bluuebunny/crossref_metadata_2025 huggingface dataset:
Tracking Development Assistance for Health: A Comparative Study of the 29 Development Assistance Committee Countries, 2011–2019
Authors: Nomura Shuhei , Sakamoto Haruka , Ishizuka Aya , Shibuya Kenji
Published: August 2021

Development assistance for health (DAH) is an important part of financing healthcare in low- and middle-income countries. We estimated the gross disbursement of DAH of the 29 Development Assistance Committee (DAC) member countries of the Organisation for Economic Co-operation and Development (OECD) for 2011–2019; and clarified its flows, including aid type, channel, target region, and target health focus area. Data from the OECD iLibrary were used. The DAH definition was based on the OECD sector classification. For core funding to non-health-specific multilateral agencies, we estimated DAH and its flows based on the OECD methodology for calculating imputed multilateral official development assistance (ODA). The total amount of DAH for all countries combined was 18.5 billion USD in 2019, at 17.4 USD per capita, with the 2011–2019 average of 19.7 billion USD. The average share of DAH in ODA for the 29 countries was about 7.9% in 2019. Between 2011 and 2019, most DAC countries allocated approximately 60% of their DAH to primary health care, with the remaining 40% allocated to health system strengthening. We expect that the estimates of this study will help DAC member countries strategize future DAH wisely, efficiently, and effectively while ensuring transparency.
The Management of the Cotyledonoid Leiomyoma of the Uterus: A Narrative Review of the Literature
Authors: Buonomo Francesca , Bussolaro Sofia , Fiorillo Clarice de Almeida , Giorda Giorgio , Romano Federico , Biffi Stefania , Ricci Giuseppe
Published: August 2021

Cotyledonoid leiomyoma is an unusual uterine myoma due to some ultrasound features that mimic a malignant lesion facilitating the choice of radical surgery. This study aims to summarize the ultrasound and the magnetic resonance imaging aspects of this atypical lesion, and also discuss surgical treatment and pathological exam. It included all English case reports or case series until August 2021 found through PubMed, Google Scholar, and Scopus. A total of 94 cotyledonoid leiomyomas were reported, with a median tumor size of 12 cm. The typical ultrasound image is characterized by a large solid heterogeneous mass, with high vascularity, no shadowing, and indistinct margins within the myometrium. Magnetic resonance imaging shows the presence of merging isointense nodules to the myometrium in T1-weighted images, hyperintense in T2-weighted images, and contrast agent enhancement. Surgical treatment consists of hysterectomy (75 cases, 80%) or myomectomy (19 cases, 20%), without evidence of recurrence if complete. The placenta-like appearance observed during surgery supports this rare fibroid hypothesis. The intraoperative frozen section can be considered. Microscopically, no atypical cells, signs of mitotic activity or cell necrosis are found. To conclude, some preoperative and intraoperative aspects of this lesion are distinctive and may lead surgeons to opt for conservative surgery.
Assessing Emotional Responses to the Spatial Quality of Urban Green Spaces through Self-Report and Face Recognition Measures
Authors: Qiao Lin , Zhuang Jingwei , Zhang Xuan , Su Yang , Xia Yiping
Published: August 2021

Although creating a high-quality urban green space (UGS) is of considerable importance in public health, few studies have used individuals’ emotions to evaluate the UGS quality. This study aims to conduct a multidimensional emotional assessment method of UGS from the perspective of spatial quality. Panoramic videos of 15 scenes in the West Lake Scenic Area were displayed to 34 participants. For each scene, 12 attributes regarding spatial quality were quantified, including perceived plant attributes, spatial structure attributes, and experiences of UGS. Then, the Self-Assessment-Manikin (SAM) scale and face recognition model were used to measure people’s valence-arousal emotion values. Among all the predictors, the percentages of water and plants were the most predictive indicators of emotional responses measured by SAM scale, while the interpretation rate of the model measured by face recognition was insufficiently high. Concerning gender differences, women experienced a significantly higher valence than men. Higher percentages of water and plants, larger sizes, approximate shape index, and lower canopy densities were often related to positive emotions. Hence, designers must consider all structural attributes of green spaces, as well as enrich visual perception and provide various activities while creating a UGS. In addition, we suggest combining both physiological and psychological methods to assess emotional responses in future studies. Because the face recognition model can provide objective measurement of emotional responses, and the self-report questionnaire is much easier to administer and can be used as a supplement.
Diabetes Related Distress in Children with Type 1 Diabetes before and during the COVID-19 Lockdown in Spring 2020
Authors: Mianowska Beata , Fedorczak Anna , Michalak Arkadiusz , Pokora Weronika , Barańska-Nowicka Inga , Wilczyńska Monika , Szadkowska Agnieszka
Published: August 2021

Our aim was to compere diabetes-related distress (DD) in young patients with type 1 diabetes mellitus (T1DM) and in their parents before and during the national COVID-19-related lockdown when schools operated on-line. Problems Areas in Diabetes-Child (PAID-Ch), Teen (PAID-T) and Parent (P-PAID-Ch, P-PAID-T) questionnaires in paper version were used to evaluate DD before COVID-19 pandemic (November 2019–February 2020) and during the lockdown (April 2020) the same surveys were performed by phone. We enrolled 76 patients (median age (Q1–Q3): 13.6 (11.8–15.2) years; 21 children, 55 adolescents; T1DM duration 3.7 (1.7–6.8) years). Initial PAID score was lower in teenage boys than in girls (34.0 (24.0–42.0) vs. 44.5 (40.0–50.5), p = 0.003). In teens PAID score decreased significantly during the lockdown (−3.0 (−11.0–3.0), p = 0.018), more in girls than boys (p = 0.028). In children (−3.0 (−14.0–7.0), p = 0.131) and parents PAID did not change (teens’ parents: 3.0 (−9.0–10.0), p = 0.376; children’s parents: −5.0 [−9.0–1.0], p = 0.227). In the studied group COVID-19 pandemic-related lockdown was associated with decrease in DD in teens with T1DM, particularly in girls, while no significant change in DD was observed in children or parents. DD decrease in teens during the pandemic should attract attention to the potential “rebound” of DD related to return to regular on-site school routine.
Environmental Factors Affecting Cognitive Function among Community-Dwelling Older Adults: A Longitudinal Study
Authors: Motohiro Atsushi , Abe Takafumi , Okuyama Kenta , Onoda Keiichi , Ito Tomoko , Isomura Minoru , Nabika Toru , Kumakura Shunichi
Published: August 2021

Although neighborhood environmental factors have been found to be associated with cognitive decline, few longitudinal studies have focused on their effect on older adults living in rural areas. This longitudinal study aimed to investigate the role of neighborhood environmental factors in cognitive decline among rural older adults. The data of 485 older adults aged ≥60 years who were living in Unnan City in Japan and had participated in two surveys conducted between 2014 and 2018 were analyzed. Cognitive function was assessed using the Cognitive Assessment for Dementia, iPad version 2. Elevation, hilliness, residential density, and proximity to a community center were determined using geographic information system. We applied a generalized estimating equation with odds ratios (OR) and 95% confidence intervals (CIs) of cognitive decline in the quartiles of neighborhood environmental factors. A total of 56 (11.6%) participants demonstrated a decrease in cognitive function at follow up. Elevation (adjusted OR 2.58, 95% CI (1.39, 4.77) for Q4 vs. Q1) and hilliness (adjusted OR 1.93, 95% CI (1.03, 3.63) for Q4 vs. Q1) were associated with a higher likelihood of cognitive decline. The second quartiles of residential density showed significantly lower likelihoods of cognitive decline compared with the first quartiles (adjusted OR 0.36, 95% CI (0.19, 0.71) for Q2 vs. Q1). Thus, an elevated hilly environment and residential density predicted cognitive decline among rural older adults.
Psychometric Validation of the Arabic Fear of Illness and Virus Evaluation
Authors: Tounsi Abrar , Alammar Shahad , Almaflehi Nassr , Bamashmous Mohamed , Al Madani Abdullah , Ibrahim Maria Salem
Published: August 2021

Global infectious pandemics can affect the psychology and behavior of human beings. Several tools were developed to evaluate the psychological impact of such outbreaks. The present study aimed to examine the psychometric properties of the Arabic translated version of Fear of Illness and Virus Evaluation scale (FIVE). FIVE is a 35-item tool consisting of four subscales that measure Fears about Contamination and Illness, Fears about Social Distancing, Behaviors Related to Illness and Virus Fears and Impact of Illness and Virus Fears. The tool was translated into Arabic by using a forward–backward translation. The online questionnaire contained the following sections: demographics, FIVE, Fear of COVID-19 Scale (FCV-19S) and face validity questions. Non-probability convenient sampling technique was used to recruit participants via a mobile instant messaging application. Reliability, concurrent validity, face validity and factor analysis were examined. The data consisted of 509 adult participants who reside in Saudi Arabia. The internal consistency of the Arabic FIVE subscales was high (0.84–0.91) with strong concurrent validity indicated by positive correlations of FIVE subscales with FCV-19S. Factor analysis suggested slightly different factor structures (Fears of Getting Sick, Fears that Others Get Sick, Fears of the Impact on Social Life and Behaviors Related to Illness and Virus Fears). Our data showed a better fit using the proposed structures. The Arabic version of the FIVE showed robust validity and reliability qualities to assess fear of COVID-19 on Arabic adult population.
Modified-Active Release Therapy in Patients with Scapulocostal Syndrome and Masticatory Myofascial Pain: A Stratified-Randomized Controlled Trial
Authors: Kanhachon Wilawan , Boonprakob Yodchai
Published: August 2021

Modified-active release therapy (mART) was developed to treat patients experiencing upper quarter pain. The objective of the study was to determine the effectiveness of the mART in treating pain, promoting function, and measuring emotions in patients with scapulocostal syndrome (SCS) and masticatory myofascial pain (MMP). A stratified-randomized controlled trial was employed in 38 participants separated into two groups. All participants underwent the same series visual analog scale (VAS), pressure pain threshold (PPT), mouth opening (MO), maximum mouth opening (MMO), craniovertebral angle (CV-angle), and pain catastrophizing scale Thai version (PCS-Thai-version) at the baseline. The mART group underwent the mART program three times a week for 4 weeks with a hot pack and an educational briefing while the control group received only a hot pack and the educational briefing. After treatment, both groups showed significant improvement (p < 0.05) in all parameters except MO, MMO, and CV-angle. When comparing outcomes between the groups, the mART group showed a statistically significant greater number of improvements than did the control group. In conclusion, the mART program can improve pain experienced by patients with SCS and MMP and it can be used as an adjuvant technique with conservative treatment.
Hepatitis B and Liver Cancer: Community Awareness, Knowledge and Beliefs of Middle Eastern Migrants in Sydney, Australia
Authors: Robotin Monica C. , Wallace Jack , Gallego Gisselle , George Jacob
Published: August 2021

Chronic hepatitis B (CHB) is a significant global health challenge given an increasing morbidity and inadequate public health response, Migrant populations are primarily affected by CHB in industrialised countries, and while more than 7% of Australians with CHB were born in Africa or the Middle East, little is known of their awareness or knowledge of viral hepatitis and its impact. This qualitative study, using semi-structured interviews with Assyrian and Arabic community leaders and focus groups (FG) with 66 community members sought to identify hepatitis and liver cancer knowledge and awareness among local Arabic and Assyrian-speaking communities in Western Sydney. Interviews were thematically analysed, with findings framing the topics for the FGs which were analysed using a framework analysis. Themes identified across both methods included limited awareness or knowledge of viral hepatitis or liver cancer, stigma associated with both conditions, variable levels of health literacy and trust in medical practitioners, and fear that receiving “bad news” would deter people from seeking care. Preferred sources of health information were family doctors, family members, the internet and the ethnic media. The study gave valuable information for the design of an educational program and provided useful information for the planning of culturally appropriate hepatitis screening and treatment services for these communities.
Spatial Interaction Spillover Effects between Digital Financial Technology and Urban Ecological Efficiency in China: An Empirical Study Based on Spatial Simultaneous Equations
Authors: Su Yaya , Li Zhenghui , Yang Cunyi
Published: August 2021

As a core component of the digital economy, digital financial technology has a complex interactive and interdependent relationship with ecological efficiency. From the holistic spatial interaction perspective, this paper uses spatial simultaneous equations and generalized spatial three-stage least squares (GS3SLS) to analyze the spatial interaction spillovers between digital financial technology and urban ecological efficiency based on data from 284 Cities in China from 2008 to 2018. The results show that: (1) Digital financial technology and urban ecological efficiency promote each other, and the latter is relatively dominant. (2) Both digital financial technology and urban ecological efficiency have significant spatial spillover effects. (3) Digital financial technology in surrounding cities has a restraining effect on local ecological efficiency, and the improvement of ecological efficiency in surrounding cities has a siphon effect on local digital financial technology. (4) There is spatial and period heterogeneity in the intensity of the spatial interaction spillover effect between the two. With resources and environment increasingly becoming rigid constraints on economic growth, these findings help identify new drivers of regional ecological efficiency and promote the coordinated development of digital finance and green ecology.
Soul of the Jukskei River: The Extent of Bacterial Contamination in the Jukskei River in Gauteng Province, South Africa
Authors: Hoorzook Kousar Banu , Pieterse Anton , Heine Lee , Barnard Tobias George , van Rensburg Nickey Janse
Published: August 2021

River water quality is an important health issue as the water is utilised for drinking, domestic and agricultural use in developing countries. This study aimed to investigate the effect water from a major city has on the water quality of the Jukskei River that daylights in Johannesburg, South Africa. The river water samples were analysed for physio-chemical properties, microbiology, antibiotic resistance of bacterial isolates, genetic markers, and potentially toxic metals. Data analysis revealed increased electrical conductivity, total dissolved solids, and turbidity since 2010. Total Coliform and Escherichia coli detected were above the South African water quality guidelines for domestic, recreational, and irrigation purposes. Additionally, sodium, zinc, nickel, lithium, and lead exceeded the guidelines in domestic, recreational, and irrigation water. Pathogenic strains of E. coli (aEPEC, EHEC, EIEC, and EAEC) were isolated from the water. Various other potentially pathogenic organisms that have been implicated as causes of gastro-intestinal, and a wide range of other diseases, were also detected and demonstrated multiple levels of resistance to antibiotics tested. The results show that the river water is a potential health threat to downstream users. These results will feed into the environmental management action plan for Water for the Future (NGO group).
Pro- and Anti-Inflammatory Cytokines in the First Trimester—Comparison of Missed Miscarriage and Normal Pregnancy
Authors: Kwiatek Maciej , Gęca Tomasz , Kwaśniewska Anna
Published: August 2021

The advantage in response of Th2 over Th1 is observed in normal pregnancy in peripheral blood. A disturbance of this balance can lead to symptoms of miscarriage and pregnancy loss. The aim of this study was to evaluate the pro- and anti-inflammatory cytokines in sera of women who were diagnosed with missed miscarriage in the first trimester and to compare this systemic immune response to the response in women with normal pregnancy. The study group consisted of 61 patients diagnosed with missed miscarriage. In total, 19 healthy women with uncomplicated first trimester created the control group. Cytokines were determined in the maternal serum by ELISA. The analysis included INF-γ, TNF-α, Il-1β, Il-4, Il-5, Il-6, Il-9, Il-10, Il-13 and TGF-β1. Th1 cytokine levels in the study group reached slightly higher values for INF-γ, Il-1β and slightly lower for IL-6 and TNF-α. In turn, Th2 cytokine levels in the study group were slightly higher (Il-9, Il-13), significantly higher (Il4, p = 0.015; Il-5, p = 0.0003) or showed no differences with the control group (Il-10). Slightly lower concentration involved only TGF-β1. Analysis of the correlation between levels of pro- and anti-inflammatory cytokines resulted in some discrepancies, without showing predominance of a specific immune response. The results did not confirm that women with missed miscarriage had an advantage in any type of immune response in comparison to women with normal pregnancy.
Pregnant Women’s Experiences during Hurricane Maria: Impact, Personal Meaning, and Health Care Needs
Authors: Silva-Suarez Georgina , Rabionet Silvia E. , Zorrilla Carmen D. , Perez-Menendez Hulda , Rivera-Leon Solaritza
Published: August 2021

During a disaster, pregnant women are considered among the most vulnerable. Background: On 20 September 2017, the Caribbean was hit by a category 4 hurricane. The purpose of the study was to explore the impact on pregnant women during and after the hurricane regarding access to health care, social services, and support systems. Methods: In-depth interviews were conducted to 10 women that were pregnant during the event. Qualitative inquiry based on the Interpretative Phenomenological Analysis framework was used to interpret the narratives. Results: Five major themes emerged: meaning of living through a disaster, fear, the dual burden of protecting themselves and their unborn baby, disruption in health care, and coping mechanisms. Despite the negative feelings, most participants experienced positive transformations. They narrated how they stayed calm and coped in order to protect their pregnancy. Their overall evaluation of the healthcare system was positive. The support of friends and family was crucial pre and post-disaster. Conclusions: The interviews provided a wealth of firsthand information of women experiencing a natural disaster while pregnant. The findings underscore the need to incorporate emotional support in the preparedness and response plans for pregnant women. Educating, empowering, and incorporating families and communities is vital in these efforts.
Household Drug Management Practices of Residents in a Second-Tier City in China: Opportunities for Reducing Drug Waste and Environmental Pollution
Authors: Luo Yumei , Reimers Kai , Yang Lei , Lin Jinping
Published: August 2021

The total amount of drug waste is expanding significantly as populations age and societies become wealthier. Drug waste is becoming a problem for health and the environment. Thus, how to reduce and effectively dispose of drug waste is increasingly becoming an issue for society. This study focuses on household drug management, which involves five sub-practices: selection, purchasing, using, storing, and disposing of drugs. A questionnaire survey was conducted in a second-tier Chinese city that reveals both problems and opportunities in these five sub-practices. The results show that consumers are aware of significant issues with regard to the safe and effective use of drugs as well as with regard to proper ways of disposing of and recycling drugs. Moreover, our analysis reveals promising opportunities for addressing these issues by developing novel services based on the idea of connecting the five involved sub-practices of household drug management. Connecting and adjusting practices in this manner can be seen as an important factor in reducing drug waste and pharmaceutical pollutants.
The Regional and Local Scale Evolution of the Spatial Structure of High-Speed Railway Networks—A Case Study Focused on Beijing-Tianjin-Hebei Urban Agglomeration
Authors: He Dan , Chen Zixuan , Pei Tao , Zhou Jing
Published: August 2021

China has entered an era of rapid high-speed railway (HSR) development and the spatial structure of urban agglomerations will evolve in parallel with the development and evolution of the spatial structure of the HSR network. In this study, we explore how the spatial structure of an HSR network evolves at regional and local scales. Existing research into HSR network structures has mostly been carried out at a regional scale, and has therefore failed to reveal the spatial connections within a city. In this work, we progress the science by exploring it at a local scale. To describe the HSR network more accurately, we use the dwell time to simulate the passenger flow between stations and use the simulated passenger flow as the network weight. We use complex network analysis to investigate the evolution of the network’s spatial structure. Our results present the evolution of station locations, of community structure, and of the locations of connections between stations at a regional scale, and also show how HSR network development within core cities has impacted structures and connectivity at a local scale. These results help us to understand the spatial structure of urban agglomerations and cities, and provide evidence that can be used to optimize the structure of the HSR network within regions and cities.
Interleukin-1β in Multifactorial Hypertension: Inflammation, Vascular Smooth Muscle Cell and Extracellular Matrix Remodeling, and Non-Coding RNA Regulation
Authors: Melton Elaina , Qiu Hongyu
Published: August 2021

The biological activities of interleukins, a group of circulating cytokines, are linked to the immuno-pathways involved in many diseases. Mounting evidence suggests that interleukin-1β (IL-1β) plays a significant role in the pathogenesis of various types of hypertension. In this review, we summarized recent findings linking IL-1β to systemic arterial hypertension, pulmonary hypertension, and gestational hypertension. We also outlined the new progress in elucidating the potential mechanisms of IL-1β in hypertension, focusing on it’s regulation in inflammation, vascular smooth muscle cell function, and extracellular remodeling. In addition, we reviewed recent studies that highlight novel findings examining the function of non-coding RNAs in regulating the activity of IL-1β and its associated proteins in the setting of hypertension. The information collected in this review provides new insights into understanding the pathogenesis of hypertension and could lead to the discovery of new anti-hypertensive therapies to combat this highly prevalent disease.
Quantum Calculations of VX Ammonolysis and Hydrolysis Pathways via Hydrated Lithium Nitride
Authors: Leverant Calen J. , Priest Chad W. , Greathouse Jeffery A. , Kinnan Mark K. , Rempe Susan B.
Published: August 2021

Recently, lithium nitride (Li3N) has been proposed as a chemical warfare agent (CWA) neutralization reagent for its ability to produce nucleophilic ammonia molecules and hydroxide ions in aqueous solution. Quantum chemical calculations can provide insight into the Li3N neutralization process that has been studied experimentally. Here, we calculate reaction-free energies associated with the Li3N-based neutralization of the CWA VX using quantum chemical density functional theory and ab initio methods. We find that alkaline hydrolysis is more favorable to either ammonolysis or neutral hydrolysis for initial P-S and P-O bond cleavages. Reaction-free energies of subsequent reactions are calculated to determine the full reaction pathway. Notably, products predicted from favorable reactions have been identified in previous experiments.
From Menopause to Neurodegeneration—Molecular Basis and Potential Therapy
Authors: Cheng Yu-Jung , Lin Chieh-Hsin , Lane Hsien-Yuan
Published: August 2021

The impacts of menopause on neurodegenerative diseases, especially the changes in steroid hormones, have been well described in cell models, animal models, and humans. However, the therapeutic effects of hormone replacement therapy on postmenopausal women with neurodegenerative diseases remain controversial. The steroid hormones, steroid hormone receptors, and downstream signal pathways in the brain change with aging and contribute to disease progression. Estrogen and progesterone are two steroid hormones which decline in circulation and the brain during menopause. Insulin-like growth factor 1 (IGF-1), which plays an import role in neuroprotection, is rapidly decreased in serum after menopause. Here, we summarize the actions of estrogen, progesterone, and IGF-1 and their signaling pathways in the brain. Since the incidence of Alzheimer’s disease (AD) is higher in women than in men, the associations of steroid hormone changes and AD are emphasized. The signaling pathways and cellular mechanisms for how steroid hormones and IGF-1 provide neuroprotection are also addressed. Finally, the molecular mechanisms of potential estrogen modulation on N-methyl-d-aspartic acid receptors (NMDARs) are also addressed. We provide the viewpoint of why hormone therapy has inconclusive results based on signaling pathways considering their complex response to aging and hormone treatments. Nonetheless, while diagnosable AD may not be treatable by hormone therapy, its preceding stage of mild cognitive impairment may very well be treatable by hormone therapy.
Receptor–Receptor Interactions and Glial Cell Functions with a Special Focus on G Protein-Coupled Receptors
Authors: Guidolin Diego , Tortorella Cinzia , Marcoli Manuela , Cervetto Chiara , Maura Guido , Agnati Luigi F.
Published: August 2021

The discovery that receptors from all families can establish allosteric receptor–receptor interactions and variably associate to form receptor complexes operating as integrative input units endowed with a high functional and structural plasticity has expanded our understanding of intercellular communication. Regarding the nervous system, most research in the field has focused on neuronal populations and has led to the identification of many receptor complexes representing an important mechanism to fine-tune synaptic efficiency. Receptor–receptor interactions, however, also modulate glia–neuron and glia–glia intercellular communication, with significant consequences on synaptic activity and brain network plasticity. The research on this topic is probably still at the beginning and, here, available evidence will be reviewed and discussed. It may also be of potential interest from a pharmacological standpoint, opening the possibility to explore, inter alia, glia-based neuroprotective therapeutic strategies.
Biomaterial-Assisted Regenerative Medicine
Authors: Nii Teruki , Katayama Yoshiki
Published: August 2021

This review aims to show case recent regenerative medicine based on biomaterial technologies. Regenerative medicine has arousing substantial interest throughout the world, with “The enhancement of cell activity” one of the essential concepts for the development of regenerative medicine. For example, drug research on drug screening is an important field of regenerative medicine, with the purpose of efficient evaluation of drug effects. It is crucial to enhance cell activity in the body for drug research because the difference in cell condition between in vitro and in vivo leads to a gap in drug evaluation. Biomaterial technology is essential for the further development of regenerative medicine because biomaterials effectively support cell culture or cell transplantation with high cell viability or activity. For example, biomaterial-based cell culture and drug screening could obtain information similar to preclinical or clinical studies. In the case of in vivo studies, biomaterials can assist cell activity, such as natural healing potential, leading to efficient tissue repair of damaged tissue. Therefore, regenerative medicine combined with biomaterials has been noted. For the research of biomaterial-based regenerative medicine, the research objective of regenerative medicine should link to the properties of the biomaterial used in the study. This review introduces regenerative medicine with biomaterial.
In Vivo Neocortical [K]o Modulation by Targeted Stimulation of Astrocytes
Authors: EbrahimAmini Azin , Mylvaganam Shanthini , Bazzigaluppi Paolo , Khazaei Mohamad , Velumian Alexander , Stefanovic Bojana , Carlen Peter L.
Published: August 2021

A normally functioning nervous system requires normal extracellular potassium ion concentration ([K]o). Throughout the nervous system, several processes, including those of an astrocytic nature, are involved in [K]o regulation. In this study we investigated the effect of astrocytic photostimulation on [K]o. We hypothesized that in vivo photostimulation of eNpHR-expressing astrocytes leads to a decreased [K]o. Using optogenetic and electrophysiological techniques we showed that stimulation of eNpHR-expressing astrocytes resulted in a significantly decreased resting [K]o and evoked K responses. The amplitude of the concomitant spreading depolarization-like events also decreased. Our results imply that astrocytic membrane potential modification could be a potential tool for adjusting the [K]o.
SARS-CoV-2: Understanding the Transcriptional Regulation of ACE2 and TMPRSS2 and the Role of Single Nucleotide Polymorphism (SNP) at Codon 72 of p53 in the Innate Immune Response against Virus Infection
Authors: Lodhi Niraj , Singh Rubi , Rajput Satya , Saquib Quaiser
Published: August 2021

Human ACE2 and the serine protease TMPRSS2 of novel SARS-CoV-2 are primary entry receptors in host cells. Expression of these genes at the transcriptional level has not been much discussed in detail. The ISRE elements of the ACE2 promoter are a binding site for the ISGF3 complex of the JAK/STAT signaling pathway. TMPRSS2, including IFNβ, STAT1, and STAT2, has the PARP1 binding site near to TSS either up or downstream promoter region. It is well documented that PARP1 regulates gene expression at the transcription level. Therefore, to curb virus infection, both promoting type I IFN signaling to boost innate immunity and prevention of virus entry by inhibiting PARP1, ACE2 or TMPRSS2 are safe options. Most importantly, our aim is to attract the attention of the global scientific community towards the codon 72 Single Nucleotide Polymorphism (SNP) of p53 and its underneath role in the innate immune response against SARS-CoV-2. Here, we discuss codon 72 SNP of human p53′s role in the different innate immune response to restrict virus-mediated mortality rate only in specific parts of the world. In addition, we discuss potential targets and emerging therapies using bioengineered bacteriophage, anti-sense, or CRISPR strategies.
Current and Future Development in Lung Cancer Diagnosis
Authors: Nooreldeen Reem , Bach Horacio
Published: August 2021

Lung cancer is the leading cause of cancer-related deaths in North America and other developed countries. One of the reasons lung cancer is at the top of the list is that it is often not diagnosed until the cancer is at an advanced stage. Thus, the earliest diagnosis of lung cancer is crucial, especially in screening high-risk populations, such as smokers, exposure to fumes, oil fields, toxic occupational places, etc. Based on the current knowledge, it looks that there is an urgent need to identify novel biomarkers. The current diagnosis of lung cancer includes different types of imaging complemented with pathological assessment of biopsies, but these techniques can still not detect early lung cancer developments. In this review, we described the advantages and disadvantages of current methods used in diagnosing lung cancer, and we provide an analysis of the potential use of body fluids as carriers of biomarkers as predictors of cancer development and progression.
Hyperbilirubinemia Maintained by Chronic Supplementation of Unconjugated Bilirubin Improves the Clinical Course of Experimental Autoimmune Arthritis
Authors: Sykora Tomas , Babal Pavel , Mikus-Kuracinova Kristina , Drafi Frantisek , Ponist Silvester , Dvorakova Monika , Janega Pavol , Bauerova Katarina
Published: August 2021

Rheumatoid arthritis (RA) is a chronic multisystem disease, therapy of which remains a challenge for basic research. The present work examined the effect of unconjugated bilirubin (UCB) administration in adjuvant-induced arthritis (AIA)—an experimental model, in which oxidative stress (OS), inflammation and inadequate immune response are often similar to RA. Male Lewis rats were randomized into groups: CO—control, AIA—untreated adjuvant-induced arthritis, AIA-BIL—adjuvant-induced arthritis administrated UCB, CO-BIL—control with administrated UCB. UCB was administered intraperitoneally 200 mg/kg of body weight daily from 14th day of the experiment, when clinical signs of the disease are fully manifested, to 28th day, the end of the experiment. AIA was induced by a single intradermal immunization at the base of the tail with suspension of Mycobacterium butyricum in incomplete Freund’s adjuvant. Clinical, hematologic, biochemical and histologic examinations were performed. UCB administration to animals with AIA lead to a significant decrease in hind paws volume, plasma levels of C-reactive protein (CRP) and ceruloplasmin, drop of leukocytes, lymphocytes, erythrocytes, hemoglobin and an increase in platelet count. UCB administration caused significantly lowered oxidative damage to DNA in arthritic animals, whereas in healthy controls it induced considerable oxidative damage to DNA. UCB administration also induced atrophy of the spleen and thymus in AIA and CO animals comparing to untreated animals. Histological signs of joint damage assessed by neutrophils infiltration and deposition of fibrin were significantly reduced by UCB administration. The effects of exogenously administered UCB to the animals with adjuvant-induced arthritis might be identified as therapeutic, in contrast to the effects of UCB administration in healthy animals rather classified as toxic.
Anti-SARS-CoV-2 Strategies and the Potential Role of miRNA in the Assessment of COVID-19 Morbidity, Recurrence, and Therapy
Authors: Narożna Maria , Rubiś Błażej
Published: August 2021

Recently, we have experienced a serious pandemic. Despite significant technological advances in molecular technologies, it is very challenging to slow down the infection spread. It appeared that due to globalization, SARS-CoV-2 spread easily and adapted to new environments or geographical or weather zones. Additionally, new variants are emerging that show different infection potential and clinical outcomes. On the other hand, we have some experience with other pandemics and some solutions in virus elimination that could be adapted. This is of high importance since, as the latest reports demonstrate, vaccine technology might not follow the new, mutated virus outbreaks. Thus, identification of novel strategies and markers or diagnostic methods is highly necessary. For this reason, we present some of the latest views on SARS-CoV-2/COVID-19 therapeutic strategies and raise a solution based on miRNA. We believe that in the face of the rapidly increasing global situation and based on analogical studies of other viruses, the possibility of using the biological potential of miRNA technology is very promising. It could be used as a promising diagnostic and prognostic factor, as well as a therapeutic target and tool.
Protein Structure Analysis and Prediction with Statistical Scoring Functions
Authors: Lackner Peter , Wiederstein Markus
Published: August 2021

The PDB database provides more than 150,000 entries for biological macromolecular structures [...]
Adipose Tissue Dendritic Cells: Critical Regulators of Obesity-Induced Inflammation and Insulin Resistance
Authors: Soedono Shindy , Cho Kae Won
Published: August 2021

Chronic inflammation of the adipose tissue (AT) is a critical component of obesity-induced insulin resistance and type 2 diabetes. Adipose tissue immune cells, including AT macrophages (ATMs), AT dendritic cells (ATDCs), and T cells, are dynamically regulated by obesity and participate in obesity-induced inflammation. Among AT resident immune cells, ATDCs are master immune regulators and engage in crosstalk with various immune cells to initiate and regulate immune responses. However, due to confounding markers and lack of animal models, their exact role and contribution to the initiation and maintenance of AT inflammation and insulin resistance have not been clearly elucidated. This paper reviews the current understanding of ATDCs and their role in obesity-induced AT inflammation. We also provide the potential mechanisms by which ATDCs regulate AT inflammation and insulin resistance in obesity. Finally, this review offers perspectives on ways to better dissect the distinct functions and contributions of ATDCs to obesity.
NMDARs Containing NR2B Subunit Do Not Contribute to the LTP Form of Hippocampal Plasticity: In Vivo Pharmacological Evidence in Rats
Authors: Ahnaou Abdallah , Heleven Kobe , Biermans Ria , Manyakov Nikolay V. , Drinkenburg Wilhelmus H.
Published: August 2021

Synaptic plasticity is the key to synaptic health, and aberrant synaptic plasticity, which in turn impairs the functioning of large-scale brain networks, has been associated with neurodegenerative and psychiatric disorders. The best known and most studied form of activity-dependent synaptic plasticity remains long-term potentiation (LTP), which is controlled by glutamatergic N-methyl-d-aspartate) receptors (NMDAR) and considered to be a mechanism crucial for cellular learning and memory. Over the past two decades, discrepancies have arisen in the literature regarding the contribution of NMDAR subunit assemblies in the direction of NMDAR-dependent synaptic plasticity. Here, the nonspecific NMDAR antagonist ketamine (5 and 10 mg/kg), and the selective NR2B antagonists CP-101606 and Ro 25-6981 (6 and 10 mg/kg), were administered intraperitoneally in Sprague Dawley rats to disentangle the contribution of NR2B subunit in the LTP induced at the Schaffer Collateral-CA1 synapse using the theta burst stimulation protocol (TBS). Ketamine reduced, while CP-101606 and Ro 25-6981 did not alter the LTP response. The administration of CP-101606 before TBS did not influence the effects of ketamine when administered half an hour after tetanization, suggesting a limited contribution of the NR2B subunit in the action of ketamine. This work confirms the role of NMDAR in the LTP form of synaptic plasticity, whereas specific blockade of the NR2B subunit was not sufficient to modify hippocampal LTP. Pharmacokinetics at the doses used may have contributed to the lack of effects with specific antagonists. The findings refute the role of the NR2B subunit in the plasticity mechanism of ketamine in the model.
Therapeutic Approaches Targeting Proteostasis in Kidney Disease and Fibrosis
Authors: Chen Jia-Huang , Wu Chia-Hsien , Chiang Chih-Kang
Published: August 2021

Pathological insults usually disturb the folding capacity of cellular proteins and lead to the accumulation of misfolded proteins in the endoplasmic reticulum (ER), which leads to so-called “ER stress”. Increasing evidence indicates that ER stress acts as a trigger factor for the development and progression of many kidney diseases. The unfolded protein responses (UPRs), a set of molecular signals that resume proteostasis under ER stress, are thought to restore the adaptive process in chronic kidney disease (CKD) and renal fibrosis. Furthermore, the idea of targeting UPRs for CKD treatment has been well discussed in the past decade. This review summarizes the up-to-date literature regarding studies on the relationship between the UPRs, systemic fibrosis, and renal diseases. We also address the potential therapeutic possibilities of renal diseases based on the modulation of UPRs and ER proteostasis. Finally, we list some of the current UPR modulators and their therapeutic potentials.
Patient-Derived Organoids of Cholangiocarcinoma
Authors: Maier Christopher Fabian , Zhu Lei , Nanduri Lahiri Kanth , Kühn Daniel , Kochall Susan , Thepkaysone May-Linn , William Doreen , Grützmann Konrad , Klink Barbara , Betge Johannes , Weitz Jürgen , Rahbari Nuh N. , Reißfelder Christoph , Schölch Sebastian
Published: August 2021

Cholangiocarcinoma (CC) is an aggressive malignancy with an inferior prognosis due to limited systemic treatment options. As preclinical models such as CC cell lines are extremely rare, this manuscript reports a protocol of cholangiocarcinoma patient-derived organoid culture as well as a protocol for the transition of 3D organoid lines to 2D cell lines. Tissue samples of non-cancer bile duct and cholangiocarcinoma were obtained during surgical resection. Organoid lines were generated following a standardized protocol. 2D cell lines were generated from established organoid lines following a novel protocol. Subcutaneous and orthotopic patient-derived xenografts were generated from CC organoid lines, histologically examined, and treated using standard CC protocols. Therapeutic responses of organoids and 2D cell lines were examined using standard CC agents. Next-generation exome and RNA sequencing was performed on primary tumors and CC organoid lines. Patient-derived organoids closely recapitulated the original features of the primary tumors on multiple levels. Treatment experiments demonstrated that patient-derived organoids of cholangiocarcinoma and organoid-derived xenografts can be used for the evaluation of novel treatments and may therefore be used in personalized oncology approaches. In summary, this study establishes cholangiocarcinoma organoids and organoid-derived cell lines, thus expanding translational research resources of cholangiocarcinoma.
Recent Applications of Retro-Inverso Peptides
Authors: Doti Nunzianna , Mardirossian Mario , Sandomenico Annamaria , Ruvo Menotti , Caporale Andrea
Published: August 2021

Natural and de novo designed peptides are gaining an ever-growing interest as drugs against several diseases. Their use is however limited by the intrinsic low bioavailability and poor stability. To overcome these issues retro-inverso analogues have been investigated for decades as more stable surrogates of peptides composed of natural amino acids. Retro-inverso peptides possess reversed sequences and chirality compared to the parent molecules maintaining at the same time an identical array of side chains and in some cases similar structure. The inverted chirality renders them less prone to degradation by endogenous proteases conferring enhanced half-lives and an increased potential as new drugs. However, given their general incapability to adopt the 3D structure of the parent peptides their application should be careful evaluated and investigated case by case. Here, we review the application of retro-inverso peptides in anticancer therapies, in immunology, in neurodegenerative diseases, and as antimicrobials, analyzing pros and cons of this interesting subclass of molecules.
The Obscure Effect of Tribulus terrestris Saponins Plus Inulin on Liver Morphology, Liver Fatty Acids, Plasma Glucose, and Lipid Profile in SD Rats with and without Induced Type 2 Diabetes Mellitus
Authors: Misiakiewicz-Has Kamila , Maciejewska-Markiewicz Dominika , Rzeszotek Sylwia , Pilutin Anna , Kolasa Agnieszka , Szumilas Paweł , Stachowska Ewa , Wiszniewska Barbara
Published: August 2021

Diabetes is a predictor of nonalcoholic fatty liver disease (NAFLD). There are data suggesting that Tribulus terrestris (TT) saponins act as antidiabetic agents and protect against NAFLD. The effect of saponins may be increased by fermentable fibers such as inulin. The aim of the present study was to investigate the influence of TT saponins and TT saponins plus inulin on the plasma lipid profile and liver fatty acids of rats with induced diabetes mellitus type 2 (T2DM). The study was performed on 36 male Sprague–Dawley rats divided into two main groups: control and diabetic. Animals of the diabetic (DM) group were fed a high-fat diet and injected with streptozotocin (low doses). Animals of the control group (nDM) were on a regular diet and were injected with buffer. After the injections, the animals were split into subgroups: three non-diabetic (nDM): (i) control (c-C); (ii) saponin-treated rats (C-Sap); (iii) rats treated with saponins + inulin (C-Sap + IN), and three diabetic subgroups (DM): (iv) control (c-DM); (v) saponin-treated rats (DM-Sap); (vi) rats treated with saponins + inulin (DM-Sap + IN). Liver fatty acids were extracted and analyzed by gas chromatography, and plasma glucose and lipids were measured. The study showed significant changes in liver morphology, liver fatty acids, plasma lipid profile, and plasma glucose. In summary, supplementation with TT saponins or saponins with inulin for one month decreased the level of steatosis in rats with induced type 2 diabetes. Moreover, there were favorable effects on the plasma lipid profile in the rats. However, additional supplementation with inulin had a negative effect on liver morphology (with a microvesicular type of steatosis) in the non-diabetes group. Moreover, supplementation with inulin had a negative effect on plasma glucose in both diabetic and non-diabetic rats. These data show that a diet enriched with fermentable fibers reveals different effects in different organisms, and not all sources and forms of fiber are beneficial to health.
Pituitary Adenylate Cyclase-Activating Polypeptide (PACAP) in Physiological and Pathological Processes within the Gastrointestinal Tract: A Review
Authors: Karpiesiuk Aleksandra , Palus Katarzyna
Published: August 2021

Pituitary adenylate cyclase-activating polypeptide (PACAP) is a neuropeptide widely distributed in the central nervous system (CNS) and many peripheral organs, such as the digestive tract, endocrine, reproductive and respiratory systems, where it plays different regulatory functions and exerts a cytoprotective effect. The multifarious physiological effects of PACAP are mediated through binding to different G protein-coupled receptors, including PAC1 (PAC1-R), VPAC1 (VPAC1-R) and VPAC2 (VPAC2-R) receptors. In the gastrointestinal (GI) tract, PACAP plays an important regulatory function. PACAP stimulates the secretion of digestive juices and hormone release, regulates smooth muscle contraction, local blood flow, cell migration and proliferation. Additionally, there are many reports confirming the involvement of PACAP in pathological processes within the GI tract, including inflammatory states, neuronal injury, diabetes, intoxication and neoplastic processes. The purpose of this review is to summarize the distribution and pleiotropic action of PACAP in the control of GI tract function and its cytoprotective effect in the course of GI tract disorders.