bluuebunny/crossref_metadata_2025 huggingface dataset:
Analyzing Answering Patterns in Progress Test Data
Authors: Sieg Miriam , Tomova Mihaela Todorova , Atanet Iván Roselló , Sehy Victoria , Mäder Patrick , März Maren
Published: June 2022

Background: The Progress Test Medicine (PTM) is a 200-question formative test administered to approximately 11,000 students at medical faculties (Germany, Austria, Switzerland) each semester. Participants receive feedback on their knowledge (development) mostly in comparison to their own semester. In this study, we use the data of the assessment to find groups with similar answer patterns.Methods: We performed k-means clustering with a dataset of 5,444 participations, selected cluster number k=5, and answers as features. Subsequently, the data was passed to XGBoost with the cluster assignment as the target enabling the derivation of cluster-relevant questions for each cluster with SHAP. Clusters were examined by total score, answer patterns, and confidence. Relevant questions were evaluated for difficulty, discriminatory index and confidence levels.Results: Three of the five clusters can be seen as ’performance clusters’: cluster 0 (n=761) consists predominantly of participants in higher semesters. Relevant questions tend to be difficult, but participants answer confidently and correctly. Participants in cluster 1 (n=1,357) are amidst their study, cluster 3 (n=1,453) consists mainly of early study stage participants. Guessed questions increase successively, relevant questions are rather easy. Two clusters are mostly ‘leaver clusters’: participants in cluster 2 (n=384) drop out of the test about halfway through after initially performing well. Cluster 4 (n=1,489) includes students from the first semesters - but also "non-serious" participants with mostly wrong guesses or no answers. Conclusion: Clusters dissolve the allocation to one's own semester and place performance in the context of the overall cooperation.
Victimization by Caregivers: Prevalence and Risk Factors in Chilean Childrens and Adolescents
Authors: Portilla-Saavedra Diego , Pinto-Cortez Cristián , Guerra Cristóbal , Cárdenas Fabiola Peña
Published: June 2022

This study examined the prevalence and risk factors associated to victimization by caregivers in a national large sample of Chilean children and adolescents. 19,687 children and adolescents aged 12–17, obtained by random probability sampling of 699 publics schools of Chile were surveyed by trained interviewers. Victimization by Caregivers was evaluated through the one module of Juvenile Victimization Questionnaire (JVQ). The prevalence (12 months) for physical abuse were (12.9%), for emotional abuse (27.9%), neglect (5.3%) and parental interference (3.5%). The results suggest as risk factors, sex, age, migration status, disability, geographical location and type of school. The findings highlight the urgent need to address the issue of child maltreatment and victimization by caregiver´s in the Chilean society and minimize its impact
Strain specific properties of Escherichia coli can prevent non-canonical amino acid misincorporation caused by scale-related process heterogeneities
Authors: Mayer Florian , Cserjan-Puschmann Monika , Haslinger Benedikt , Shpylovyi Anton , Dalik Thomas , Sam Christian , Hahn Rainer , Striedner Gerald
Published: June 2022

Background: Escherichia coli is one of the most important hosts for production of recombinant proteins in biopharmaceutical industry. However, when selecting a suitable production strain, it is often not considered that a lot of different sub-species exist, which can differ in their genotypes and phenotypes. Another important development step is the scale-up of bioprocesses with the particular challenge that heterogeneities and gradients occur at production scale. These in turn can affect the production organism and can have negative impact on the process and the product quality. Therefore, researchers developed scale-down reactors, which are used to mimic manufacturing conditions in laboratory scale. The main objectives of this study were to determine the extent to which scale-related process inhomogeneities affect the misincorporation of non-canonical amino acids into the recombinant target protein, which is an important quality attribute, and whether strain specific properties may have an impact.Results: We investigated two industrially relevant E. coli strains, BL21(DE3) and HMS174(DE3), which produced an antigen binding fragment (Fab). The cells were cultivated in high cell density fed batch mode at laboratory scale and under scale-down conditions. We demonstrated that the two host strains differ significantly with respect to norleucine misincorporation into the target protein, especially under heterogeneous cultivation conditions in the scale-down reactor. No norleucine misincorporation was observed in E. coli BL21(DE3) for either cultivation condition. In contrast, norleucine incorporation into HMS174(DE3) was already detectable in the reference process and increased dramatically in scale-down experiments. Norleucine incorporation was not random and certain positions were preferred over others, even though only a single codon exists. Differences in biomass and Fab production between the strains during scale-down cultivations could be observed as well. Conclusions: All in all, this study has shown that E. coli BL21(DE3) is much more robust to scale-up effects in terms of norleucine misincorporation than the K12 strain tested. In this respect, BL21(DE3) enables better transferability of results at different scales, simplifies process implementation at production scale, and helps to meet regulatory quality guidelines defined for biopharmaceutical manufacturing.
Hyperlocal super-learned PM2.5 components across the contiguous US
Authors: Amini Heresh , Danesh-Yazdi Mahdieh , Di Qian , Requia Weeberb , Wei Yaguang , Abu-Awad Yara , Shi Liuhua , Franklin Meredith , Kang Choong-Min , Wolfson Jack , James Peter , Habre Rima , Zhu Qiao , Apte Joshua , Andersen Zorana , kloog Itai , Dominici Francesca , Koutrakis Petros , Schwartz Joel
Published: June 2022

Particulate matter with aerodynamic diameter less than 2.5 μm (PM2.5) increases mortality and morbidity.1,2 PM2.5 is composed of a mixture of chemical components that vary across space and time.3 Due to limited hyperlocal data availability, less is known about health risks of PM2.5 components, their US-wide exposure disparities, or which species are driving the biggest intra-urban changes in PM2.5 mass. Here, we developed the first national super-learned models across the US for hyperlocal estimation of annual mean elemental carbon (EC), ammonium (NH4+), nitrate (NO3-), organic carbon (OC), and sulfate (SO42-) concentrations across 3,535 urban areas at a 50-m spatial resolution, and at a 1-km resolution for non-urban areas from 2000 to 2019. Using ensembles of machine learning models and ~82 billion predictions across 20 years, hyperlocal super-learned PM2.5 components are now available for further research. We found remarkable spatiotemporal intra-urban and inter-urban variabilities in PM2.5 components. We anticipate our work to be a critical milestone for conducting new studies on individual and combined health risks of PM2.5 components, environmental justice analysis, or understanding fine-scale spatiotemporal variabilities of PM2.5 composition. Urban planners and regulators may also use these predictions for selecting locations of new daycares, schools, nursing homes, or air-quality monitors.
Role of hematological and platelet parameters in diagnosis of papillary thyroid carcinoma
Authors: Amiri Amir , Saed Lotfollah , Erfan Mohamaad Bagher Khadem , Mansouri Nasrin , Azizi Ali , Shaveisi-Zadeh Jila , Rostami-Far Zahra
Published: June 2022

Objective
Thyroid cancer is the most common cancer of the endocrine and is apparent in about 5 percent of thyroid nodules. Platelets have been shown to play an important role in chronic inflammation, cancer progression, and metastases. Recent research has been done on the correlation between platelet factor and many other types of cancer. This study aimed to investigate the diagnostic accuracy of platelet factor and other CBC parameters in papillary thyroid carcinoma.
Material and Methods
Thirty hundred and fifty patients were divided into two groups retrospectively. Group 1: papillary thyroid carcinoma patients (n = 150). Group 2: normal healthy subjects (n = 200). PLT, MPV, PDW, and CBC parameters were compared between groups, and p < 0.05 was accepted as significant
Results
The neutrophil count and NLR (neutrophil to lymphocyte ratio) were significantly higher, while the Hb, PLT, MPV, RDW, lymphocyte, and monocyte count, were significantly lower in patients compared with the control group. These parameters scored low in all parameters of diagnostic accuracy, with overall accuracy ranging between 41 and 66%.
Conclusions
NLR, MPV, and PLT are relatively inexpensive and widely available from routine blood tests. Although we found higher NLR values and lower PLT and MPV values in patients with papillary thyroid carcinoma, these factors cannot effectively diagnose thyroid cancer.
NRAV, a newly identified Ferroptosis-related lncRNAs, affects the prognosis of hepatocellular carcinoma through the miR-375- 3P/SLC7A11 axis
Authors: Zong Ke , hu jianfei , Luo Kai , Deng Yilei , Wang Hongfei , Chen Shi , Li Renfeng
Published: June 2022

Background: Ferroptosis has important value in cancer treatment. It is significant to explore the new Ferroptosis-related lncRNA prediction model in Hepatocellular carcinoma (HCC) and the potential molecular mechanism.Methods: We constructed a prognostic multilncRNA signature based on ferroptosis-related differentially expressed lncRNAs in HCC. qRT-PCR was applied to determine the expression of lncRNA in HCC cells and tissues. The biological roles of NRAV in vitro and in vivo were determined by performing a series of functional experiments. Further, dual-luciferase reporter and RNA immunoprecipitation (RIP) assays were used to confirm the interaction of NRAV with miR-375-3P.Results: We identified 19 differently expressed lncRNAs associated with the prognosis of HCC. Kaplan-Meier analyses revealed the high-risk lncRNAs signature associated with poor prognosis of HCC. Moreover, the AUC of the lncRNAs signature was 0.803, underscoring their utility in predicting HCC prognosis. Indeed, our risk assessment model was superior to standard clinicopathological features in predicting HCC prognosis. Further functional experiments show that the high expression of NRAV can strengthen the viciousness of HCC. NRAV via miR-375-3P/SLC7A11 axis enhances iron export and ferroptosis resistance, affecting the prognosis of patients with HCC.Conclusion: A novel ferroptosis-related lncRNAs signature impacts the prognosis of HCC.NRAV may play a role in induced ferroptosis, which can be considered a potential therapeutic target in HCC.
TRPV1 modulated NLRP3 inflammasome activation via calcium in experimental subarachnoid hemorrhage
Authors: Zhang Keke , Guo Gengyin , Wang Haocong , Chen Jinyan , Wang Feng , Zhang Zhen
Published: June 2022

Neuroinflammation plays a key role in early brain injury (EBI) of subarachnoid hemorrhage (SAH), and NLRP3 inflammasome plays an important role in the development of neuroinflammation after SAH, but the mechanism of NLRP3 inflammasome activation after SAH is still unclear. TRPV1 is a non-selective calcium channel that is involved in the pathology of neuroinflammation, but its role in SAH has not been revealed. Our study showed that TRPV1 was significantly upregulated after SAH and was predominantly expressed in microglia/macrophages. Antagonism of TRPV1 was effective in ameliorating neurological impairment, brain edema, neuronal damage, and reducing the inflammatory response (evidenced by reducing the number of CD16/32 positive microglia/macrophages, inhibiting the expression of CD16, CD32, CD86, IL-1b, TNF-a and blocking NLRP3 inflammasome activation). However, this effect can be abolished by NLRP3 inflammasome antagonist MCC950. In vitro experiment confirmed that TRPV1 activated NLRP3 inflammasome by increasing intracellular calcium levels. In conclusion, TRPV1 mediates EBI after SAH via calcium/NLRP3, and TRPV1 is a potential therapeutic target after SAH.
Ethiopic Characters Recognition Model using Deep Learning
Authors: Addis Maru Tesfaye
Published: June 2022

Purpose: - Many approaches have been developed to recognize different writing scripts, most of which focus on Latin scripts. However, in the Ethiopic script unavailability of readymade datasets and the attempts of a few studies show that the script requires further investigation by applying different recognition techniques. In addition, image quality degradation and numerous characters in the alphabet are other major problems with Ethiopic-script documents. In this study, a convolutional neural network-based character recognition model for Ethiopic character recognition is proposed. The contribution of this work is the development of a character recognition model using a convolutional neural network.Method: - The model is designed using seven convolutional layers, four max-pooling layers, and two fully connected layers. Automatic features are extracted from each cropped 28 by 28 images using convolutional and max-pooling layers to prepare for recognition. Results: - The proposed model is trained and tested with customized datasets and achievement of accuracy 97%, which is a promising recognition result of the script.Conclusion: - In future works, the dataset should include all the letters, punctuation marks, and symbols found in Ethiopic scripts for both printed and handwritten text and increase the dataset size for different deep learning algorithms to get better results.
Assessment of soil quality across differently aged, naturally recovered old crop fields and natural sites in a Grassland biome
Authors: Coetzer Willem G. , Coetzer Kayleigh
Published: June 2022

Cropland abandonment for natural recovery has increase globally over the las few decades. Changing land-use practices in South Africa, has led to an increased rate of cropland abandonment. The rate and magnitude of soil quality recovery following abandonment varies from location to location. Several soil quality studies have been conducted in the Eastern Cape Province of South Africa, mainly focusing on the impact of different cropping strategies on soil quality or the effect of different grazing practices on soil quality. Only a few studies on the effect of cropland abandonment and soil quality have been performed. We, therefore, aimed to assess the change in soil quality of differently aged, recovering old crop fields compared to the surrounding natural veld. The study site is located in the Winterberg Mountains of the Eastern Cape, South Africa. Soil characteristics, including soil water-holding capacity, density, pH, total dissolved solids and electrical conductivity, C %, N %, C stock, N stock, as well as sand, silt clay composition was assessed for three recovering old crop fields. Samples from the surrounding natural habitat were also included for comparison. Significant positive change in soil water-holding capacity (WHC), C %, N %, C stock and N stock were observed with increased age since abandonment. It is clear from our results that soil recovery is taking place, with the older former crop field most closely resembling the natural habitat. It will, however, still take a significant amount of time for total recovery to be achieved. Continuous monitoring of old crop fields in agricultural, as well as, formally protected areas is needed to fully understand the long-term effects of cropping on soil quality in this region. Significance • Cropland abandonment is a global occurrence, with old croplands allowed to recover to a natural state. • The effect of old cropland abandonment on soil quality in the Eastern Cape Province of South Africa is not well studied. • No significant differences in pH and electrical conductivity was observed between differently aged old crop fields, but an increase in water-holding capacity, % soil N and % soil C was observed with increase old crop field abandonment age. • These results contribute to the limiting amount of data on soil physical characteristics natural recovery of old crop fields in the Eastern Cape of South Africa
Computerized text and voice analysis - a quantitative single case study of seven chronically schizophrenic patients in art therapy
Authors: Sprotte Yvonne
Published: June 2022

This explorative study of chronic schizophrenic patients aims to clarify whether group art therapy followed by a therapist-guided picture review could influence the patients' communication behavior. Characteristics of voice and speech were obtained via objective technological instruments and selected as indicators of communication behavior. Seven patients were recruited to participate in weekly group art therapy over a period of six months. Three days after each group meeting, they talked about their last picture during a standardized interview that was digitally recorded. The audio documents were evaluated using validated computer-assisted procedures, the transcribed texts using the German version of LIWC2015, and the voices using the audio analysis software VocEmoApI. The dual methodological approach was intended to form an internal control of the study results. An exploratory factor analysis of the complete sets of output parameters was carried out in the expectation of obtaining disease typical characteristics in speech and voice that map barriers to communication. The parameters of both methods were thus processed into five factors each, i.e., into a quantitative digitized classification of the texts and voices. The scores of the factors were subjected to a linear regression analysis to capture possible process-related changes. Most patients continued to participate in the study. This resulted in high quality data sets for statistical analysis. In answer to the study question, two results were summarized: A text analysis factor called presence proved a potential surrogate parameter for positive language development. Quantitative changes in vocal emotional factors were detected, demonstrating differentiated activation patterns of emotions. These results can presumably be interpreted as an expression of a cathartic healing process. The methods presented in this study make a potentially significant contribution to quantitative research into the effectiveness and mode of action of art therapy. Trial Registration: ISRCTN12365070 Acronym: Linguistic and Voice inquiry of patients talking about their own Pictures (LiVoPict)
Damage Constitutive and Failure Prediction of Artificial Single-Joint Sandstone Based on Acoustic Emission
Authors: Sun Bing , Yang Haowei , Zeng Sheng , Luo Yu
Published: June 2022

The effect law of deformation and failure of a jointed rock mass is essential for underground engineering safety and stability evaluation. In order to study the evolution mechanism and precursory characteristics of instability and failure of jointed rock masses, uniaxial compression and acoustic emission (AE) tests are conducted on sandstones with different joint dip angles. To simulate the mechanical behavior of the rock, a jointed rock mass damage constitutive model with AE characteristic parameters is created based on damage mechanics theory and taking into account the effect of rock mass structure and load coupling. To quantify the mechanism of rock instability, a cusp catastrophe model with AE characteristic parameters is created based on catastrophe theory. The results indicate that when the joint dip angle increases from 0° to 90°, the failure mechanism of sandstone shifts from tensile to shear, with 45° being the critical failure mode. Sandstone's compressive strength reduces initially and subsequently increases, resulting in a U-shaped distribution. The developed damage constitutive model's theoretical curve closely matches the test curve, indicating that the model can reasonably describe the damage evolution of sandstone. The cusp catastrophe model has a high forecast accuracy, and when combined with the damage constitutive model, the prediction accuracy can be increased further. The research results can provide theoretical guidance for the safety and stability evaluation of underground engineering.
whiteness
Authors: Spatz Ben , Erçin Nazlıhan Eda , Krawczyk Ilona , Mendel Agnieszka
Published: June 2022

This “illuminated” video essay works through the juxtaposition of textual and audiovisual material to interrogate the cultural and philosophical whiteness of bodies and institutions. It demonstrates a reciprocal and circular relationship between textuality and audiovisuality insofar as the documented practice responds to a textual object — a physical copy of Giorgio Agamben’s book The Open: Man and Animal — while another layer of critical poetic text interrupts, critiques, analyzes, and illuminates the video. Agamben’s treatment of Heidegger is taken as a reference point to deconstruct the racialized human/animal binary, while the productively ambiguous perspective on whiteness found in contemporary Black studies and critical race theory is invoked as a possible alternative. At the same time, the tactile and sensory qualities of the documented practice — hovering between song and speech, gesture and action — emphasize the embodied, material, and affective dimensions of both whiteness and our attempts to escape it. The video asks: Can the white body be decolonized without killing it? Its multimedial form implies that answers to such a question can only be found through forms of thought that displace the tyranny of writing, or logocentrism, as is also suggested by Fred Moten in the video’s closing epigraph.
being surface
Authors: Zacharopoulou Despina
Published: June 2022

This paper problematizes the ways in which performance art might be philosophy, and vice versa, that is; how philosophy might operate as embodied praxis and method. The main hypothesis adopted is based on the argument that philosophy, though predominantly thought of as a rational ideological construction, is essentially an invitation towards change and a method on how to lead one’s life (Hadot 2001, 148). This position has been stressed by philosophers Pierre Hadot and Michel Foucault, who revisited ancient Greek philosophy in order to indicate how corporeal practices and techniques might operate as methodologies towards "new forms of life" (Rabinow 2000, 164). Foucault was particularly interested in the Cynics because of their visceral approach to philosophy as expressed by their "radical asceticism" (Foucault 2011, 167), that stood as an indication for a life which is radically other (Foucault 2011, 269-270). It is in that respect that one should also look at Foucault’s engagement with the gay leather scene; as a laboratory (Rabinow 2000, 151) towards a  "[...] possibility for creative life" (Rabinow 2000, 163). In light of the above, this paper discusses Despina Zacharopoulou's performance works in order to investigate how performance strategies related to violence might suggest a radical re-thinking and revisiting of philosophy as embodied practice and method towards a life-as-surface, that is; a life experienced in its full intensity and in pure joy.
OGUZ KAGAN DESTANI’NA GÖRE HİNDİSTAN’IN KUZEYİ
Authors: GÖMEÇ Saadettin Yağmur , FİDAN Ayşe Gül
Published: June 2022

Bilindiği üzere Hindistan kıtası dünyanın en eski topraklarından birisidir ve burada tarih boyunca çok çeşitli halklar barınmıştır. Hindistan zengin yeraltı ve yerüstü kaynaklarına sahip bulunması itibarıyla Türklerin de dikkatini çekmiştir. Bilhassa bu toprakların kuzey tarafları Türkler açısından cazibe merkezi olmuş, buna binaen de değişik Türk sülaleleri bu memlekette uzun yıllar hâkimiyet sürmüştür. Durum böyle olunca ta Hunlar çağından beri Hindistan kıtasında Türk izlerine rastlamaktayız. Ak Hun-Avar, Kök Türk, Gazneli, Delhi Türk Sultanları, Harezmşahlı, Temürlü ve Baburlü gibi hanedanlar bu topraklarda söz sahibi oldular. İşte bu Türk iktidarlarının izleri bir şekilde Oguz Kagan Destanı’nda yer bulmuş ve meşhur Oguz ile çocukları kanalıyla Türkler destani çağlardan itibaren burasıyla ilgilenmiştir.
Synthesis and Evaluation of Antibacterial Activity of 1,2,3-Triazole and Ether Derivatives of Paeonol
Authors: Figueroa Laura , dos Santos Nayara , Santiago Pedro , Romão Wanderson , Lacerda Junior Valdemar , Ellena Javier , Micheletti Ana , Borges Warley
Published: June 2022

Multi-drug-resistant bacteria (MDR) are the cause of different infections and diseases that have affected humanity for a long time, and have been an emerging global health problem that has led to increased morbidity and mortality. The growing emergence of MDR bacteria has underlined the need for development and discovery of new antibacterial compounds. In this context, a series of new paeonol 1,2,3-triazole and ether derivatives were synthesized using copper(I)-catalyzed azide-alkyne cycloaddition (CuAAC) reaction and nucleophilic substitution. Paeonol has been a natural product widely studied due to its many biological activities, as well as its derivatives. Three ether derivatives (two unpublished) and ten triazole derivatives (six unpublished) of paeonol were obtained, which were determined by nuclear magnetic resonance (NMR), Fourier transform infrared spectrometry (FTIR), Fourier-transform ion cyclotron resonance mass spectrometry (FT-ICR MS) and six of them by X-rays, which is the first study of this type presented for these compounds. All the synthesized compounds were evaluated as antibacterial agents against Staphylococcus aureus and Escherichia coli, obtaining a minimum inhibitory concentration (MIC) above 100 µg mL-1. The results showed that CuAAC and nucleophilic substitution were very useful to obtain new paeonol triazole and ether derivatives and the products were obtained in yields from 21.3 to 98.5%. The advantages of these reactions (high yield in most compounds, reaction time, low impurities) show that using the method to produce new derivatives is advisable thus assisting in the discovery of new potential bioactive compounds.
Experimental optimization of enzymatic and thermochemical pretreatments of bread waste by central composite design study for bioethanol production
Authors: Kahlouche Fatima Zohra , Zerrouki Souhaib , Bouhelassa Mohammed , Rihani Rachida
Published: June 2022

The present study aimed at optimizing the combined effect of enzymatic and thermo-chemical pretreatment hydrolysis of bread waste (BW) for enhancing the yield of reducing sugars (RS). Statistical optimization of enzymatic and thermochemical pretreatment processes was performed using the central composite design (CCD) tool of response surface methodology (RSM) using four process parameters (waste bread ratio, alpha-amylase concentration, temperature and pH) on total sugars yield as response variable. It was found that the optimal conditions for maximally RS yield were at bread ratio of 0.03 g/mL, alpha-amylase concentration of 0.2 mL/L, temperature of 100 °C and pH 5.3. Under these conditions, the yield of RS reached 90%, with bioethanol concentration of about 85.8 g/L after 72 h of batch fermentation. The modified Gompertz equation was used to describe the cumulative bioethanol production. A good agreement was found between simulated and experimental data.
Assessing the impact of micropollutant mitigation measures using vertical flow constructed wetlands for municipal wastewater catchments in the greater region: a reference case for rural areas
Authors: Venditti Silvia , Kiesch Anne , Brunhoferova Hana , Schlienz Markus , Knerr Henning , Dittmer Ulrich , Hansen Joachim
Published: June 2022

The present research aims at giving an approach to the issue of surface water contamination due to micropollutants in rural areas. The catchment of the Sûre river was selected as a reference case for the Greater Region, characterized mainly by settlements with low population density, small water bodies and small- to medium-sized wastewater treatment plants (WWTPs). For these WWTPs, conventional technical solutions for micropollutant elimination are not suitable; therefore, an adapted mitigation strategy is needed to prevent the impact of micropollutants, especially during the dry season. As a suitable alternative to more intensive technologies, Constructed Wetlands (CW) in Vertical Flow (VF) configuration have been successfully tested over a 1-year period and the elimination rate of 27 micropollutants was quantified. Emission reduction by VF was then considered in a static mass balance model that calculates the longitudinal concentration profile for the entire river catchment. The EmiSûre approach, which focuses on river quality (concentrations of pollutants) instead of emitted loads, effectively allowed simulation of adopted measures a priori and resulted in efficient support for decision-makers with WWTP upgrade scenarios.
Approaches to Address PK-PD Challenges of Conventional Liposome Formulation
with Special Reference to Cancer, Alzheimer's, Diabetes, and Glaucoma: An Update
on Modified Liposomal Drug Delivery System
Authors: Kesharwani Payal , Kumari Kajal , Gururani Ritika , Jain Smita , Sharma Swapnil
Published: June 2022

Liposomes nowadays have become a preferential drug delivery system since they provide facilitating
properties to drugs, such as improved therapeutic index of encapsulated drug, target and controlled drug delivery, and
less toxicity. However, conventional liposomes have shown some disadvantages, such as less drug loading capacity,
poor retention, clearance by kidney or reticuloendothelial system, and less release of hydrophilic drugs. Thus, to
overcome these disadvantages recently, scientists have explored new approaches and methods, viz., ligand conjugation,
polymer coating, and liposome hybrids, including surface-modified liposomes, biopolymer-incorporated liposomes,
guest-in-cyclodextrin-in-liposome, liposome-in-hydrogel, liposome-in-film, liposome-in-nanofiber, etc. These
approaches have been shown to improve the physiochemical and pharmacokinetic properties of encapsulated drugs.
Lately, pharmacokinetic-pharmacodynamic (PK-PD) computational modeling has emerged as a beneficial tool for
analyzing the impact of formulation and system-specific factors on the target disposition and therapeutic efficacy of
liposomal drugs. There has been an increasing number of liposome-based therapeutic drugs, both FDA approved and
those undergoing clinical trials, having application in cancer, Alzheimer's, diabetes, and glaucoma. To meet the continuous
demand of health sectors and to produce the desired product, it is important to perform pharmacokinetic
studies. This review focuses on the physical, physicochemical, and chemical factors of drugs that influence the target
delivery of drugs. It also explains various physiological barriers, such as systemic clearance and extravasation. A novel
approach, liposomal-hybrid complex, an innovative approach as a vesicular drug delivery system to overcome limited
membrane permeability and bioavailability, has been discussed in the review. Moreover, this review highlights the
pharmacokinetic considerations and challenges of poorly absorbed drugs along with the applications of a liposomal
delivery system in improving PKPD in various diseases, such as cancer, Alzheimer's, diabetes, and glaucoma.
Can In-house HIV-2 Viral Load Assay be a Reliable Alternative to Commercial
Assays for Clinical and Therapeutic Monitoring?
Authors: Kannangai Rajesh , Ramalingam Veena Vadhini , Fletcher Gnanadurai John , Kasirajan Anand , Demosthenes John Paul , Rupali Priscilla , Varghese George Mannil , Pulimood Susanne Alexander , Rebekah Grace
Published: June 2022

Background:

Currently, there is a global contemplation to end the AIDS epidemic by
2030. HIV-2 poses unique challenges to this end. The burden of HIV-2 is higher in resource-limited
countries, and it is intrinsically resistant to NNRTI drugs. In addition, there is no FDA-approved
plasma viral load assay to monitor disease progression and therapeutic efficacy. To overcome these
challenges, we have developed and evaluated an in-house quantitative HIV-2 viral load assay.

Methods:

Blood samples were collected from 28 HIV-2 treatment-naïve monoinfected individuals
and tested using an in-house qPCR HIV-2 viral load assay. The extracted RNA was amplified using
Quantifast pathogen + IC kit.

Results:

The in-house qPCR has a limit of detection of 695 copies/ml. The intra- and inter-assay
variation (% CV) of the assay was 0.61 and 0.95, respectively. The in-house assay quantified HIV-2
NIBSC accurately (1000 IU) with a mean of 1952 copies/mL. Among the 28 samples tested by
in-house qPCR assay, 11 (39.2%) samples were quantified, whereas 17 (60.7%) samples were not
detected. In comparison with Altona RealStar HIV-2 RT PCR and Exavir Load RT assay, the results
were 96.4% and 69.6% concordant, respectively. No significant (p = 0.99 and p = 0.13) difference
in quantifying viral load between the three assays. Based on clinical and immunological (CD4)
staging, the performance characteristics were comparable.

Conclusion:

To the best of our knowledge, this is the first in-house qPCR developed in India. The
performance characteristics of the in-house assay are comparable to the commercial assays, and
they can be used assertively to monitor HIV-2 patients.
Regulation of Exosomes-Mediated circNR4A1 on Chemoresistance and
Biological Effects of Oral Squamous Cell Carcinoma Cells
Authors: Dong Yang , Zhang Lei , Chang Huaiguang
Published: June 2022

Introduction:

The current study aimed to construct a circNR4A1 loaded exosome (EXO) nano
system for the treatment of oral squamous cell carcinoma (OSCC) and elucidate the related regulation
mechanism in chemoresistance and tumor biology.

Methods:

Exosomes were isolated from the HEK293 cells by the ultracentrifugation method. Then, the
purified nanoproduction was characterized and identified by transmission electron microscopy, dynamic
light scattering, and Western blot. The hydrophobic circNR4A1 was then loaded into exosomes by the coincubation method. The effects of circNR4A1 on chemotherapy and apoptosis were evaluated in three multiresistant OSCC cell lines.

Results:

The range of size distribution of the exosomes was found to be 40-170 nm. Positive TSG101 and
CD63 expressions were observed, and the expression of calnexin was negative. In the cisplatin group,
circNR4A1 could sensitize 67% of cell lines, while circNR4A1-EXO could sensitize 100% of cell lines.
In the 5FU group, circNR4A1 could only sensitize 33% of cell lines, while circNR4A1-EXO could sensitize
67% of cell lines. circNR4A1-EXO is involved in multiple signaling pathways, which can not only
activate K-RAS/ERK and MDR-1 signaling pathways but activate DNMT-1 gene expression simultaneously.

Conclusion:

circNR4A1-EXO can increase the sensitivity of OSCC to anticancer drugs, which may be
due to the regulation of the K-RAS/ERK and p53 signaling pathway.
Nerves of the Thorax: Anatomy, Clinical Signs, and Imaging Findings of
Pathological Conditions
Authors: Durhan Gamze , Düzgün Selin Ardalı , Öcal Osman , Arıyürek Orhan Macit
Published: June 2022

Background:

Radiological diagnosis of thoracic nerve diseases is difficult because they are rare and nerves cannot be seen directly on radiological images. The major nerves of the thorax can be listed as the phrenic, vagus, recurrent laryngeal, long thoracic nerve pairs, sympathetic chains, costal nerves, and brachial plexus. Diseases of thoracic nerves have various causes including traumatic injury, neuromuscular diseases, infection, compression, radiation, drugs, and tumors.

Objective:

The aim of this pictorial review is to describe the anatomic locations of the major thoracic nerves on radiological images, comprehensively describe the causes of thoracic nerve diseases and to define the clinical signs, and primary and secondary imaging findings of dysfunction of the thoracic nerves.

Methods:

This paper was designed to illustrate primary and secondary imaging findings of nerve diseases. Firstly, normal anatomy of nerves is shown with diagrams. Secondly, we explained primary and secondary imaging features with variable radiological methods including chest X-Ray, magnetic resonance imaging, computed tomography.

Conclusion:

Primary findings of nerve diseases can be detected if radiologists are familiar with the courses of the nerves on radiological images. Knowledge of the normal functions of the nerves can aid in the diagnosis of thoracic nerve diseases identified from secondary imaging findings such as diaphragmatic elevation, muscular atrophy, and winged scapula. It is essential to know the normal anatomy, function, and possible causes of thoracic nerve diseases to be able to make a correct diagnosis and apply prompt treatment.
The Role of Growth Factor Delivery Systems on Cellular Activities of Dental
Stem Cells: A Systematic Review (Part II)
Authors: Shamszadeh Sayna , Shirvani Armin , Asgary Saeed
Published: June 2022

Objective:

The current systematic review aims to provide the available ex vivo evidence evaluating
the biological interactions of dental stem cells (DSCs) and growth factor delivery systems.

Methods:

Following the Preferred Reporting Items for a Systematic Reviews and Meta-Analyses (PRISMA)
guidelines, systematic search was conducted in the electronic databases (PubMed/Medline, Scopus,
Web of Science, and Google Scholar) up to January 2022. Studies evaluating the biological interactions
of DSCs and growth factor delivery systems were included. The outcome measures were cell cytocompatibility,
mineralization, and differentiation.

Results:

Sixteen studies were selected for the qualitative synthesis. The following growth factor delivery
systems exhibit adequate cytocompatibility, enhanced mineralization, and osteo/odontoblast differentiation
potential of DSCs: 1) Fibroblast growth factor (FGF-2)-loaded-microsphere and silk fibroin, 2) Bone morphogenic
protein-2 (BMP-2)-loaded-microsphere and mesoporous calcium silicate scaffold, 3) Transforming
growth factor Beta 1 (TGF-ß1)-loaded-microsphere, glass ionomer cement (GIC), Bio-GIC and liposome, 4)
TGF-ß1-loaded-nanoparticles/scaffold, 5) Vascular endothelial growth factor (VEGF)-loaded-fiber and hydrogel,
6) TGF-ß1/VEGF-loaded-nanocrystalline calcium sulfate/hydroxyapatite/calcium sulfate, 7) Epidermal
growth factor-loaded- nanosphere, 8) Stem cell factor/DSCs-loaded-hydrogel and Silk fibroin, 9)
VEGF/BMP-2/DSCs-loaded-Three-dimensional matrix, 10) VEGF/DSCs-loaded-microsphere/hydrogel,
and 11) BMP-2/DSCs and VEGF/DSCs-loaded-Collagen matrices. The included delivery systems
showed viability, except for Bio-GIC on day 3. The choice of specific growth factors and delivery systems
(i.e., BMP-2-loaded-microsphere and VEGF-loaded-hydrogel) resulted in a greater gene expression.

Conclusions:

This study, with low-level evidence obtained from ex vivo studies, suggests that growth
factor delivery systems induce cell proliferation, mineralization, and differentiation toward a therapeutic
potential in regenerative endodontics.
Insights into the Association of Chronic Kidney Disease (CKD) and Cardiovascular Risk Among Diabetic vs Non-Diabetic Patients
Authors: Singh Akashkumar N , Swathi Tatineni
Published: June 2022

Diabetic patients with chronic kidney disease have a high risk of developing cardiovascular
disease-related mortality and morbidity compared to non-diabetic chronic kidney disease
patients. The Majority of chronic kidney disease patients with diabetes remain undiagnosed and
have a higher incidence of cardiovascular comorbidities even when they do not progress to endstage
renal failure. Both traditional cardiovascular risk factors and non-traditional cardiovascular
risk factors are known to be present in a higher magnitude in diabetic patients with chronic kidney
disease and are known to partially account for the increased incidence of cardiovascular disease
compared to non-diabetic chronic kidney disease patients. Moreover, there is no definitive evidence
for potential therapeutic treatment options for cardiovascular disease among diabetic patients
with chronic kidney disease, as these patients have often not been included in major cardiovascular
trials. Therefore, there is a need to recognize diabetic patients with chronic kidney disease
patients having a high cardiovascular disease risk for definite and immediate medical attention at
an individual patient level. Increased awareness, timely diagnosis, and intervention with respect to
control these plays a pivotal role in avoiding undesirable cardiovascular disease events and lead to
improved treatment outcomes among these patients. Further research is warranted to understand
the risk factors for cardiovascular disease and to develop and implement preventive and treatment
strategies to decrease the high morbidity and mortality among diabetic patients with chronic kidney
disease. This review summarizes the available epidemiological data, and risk factors, discusses
clinical presentations, and suggests prevention and management strategies for cardiovascular disease
risk among diabetic patients with chronic kidney disease.
Selective Inhibition of Soluble TNF using XPro1595 Improves Hippocampal
Pathology to Promote Improved Neurological Recovery Following
Traumatic Brain Injury in Mice
Authors: Larson Katelyn , Damon Melissa , Randhi Rajasa , Nixon-Lee Nancy , Dixon Kirsty J.
Published: June 2022

Aims:

To determine the efficacy of XPro1595 to improve pathophysiological and functional
outcomes in a mouse model of traumatic brain injury (TBI).

Background:

Symptoms associated with TBI can be debilitating, and treatment without off-target side
effects remains a challenge. This study aimed to investigate the efficacy of selectively inhibiting the
soluble form of TNF (solTNF) using the biologic XPro1595 in a mouse model of TBI.

Objectives:

Use XPro1595 to determine whether injury-induced solTNF promotes hippocampal inflammation
and dendritic plasticity and associated functional impairments.

Methods:

Mild-to-moderate traumatic brain injury (CCI model) was induced in adult male C57Bl/6J
WT and Thy1-YFPH mice, with XPro1595 (10 mg/kg, S.C.) or vehicle being administered in a clinically
relevant window (60 minutes post-injury). The animals were assessed for differences in neurological
function, and hippocampal tissue was analyzed for inflammation and glial reactivity, as well as
neuronal degeneration and plasticity.

Results:

We report that unilateral CCI over the right parietal cortex in mice promoted deficits in learning
and memory, depressive-like behavior, and neuropathic pain. Using immunohistochemical and
Western blotting techniques, we observed the cortical injury promoted a set of expected pathophysiology’s
within the hippocampus consistent with the observed neurological outcomes, including glial reactivity,
enhanced neuronal dendritic degeneration (dendritic beading), and reduced synaptic plasticity
(spine density and PSD-95 expression) within the DG and CA1 region of the hippocampus, that were
prevented in mice treated with XPro1595.

Conclusion:

Overall, we observed that selectively inhibiting solTNF using XPro1595 improved the
pathophysiological and neurological sequelae of brain-injured mice, which provides support for its use
in patients with TBI.
Chemical Composition and Antioxidant, Anti-Inflammatory and Neuroprotective
Properties of Hexane Extracts from the Roots of Centaurea
acaulis and Centaurea pullata
Authors: Benhamidat Lyna , Dib Mohammed El Amine , Bensaid Okkacha , Keniche Assia , ouar Ibtisem El , Muselli Alain
Published: June 2022

Background:

In herbal medicine, Centaurea is used in the treatment of many diseases such
as dizziness, headaches, etc. It also reduces inflammatory pain and is used to treat liver diseases. The
roots of Centaurea acaulis and Centaurea pullata have not yet been studied for biological properties

Objective:

The aim of this research was to evaluate the chemical composition and the antiinflammatory, antioxidant and neuroprotective properties of hexane extracts of Centaurea acaulis and
Centaurea pullata roots, and their major component, aplotaxene.

Methods:

The hexane extract was prepared by the maceration process and identified by GC and GCMS. Aplotaxene was isolated by flash chromatography. The antioxidant activity was assessed using 2,2-
diphenyl 1-picrylhydrazyle DPPH, the β-carotene bleaching, and Ferric Reducing Antioxidant Power
(FRAP) methods. The anti-inflammatory effect was assessed by egg albumin denaturation assay and the
neuroprotective activity was assessed against acetyl cholinesterase (AChE) and Butyrylcholinesterase
(BChE).

Results:

The chemical composition of hexane extract of Centaurea pullata was mainly represented by
non-terpenic compounds such as Aplotaxene (80.3%), while, hexane extract of Centaurea acaulis was
characterized by high levels of Aplotaxene (56.9%), 9-oxabicyclo(6,1,0)nonane (9.2%), Caryophyllene
oxide (8.3%) and Isocaryophyllene (6.0%). The hexane extracts of the two Centaurea showed very
good antioxidant activities with all three methods. Aplotaxene has shown excellent antioxidant activity
compared to Butylated hydroxytoluene (BHT) and ascorbic acid. Centaurea acaulis hexane extract
showed very high anti-inflammatory activity with an IC50 of 0.76 mg/L in the egg albumin denaturation
test compared to diclofenac (IC50 of 1.01 mg/L). The extract of Centaurea pullata and Aplotaxene
showed an interesting anti-inflammatory activity with IC50s of 1.72 and 1.36 mg/L, but which remains
lower than that of diclofenac sodium. The neuroprotective activity of Centurea pullata and Centaurea
acaulis extracts, and Aplotaxene did not show inhibition against AChE, whereas they inhibited BChE
with IC50 values of 92.3, 583, and 81.5 mg/L, respectively.

Conclusion:

Further analysis is still needed to further demonstrate the biological efficacy of Centaurea
acaulis and Centaurea pullata extracts and Aplotaxene.
Estimating COVID-19 Cases Using Machine Learning Regression Algorithms
Authors: Yadav Vikash , Deshwal Vaishali , Kumar Vimal , Shukla Rati
Published: June 2022

Background:

Coronavirus refers to a large group of RNA viruses that infects the respiratory
tract in humans and also causes diseases in birds and mammals. SARS-CoV-2 gives rise to the
infectious disease “COVID-19”. In March 2020, coronavirus was declared a pandemic by the WHO.
The transmission rate of COVID-19 has been increasing rapidly; thus, it becomes indispensable to
estimate the number of confirmed infected cases in the future.

Objective:

The study aims to forecast coronavirus cases using three ML algorithms, viz., support
vector regression (SVR), polynomial regression (PR), and Bayesian ridge regression (BRR).

Methods:

There are several ML algorithms like decision tree, K-nearest neighbor algorithm, Random
forest, neural networks, and Naïve Bayes, but we have chosen PR, SVR, and BRR as they have
many advantages in comparison to other algorithms. SVM is a widely used supervised ML algorithm
developed by Vapnik and Cortes in 1990. It is used for both classification and regression. PR
is known as a particular case of Multiple Linear Regression in Machine Learning. It models the relationship
between an independent and dependent variable as nth degree polynomial.

Results:

In this study, we have predicted the number of infected confirmed cases using three ML
algorithms, viz. SVR, PR, and BRR. We have assumed that there are no precautionary measures in
place.

Conclusion:

In this paper, predictions are made for the upcoming number of infected confirmed
cases by analyzing datasets containing information about the day-wise past confirmed cases using
ML models (SVR, PR and BRR). According to this paper, as compared to SVR and PR, BRR performed
far better in the future forecasting of the infected confirmed cases owing to coronavirus.