide-ranging and diverse roles in carcinoma as a biomarker, suppressor, or positive regulator of carcinogenesis, closely correlated to specific organs and dominant signaling pathways. The aim of this work was to investigate the structure of RUNX1T1, which contains four conserved nervy homolog domains, and to demonstrate crosstalk with the Notch signaling pathway. Moreover, we endeavored to illustrate the effects of RUNX1T1 on cell fate from multiple aspects, including its influence on hematopoiesis, neuronal differentiation, microglial activation, intestinal development, adipogenesis, angiogenesis, and carcinogenesis.
Exosome from indoleamine 2,3-dioxygenase-overexpressing bone marrow mesenchymal stem cells accelerates repair process of ischemia/reperfusion-induced acute kidney injury by regulating macrophages polarization
Authors: Xie Xiangcheng , Yang Xiu , Wu Junxia , Tang Shengjie , Yang LiLi , Fei Xiao , Wang Ming
Published: July 2022

Background

Ischemia–reperfusion injury (IRI)-induced acute kidney injury (AKI) can repair itself completely. However, most moderate and severe patients undergoing IRI-AKI progress to chronic kidney disease due to incomplete repair. The present study is aimed to investigate the role of bone marrow mesenchymal stem cell-derived exosomes (MSC-Exo) with indoleamine 2,3-dioxygenase (IDO) overexpression on incomplete repair in mice after IRI.

Methods

IRI mice was established by clamping the unilateral renal pedicles and challenged with MSC-Exo. Blood biochemical indexes and inflammation factors contents were measured by ELISA assay. Histopathological examinations were monitored by HE, Masson, Immunohistochemical and TUNEL staining. Immunofluorescence, flow cytometry and immunoblotting were used to detect the polarization of macrophages, respectively.

Results

As compared to sham operation mice, IRI mice showed high contents of serum BUN and Scr, and more severe damaged kidney tissues on days 1 and 3, which all gradually declined over time, showing the lowest level on day 7 after injury. Once treated with MSCs-Exo that could directly transfer to kidney tubular cells, the restoration of kidney functions significantly accelerated by contrast to IRI mice, and the promotive effects were more obvious in IDO-overexpressed MSCs-Exo (MSCs-Exo-IDO)-treated IRI mice. Furthermore, MSCs-Exo-IDO administration also accelerated renal tubular cells proliferation, restrained tubular cells apoptosis, fibrosis and inflammation factor secretions during self-repair process compared to IRI mice, whose effects were higher than MSCs-Exo-NC-challenged IRI mice and IDO overexpressing plasmid-injected IRI mice. Mechanistically, MSCs-Exo-NC and MSCs-Exo-IDO exposure promoted the polarization from M1 macrophage to M2 macrophage, leading to more anti-inflammatory factors production, and subsequently altered the inflammatory microenvironment of renal tubular cells, which facilitated the self-repair process in mice after IRI.

Conclusion

MSCs-derived exosome accelerated renal self-repair in IRI mice by activating M2 macrophages polarization, which effects were amplified by IDO overexpression in MSCs. Potentially, genetically modified MSCs-Exo is an effective approach to improve renal self-repair in IRI-AKI mice.
Dysregulation of Tweak and Fn14 in skeletal muscle of spinal muscular atrophy mice
Authors: Meijboom Katharina E. , Sutton Emma R. , McCallion Eve , McFall Emily , Anthony Daniel , Edwards Benjamin , Kubinski Sabrina , Tapken Ines , Bünermann Ines , Hazell Gareth , Ahlskog Nina , Claus Peter , Davies Kay E. , Kothary Rashmi , Wood Matthew J. A. , Bowerman Melissa
Published: July 2022

Background

Spinal muscular atrophy (SMA) is a childhood neuromuscular disorder caused by depletion of the survival motor neuron (SMN) protein. SMA is characterized by the selective death of spinal cord motor neurons, leading to progressive muscle wasting. Loss of skeletal muscle in SMA is a combination of denervation-induced muscle atrophy and intrinsic muscle pathologies. Elucidation of the pathways involved is essential to identify the key molecules that contribute to and sustain muscle pathology. The tumor necrosis factor-like weak inducer of apoptosis (TWEAK)/TNF receptor superfamily member fibroblast growth factor-inducible 14 (Fn14) pathway has been shown to play a critical role in the regulation of denervation-induced muscle atrophy as well as muscle proliferation, differentiation, and metabolism in adults. However, it is not clear whether this pathway would be important in highly dynamic and developing muscle.

Methods

We thus investigated the potential role of the TWEAK/Fn14 pathway in SMA muscle pathology, using the severe Taiwanese Smn−/−; SMN2 and the less severe Smn2B/− SMA mice, which undergo a progressive neuromuscular decline in the first three post-natal weeks. We also used experimental models of denervation and muscle injury in pre-weaned wild-type (WT) animals and siRNA-mediated knockdown in C2C12 muscle cells to conduct additional mechanistic investigations.

Results

Here, we report significantly dysregulated expression of Tweak, Fn14, and previously proposed downstream effectors during disease progression in skeletal muscle of the two SMA mouse models. In addition, siRNA-mediated Smn knockdown in C2C12 myoblasts suggests a genetic interaction between Smn and the TWEAK/Fn14 pathway. Further analyses of SMA, Tweak−/−, and Fn14−/− mice revealed dysregulated myopathy, myogenesis, and glucose metabolism pathways as a common skeletal muscle feature, providing further evidence in support of a relationship between the TWEAK/Fn14 pathway and Smn. Finally, administration of the TWEAK/Fn14 agonist Fc-TWEAK improved disease phenotypes in the two SMA mouse models.

Conclusions

Our study provides mechanistic insights into potential molecular players that contribute to muscle pathology in SMA and into likely differential responses of the TWEAK/Fn14 pathway in developing muscle.
Arcuate AgRP, but not POMC neurons, modulate paraventricular CRF synthesis and release in response to fasting
Authors: Fernandes Alan Carlos Alves , de Oliveira Franciane Pereira , Fernandez Gimena , da Guia Vieira Luane , Rosa Cristiane Gugelmin , do Nascimento Taís , de Castro França Suzelei , Donato Jose , Vella Kristen R. , Antunes-Rodrigues Jose , Mecawi André Souza , Perello Mario , Elias Lucila Leico Kagohara , Rorato Rodrigo
Published: July 2022

Background

The activation of the hypothalamic–pituitary–adrenal (HPA) axis is essential for metabolic adaptation in response to fasting. However, the neurocircuitry connecting changes in the peripheral energy stores to the activity of hypothalamic paraventricular corticotrophin-releasing factor (CRFPVN) neurons, the master controller of the HPA axis activity, is not completely understood. Our main goal was to determine if hypothalamic arcuate nucleus (ARC) POMC and AgRP neurons can communicate fasting-induced changes in peripheral energy stores, associated to a fall in plasma leptin levels, to CRFPVN neurons to modulate the HPA axis activity in mice.

Results

We observed increased plasma corticosterone levels associate with increased CRFPVN mRNA expression and increased CRFPVN neuronal activity in 36 h fasted mice. These responses were associated with a fall in plasma leptin levels and changes in the mRNA expression of Agrp and Pomc in the ARC. Fasting-induced decrease in plasma leptin partially modulated these responses through a change in the activity of ARC neurons. The chemogenetic activation of POMCARC by DREADDs did not affect fasting-induced activation of the HPA axis. DREADDs inhibition of AgRPARC neurons reduced the content of CRFPVN and increased its accumulation in the median eminence but had no effect on corticosterone secretion induced by fasting.

Conclusion

Our data indicate that AgRPARC neurons are part of the neurocircuitry involved in the coupling of PVNCRF activity to changes in peripheral energy stores induced by prolonged fasting.
Sharp subcritical and critical $L^{p}$ Hardy inequalities on the sphere
Authors: Abdelhakim Ahmed A.
Published: July 2022

We obtain sharp inequalities of Hardy type for functions in the Sobolev space $W^{1,p}$

W

1
,
p

on the unit sphere $\mathbb{S}^{n-1}$

S

n
−
1

in $\mathbb{R}^{n}$

R
n

. We achieve this in both the subcritical and critical cases. The method we use to show optimality takes into account all the constants involved in our inequalities. We apply our results to obtain lower bounds for the the first eigenvalue of the p-Laplacian on the sphere.
BVFLEMR: an integrated federated learning and blockchain technology for cloud-based medical records recommendation system
Authors: Hai Tao , Zhou Jincheng , Srividhya S. R. , Jain Sanjiv Kumar , Young Praise , Agrawal Shweta
Published: July 2022

Blockchain is the latest boon in the world which handles mainly banking and finance. The blockchain is also used in the healthcare management system for effective maintenance of electronic health and medical records. The technology ensures security, privacy, and immutability. Federated Learning is a revolutionary learning technique in deep learning, which supports learning from the distributed environment. This work proposes a framework by integrating the blockchain and Federated Deep Learning in order to provide a tailored recommendation system. The work focuses on two modules of blockchain-based storage for electronic health records, where the blockchain uses a Hyperledger fabric and is capable of continuously monitoring and tracking the updates in the Electronic Health Records in the cloud server. In the second module, LightGBM and N-Gram models are used in the collaborative learning module to recommend a tailored treatment for the patient’s cloud-based database after analyzing the EHR. The work shows good accuracy. Several metrics like precision, recall, and F1 scores are measured showing its effective utilization in the cloud database security.
Olfactory swab sampling optimization for α-synuclein aggregate detection in patients with Parkinson’s disease
Authors: Bongianni Matilde , Catalan Mauro , Perra Daniela , Fontana Elena , Janes Francesco , Bertolotti Claudio , Sacchetto Luca , Capaldi Stefano , Tagliapietra Matteo , Polverino Paola , Tommasini Valentina , Bellavita Giulia , Kachoie Elham Ataie , Baruca Roberto , Bernardini Andrea , Valente Mariarosaria , Fiorini Michele , Bronzato Erika , Tamburin Stefano , Bertolasi Laura , Brozzetti Lorenzo , Cecchini Maria Paola , Gigli Gianluigi , Monaco Salvatore , Manganotti Paolo , Zanusso Gianluigi
Published: July 2022

Background

In patients with Parkinson’s disease (PD), real-time quaking-induced conversion (RT-QuIC) detection of pathological α-synuclein (α-syn) in olfactory mucosa (OM) is not as accurate as in other α-synucleinopathies. It is unknown whether these variable results might be related to a different distribution of pathological α-syn in OM. Thus, we investigated whether nasal swab (NS) performed in areas with a different coverage by olfactory neuroepithelium, such as agger nasi (AN) and middle turbinate (MT), might affect the detection of pathological α-syn.

Methods

NS was performed in 66 patients with PD and 29 non-PD between September 2018 and April 2021. In 43 patients, cerebrospinal fluid (CSF) was also obtained and all samples were analyzed by RT-QuIC for α-syn.

Results

In the first round, 72 OM samples were collected by NS, from AN (NSAN) or from MT (NSMT), and 35 resulted positive for α-syn RT-QuIC, including 27/32 (84%) from AN, 5/11 (45%) from MT, and 3/29 (10%) belonging to the non-PD patients. Furthermore, 23 additional PD patients underwent NS at both AN and MT, and RT-QuIC revealed α-syn positive in 18/23 (78%) NSAN samples and in 10/23 (44%) NSMT samples. Immunocytochemistry of NS preparations showed a higher representation of olfactory neural cells in NSAN compared to NSMT. We also observed α-syn and phospho-α-syn deposits in NS from PD patients but not in controls. Finally, RT-QuIC was positive in 22/24 CSF samples from PD patients (92%) and in 1/19 non-PD.

Conclusion

In PD patients, RT-QuIC sensitivity is significantly increased (from 45% to 84%) when NS is performed at AN, indicating that α-syn aggregates are preferentially detected in olfactory areas with higher concentration of olfactory neurons. Although RT-QuIC analysis of CSF showed a higher diagnostic accuracy compared to NS, due to the non-invasiveness, NS might be considered as an ancillary procedure for PD diagnosis.
Improved Meta-learning Neural Network for the Prediction of the Historical Reinforced Concrete Bond–Slip Model Using Few Test Specimens
Authors: Zhang Chengwen , Chun Qing , Sun Ao , Lin Yijie , Wang HaoYu
Published: July 2022

The bond–slip model plays an important role in the structural analysis of reinforced concrete structures. However, many factors affect the bond–slip behavior, which means that a large number of tests are required to establish an accurate bond–slip model. This paper aims to establish a data-driven method for the prediction of the bond–slip model of historical reinforced concrete with few test specimens and many features. Therefore, a new Mahalanobis-Meta-learning Net algorithm was proposed, which can be used to solve the implicit regression problem in few-shot learning. Compared with the existing algorithms, the Mahalanobis-Meta-learning Net achieves fast convergence, accurate prediction and good generalization without performing a large number of tests. The algorithm was applied to the prediction task of the bond–slip model of square rebar-reinforced concrete. First, the first large pretraining database for the bond–slip model, BondSlipNet, was established containing 558 samples from the existing literature. The BondSlipNet database can be used to provide a priori knowledge for learning. Then, another database, named SRRC-Net, was obtained by 16 groups of pull-out tests with square rebar. The SRRC-Net database can be used to provide the posteriori knowledge. Finally, based on the databases, the algorithm not only successfully predicted the bond–slip model of square rebar-reinforced concrete, but also that of the other 23 types of reinforced concrete. The research results can provide a scientific basis for the conservation of square rebar-reinforced concrete structures and can contribute to the bond–slip model prediction of the other types of reinforced concrete structures.
Age–period–cohort analysis of pulmonary tuberculosis reported incidence, China, 2006–2020
Authors: Dong Zhe , Wang Qi-Qi , Yu Shi-Cheng , Huang Fei , Liu Jian-Jun , Yao Hong-Yan , Zhao Yan-Lin
Published: July 2022

Background

Tuberculosis (TB) poses a severe public health challenge in China and worldwide. This study evaluated the effects of age, period, and birth cohort on reported incidence trends of TB based on population and refined the characteristics of high-risk groups.

Methods

Aggregate data that reported pulmonary tuberculosis (PTB) cases from China Tuberculosis Management Information System (TBIMS) from 2006 to 2020 were used to analyze effect coefficients through the age–period–cohort (APC) model based on intrinsic estimator (IE) method, and converted them into relative risk (RR) to estimate trends.

Results

A total of 14.82 million cases of PTB were reported in China from 2006 to 2020, showing a continuous downward trend. The reporting rate increased with age by age group, with 70–74 years old being 2–3 times higher than that in 20–24 years old. APC analysis model showed that age effects were bimodal in 20–24 years old [RR = 2.29, 95% confidence interval (CI): 1.73–3.03] and 70–74 years old (RR = 1.95, 95% CI: 1.67–2.27), and lower than the overall average in the groups under 15 years old. Stratified results showed that the risk was higher for women under age 40 than men and higher for men over 40. The risk was higher in urban than in rural areas under 30 years old and slightly higher in rural than in urban between 30 and 64 years old. The risk for 15–34 years old was significantly higher in the east than in other regions. The period effects showed a decreasing trend, and the risk was higher in rural in recent years. Except for cohorts born in 1961–1965 and 2001–2005, where the RR increased, the later the cohort was born, the lower the risk. The cohort 1926–1930 in eastern had the highest risk (RR = 3.49, 95% CI: 2.44–4.98).

Conclusions

The reported incidence of PTB continued to decline in China from 2006 to 2020. The young (20–24 years old) and the elderly (70–74 years old) were equally at high risk. There were differences in the age, period and cohort effects on PTB incidence among gender, urban–rural and regions. Our findings better reflected the characteristics of high-risk populations, thus contributing to the development of timely and effective intervention strategies, and providing clues for etiological research.

Graphical abstract
Circ_0000144 acts as a miR-1178-3p decoy to promote cell malignancy and angiogenesis by increasing YWHAH expression in papillary thyroid cancer
Authors: Ma Yinli , Yang Dan , Guo Pingan
Published: July 2022

Papillary thyroid cancer (PTC) is the most common subtype of thyroid cancer. Circular RNA hsa_circ_0000144 (circ_0000144) is related to the progression of thyroid cancer. However, the mechanism by which circ_0000144 accelerates PTC progression is still unclear. Circ_0000144 and YWHAH were upregulated in PTC tissues and cells, while miR-1178-3p had an opposite result. Circ_0000144 silencing constrained PTC cell growth in vitro and in vivo and induced apoptosis and repressed migration, invasion, and angiogenesis of PTC cells in vitro. Circ_0000144 acted as a molecular sponge for miR-1178-3p, which targeted YWHAH. MiR-1178-3p inhibitor reversed circ_0000144 silencing-mediated influence on PTC cell malignancy and angiogenesis. Furthermore, YWHAH overexpression overturned miR-1178-3p mimic-mediated influence on malignant behaviors and angiogenesis of PTC cells. Notably, circ_0000144 regulated YWHAH expression by adsorbing miR-1178-3p. Circ_0000144 promoted cell malignancy and angiogenesis by regulating the miR-1178-3p/YWHAH axis in PTC, offering a novel mechanism for the malignancy and angiogenesis of PTC cells.

Graphical Abstract
Probing a southern hemisphere VLBI Intensive baseline configuration for UT1 determination
Authors: Böhm Sigrid , Böhm Johannes , Gruber Jakob , Kern Lisa , McCallum Jamie , McCallum Lucia , McCarthy Tiege , Quick Jonathan , Schartner Matthias
Published: July 2022

The deviation of Universal Time from atomic time, expressed as UT1−UTC, reflects the irregularities of the Earth rotation speed and is key to precise geodetic applications which depend on the transformation between celestial and terrestrial reference frames. A rapidly varying quantity such as UT1−UTC demands observation scenarios enabling fast delivery of good results. These criteria are currently met only by the Very Long Baseline Interferometry (VLBI) Intensive sessions. Due to stringent requirements of a fast UT1−UTC turnaround, the observations are limited to a few baselines and a duration of one hour. Hence, the estimation of UT1−UTC from Intensives is liable to constraints and prone to errors introduced by inaccurate a priori information. One aspect in this context is that the regularly operated Intensive VLBI sessions organised by the International VLBI Service for Geodesy and Astrometry solely use stations in the northern hemisphere. Any potential systematic errors due to this northern hemisphere dominated geometry are so far unknown. Besides the general need for stimulating global geodetic measurements with southern observatories, this served as a powerful motivation to launch the SI (Southern Intensive) program in 2020. The SI sessions are observed using three VLBI antennas in the southern hemisphere: Ht (South Africa), Hb (Tasmania) and Yg (Western Australia). On the basis of UT1−UTC results from 53 sessions observed throughout 2020 and 2021, we demonstrate the competitiveness of the SI with routinely operated Intensive sessions in terms of operations and UT1−UTC accuracy. The UT1−UTC values of the SI reach an average agreement of 32 µs in terms of weighted standard deviation when compared with the conventional Intensives results of five independent analysis centers and of 27 µs compared with the 14C04 series. The mean scatter of all solutions of the considered northern hemisphere Intensives with respect to C04 is at a comparable level of 29 µs. The quality of the results is only slightly degraded if just the baseline HtHb is evaluated. In combination with the e-transfer capabilities from Ht to Hb, this facilitates continuation of the SI by ensuring rapid service UT1−UTC provision.

Graphical Abstract
Promising results of captopril in improving knee arthrofibrosis and cartilage status: an animal model study
Authors: Hashemi Seyed Ali , Azad Ali , Erfani Amirhossein , Shahriarirad Reza , Azarpira Negar
Published: July 2022

Purpose

Several cytokines and growth factors start and progress the destruction process of joint hyaline cartilage and fibrosis formation. Captopril is classified as an Angiotensin-converting enzyme inhibitor in which several studies revealed that captopril significantly decreases fibrosis formation in some organs like the liver, heart, and kidney. This study aimed to evaluate the use of captopril in reducing the possibility of arthrofibrosis and osteoarthritis in an animal model.

Method

In this in-vivo animal model study, the anterior cruciate ligament of 24 rabbits was transected to induce osteoarthritis and arthrofibrosis. The control group contained 11 rabbits and the second group consisted of 13 rabbits. The second group was treated with 10 mg/ kilogram/day captopril through a nasogastric tube. The control group was treated with normal saline in the same way. Cartilage damage and osteoarthritis were evaluated by Osteoarthritis Research Society International (OARSI) scoring system. After 30 days, animals were sacrificed, and arthrofibrosis and cartilage damage were evaluated microscopically and macroscopically.

Results

According to macroscopic and microscopic evaluation, captopril dramatically reduced arthrofibrosis formation based on visual scoring and the Masson trichrome staining system. Cartilage damage was lower in the intervention group compared to the control group.

Conclusions

Captopril is an angiotensin-converting enzyme inhibitor that demonstrated to significantly decreases the possibility of arthrofibrosis. Although the beneficial preventive effect of captopril on osteoarthritis was not proved statistically, better results may be obtained if the route of administration or drug dosage is changed.
Efficacy and safety of brolucizumab versus aflibercept in patients with neovascular age-related macular degeneration: a randomized trial in Indian patients
Authors: Mishra Sanjay Kumar , Kumar Pradeep , Khullar Srishti , Joshi Amrita , Sati Alok , Kumar Sonali Vinay , Unni Deepesh , Kumar Atul
Published: July 2022

Background

The current standard treatment for neovascular age-related macular degeneration (nAMD) involves intravitreal injections of anti-vascular endothelial growth factor (anti-VEGF) agents. The aim of the present study was to compare the effectiveness and safety of two anti-VEGF drugs: brolucizumab and aflibercept, in treatment-naïve nAMD Indian patients over a period of 48 weeks.

Methods

A prospective, randomized, single-centre, single-blinded, two-arm comparative study was conducted between March 2021 and February 2022. Of the 114 patients, 56 received intravitreal injections of brolucizumab (6 mg/50 µL) while 58 received aflibercept (2 mg/50 µL). The patients received 03 initial loading doses at 4-week intervals of both the agents and then respective therapies were given as individualized pro re nata (PRN) regimen based on the signs of active macular neovascularization. The functional and anatomical outcomes measured were mean change in best-corrected visual acuity (BCVA, logMAR), central macular thickness (CMT, µm), presence of intraretinal fluid, subretinal fluid or subretinal hyper-reflective material. Furthermore, the average number of additional injections required after the loading doses, the injection-free interval and safety of both the drugs were also assessed.

Results

Brolucizumab was found to be non-inferior to aflibercept in terms of mean change in BCVA (−0.13 ± 0.21 logMAR vs. −0.10 ± 0.15 logMAR) and reduction in CMT (−112.59 ± 81.23 µm vs. −86.38 ± 71.82 µm). The percentage of eyes with IRF and SHRM was comparable between both the groups while fewer eyes treated with brolucizumab indicated SRF presence than aflibercept after the loading doses. These beneficial effects of brolucizumab were observed with significant (p < 0.0001) lesser number of injections (1.8 ± 1.1 vs. 3.8 ± 1.5) from week 12 to week 48. Moreover, the probability of no injections after the loading doses was significantly higher with brolucizumab compared to aflibercept indicating prolonged injection-free intervals. The average ocular side effects were comparable in the two groups. One adverse event of severe vitritis requiring treatment with oral steroids occurred in Brolucizumab group, while no such event occurred in Aflibercept group.

Conclusion

The results of the present study suggest non-inferiority of brolucizumab PRN regimen to aflibercept PRN regimen in treatment naïve nAMD Indian patients while achieving longer inter-injection intervals.

Trial registration Clinical Trial Registration of India (CTRI/2021/06/034415). Registered 03 March, 2021, http://ctri.nic.in/Clinicaltrials/pmaindet2.php?trialid=54328&EncHid=&userName =
Phosphorus-solubilizing bacteria isolated from the rhizosphere of wild potato Solanum bulbocastanum enhance growth of modern potato varieties
Authors: Pantigoso Hugo A. , He Yanhui , Manter Daniel K. , Fonte Steven J. , Vivanco Jorge M.
Published: July 2022

Background

Wild potato species harbor a distinctive rhizosphere microbiome relative to their modern counterparts, thus providing a competitive advantage for acquiring phosphorus (P) in their native habitats. Despite this, the effects of transferring  phosphorus-solubilizing bacteria (PSB), recruited from wild potatoes rhizosphere, on modern potato varieties’ performance has not been investigated. Here, it was hypothesized that PSB isolated from wild potatoes could enhance plant growth and solubilization of various P forms when co-inoculated with commercial potatoes (Solanum tuberosum).

Results

To test this hypothesis, three bacteria Enterobacter cloacae, Bacillus thuringiensis, and Pseudomonas pseudoalcaligenes were isolated from the rhizosphere of the wild potato Solanum bulbocastanum grown under greenhouse conditions and characterized for their P-solubilizing activities. It was found that both individual bacterial species and the consortium of the three bacteria, dissolved organic (i.e., phytin) and inorganic P (i.e., calcium phosphate) in vitro. The bacterial consortium increased dissolved P by 36-fold for calcium phosphate and sixfold for phytin compared to a sterile control and surpassed the effect of each individual PSB strain. To further evaluate the effect of the PSB consortium on plant growth and P use efficiency, the bacteria were co-inoculated on a commercial potato cultivar and amended separately with phytin, calcium phosphate, commercial P fertilizer, or a combination of the three P sources. The results showed an overall increase in total dry biomass and shoot P content in treatments co-inoculated with PSB.

Conclusions

Our findings indicate that PSB isolated from wild potatoes and inoculated with modern potato varieties have the potential to enhance yield and nutrient uptake.
The potatoes of Otro: the reconstitution of an element of the Walser food heritage in NW Italy
Authors: Fontefrancesco Michele F. , Mello Margherita
Published: July 2022

The article analyzes the trajectory of the reconstitution of the gastronomic heritage among the Italian Walser community. It focuses on the case study of potato production in the Otro Valley, in Alagna Valsesia (VC), and explores how the process of heritagization linked to these products allowed the community to reconstitute a trait of their biocultural diversity lost during the twentieth century. In so doing, it offers details about the gastronomy of potatoes among the Walser and shows that food heritagization is not always coupled with the commodification of local heritage products, but rather can foster processes of reappropriation of a traditional gastronomy.
Correlation of chest CT severity score with clinical parameters in COVID-19 pulmonary disease in a tertiary care hospital in Delhi during the pandemic period
Authors: Sharma Swati , Aggarwal Anjali , Sharma Rajat K. , Patras Elisheba , Singhal Annu
Published: July 2022

Background

Since November 2019, the rapid outbreak of coronavirus disease 2019 (COVID-19) has become a public health emergency of international concern. COVID-19 disease is caused by a new variant of coronavirus, named as ‘severe acute respiratory syndrome coronavirus 2.’ Chest CT has a potential role in the diagnosis, detection of complications and in predicting clinical recovery of patients or progression of coronavirus disease 2019. Degree and severity of lung involvement can be assessed by 25 point CT severity score. This quantification plays an important role to modify the treatment plan at times in critically ill patient of COVID-19. Hence, the purpose of present study was to describe and quantify the severity of COVID-19 infection on chest computed tomography (CT) by 25-point CT severity score and to determine the relationship of CT severity score with clinical and laboratory parameters.

Results

A total of 150 patients with COVID-19 disease were assessed. Mean age of the study group was 54.46 years (62.7% males and 37.3% females). The most common comorbidity present in the study group was diabetes mellitus, which was present in 17.3% cases. Severity of disease was significantly associated with age of the patient. CT severity score was positively correlated with lymphopenia and raised CRP, D-dimer and serum ferritin levels. A significant statistical correlation was found between CT severity grade and patient survival.

Conclusions

This is a large comprehensive study, collecting data from 150 cases of COVID-19 pneumonia patients, in a tertiary care hospital in India to describe the correlation of CT severity score with clinical land laboratory parameters. Chest CT severity score correlates well with laboratory parameters and can aid in predicting COVID-19 disease outcome.
Effectiveness of clinical imaging guidelines to reduce inappropriate head computed tomography imaging: a case of Uganda
Authors: Kawooya Michael G. , Kisembo Harriet Nalubega , Malumba Richard , Nsereko Ezra
Published: July 2022

Background

Clinical imaging guidelines (CIGs) have been demonstrated to reduce inappropriate diagnostic imaging. There is insufficient evidence for CIG effectiveness to reduce inappropriate imaging in Africa. We assessed the effectiveness of CIGs training and implementation to reduce inappropriate diagnostic imaging at Mengo Hospital, Uganda.

Methods

A clinical audit of head CT examinations was conducted at Mengo Hospital. A baseline review of 262 requisitions was done to determine the level of appropriateness for imaging requisitions. We also determined the baseline knowledge level on radiation protection (RP) and CIG use among 15 referrers. We trained these referrers on RP, awareness and use of CIGs and uploaded the iGUIDE onto their smart phones and computer work stations for use. This was followed by a post-intervention assessment where we reviewed 154 requisitions to determine the level of appropriateness. We also assessed the post-intervention knowledge level on radiation protection (RP) and CIG use among the referring clinicians.

Results

We found 53% and 47% levels of inappropriate head CT requisitions for pre- and post-intervention, respectively. At pre-intervention, we found a 73% level of knowledge on radiation protection and CIGs use while we found a 93% at post-intervention assessment among referrers.

Conclusions

Implementation and training referring clinicians on CIGs are effective in reducing inappropriateness of head CT requisitions.
Efficacy and safety of selective renal arterial embolization in renal angiomyolipoma: a prospective single-center study
Authors: Abouelkheir Rasha Taha , El-Ksas Mostafa , Abdel Fattah Sherif , Amer Talal , El-Diasty Tarek
Published: July 2022

Background

Preventing acute complication of renal angiomyolipoma (AML), preserving renal parenchyma, and improving long-term renal function are the treatment targets of renal angiomyolipoma. Treatment should be considered for symptomatic lesions or those who are at risk of complications, especially bleeding symptoms, which are linked to tumor size, angiogenic component grade, and presence of tuberous sclerosis complex (TSC). Selective arterial embolization (SAE) has become the new norm for preventive or emergency treatment of renal AMLs with minimally invasive selective targeting of small arterial feeders, we aimed to assess the efficacy and safety of selective renal arterial embolization (SAE) in the management of complicated renal angiomyolipoma and to detect the predictors of prophylactic SAE in cases of non-complicated AML.

Results

Bleeding symptoms were significantly more frequent in patients with TSC-associated renal AMLs (C = 0.333 andp = 0.036) and patients with intra-lesional aneurysm > 3 mm (C = 0.387 andp = 0.013). Overall success rate: thirty-three (91.7%) renal AMLs were successfully embolized with no recurrence. While three (8.3%) renal AMLs were not; one (2.8%) renal AML was not embolized due to technical failure and two (5.5%) renal AMLs showed recurrence. Primary (technical) success rate: thirty-three (86.9%) successful embolization, five (13.1%) arteriographies were done with failed embolization. The maximum diameter and volume of the lesions after SAE showed statistically significant reduction (z = 4.25 andp < 0.001).

Conclusions

SAE is an effective and safe technique to manage renal AMLs preoperatively or in an emergency. TSC-associated lesions, and intra-lesional aneurysms (aneurysms > 3 mm in diameter) were significantly more associated with bleeding symptoms, considering them significant predictors for prophylactic SAE in non-complicated AML.
Impact of the COVID-19 on foreign direct investment inflows in emerging economies: evidence from panel quantile regression
Authors: Koçak Sinem , Barış-Tüzemen Özge
Published: July 2022

The study explores the role of the COVID-19 pandemic on foreign direct investment in 12 emerging countries for the period between 2014 and 2021. The world pandemic uncertainty index is used, and panel quantile regression approach is employed to analyze the effect of the pandemic on foreign investment inflows. Unlike the conditional mean regression analysis, panel quantile regression gauges the independent variables at the different locations of the dependent variable. For this reason, it provides a more comprehensive illustration of the impact of the independent variables on dependent variables. The results show that the pandemic has an inverse effect on foreign direct investment in low- and middle-foreign investment receiving countries, while the effect is insignificant in high-foreign investment receiving countries. Apparently, the health crisis has been further harmful to the countries that have weaker economic structures.
Dissolution of a Biopharmaceutics Classification System Class II Free Acid from Immediate Release Tablets Containing a Microenvironmental pH Modulator: Comparison of a Biorelevant Bicarbonate Buffering System with Phosphate Buffers
Authors: Haznar-Garbacz Dorota , Hoc Dagmara , Garbacz Grzegorz , Lachman Marek , Słomińska Daria , Romański Michał
Published: July 2022

Poor water dissolution of active pharmaceutical ingredients (API) limits the rate of absorption from the gastrointestinal tract. Increasing the pH of a solid form microenvironment can enhance the dissolution of weakly acidic drugs, but data on this phenomenon in a physiologically relevant bicarbonate media are lacking. In this paper, we examined the effect of a microenvironmental pH modulator (Na2HPO4) on the dissolution of a Biopharmaceutics Classification System (BCS) class II free weak acid (ibuprofen) at biorelevant conditions, including an automatic bicarbonate buffering system, as well as in compendial (50 mM) and low-concentration (10 mM) phosphate buffers with no external pH control. The tablets of 200 mg ibuprofen with either Na2HPO4 (phosphate formulation, PF) or NaCl (reference formulation, RF) were manufactured using a compression method. In a pH 2 simulated gastric fluid, only PF produced a transient supersaturation of ibuprofen, dissolving a fourfold higher drug amount than RF. In a bicarbonate-buffered simulated intestinal fluid with a dynamically controlled pH (5.7, 7.2, and 5.8 to 7.7 gradient), PF dissolved more drug within 30 min than RF (p ≤ 0.019). Of note, the use of a 50 mM phosphate buffer pH 7.2 provided opposite results—RF dissolved the API much faster than PF. Moreover, 10 mM phosphate buffers of pH 5.6 and 7.2 could neither maintain a constant pH nor mimic the bicarbonate buffer performance. In conclusion, the use of a bicarbonate-buffered intestinal fluid, instead of phosphate buffers, may be essential in dissolution tests of BCS class II drugs combined with pH modulators.

Graphical abstract
Convolution- and Deconvolution-Based Approaches for Prediction of Pharmacokinetic Parameters of Diltiazem Extended-Release Products in Flow-Through Cell Dissolution Tester
Authors: Taha Nesrin F. , Emara Laila H.
Published: July 2022

The present study evaluated the effect of different configuration setups of the Flow-Through Cell (USP IV) dissolution tester in developing in vitro–in vivo correlation (IVIVC). A Biopharmaceutics Classification System (BCS) Class I Diltiazem (DTZ), formulated in extended-release (ER) gel-matrix system, was employed for this purpose. The study also assessed the validity and predictability of IVIVC employing both deconvolution- and convolution-based approaches. In vitro release was conducted in USP IV as open- or closed-loop setups, while the pharmacokinetic (PK) data were obtained from a previous fasted-state cross-over study conducted on 8 healthy male volunteers, after oral administration of ER matrix tablets against market product (Tildiem Retard® 90 mg). PK parameters (Cmax, AUC0-t and AUC0-∞) were predicted, and compared with actual data to establish the strength of correlation models. Results showed that DTZ release from ER products was influenced by operating the FTC in different configuration-setups, where ≥ 75% of labeled DTZ was released after 6 h and 12 h using the open- and closed-loop settings, respectively. Correlation between fraction-dissolved versus fraction-absorbed for both ER products displayed linear relation upon employing FTC open-loop setup. Convolution-based approach was more discriminative in predicting DTZ in vivo PK parameters with a minimal prediction error, compared to deconvolution-based approach. A successful trial to predict DTZ PKs from individual in vitro data performed in USP IV dissolution model was established, employing convolution technique. Basic principle of the convolution approach provides a simple and practical method for developing IVIVC, hence could be utilized for other BCS Class I extended-release drug products.

Graphical abstract
Keywords in Caribbean Studies
Authors: Pérez-Rosario Vanessa , Jobson Ryan Cecil
Published: July 2022

This essay introduces a new featured section, to be published in Small Axe annually, that explores the critical vocabulary of the field of Caribbean studies.
The Synthesis and Photocatalytic Properties of a Cuprous Iodide-based Coordination Polymer
Authors: Sun Rui , Xiao Yu-Qing , Hu Chu-Xing , Shang Ping , Wang Ju-Ping , Jiang Xuan-Feng
Published: July 2022

A staple-shaped linear coordination polymer containing a single metal node was constructed via a conformational adaptive synthesis strategy. Such well-defined coordination polymer CP 1 could aggregate into a highly-ordered two-dimensional supramolecular framework with ultrasmall pores through weak intermolecular π⋯π stacking interactions. The emissive complex CP 1 showed excellent photocatalytic activity for azide-alkyne cycloaddition reaction (CuAAC) in solution at room temperature.
Como otimizar a logística sem gastar muito
Authors: Medeiros Fabio , Di Serio Luiz Carlos , Moreira Alessandro
Published: July 2022

Nesse momento de crise, a aplicação de ferramentas de melhoria contínua oferece ganhos em eficiência operacional sem a necessidade de grandes investimentos.
Systematic design, deployment and evaluation of gamified cybersecurity learning environments
Authors: Καραγιάννης Στυλιανός
Published: July 2022

Η παρούσα διατριβή έχει ως στόχο την επικύρωση της θεωρίας μάθησης του κονστρουκτιβισμού και να αποδώσει τις πιθανές συστηματικές προσεγγίσεις που επιτρέπουν στις προκλήσεις Capture the Flag (CTF) και στα Cyber Ranges να παρέχουν σημαντικό μαθησιακό αντίκτυπο. Η παρούσα έρευνα συμβάλει στην κατανόηση σχετικά με τον σχεδιασμό της έρευνας και τη μεθοδολογική ανάπτυξη που απαιτείται για την ενίσχυση του μαθησιακού αντίκτυπου των προκλήσεων CTF και των Cyber Ranges ως εικονικών περιβαλλόντων μάθησης στον κυβερνοχώρο. Ο πειραματικός σχεδιασμός στηρίζεται μεθοδολογικά στο Action Design Research (ADR) και αξιοποιήθηκε για την παροχή δεδομένων σχετικά με το σχεδιασμό και την ανάπτυξη ψηφιακών περιβαλλόντων εκμάθησης στην κυβερνοασφάλεια. Στην έρευνα συμπεριλαμβάνεται κριτική αξιολόγηση των περιβαλλόντων μάθησης στον κυβερνοχώρο λαμβάνοντας υπόψη τις έννοιες της παιχνιδοποίησης (gamification) και της μάθησης που βασίζεται σε παιχνίδι (Game-Based Learning). Η έρευνα παρέχει τη βάση για έναν νέο τρόπο σχεδίασης και ανάπτυξης περιβαλλόντων μάθησης στον κυβερνοχώρο και την δημιουργία συναφών σεναρίων στην κυβερνοασφάλεια ως βάσης για την απόκτηση τεχνικών δεξιοτήτων στον τομέα της πληροφορικής.