bluuebunny/crossref_metadata_2025_split huggingface dataset:
A standardised pre-clinical in-vitro blood-brain barrier mouse assay validates endocytosis dependent antibody transcytosis using transferrin receptor-mediated pathways.
Authors: Morrison Jamie I. , Petrovic Alex , Metzendorf Nicole G. , Rofo Fadi , Yilmaz Canan U. , Stenler Sofia , Laudon Hanna , Hultqvist Greta 
Published: August 2022

Abstract
The presence of the blood brain barrier (BBB) creates a nigh on impenetrable obstacle for large macromolecular therapeutics that need to be delivered to the brain milieu to treat neurological disorders. To overcome this, one of the strategies used is to bypass the barrier with what is referred to as a “Trojan Horse” strategy, where therapeutics are designed to use endogenous receptor-mediated pathways to piggyback their way through the BBB. Even though in vivo methodologies are commonly used to test the efficacy of BBB penetrating biologics, comparable in vitro BBB models are in high demand, as they benefit from being an isolated cellular system devoid of physiological factors that can on occasion mask the processes behind BBB transport via transcytosis. We have developed an in vitro BBB model (In-Cell BBB-Trans assay) based on the murine cEND cells that helps delineate the ability of modified large bivalent IgG antibodies, conjugated to the transferrin-receptor binder scFv8D3, to cross an endothelial monolayer grown on porous cell culture inserts (PCIs). Following the administrating of bivalent antibodies to the endothelial monolayer, a highly sensitive ELISA method is used to determine the concentration in the apical (blood) and basolateral (brain) chambers of the PCI system, allowing for the evaluation of apical recycling and basolateral transcytosis respectively. Our results show that antibodies conjugated to scFv8D3 transcytose at considerably higher levels compared to unconjugated antibodies in the In-Cell BBB-Trans assay. Interestingly, we are able to show that these results mimic in vivo brain uptake studies using identical antibodies. In addition, we are able to transversely section PCI cultured cells, allowing for the identification of biomarkers pertinent to transcytosis of the antibodies. Furthermore, studies using the In-Cell BBB-Trans assay revealed transcytosis of the transferrin-receptor targeting antibodies is dependent on endocytosis. In conclusion, we have designed a simple, reproducible In-Cell BBB-Trans assay based on murine cells that can be used to rapidly determine the BBB penetrating capabilities of transferrin-receptor targeting antibodies. We believe the In-Cell BBB-Trans assay can be used as a powerful, pre-clinical screening platform for therapeutic neurological pathologies.
Lack of evidence for fentanyl as the optimal opioid for critically ill patients on mechanical ventilation: a systematic review and meta-analysis
Authors: Aoki Yoshitaka , Kato Hiromi , Fujimura Naoyuki , Suzuki Yuji , Sakuraya Masaaki , Doi Matsuyuki 
Published: August 2022

Abstract
Background: Fentanyl is selected to manage pain in critical care patients in the intensive care unit (ICU). However, the usefulness of fentanyl has not been established. This study examined the evidence for the use of fentanyl to improve the clinical outcomes in ICU patients, using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system.Methods: We searched the MEDLINE, Cochrane Central Register of Controlled Trials, and Igaku Chuo Zasshi databases in June 2021. Two independent assessors reviewed studies to identify randomized, controlled trials that compared the intravenous administration of fentanyl and other opioids in mechanically ventilated patients. The study quality was assessed using the GRADE system and Cochrane methodology. The primary outcome was mortality. Secondary outcomes were the duration of mechanical ventilation, duration of the ICU stay, incidence of severe adverse events, and incidence of delirium. We integrated outcome data using a random-effects model and showed absolute values and certainty of evidence in the GRADE evidence profile.Results: Eleven Randomized Controlled Trials met the study inclusion criteria with 1312 patients (643 were treated with fentanyl and 669 with other opioids, including 628 with remifentanil and 41 with morphine). Among 816 participants from 4 RCTs, fentanyl was not associated with mortality (risk ratio [RR], 0.74; 95% confidence interval [CI], 0.28 to 2.00; low-quality evidence). Regarding the secondary outcomes, fentanyl did not shorten the duration of mechanical ventilation (mean difference [MD], −1.71 h; 95% CI, −3.79 to 0.37; moderate-quality evidence) or the duration of the ICU stay (MD, −1.89 h; 95% CI, −5.00 to 1.22; moderate-quality evidence) compared with other opioids. Fentanyl also did not increase the incidence of severe adverse events (RR, 0.80; 95% CI, 0.56 to 1.15; moderate-quality evidence) or delirium (RR, 1.27; 95% CI, 0.79 to 2.04; low-quality evidence). Conclusions: Although fentanyl is a frequently administered opioid in ICUs worldwide, the current analysis found no evidence to support its clinical use. However, the GRADE evaluation provides little certainty to support the results of this systematic review, and further large RCTs are therefore needed to confirm the conclusions.Trial registration: PROSPERO, CRD42019130648https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=130648
A retrospective study of 18 children with subcutaneous panniculitis-like T-cell lymphoma: Multidrug combination chemotherapy or immunomodulatory therapy?
Authors: Duan Yanlong , Gao Huixia , Zhou Chunju , Jin Ling , Yang Jing , Huang Shuang , Zhang Meng , Zhang Yonghong , Wang Tianyou 
Published: August 2022

Abstract
Background Subcutaneous panniculitis T-cell lymphoma (SPTCL) is a rare, cytotoxic T-cell lymphoma with which some patients have accompanying hemophagocytic syndrome (HPS). There is currently no standard treatment regimen. In the past, the most commonly used treatment was multidrug chemotherapy. In contrast, numerous case reports or small series suggest that immunosuppressive drugs could also be effective for some patients. Since this NHL subtype is extremely rare in children and adolescents, to improve the understanding of this disease and standardize its rational treatment, we retrospectively summarized the treatment regimens of 18 pathologically diagnosed children with SPTCL to compare the clinical efficacy of multidrug chemotherapy and immunomodulatory therapy.Results The male to female ratio was 1:5. The median age of onset was 11.1 years. Painless subcutaneous nodules or skin patchy lesions were found in all patients, most commonly involving the lower extremities and/or trunk. The pathology and immunophenotype results of all patients were consistent with SPTCL, and atypical lymphocytes infiltrated and rounded the lipocytes like rosettes in subcutaneous adipose tissue. Tumor cells showed a cytotoxic immunophenotype of cytotoxic T lymphocytes. There were 7 patients (38.9%) with hemophagocytic syndrome (HPS) and 4/5 screened patients (80%) with positive HAVCR2 gene mutations. Before January 1, 2019, the treatment was mainly chemotherapy, and 10 patients were initially treated with chemotherapy, among whom was one patient who progressed during initial treatment, was voluntarily discharged and was subsequently lost to follow-up, one patient who died of disease progression, and the remaining 8 patients who all achieved sustained remission, with a complete remission (CR) rate of 80% (8/10). Corticosteroids combined with cyclosporine A or ruxolitinib were the most common initial immunosuppressive agents at our center after January 1, 2019 and had a CR rate of 71.4% (5/7). In addition, 1 patient achieved partial remission (PR) during follow-up, and one had autologous hematopoietic stem cell transplantation (AHSCT) after 4 months of drug withdrawal. The median follow-up was 17 months. Conclusion The incidence of SPTCL is extremely low, but its prognosis is relatively good. Immunoregulatory therapy can be considered a first-line treatment.
A Life-course Approach to Depression among Middle-aged and Elderly in India: Evidence from the Longitudinal Aging Study in India - 2018-2019
Authors: . Farheen , Dixit Priyanka 
Published: August 2022

Abstract
Background
Depression is a major public health concern in India contributing significantly to morbidity, dysfunction, reduced quality of life, and economic loss. Evidence from previous studies suggest that risk to developing mental illness begins in the early years of life. Thus, we aim to examine the effect of early life conditions-childhood health status and childhood socioeconomic status on depression later in life and the mediating role of other risk factors along life-course- education, current economic status, chronic physical condition(s), and health behaviours - in the effect of early life conditions on depression later in life.
Methods
We used data from Longitudinal Aging Study in India (2018–2019) to find the association between the possible risk factors, including early life conditions, and depression later in life using logistic regression. The factors that were found to be significantly associated with depression later in life were used in the second step of mediation analysing using Karlson-Holm-Breen method, to examine the role of mediators in the effect of early life conditions on depression later in life.
Results
Childhood health, childhood socioeconomic status, education, current economic status, chronic physical condition(s), and tobacco use were found to be associated with depression later in life. Childhood health directly influences the occurrence of depression later in life and its effect is not mediated by risk factors along life course. On the contrary, the effect of childhood socioeconomic status on depression later in life is at least partially mediated by risk factors along life course- education, current economic status, chronic physical condition(s), experience of depression and tobacco use. The greatest contribution to this mediation is by discrimination, followed by tobacco use and education. Chronic physical condition is also a major contributor but it acts as a suppressor. Furthermore, the childhood health also mediates the influence of early life socioeconomic status on depression later in life.
Conclusions
Our findings demonstrate the pertinence of childhood health in reducing the burden of depression later in life. It also underscores the importance of focussing on risk factors along life course- discrimination, tobacco use, and education, health behaviours- for individuals who belonged to families having low socioeconomic status during childhood, and initiatives to prevent chronic physical conditions particularly among those who did not have adverse socio economic status during childhood in order to reduce the burden of depression among middle-aged and elderly population in India.
Effects of long-term dehydration and quick rehydration on the camel kidney: pathological changes and modulation of the expression of solute carrier proteins and aquaporins
Authors: Damir Hassan Abu , Ali Mahmoud , adem Muna , Amir Naheed , Tariq Saeed , Adeghate Ernest , Greenwood Michael , Lin Panjiao , Gillard Benjamin , Alvira-Iraizoz Fernando , Murphy David , ADEM ABDU 
Published: August 2022

Abstract

The kidney of the one-humped camel has a remarkable capacity to preserve water and solute during extremes of long-term dehydration. We investigated the effects of dehydration and subsequent rehydration on camel kidney morphology at the ultrastructural level and the expression of aquaporins and solute carrier proteins. In light microscopy, dehydration induced few degenerative and necrotic changes in cells of the cortical tubules with little effect on medullary cells. Ultrastructural changes were mainly observed in some of the glomerular and tubular cells with insignificant changes in the collecting ducts of medulla. These changes included condensation of nuclear chromatin, vacuolization of cytoplasm, swelling of mitochondria, degradation or loss of brush borders of proximal tubules, cracking of major processes of some podocytes and degeneration of lysosomes and endoplasmic reticulum. Cell death, apoptotic-like bodies and changes in the basolateral membranes were infrequent and nephrolithiasis was not detected. Chronic nephropathy, mainly interstitial fibrosis and glomerular sclerosis induced by recurrent dehydration in human and animal models were not observed. Modulation of SLC proteins, AQP 1, 2, 3, 4, 9 and regulation of gene mRNAs expression levels during dehydration/rehydration play important role in water conservation and cell protection favoring kidney cellular restoration to near normal.
CEGAN: Crystal Edge Graph Attention Network for multiscale classification of materials environment
Authors: Sankaranarayanan Subramanian , Banik Suvo , Dhabal Debdas , Chan Henry , Manna Sukriti , Cherukara Mathew , Molinero Valeria 
Published: August 2022

Abstract
Machine learning models and applications in materials design and discovery typically involve the use of feature representations or “descriptors” followed by a learning algorithm that maps it to a user-desired property of interest. Most popular mathematical formulation-based descriptors are not unique across the atomic environments or suffer from transferability issues across different application domains and/or material classes. In this work, we introduce the Crystal Edge Graph Attention Network (CEGAN) workflow that uses graph attention-based architecture to learn unique feature representations and perform classification of materials across multiple scales (from atomic to mesoscale) and diverse classes ranging from metals, oxides, non-metals and even hierarchical materials such as zeolites. We first demonstrate a case study where the classification is based on a global, structure-level representation such as space group and structural dimensionality (e.g., bulk, clusters, 2D, etc.). Using representative materials such as polycrystals and zeolites, we next demonstrate the transferability of our network in successfully performing local atom level classification tasks, such as grain boundary identification and other heterointerfaces. Finally, we demonstrate classification in (thermal) noisy dynamical environments using a representative example of crystal nucleation and growth of a zeolite polymorph from an amorphous synthesis mixture. Overall, our approach is agnostic to the material type and allows for multiscale classification of features ranging from atomic-scale crystal structures to heterointerfaces to microscale grain boundaries.
Fuzzy and CNN Based Novel approach for Real Time Image De-noising
Authors: mehra rajni , Chaudhary Prahi 
Published: August 2022

Abstract
The discriminative Model for image de-noising has been recently attracting considerable attention due to its favorable de-noising performances. In this paper, a model has been constructed for image de-noising for the standard dataset and real-time dataset. In this paper a novel approach has been implemented known as adaptive fast and flexible de-noising network (AFFDNet). This model is totally based upon the fuzzy and CNN network, with the combination of both image de-noising has been done. Our AFFDNet model is able to capable for handling the different noise level as well as different image sizes. The noise level has been taken 15, 25 & 50 with image size 256*256, 512*512 & 1024*1024. Our model give better result at all noise level also on different size of images. The residual learning is used in this novel approach to remove the latent clean image from hidden layer. In the future scope it can be used in for reduce the complexity because real-time makes algorithm very complex.
BMP-2 Promotes Breast Cancer Metastasis by Inducing EMT via PI3K/Akt Signaling Pathway
Authors: Zhang Li , Shi WeiFeng , Wang Shuling , Wu Yansheng , Tong Zhongsheng 
Published: August 2022

Abstract
Purpose:Bone morphogenetic proteins (BMPs) are important members of the TGF-β superfamily and can be abnormally expressed in various tumors. The purpose of this paper is to investigate the expression of bone morphogenetic proteins-2(BMP-2) in breast cancer and its effects on breast tumor cells and the regulation mechanism.Method:The effects of BMP-2 on the proliferation, cloning, apoptosis, migration and invasion of breast cancer cells were investigated by MTT assay, plate cloning experiment, flow cytometry (FCM), scratch test and transwell assay. The relationship between BMP-2 and epithelial-mesenchymal transition (EMT)-related indicators in cell lines, and the relationship between BMP-2 and PI3K/Akt pathway-related proteins were analyzed using real-time PCR and Western blot. Breast cancer xenograft models were established to observe effects of BMP-2 on the growth and metastasis of xenograft tumors, and real-time PCR and immunohistochemistry were used to detect changes in EMT-related protein expression in xenograft tumors.Results:BMP-2 was highly expressed in MBA-MD-231 and T47D cell lines. The results of in vitro experiments showed that rhBMP-2 could promote the proliferation, colony formation, migration and invasion of breast cancer cells, and reduce the apoptosis ability. The expression of BMP-2 was significantly correlated with EMT. With increasing BMP-2 concentration, the expression of E-cadherin and Cx43 was significantly down-regulated in the epithelial phenotype, while the expression of N-cadherin, fibronectin (FN), and vimentin mRNA was significantly up-regulated in the mesenchymal phenotype. BMP-2 could promote p-PI3K, p-Akt and p-mTOR expression in the PI3K/Akt signaling pathway, which in turn regulated the EMT process. However, after the addition of LY294002, an inhibitor of this signaling pathway, no significant up-regulation of p-PI3K, p-Akt, and p-mTOR was observed, and there was no significant change in EMT-related indicators. Through the establishment of the BMP-2 high expression xenograft model in nude mice, it was found that the growth rate of xenograft in the BMP-2 group was significantly faster than that in the control group, and metastasis to lymph node and bone were likely to occur. Compared with the control group, E-cadherin expression was attenuated and vimentin expression was enhanced in the BMP-2 group, suggesting EMT.Conclusion:BMP-2 is highly expressed in breast cancer tissues and is a malignant regulator of breast cancer cells. Its mechanism of action may be the induction of the EMT via PI3K/Akt pathway. BMP-2 is expected to be a new target for controlling the growth and metastasis of breast cancer.
Design, synthesis, anti-inflammatory evaluation and in silico molecular docking of novel furan-based derivatives with promising TNF-α inhibitory activity
Authors: Bhoge Satish , Singh Prabal P. , Das Deepak K. , Ali Yakub , Dhulap Abhijeet 
Published: August 2022

AbstractInflammation is the first response and an alarming signal for onset of chronic disease. Most of the anti-inflammatory drugs available in market are reported to have undesirable gastrointestinal toxicities. Therefore, it is of urgently significance to develop anti-inflammatory drugs with low toxicity and good efficacy. Based on literature survey, we designed a targeted scaffold by condensing distinct structural features of furan and benzyl amides into one pharmacophore. The inspiration for drug design approach of targeted molecule was based on marketed drugs.A series of eighteen furan-based derivatives(1-18)were designed, synthesized forin-vitroandin-vivoanti-inflammatory activity. The characterization of synthesized compounds was elucidated by techniques like 1H-NMR, 13C-NMR, FT-IR and MS. The synthetic compounds were examined through molecular docking studies on TNF-α for probable binding mode and interactions with hydrophilic and hydrophobic pocket of TNF-α in comparison to standard drug (Indomethacin). Compounds 18, 15 and 9 produced comparablein-vitroTNF-α inhibition andin-vivoinflammatory activity when compared to the standard drug along with no damage to stomach and with reduction of LPO. The compounds18, 15and9might be a good consideration for potential anti-inflammatory agents.
A study on the dynamics of pest population with biocontrol using predator, parasite in presence of awareness
Authors: G Suganya , R Senthamarai 
Published: August 2022

Abstract
The coconut tree is often mentioned as the “tree of life” due to its immense benefits to the human community ranging from edible products to building materials. Rugose spiraling whitefly (RSW), a natural enemy seems to be a major threat to farmers in bringing up these coconut trees. A mathematical model to study the dynamics of pest population in presence of predator and parasite is developed. The biologically feasible equilibrium points are derived. Local asymptotic stability as well as global asymptotic stability is analyzed at the points. Furthermore, in order to educate farmers on pest control , we have added the impact of awareness programs in the model. The conditions of existence and stability properties of all feasible steady states of this model are analyzed. The result reveals that predator and parasite plays a major role in reducing the immature pest. It also shows that pest control activities through awareness programs further reduces the mature pest population which decreases the egg laying rate which in turn reduces the immature population.
Religiosity and Spirituality as Agents of Change in Hard Drugs Usage in the Niger Delta area of Nigeria
Authors: Ekeke Emeka C. 
Published: August 2022

AbstractDrug usage is a global phenomenon that has been seen throughout human history, whether it is done for therapeutic, spiritual, or recreational reasons. Hard drug use and misuse have become a severe concern, especially for those living in Nigeria's Niger Delta, where Christianity is the predominant faith. One can wonder if such a phenomenon should be attributed to the churches' lack of dedication to their religion or if their members have not taken spirituality seriously. In order to explore how religion and spirituality might affect drug use, the current study looks at the usage and abuse of hard and illegal substances in the Niger Delta. The study uses a survey research design and the quantitative research methodology. Responses to closed-ended, structured, electronic and paper-based questionnaires dispersed throughout the study region make up the primary data. The information was gathered both manually and electronically (through email). The study shows that the use of hard drugs is very common in the area and that religious organizations are not doing enough to rehabilitate and treat local drug users on a religious and spiritual level. As the keeper of public morals, the report advises the Church to focus its efforts on preaching against the use and misuse of illegal and hard substances.
Molecular identification of yeasts in oral cavity in immunocompetent teenagers from the North of Mexico
Authors: Rojas Olga C. , Amaral-Montesino Cintia , Mendoza-Olazaran Soraya , González-Álvarez Rafael , Montoya Alexandra M. 
Published: August 2022

Abstract
Human oral cavity is normally colonized for microorganisms including bacteria, fungi, archaea, viruses and protozoa. The aim of this study was to determine the frequency of Candida albicans in de oral cavity in a group of medicine students from the north of Mexico. 240 oral samples from healthy students were analyzed by traditional microbiology cultures and DNA sequencing. 57 samples grew in media cultures. Sequence analysis identified the yeast as follow: 28 Clavispora lusitaniae, 20 Candida albicans, 5 Pichia kudriavzevii and 4 Candida parapsilosis. Our finding revealed that 23.75% of healthy population has a potential pathogen in its mouth. Surprisingly Candida albicans is not the predominant yeast, instead of others non-Candida species are the colonizers of the oral cavity in immunocompetent individuals. Oral cavity is colonized by potential pathogen yeast being Clavispora lusitaniae, Candida albicans, Pichia kudriavzevii and Candida parapsilosis.